I & I Flashcards

Question

# `Development of Immune Cells by Dr José Saldana` Define positive selection ## Footnote *LOB: Understand the concept of self/immunological tolerance

Answer 1

Only lymphocytes that express Ag receptors that can recognise Ags/MHC molecules mature & are retained in repertoire

Answer 2

Lymphocytes with Ag receptors that recognise self Ags/MHC molecules too strongly are eliminated (die by apoptosis) **PREVENTS AUTOIMMUNE**

Answer 3

Lymphocytes that express Ag receptors that do not recognise Ags/MHC molecules are eliminated (do not receive survival signals through their Ag receptors and die by apoptosis )

Answer 4

The ability to regulate immune cells to prevent autoimmune disease Recognition of self.

Answer 5

induction of tolerance to self Ags during lymphocyte development in central lymphoid organs In the thymus as only self Ags can be encountered peripheral tissue-restricted self Ags: AIRE (AutoImmune Regulator Protein) allows expression of tissue restricted peripheral self Ags in thymic medullary epithelial cells Self tolerance – mechanisms (T cells)

Answer 6

Functional unresponsiveness between immature immune cell and effector.

Answer 7

Block in activation of immature cell by TReg

Answer 8

tolerance to self Ags is induced when mature lymphocytes respond to Ags in peripheral lymphoid organs or peripheral tissues

Answer 9

Immature B cells that recognise self Ags with high avidity (strongly) in bone marrow can: - change the specificity of their Ag receptors so that they no longer recognise strongly self Ags B cell central tolerance: receptor editing - mechanism: rearranging the genes for the light chain occurs in the lymph nodes and spleen

Answer 10

T Cells: TCR CD4 CD8 Non-T Cells: MHC1 MHC2

Answer 11

tolerance to self Ags is induced when mature lymphocytes respond to Ags in peripheral lymphoid organs or peripheral tissues

Answer 12

derived from arachidonic acid (20c chain) include prostaglandins, prostacyclins, and thromboxanes These steps are triggered by many agents, e.g. thrombin on platelets and antigen-antibody reactions on mast cells

Answer 13

formed from arachidonic acid synthesized and released by immune cells, such as leukocytes (white blood cells) and mast cells.

Answer 14

deriving from "eicosa," which means twenty, referring to the 20 carbon chain arachadonic acid

Answer 15

**Inflammatory steps (5Rs)** Recognition of the injurious agent Recruitment of leukocytes Removal of the agent Regulation (control) of response Resolution (repair) – inflammation initiates repair

Answer 16

**H1 - Gq/PLC**, PIP2 production, generation of **DAG/IP3**, PKC: smooth muscle, endothelium, CNS, sensory nerves **H2 - Gs/AC, **generation of **cAMP**, stimulation of PKA: parietal cells, heart, uterus, mast cells, neutrophils H3 - Gi, decrease in cAMP levels: neuronal presynaptic terminals (autoreceptor: ↓ release of histamine) H4 - Gi, decrease in cAMP levels: basophils, bone marrow, gut

Answer 17

**Exposure**: TB spreads when someone with active TB coughs or sneezes, releasing bacteria into the air that can be inhaled by others. **Infection**: Not everyone exposed gets infected. The immune system usually keeps the bacteria in check, leading to latent TB infection (LTBI). ** Latent TB Infection (LTBI)**: In LTBI, bacteria are dormant, causing no symptoms, and individuals are not contagious. A chest X-ray is often normal. However, they can develop active TB if their immune system weakens. ** Active TB Disease:** Immune system compromise can lead to reactivation of the bacteria, causing active TB with symptoms like cough, fever, night sweats, weight loss, and fatigue. Active TB is contagious and spreads through the air.

Answer 18

1. Inhalation 2. Alveolar macrophages 3. Lymph nodes 4. Haematogenous spread to other parts of lung via lymphatics and capillaries 5. A brief acute inflammatory response - neutrophils, cytokine storms macrophage recruitment and activation 6. recruitment of CD4, CD8 and NK cells - production of IFN- 7. Down regulation of acute inflammation  chronic inflammation 8. Formation of granuloma - immune containment 9. Caseation 10. Liquifaction, cavitation and release 11. Transmission Pathogenesis

Answer 19

All G-protein-coupled receptors which produce physiological effects by activating second messenger systems Synthesised, stored and released from: – Mast cells, which express receptors for IgE, C3a and C5a on cell surface (connective tissues) – Basophils (blood) – Neurons in brain – Histaminergic cells in gut (ECL, enterochromaffin-like cells) Released by allergic reactions (IgE-mediated), production of complement agents (C3a and C5a), insect stings, trauma, etc. through a rise in [Ca2+]i

Answer 20

Conversion of Arachadonic Acid to prostanoids requires the enzyme cyclooxygenase (COX) **COX 1:** Constitutively active, involved in regulation of peripheral vascular resistance, renal blood flow, platelet aggregation, gastric cytoprotection **COX 2:** Needs to be stimulated (e.g. by inflammatory cytokines- IL-1, TNF) - Responsible for role of PGs/TXs in inflammatory responses (pain and fever) | COX 3 is similar to COX 1 but pain perception of CNS

Answer 21

**Cardiovascular** dilates arterioles, ↓ TPR (H1) Increased permeability of post-capillary venules, ↓ BV (H1) Increase in heart rate (H2) - in vivo reflex to try to retain BP to normal Generally involved in ↓BP (↓ vascular resistance) **Non-vascular smooth muscle (airways, gut etc.)** Contraction (H1), e.g. bronchoconstriction Algesia Pain, itching, and sneezing caused by stimulation of sensory nerves (H1) Associated exocrine secretions Increased, due to increased blood flow **Gastric acid** Increase secretion (H2 –mediated effects are of interest)

Answer 22

Characterised by reddening, wheal and flare. Refers to LOCAL histamine response **Reddening (Rubor):** initial response to histamine release in the skin. localized vasodilation Increased blood flow leads to redness and warmth **Wheal**: raised, swollen, and palpable area at the site of histamine release the increased permeability of capillaries, allows fluid to accumulate **Flare**: spreading of redness beyond the immediate area due to the dilation of larger blood vessels

Answer 23

Sensory nerves and **C fibers**, are involved in the perception of pain and sensory information during inflammation. Substance P is released from C fibers Substance P contributes to **vasodilation** The **orthodromic** (normal direction) and **antidromic** (opposite direction) responses of sensory nerves can influence the spread of pain signals and inflammation. This leads to a flare of the original inflammation beyond its micro localised area.

Answer 24

When histamine stimulates **afferent** fibres, it is known to stimulate an axon reflex: It **orthodromically** stimulates nerve impulse which travel towards the spinal cord and the dorsal root ganglia, passing antidromically **down the other branches of sensory nerves**. These antidromic impulses release nerve impulses → **vasodilation** (flare, reddening) distant from the site of irritation This is now being explored as reasoning for migraines dermatographia

Answer 25

**Bradykinin** Synthesised by activation of: Hageman factor (HF, factor XII) & production of plasma kallikrein *(makes sense when you think of wound healing)* Production of lysylbradykinin by tissue kallikreins; Action of cellular proteases

Answer 26

Potent vasoactive peptide with wide-ranging effects: Increases vascular permeability Promotes vasodilation (↓BP) Pain Contraction of visceral smooth muscle (gut and bronchus) Stimulation of arachidonic acid metabolism (initiates phospholipase action → release of numerous lipid mediators of inflammation) Chemotactic to leukocytes, which defend the body against infections Dry cough (*sensitization of airway sensory nerves via rapidly adapting stretch receptors and C-fiber receptors and substance P)* Metabolism of bradykinin: kininases, I and II (ACE, aminopeptidase P, carboxypeptidase)

Answer 27

H1 Antagonists – Treat Acute Inflammation *such as mepyramine, promethazine, diphenhydramine, Terfenadine* H2 Antagonists – Gastric Problems *such as cimetidine, famotidine*

Answer 28

**H1** Reduce minor inflammatory reactions (e.g. insect bites, hay fever), BUT NO significant value in asthma – 1st generation drugs are sedative – drowsiness is a major side effect, but sometimes used as a therapeutic effect – Some (e.g. promethazine) are anti-emetic – ‘motion sickness’ – Anti-muscarinic actions (common in 1st generation drugs) e.g. atropine-like effects of blurred vision, constipation, etc. H1 Antagonists – Treat Acute Inflammation **H2** Reduce gastric acid secretion in the treatment of duodenal and gastric ulcers and Zollinger-Ellison syndrome (duodenum & pancreas tumours increasing gastrin secretion) – Increase INMT activity so more rapid breakdown of histamine – Mental confusion, dizziness, tiredness & diarrhoea sometimes as side effects – Cimetidine decreases cytochrome P450 activity so potential for adverse drug interactions; gynecomastia

Answer 29

NSAIDs Glucocorticoids Lipoxygenase inhibitors Leukotriene antagonists Conversion of AA to prostanoids requires the enzyme cyclooxygenase (COX) **COX-1 **is constitutively expressed at low levels in many cell types. The expression of **COX-2** is highly regulated. ***For example Aspirin interacts with thromboxane synthase and Epoprostenol interacts with prostacyclin synthase****

Answer 30

**Inflammation**: Example: Prostaglandins and leukotrienes **Vasoconstriction and Vasodilation: **Example: Prostacyclin (PGI2) promotes vasodilation, and thromboxane A2 (TXA2) promotes vasoconstriction. **Pain and Fever: **Example: Prostaglandins sensitize pain receptors and raise body temperature, leading to fever. **Platelet Aggregation: **Example: Thromboxane A2 (TXA2) Bronchoconstriction: Example: Leukotrienes, particularly leukotriene D4 (LTD4) **Regulation of Blood Flow: **Example: Prostaglandins **Gastrointestinal Protection: **Example: Prostaglandins **Reproductive Function: **Example: Prostaglandins **Immunomodulation**: Example: Various eicosanoids can influence immune cell function, including prostaglandins and leukotrienes.

Answer 31

This is important to allow **resolution** to occur. Recruit monocytes for clearance **CyPG** **CYCLIC PROSTAGLANDINS** – inhibits macrophage activation→ ↓ uncontrolled tissue damage; ↓NF-B activation (helps to ↓ activation of inflammatory genes)

Answer 32

Eicosanoids, such as thromboxane A2 (TXA2), play a crucial role in hemostasis. Thromboxane A2 is produced by platelets and promotes vasoconstriction and platelet aggregation. imbalance- clotting disorders

Answer 33

prostaglandins, are significant regulators of the gastrointestinal system. Prostaglandins help maintain the integrity of the gastrointestinal mucosa by promoting the secretion of mucus and bicarbonate. This protective action helps prevent damage to the stomach lining and the development of gastric ulcers. NSAIDs that inhibit this can cause ulcers

Answer 34

↑ cellular infiltration of eosinophils, neutrophils ↑ mucus secretion ↑ bronchoconstriction (similar to vascular mechanism) ↑ airway oedema Leuokotriene are more potent. Smooth muscle cells in the bronchial airways express receptors for leukotrienes. Gs -> PLC -> IP DAG

Answer 35

Receptor blockade is useful in following: Prevention of mild to moderate asthma Early to late bronchoconstrictor effects of allergens Exercise-induced asthma and asthma provoked by NSAIDs Side effects: GI upset Dry mouth, thirst Rashes, oedema Irritability

Answer 36

Pleural disease Lymph nodes – scrofula Pericardial Skeletal –Potts disease Genitourinary Gut Peritoneal Miliary Meningeal

Answer 37

**Granuloma Formation: **Immune response to M. tuberculosis leads to granulomas, organized collections of immune cells like macrophages and lymphocytes, containing the bacteria and preventing their spread. **Caseous Necrosis: **Within granulomas, infected tissue undergoes caseous necrosis, a type of tissue death causing a cheese-like appearance. Accumulation of this necrotic material can create lung cavities. ** Ghon Focus and Ghon Complex: **Initial infection can result in a Ghon focus, a small lung lesion where bacteria enter. If the immune response successfully controls the infection, it forms a Ghon complex, combining the Ghon focus with associated lymph node involvement. **Miliary TB:** In severe cases, the infection can disseminate via the bloodstream, leading to miliary TB. It involves widespread distribution of small TB lesions throughout various organs, resembling millet seeds. **Fibrosis and Scarring:** The immune system's efforts to control the infection often lead to fibrosis and scarring, particularly in affected organs like the lungs.

Answer 38

eading cause of morbidity and mortality worldwide High prevalence in developing countries Significant impact on children and the elderly Increased risk in crowded or unsanitary living conditions Major contributors to healthcare costs and economic burden

Answer 39

Sudden onset of symptoms High fever Productive cough with purulent sputum Shortness of breath Chest pain Systemic symptoms (fatigue, malaise)

Answer 40

Gradual onset of symptoms Low to moderate fever Dry or minimally productive cough Runny or stuffy nose Sore throat Headache and muscle aches

Answer 41

Nasal congestion Sneezing Runny nose Sore throat Cough (usually dry) Mild fever Generalized malaise

Answer 42

Persistent cough with or without sputum Shortness of breath Chest discomfort or pain Wheezing or difficulty breathing Fever and chills Cyanosis in severe cases

Answer 43

Streptococcus pneumoniae (most common) Haemophilus influenzae Mycoplasma pneumoniae Chlamydia pneumoniae Staphylococcus aureus Legionella pneumophila Influenza virus Respiratory syncytial virus (RSV) Klebsiella pneumoniae (especially in older adults and those with underlying conditions)

Answer 44

Parainfluenza viruses (especially type 1) In some cases, other respiratory viruses like influenza, adenovirus, and respiratory syncytial virus (RSV)

Answer 45

Haemophilus influenzae type b (Hib) used to be the most common cause in children (before the introduction of the Hib vaccine). Streptococcus pneumoniae and Streptococcus pyogenes (Group A Streptococcus) can also cause epiglottitis. In adults, various bacteria, including Staphylococcus aureus and Streptococcus species, can be responsible.

Answer 46

Bacterial Tonsillitis: Streptococcus pyogenes (Group A Streptococcus) is a common bacterial cause of tonsillitis. It can lead to a condition known as streptococcal pharyngitis or strep throat. Viral Tonsillitis: Numerous respiratory viruses can cause viral tonsillitis, including: Rhinovirus (common cold) Adenovirus Epstein-Barr virus (EBV, causing infectious mononucleosis) Influenza virus Herpes simplex virus Cytomegalovirus (CMV) Other Possible Causes: Fungal infections, although rare, can lead to tonsillitis. Candida species are typically responsible for fungal tonsillitis.

Answer 47

Viral Pharyngitis: Rhinovirus (common cold) Adenovirus Influenza virus Epstein-Barr virus (EBV, causing infectious mononucleosis) Enteroviruses Coronavirus (including SARS-CoV-2, which causes COVID-19) Bacterial Pharyngitis (Strep Throat): Streptococcus pyogenes (Group A Streptococcus) is the most common bacterial cause of pharyngitis in children and adults. Other Bacterial Causes (Less Common): Mycoplasma pneumoniae Chlamydia pneumoniae Neisseria gonorrhoeae (usually in the context of sexual transmission) Arcanobacterium haemolyticum Corynebacterium diphtheriae (causing diphtheria, a rare but serious condition)

Answer 48

Laboratory Investigations: Respiratory Viral PCR Testing: Collect respiratory specimens (nasopharyngeal swabs, sputum) for PCR testing. Identify common viruses like influenza, respiratory syncytial virus (RSV), and SARS-CoV-2 (COVID-19). Microbiological Cultures: Obtain sputum or tracheal aspirates for bacterial culture and sensitivity testing. Useful for diagnosing bacterial pneumonia and determining appropriate antibiotics. Blood Tests: Complete Blood Count (CBC): Evaluate white blood cell count and differential to assess for infection. C-reactive protein (CRP) and Procalcitonin: Markers of inflammation and infection. Chest X-ray: Consider a chest X-ray for patients with severe or atypical symptoms. Useful for detecting pneumonia and assessing lung involvement. Additional Investigations (if indicated): Pulse Oximetry: Measure oxygen saturation, especially in patients with respiratory distress. Arterial Blood Gas (ABG) Analysis: Assess oxygen and carbon dioxide levels in severe cases. Bronchoscopy: May be necessary in select cases for obtaining deeper respiratory samples. Viral Serology: In some cases, serological tests may be used to detect past infections or antibodies (e.g., for Mycoplasma pneumoniae or other atypical pathogens). Molecular Testing: Polymerase chain reaction (PCR) testing for atypical pathogens like Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophila may be considered in specific clinical scenarios. Urine Antigen Tests: Utilize urine antigen tests to diagnose Streptococcus pneumoniae or Legionella pneumophila in certain cases. Consider Comorbidities: Evaluate underlying conditions (e.g., chronic lung disease, immunosuppression) that may influence diagnosis and management. Patient Isolation: Based on clinical and laboratory findings, implement appropriate infection control measures to prevent the spread of contagious RTIs. Consultation: Collaborate with microbiologists, radiologists, and infectious disease specialists for challenging cases. Antibiotic Stewardship: Prescribe antibiotics judiciously, guided by laboratory results and clinical assessment, to combat antibiotic resistance.

Answer 49

Increased Inflammation Mucus Production Bronchospasm Worsening Airway Obstruction Reduced Lung Function Exacerbation of Symptoms Increased Risk of Hospitalization Prolonged Recovery Potential for Long-Term Damage

Answer 50

Persistent Cough: A cough that lasts for more than three weeks is one of the most common symptoms of TB. Coughing Up Blood or Phlegm: Sometimes, coughing may produce blood-tinged sputum. Chest Pain: Pain or discomfort in the chest, often localized. Fever: Low-grade or high-grade fever, especially in the afternoon or evening. Night Sweats: Profuse sweating, particularly during the night. Unintentional Weight Loss: Significant weight loss without diet or exercise changes. Fatigue: Persistent tiredness and weakness. Loss of Appetite: A reduced desire to eat and a general feeling of malaise. Shortness of Breath: Difficulty breathing or shortness of breath, especially with physical activity. Swelling of Lymph Nodes: Enlarged and tender lymph nodes, typically in the neck or under the armpits.

Answer 51

Tuberculin Skin Test (TST) or Interferon-Gamma Release Assay (IGRA) Chest X-ray Sputum Smear Microscopy Sputum Culture Nucleic Acid Amplification Tests (NAATs) Bronchoscopy Tissue Biopsy Blood Tests HIV Testing Drug Susceptibility Testing (DST) Chest CT Scan Tuberculosis Contact Tracing

Answer 52

Mature naïve B cells express a membrane-bound IgM Ag recognition by membrane IgM => activation of signalling pathways => B cell activation

Answer 53

Co express IgD and IgM IgM is the 1st immunoglobulin to be produced; Ag receptor

Answer 54

During an immune response B cells become capable to produce Abs of different classes but without changing specificity (respond to the same Ag)- IgM switch to => IgG, IgA, IgE IgG switch to => IgA, IgE Isotype switching does not alter specificity for Ag ! Isotype switching does not alter the light chain !

Answer 55

1. CD40L on T cell interacts with CD40 on activated B cells 2. Cytokines produced by T cell IFN-γ => switch to IgG1, IgG3 IL-4 => switch to IgE TGF-β, IL-5 => switch to IgA

Answer 56

Abs retain already rearranged variable regions whilst exchanging constant regions for different Ig classes

Answer 57

Limited no of genes for diversity of antigen receptors. Variable regions= gene segments. - VH encoded in 3 gene segments (V, D, J) - VL encoded in 2 gene segments (V, J) - Gene segment recombination => Ab diversity Gene segment recombination = random arrangement of gene segments in different combinations: SOMATIC DNA RECOMBINATION T and B cells Gene segments rearrangements (VDJ/VJ) take place during B cell development in bone marrow Immature B cells: 1st: successful VDJ rearrangement => heavy chain produced 2nd: successful VJ rearrangement => light chain produced Mature naïve B cells express full IgM/antigen receptor

Answer 58

Sustained B cell proliferation and differentiation. Plasma cells or memory B cells. Grows in size with immune response, disappears when infection cleared. 3-4 weeks More effective antibodies vs primary focus. Dark zone vs light zone Somatic hypermutation and Affinity maturation. Survival of B cell that has a high affinity for the antigen.

Answer 59

Over 10^7-10^9 different types of B cells generated randomly Each of these B cells makes a different antibody B cells generated in bone marrow where they go through different developmental stages Naive B cells populate lymph nodes/spleen and ‘wait’ for antigens In the presence of Infection, Antigens are recognised by lymphocyte clone with the specific antigen receptor for that antigen => expansion of antigen-specific clone => generation of Abs specific for that Ag only

Answer 60

two identical heavy chains + two identical light chains held together by disulphide bonds 5 types of heavy chains: μ,γ,α,δ,ε (IgM, IgG, IgA, IgD, IgE) 2 types of light chains: κ,λ Heavy chain (H): 3-4 constant (C) domains + 1 variable (VH) domain Light chain (L): 1 constant domain and 1 variable (VL) domain Variable domains: amino acid sequence varies highly between different immunoglobulins Antigen binding site: VL + VH

Answer 61

Process of introducing mutations in the variable region of Immunoglobulins (rearranged VDJ/VJ) Initiated by enzyme AID expressed in Germinal centre B cells only. Mutations with decreased affinity for binding to Ag= NEGATIVE selection (majority) Mutations with decreased affinity for binding to Ag= POSITIVE selection higher affinity antibodies => stronger cell signalling; faster proliferation of B cells => advantage over low affinity B cells Role of T cell in selection

Answer 62

**Goal: Production of high affinity antibodies = more efficient. ** Abs produced early during primary (1st) immune response have lower affinity (weak binding) for antigen Later 1st immune response/ 2nd immune responses => production of high affinity antibodies Achieved through process of Somatic Hypermutation

Answer 63

**Follicular B cells** recognise protein antigens => antibodies (anti-protein Ag) produce mainly high-affinity IgG class/switched antibodies **Marginal zone B cells** recognise polysaccharide; glycolipid; nucleic acid antigens produce mainly IgM class antibodies **B-1 cells** peritoneal cavity, mucosal tissues recognise polysaccharide; glycolipid; nucleic acid antigens produce mainly natural low-affinity IgM class antibodies

Answer 64

Innate System Cascade complex Activation of small soluble heat sensitive protein that can combine and create complexes with proteolytic activity. RECOGNITION OPSONISATION EFFECTOR- inflammation, phagocytosis and membrane attack

Answer 65

RECOGNITION Innate recognition of non self Antibodies Apoptopic cells OPSONISATION EFFECTOR- Lysis, Inflammation, Phagocytosis. OTHER FUNCTIONS: Chemotaxis, adhesion of inflammatory cells Vascular permeability, contraction of smooth muscle cells Disposal of waste- clearance of immune complexes and apoptotic cells

Answer 66

3 DISTINCT PATHWAYS Antibody triggered (Classical) Presence of pathogen alone (Alternative) Lectin type protein activation (Lectin) 1 COMMON PATHWAY -Terminal pathway- lysis

Answer 67

When antibodies bind Formation of C1 Complex Cascade Activation: C1 activation sets off a series of reactions (a cascade), leading to the activation of other complement proteins, like C4 and C2. C3 Convertase Formation: The activated C4 and C2 proteins join together to form a new complex called C3 convertase. C3 Activation: C3 convertase then activates a protein called C3, splitting it into C3a and C3b. Effector Functions: C3b helps tag the invader for destruction by immune cells and also contributes to the formation of a membrane attack complex (MAC) that punches holes in the invader's membrane, leading to its destruction.

Answer 68

Spontaneous Activation: "always-on" mode of the complement system, activated by small amounts of complement proteins present in the blood. C3 Activation: Spontaneous activation causes a protein called C3 to split into C3a and C3b, similar to the classical pathway. Effector Functions: C3b helps tag invaders for destruction and contributes to the formation of the membrane attack complex (MAC), which can damage and kill invaders.

Answer 69

Lectins recognize sugar molecules on the surface such as bacteria. Complex Formation Cascade Activation leading to the activation of complement proteins like C4 and C2. C3 Activation: The activated C4 and C2 proteins combine to form C3 convertase, which then activates C3, splitting it into C3a and C3b. Effector Functions: C3b helps label the invader for destruction and contributes to the formation of the membrane attack complex (MAC), which can damage and kill the invader.

Answer 70

Formation of MAC membrane attack complex a group of complement proteins that come together and create holes in the membranes of invaders

Answer 71

Protection against Self-Attack Avoidance of Excessive Inflammation Prevention of Autoimmunity Minimization of Infection Risk Tissue Homeostasis Prevention of Allergic Reactions Protection of Host Microbiota Preservation of Cellular Integrity Fine-Tuning of Immune Responses Avoidance of Chronic Inflammation Minimization of Secondary Tissue Damage

Answer 72

**Atypical haemolytic uraemic syndrome AHUS** Genetic Defects: Thrombocytopenia Microangiopathic haemolytic anaemia Acute renal failure Failure to control the alternative pathway **Paroxysmal Nocturnal Haemoglobinuria (PNH)** Lack of glycosylphosphatidylinositol protein in host cells walls reduces anchoring of CD55 and CD59 control factors on erythrocytes Susceptible to lysis C3b accumulates on Erythrocyte Surface Activation of complement Terminal/ Mac pathway Destruction of Erythrocytes

Answer 73

T cells recognise antigen processed and presented by APC APCs process antigens into peptides (for αβ T cells) peptides bind to MHC molecules peptide:MHC complexes are presented on the APC surface **CD4+ helper T cells: antigens (peptides) displayed by MHC class II CD8+ cytotoxic T cells: antigens (peptides) displayed by MHC class I**

Answer 74

B cells recognize antigens directly through their surface immunoglobulins

Answer 75

Dendritic cells → the only APCs capable to present to naïve T cells (occurs in lymph node) Macrophages → present to previously activated effector T cells (Ag presentation to effector CD4+ T cells (Th1)) B cells → present to previously activated effector T cells (presentation peptides to effector CD4+ T cells (Th2)) (- regulate class switch (e.g. IFN-γ & IgG; IL-4 & IgE))

Answer 76

MHC:peptide // TCR (B7 family) CD80:CD86 // CD28 Cytokines (IL-12)

Answer 77

2 chains: α and β (most common TCR type) *(γ and δ (TCR in γδ T cells) )* each chain: 1 variable (V) domain + 1 constant (C) domain Antigen binding site formed by: Vα + Vβ V and C domains of TCR and BCR are homologous

Answer 78

**MHC I:** presentation of peptides to** CD8**+ T cells composed of α chain + β2-microglobulin MHC I: all nucleated cells **MHC II**: presentation of peptides to **CD4**+ T cells composed of α chain + β chain MHC II: antigen presenting cells: dendritic cells macrophages

Answer 79

Extracellular antigens are engulfed by APCs. Antigens are broken down into peptides in endosomes. Peptides are presented by MHC II to CD4+ T cells. CD4+ T cells are activated to help B cells and other immune responses.

Answer 80

Intracellular antigens are processed by the proteasome. Peptides are transported to the endoplasmic reticulum and loaded onto MHC I. MHC I-peptide complex is presented on the cell surface for CD8+ T cell recognition. CD8+ T cells are activated to kill infected cells.

Answer 81

Prevention of Anergy: Co-stimulation helps prevent the induction of anergy (unresponsiveness) in T cells. In the absence of co-stimulatory signals, T cells may become tolerant to the antigen and lose their ability to mount an immune response Also: * Discrimination Between Self and Non-Self * Immune Tolerance * Immune Memory * Balancing Immune Responses * Preventing Hyperactivation

Answer 82

All blood cells have antigens A and B antigens very common (55% UK) Anti-A, anti-B or anti-A,B antibodies very common (97% UK) AA or AO -> **A** BB or BO -> **B** OO -> **O** AB -> **AB**

Answer 83

Most important antigen is called D. People with D antigen are D positive (85% of UK) People who do not produce any D antigen are D negative (15%) The other 4 main Rh antigens are known as C, c, E and e D antigen is very immunogenic and anti-D is easily stimulated

Answer 84

Rh antibodies are usually IgG and can cause haemolytic disease of the newborn. Anti-D is still most common cause of severe HDN D antigens from the developing fetus can enter the mother’s blood during delivery The mother will produce anti-D antibodies In a following pregnancy anti-D antibodies will cross the placenta and damage the fetus

Answer 85

Through blood tests. If a mother is Rh-negative and has not been sensitized, she is usually given a drug called Rh immunoglobulin, or RhoGAM. An injection of anti-D will bind to and remove any fetal D positive red cells in the circulation In some hospitals 2 smaller (500 iu) doses are given at 28 and 34 weeks instead of the 1 larger dose Anti-D is also given after any event that may cause a feto-maternal haemorrhage (bleed between mum and fetus) such as: Abdominal trauma Intrauterine death Spontaneous or therapeutic abortion

Answer 86

An acute immune hemolytic reaction ABO antibodies can activate complement causing INTRAVASCULAR HAEMOLYSIS

Answer 87

* Test patient’s red cells with anti-A, anti-B and anti-D * Agglutination shows that a particular antigen is on the red cells * No agglutination shows the antigen is absent

Answer 88

Patients serum is mixed with 3 selected screening cells, incubated for 15 minutes at 37oc and then centrifuged for 5 minutes. Any clinically significant antibodies reacting at body temp should be detected and then identified using panel of known phenotyped red cells.

Answer 89

Used to detect IgG antibodies Uses low ionic strength saline Results in agglutination Used for: Screening for antibodies Identifying antibodies Cross-matching donor blood with recipient plasma when there are known antibodies or a previous history of antibodies. **NOTE COOL SCIENCE** IgM antibodies can span the gap between RBCs IgG can not, because too small to overcome ZETA potential (+ve charge) LISS (low ionic strength saline) is negatively charged, so neutralises positive ZETA potential. Therefore IgG can now span the gap.

Answer 90

Trying to detect IgG IgM antibodies can span the gap between RBCs IgG can not, because too small to overcome ZETA potential (+ve charge) LISS (low ionic strength saline) is negatively charged, so neutralises positive ZETA potential. Therefore IgG can now span the gap.

Answer 91

**Immediate spin cross-match (ISX)** Antibody screen is negative Checking donor red cells against patients plasma ABO check Incubate for 2 – 5 minutes (room temp), spin and read. **Full Indirect Antiglobulin test (IAT) cross-match** Antibody screen positive or patient has known antibody history. Select antigen negative donor red cells and incubate with patient serum for 15 minutes at 37oC

Answer 92

Natural genetic variance causing variance in blood group

Answer 93

Media that allow the **differentiation of different** bacterial species based on specific growth characteristics or biochemical reactions. Example: MacConkey's agar, which differentiates lactose fermenters from non-fermenters based on the ability to produce acid and turn the agar pink.

Answer 94

Media that **selectively inhibit **the growth of certain types of bacteria while allowing others to thrive. Example: Mannitol salt agar, which selects for halophilic bacteria like Staphylococcus species while inhibiting the growth of most other bacteria.

Answer 95

Media that provide a**dditional nutrient**s to support the growth of fastidious or nutritionally demanding bacteria. Example: Blood agar, which contains blood to support the growth of a wide range of bacteria, including those with complex nutritional requirements.

Answer 96

Incomplete hemolysis of red blood cells, resulting in a greenish discoloration around bacterial colonies on blood agar. Complete hemolysis of red blood cells, leading to a clear zone around bacterial colonies on blood agar.

Answer 97

Bacteria that can metabolize lactose to produce acid and gas.

Answer 98

Bacteria that can grow in the absence of oxygen.

Answer 99

: Blood agar is valuable for identifying bacterial species based on their hemolytic activity (alpha or beta hemolysis) and their ability to utilize blood components for growth. It can help differentiate between different Streptococcus species and other pathogens.

Answer 100

MacConkey's agar is useful for identifying lactose fermenters from non-fermenters. It is commonly used in the identification of Enterobacteriaceae, including Escherichia coli, based on their ability to ferment lactose.

Answer 101

An increased number of bacteria in a urine specimen, especially in midstream or catheterized samples, is often indicative of a urinary tract infection (UTI). Normally, urine is sterile or contains only a small number of commensal bacteria. The extent of bacterial growth can be quantified by colony-forming units (CFUs) per milliliter of urine, with a high CFU count indicating a more severe infection.

Answer 102

: Commensal bacteria commonly found in the nasopharynx include Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus.

Answer 103

Commensal organisms on the skin can include Staphylococcus epidermidis, Corynebacterium species, and various yeast species like Candida.

Answer 104

Bacteroides, Firmicutes, and Escherichia coli.

Answer 105

Lactobacillus species, which help maintain the acidic pH and prevent overgrowth of pathogenic bacteria.

Answer 106

Analgesic Anti-pyretic Anti-inflammatory Treat: Low grade pain, Bone pain, Fever, Inflammation

Answer 107

COX converts AA to PGs and TXs COX-1 (constitutively active, platelets) COX-2 (inducible enzyme e.g. by IL-1β & TNFα) Inhibition of COX-2 reduces PGs/TXs inflammatory agents Aspirin acts irreversibly on COX; others act reversibly and this is significant in its use as a prophylactic in cardiovascular disease

Answer 108

Endotoxins from bacteria release IL-1β IL-1β at hypothalamus releases PGE2 PGE2 depresses temperature sensitive neurons and causes fever by elevating end point of body temp NSAIDs block PGE2 production Reduces fever back to normal body temperature. Doesnt affect core Body Temp

Answer 109

PGs sensitise and stimulate nociceptors PGs interact with other pain producing substances (e.g. kinins, 5-HT, histamine) to produce hyperalgesia and pain sensitivity Blockade of PG production leads to pain relief

Answer 110

PGE2 and PGI2 have powerful acute inflammatory effects Aspirin inhibits the activation of NF-B Inhibition of their formation reduces redness and swelling NSAIDs provide only ‘symptomatic relief’

Answer 111

Not really Weakly inhibits COX-3 in CNS Analgesic Not anti-inflammatory

Answer 112

↓ mucus secretion: ↓ HCO3-: ↑ acid secretion: ↑ LT production: ↑ blood loss: Interfere with tissue healing (COX-2 inhibition) Nausea, dyspepsia, GI contraction (COX-1 inhibition)

Answer 113

Aminosalicylates (5-ASA) target inflammation in the colon by inhibiting the production of prostaglandins and leukotrienes. Corticosteroids to reduce inflammation. Immunomodulators suppress the immune system to reduce inflammation by inhibiting the proliferation of immune cells. Biologics block cytokines (e.g., TNF-α) involved in the inflammatory process. Janus Kinase (JAK) Inhibitors Mechanism: Inhibit the activity of JAK enzymes, which are involved in immune signaling and inflammatory pathways. Common Examples: Tofacitinib.

Answer 114

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) to inhibit COX Colchicine disrupts microtubules in inflammatory cells, reducing their ability to migrate and respond to urate crystals.

Answer 115

NSAIDs (Nonsteroidal Anti-Inflammatory Drugs) to reduce COX Corticosteroids to suppress inflammation Disease-Modifying Antirheumatic Drugs (DMARDs) Biologics target specific cytokines

Answer 116

Good bacteria, local colonies our microbiota effect on mood weight cancer etc

Answer 117

asymptomatic until immune system reduced such as MRSA and nasal flora

Answer 118

is the process by which a disease develops or the mechanism through which a particular disease or condition is cause

Answer 119

What causes disease: Promote colonisation and adhesion Can evade immune defences Promote tissue damage SUCH AS: Adherence factors, Invasion factors Capsules Endotoxins Exotoxins Siderophores (iron binding)

Answer 120

Colonization refers to the establishment of microorganisms on or within a host, without necessarily causing disease. In the context of normal flora, colonization involves the presence of non-pathogenic microorganisms in or on the body, which can help protect the host and prevent the growth of harmful pathogens.

Answer 121

Asymptomatic carriage refers to the presence of a pathogen in a host without causing any noticeable symptoms or disease. In some cases, individuals may carry pathogens without getting sick themselves but can still potentially transmit the pathogen to others.

Answer 122

3 types Local: surface or epithelial such as V Cholera Invasvie: penetrates barriers such as a wound such as Shigella, Staph A Systemic: via blood and lymph to multiple sites, S.typhi | Can have effects at different site to colony

Answer 123

Inflammation Cross reactive antigens (rheumatic heart disease) Granuloma (TB) !Not the bacteria but the body response)

Answer 124

Natural barriers Defensive cells Complement Immune response Commensal bacteria

Answer 125

Colonize mucosal sites by using pili (fimbriae) to adhere to cells.

Answer 126

Polysaccharides protect from opsonisation and phagocytosis.

Answer 127

Protein toxins and enzymes produced and/or secreted suchas cytotoxins, neurotoxins, enterotoxins,

Answer 128

Days to weeks Acquisition Colonisation and Adherence Penetration Multiplication and spread Immune evasion Damage Transmission and shedding Resolution | Note: disease not always required for transmission- asymptomatic sheddin

Answer 129

inflammatory response, immune cell activation, cytokine storms, toxin production, immune-mediated damage, vascular damage, secondary infections, tissue ischemia, and host-microbiota disruption

Answer 130

T1) S.aureus TSST T1) Streptococcus pyogenes erythrogenic toxin Scarlet fever T2) Staphylococcus aureus α-toxin Τ2) Strep.pyogenes streptolysin Τ2) Strep.pneumoniae pneumolysin T2) Clostriduim perfringens- GANGRENE T3) Classified by enzyme action or molecular target and effect T3) cholera; diphtheria;pertussis T3) C.difficile Botulism; tetanus

Answer 131

Type 1 - at cell membrane - not transported in Type II - on cell membrane - membrane damage Type III - intracellular effect after translocation Extracellular - cellular matrix or connective tissue

Answer 132

Disruption of Cellular Function Direct Damage Neurological Effects Fluid and Electrolyte Imbalance Inflammation Systemic Effects Immune System Modulation Secondary Complications Tissue and Organ Damage

Answer 133

A microorganism has to: Be present in every case of the infection. Be cultured from cases in vitro. Reproduce disease in an animal. Be isolated from the infected animal. **HOWEVER** Not possible for non-culturable organisms e.g. leprosy, syphilis Need molecular tests e.g. PCR - e.g. HepC What about food poisoning – B. cereus and toxins - no infection with organism, but disease

Answer 134

* Adherence and Colonization * Invasion * Toxin Production: * Inflammation and Immune Response: * Immune Evasion: * Tissue Damage: * Dissemination/ systemic inflammation * Secondary Infections * Adaptive Immune Response: * Antibiotic Resistance: * Host factors such as age

Answer 135

Recognition of Bacterial Pathogens Recruitment of Immune Cells Neutrophil Infiltration Macrophage Activation Release of Antimicrobial Proteins Phagocytosis and Killing Inflammatory Response Amplification Local Tissue Damage Systemic Effects Resolution of Inflammation

Answer 136

Facilitate bacterial invasion of host tissues by breaking down the extracellular matrix. Collagenase produced by Clostridium species.

Answer 137

Directly damage host cells and interfere with cellular functions. Contribute to tissue damage, immune response disruption, and sepsis pathogenesis. Staphylococcus aureus produces exotoxins, such as Toxic Shock Syndrome Toxin-1 (TSST-1).

Answer 138

Stimulate a potent and uncontrolled immune response, leading to systemic inflammation. Release of proinflammatory cytokines contributes to organ dysfunction in sepsis. Lipopolysaccharides (LPS) in the cell walls of Gram-negative bacteria like Escherichia coli.

Answer 139

Influenza virus, Candida fungi, Plasmodium parasites causing malaria.

Answer 140

SS is a specific condition associated with the release of bacterial exotoxins, such as the toxic shock syndrome toxin-1 (TSST-1) produced by Staphylococcus aureus. TSST-1 acts as a superantigen, stimulating a massive immune response. HOW: Binds to MHC Class II Molecules directly Cross-linking with T Cell Receptors Activation of T Cells Uncontrolled release of proinflammatory cytokines Systemic Inflammatory Response

Answer 141

Formation of Immune Complexes Antibodies binding to antigens, including those from infectious agents. Tissue Deposition Immune complexes deposit in various tissues. Inflammation and Tissue Damage Immune complexes trigger inflammation and tissue damage in affected organs. Examples Immune complex-mediated glomerulonephritis, systemic lupus erythematosus (SLE).

Answer 142

Pathogen Antigens Resembling Host Molecules Pathogens express antigens that structurally resemble host molecules. Cross-Reactive Immune Responses Immune responses (antibodies or T cells) target both pathogen and host antigens. Autoimmune Diseases Autoimmune diseases can develop as the immune system mistakenly attacks host tissues. Examples Rheumatic fever (Streptococcus pyogenes), Guillain-Barré syndrome (Campylobacter jejuni).

Answer 143

Induction of Autoimmunity Infections can initiate or exacerbate autoimmune responses. Mechanisms Molecular mimicry, bystander activation, epitope spreading. Autoimmune Diseases Immune response targets self-antigens due to cross-reactivity. Examples Multiple sclerosis (Epstein-Barr virus), Type 1 diabetes (enteroviruses).

Answer 144

Hypersensitivity Reactions Allergic and hypersensitivity reactions can result from microbial antigens. Sensitization to Microbial Antigens Exposure to microbial antigens triggers immune responses. Clinical Manifestations Allergies, asthma, and other hypersensitivity disorders may develop. Examples Allergic rhinitis (pollens), asthma (dust mites, mold), food allergies.

Answer 145

The isolate is inoculated on semisolid agar medium with antibiotic impregnated discs and incubated for 18-20 hours. The diameter of the zone of inhibition of growth around the disc is measured and the bacterium is categorised as resistant, intermediate or susceptible depending on the zone size and pre-defined criteria

Answer 146

Disc diffusion zones correspond to minimum inhibitory concentrations (MIC) MIC have been pre-determined by testing large numbers of organisms using disc-diffusion and quantitative methods in parallel. Each antibiotic has a “breakpoint” MIC for a particular bacterial species. If the concentration **needed to inhibit** the bacterium is **below the breakpoin**t, the bacterium is **susceptible**. If the concentration is** higher than the breakpoint**, the bacterium is **resistant**.

Answer 147

Minimum bactericidal concentration - MBC the lowest concentration of an antibacterial agent required to kill a bacterium over a fixed, somewhat extended period, such as 18 hours or 24 hours, under a specific set of conditions.

Answer 148

As the amount of antibiotics that bind to serum proteins will vary between individuals determine the precise amount of the drug that is bound to serum proteins and how much is free in the blood, in order to be able to accurately** calculate the optimum dosage** ** avoid the risks associated with potentially toxic levels**

Answer 149

Nanotechnology, Assays, Breath tests,

Answer 150

measuring bacterial growth in the presence of the antibiotic being tested Disc diffusion

Answer 151

antimicrobial substance active against bacteria

Answer 152

Natural products of fungi and bacteria - soil dwellers - natural antagonism and selective advantage - kill or inhibit the growth of other microorganisms most derived from natural products by fermentation, then modified chemically :- incr pharmacological properties; incr antimicrobial effect Some completely synthetic - sulphonamides

Answer 153

* Competition for Resources * Predation and Defense * Biofilm Formation * Nutrient Cycling * Communication and Signaling * Virulence Regulation * Antibiotic Resistance Mechanisms * Symbiotic Relationships * Biological Control

Answer 154

Selective toxicity Good killing activity Slow emergence of resistance Narrow spectrum of activity Non-toxic to host Long plasma half-life Oral and parenteral dosing forms No interaction with other drugs

Answer 155

Distribution in body - relative to distribution of bacteria - some not absorbed from gut - many do not cross blood-brain barrier - some do not penetrate abscess - few accumulate inside cells Spectrum of activity - cidal or static Toxicity Excretion Patient age (renal capacity) Route of administration (oral , i/v i/m, topical) Clinical condition Type of bacteria Sensitivity of bacteria - mechanism of action of antibiotic - resistance mechanisms Cost Specialist - Medical Microbiologist - Local Policies

Answer 156

Therapeutic index (TI) = a ratio comparing the blood concentration at which a drug becomes toxic and the ratio at which it is effective active dose (MIC) versus toxic effect ** The larger the TI, the safer the drug **

Answer 157

Mechanism of action exploits differences in structure and metabolic pathways between host and pathogen Aim: harm microorganisms, not the host More difficult for viruses (intracellular), fungi and parasites (more similar to host cells)

Answer 158

Broad versus narrow spectrum Appropriate at different stages of infection Patient is unwell, cause of sepsis is unknown -> start with broad spectrum Results of cultures and other Ix come back, patient improving -> rationalise to targeted choice

Answer 159

Cell Wall Synthesis Protein Synthesis Nucleic Acid Synthesis Metabolic Pathways Cell membrane function

Answer 160

Peptidoglycan Lipopolysaccharide Teichoic Acids (gram positive) Lipoteichoic Acids (gram positive)

Answer 161

Cross links: PBPs catalyze the cross-linking of adjacent peptide chains within the peptidoglycan layer. This provides structural integrity However, PBPs are a target for antibiotics like penicillins and cephalosporins. These antibiotics contain a β-lactam ring, which binds to and inhibits PBPs.

Answer 162

Beta lactams target PBP, prevent crosslinking This disruption weakens the cell wall, and as the bacterium grows and divides, it is unable to form a strong, intact cell wall. This eventually leads to cell lysis and death. Gram positive

Answer 163

enzymes that chemically modify or degrade antibiotics, rendering them inactive. Beta-lactamase enzymes break down the β-lactam ring present in antibiotics like penicillins and cephalosporins so they cannot break the cell wall.

Answer 164

Altered target resistance involves changes in the target of an antibiotic within the bacterium MRSA strains have altered penicillin-binding proteins (PBPs), making them less susceptible to β-lactam antibiotics like penicillin. ** PBPs reduce the binding affinity of the antibiotic**

Answer 165

Bacteria can develop alternative metabolic pathways that bypass the steps inhibited by an antibiotic. By acquiring or amplifying genes encoding an alternative. such as encoding an alternative enzyme that is not affected by an antibiotic, allowing them to synthesize folate despite the antibiotic's presence

Answer 166

changing the transport systems that allow antibiotics to enter the bacterial cell or expel them, preventing effective drug uptake or increasing drug efflux. multidrug-resistant Escherichia coli may have increased expression of efflux pumps, preventing the buildup of antibiotics

Answer 167

Often polymicrobial Often form at site of foreign bodies e.g. prosthetic joints Bacteria secrete a protective matrix Decrease in gradient of nutrients and oxygen -> decrease in metabolic activity -> elevates proportion of persistent bacteria

Answer 168

1. penicillinase that degrades beta-lactam ring 2. Porin mutates or new porin type 3. PBP - mutates or bacteria acquires a new PBP 4. . Efflux pumps pump out the Penicillin more efficiently

Answer 169

the process by which a virus transfers genetic material from one bacterium to another. Viruses called bacteriophages

Answer 170

a major horizontal gene transfer mechanism through which DNA is transferred from a donor to a recipient bacterium by direct contact.

Answer 171

transformation is the genetic alteration of a cell resulting from the direct uptake and incorporation of exogenous genetic material from its surroundings through the cell membrane.

Answer 172

Plasmid Acquisition Resistance Gene Presence Horizontal Gene Transfer Selective Advantage/ Survival Plasmid Replication independently to daughter cells and horizontal. The resistance genes may encode for proteins or enzymes that protect against anitbiotics such as inactivating pores, or strengthening cell wall glycans.

Answer 173

Incomplete Treatment Courses leads to selective advantage survival bias. Overuse and Inappropriate Prescribing Self-Medication and Non-Prescription Use: Suboptimal Antibiotic Choice Antibiotic Use in Agriculture leads to resistance which can cross into human population

Answer 174

* Antibiotic Stewardship ( NICE and UKHSA provide guidelines and recommendations to make informed decisions) * Targeted Therapy: * Dosing and Duration: * Patient Education: * Infection Control: * Surveillance and Monitoring: * Research and Innovation:

Answer 175

Gram negative have a cell wall which protects against Beta-lactams. Gram negative LPS can select for entry, neutralize or modify the action of some antibiotics. Gram-negative bacteria often possess efflux pumps that are better than gram positive Gram-negative and Gram-positive bacteria may have different genetic characteristics and enzymes that affect antibiotic sensitivity and resistance. For example, the production of β-lactamases, enzymes that break down β-lactam antibiotics, is more common in Gram-negative bacteria.

Answer 176

Breakdown of protein and fats (muscle wasting, etc.) Decreased glucose usage & increased gluconeogenesis Tendency to hyperglycaemia and increased glycogen storage

Answer 177

Decrease in both microvascular permeability & vasodilatation Hypertension

Answer 178

Negative feedback on both hypothalamus & pituitary gland

Answer 179

Decreased microvascular fluid exudation - Reduces influx of cells to areas of inflammation Decreased inflammatory mediators and cytokines - Decrease expression of COX-2 - Reduced levels of eicosanoids - Decreased levels of cytokines and complement levels Decreased function of inflammatory effector cells - Inhibition of cell migration and mediator release - Reduced clonal expansion of T and B cells (↓ adaptive immunity) - Reduction in chronic inflammatory events - NB healing and repair are inhibited | Results in impaired keratinocyte migration

Answer 180

mood changes, linked with changes in memory/stress

Answer 181

increase hemoglobin and red cell content of blood ( demonstrated by the occurrence of polycythemia in Cushing disease and mild normochromic anemia in Addison disease) A single dose of cortisol results in a 70% decrease in lymphocytes and a 90% decrease in monocytes

Answer 182

Adrenal insufficiency or failure (Addison’s disease) congenital or drug-induced treatment requires combined GC and MC Treatment of inflammation asthma, rhinitis, skin disorders, sports injuries, reduction of cerebral oedema in patients with brain tumours Immunosuppression inhibit graft v host reaction in tissue transplantation Examples of glucorcoticoids: Hydrocortisone, prednisolone, dexamethasone, betamethasone, beclomethasone

Answer 183

1) Interaction of steroid/receptor with promoter regions - these gene promoters have ‘glucocorticoid response elements’ (GREs) and occupancy of GREs turn on/off certain genes 2) Steroid/receptor complexes PREVENT gene activation by other transcription factors - e.g. AP-1, NFkB: transcription factors involved in switching on COX-2; PLA2, IL-1, ICAM-1, IL-8, eotaxin, IκB-α etc. Induction of IκBα (inhibitor of NF-κB) which causes NF-κB repression

Answer 184

Adrenal insufficiency e.g. Addison’s disease Orthostatic hypotension (postural hypotension) Failure of baroreceptor reflex Electrolyte disorders - cerebral salt wasting Example: Fludrocortisone

Answer 185

Think Aldosterone Sodium & water retention → hypertension Potassium and H+ loss- disturbance of acid base balance calcium loss.

Answer 186

Cushing’s syndrome Opportunistic infection Osteoporosis Gastric ulceration Growth suppression Behavioural or reproductive problems Prolonged HPA suppression after cessation of therapy Diabetes Hypertension Cataracts, etc.

Answer 187

Glucocorticoids (zona fasciculata) ‘Sugar’ hormone, carbohydrate & protein metabolism Potent anti-inflammatory / immunosuppressant Mineralocorticoids (zona glomerulosa) ‘Salt’ hormone, controls electrolyte & H2O in the kidney

Answer 188

Type and organisation of genome *DNA/RNA *Single stranded/double stranded *Genome relatedness *Viral replication strategy *For example does it go through reverse transcription? *Structure and size of the virion *Does it have an envelope? *Viral structure – most are icosahedral Host range *Tissue tropism *Pathogenicity *Mode of transmission *Physiochemical properties *Antigenic properties of the virion

Answer 189

Envelope Viral gp120 & gp41 2 copies of RNA Reverse transcriptase Integrase Protease

Answer 190

Herpesviridae •Icosahedral nucleocapsid •dsDNA linear •Enveloped •Latency and reactivation

Answer 191

lipid envelope ●this is derived from the host cell membrane. proteins including: ●hemagglutinin (HA), ●neuraminidase (NA), ●and an ion channel protein (matrix protein 2, M2) ●These are embedded in the lipid bilayer of the viral envelope. The ribonucleoprotein complex comprises viral RNA segments associated with the viral proteins. ●The matrix (M1) protein is associated with both ribonucleoprotein and the envelope.

Answer 192

Most common viral hepatitis •Picornaviridae family •Naked •Icosahedral •Single stranded RNA •+ve sense

Answer 193

Hepadnaviridae family •Enveloped •42nm Icosahedral nucleocapsid •Circular DNA partially double stranded •Complete virus and incomplete particles •Tubular filaments & spherical particles composed of envelope proteins – hep B surface antigen

Answer 194

Flaviviridae family •Enveloped •Icosahedral nucleocapsid •Single stranded RNA •NS1 non structural protein 1 •E proteins are major envelope proteins of the virus

Answer 195

Reoviridae Double stranded RNA RNA segmented 11 Non enveloped Triple layer capsule Icosahedral structure Structural proteins and non structural proteins

Answer 196

Caliciviridae •27nm •Icosahedral •Non-enveloped •Single stranded RNA •Old name Norwalk virus

Answer 197

Paramyxovirus •pleomorphic •enveloped •helical nucleocapsid •ss RNA linear genome

Answer 198

Enveloped •RNA single stranded •Negative sense •Paramyxoviridae •Pleomorphic •100-300nm

Answer 199

Togavirus family •enveloped •ssRNA •icosahedral

Answer 200

Different serotypes exist Adenoviridae •No envelope •Icosahedral •DNA double stranded, linear

Answer 201

Herpes Simplex Virus (HSV): Cold sores Genital herpes Influenza Virus: Influenza (flu) Hepatitis A Virus (HepA): Hepatitis A Hepatitis B Virus (HepB): Hepatitis B Hepatitis C Virus (HepC): Hepatitis C Rotavirus: Gastroenteritis (especially in children) Norovirus: Gastroenteritis Mumps Virus: Mumps Measles Virus: Measles Rubella Virus: Rubella (German measles) Enteroviruses: Various, including hand, foot, and mouth disease Adenovirus: Respiratory and gastrointestinal infections

Answer 202

Influenza Subtyped according to its surface antigens - haemagglutinin (HA) and neuraminidase (NA) Viral attachment- uses haemagglutinin to attach to sialic acid ●Internalised by endocytosis Inside endosome pH is low ●Virus envelope fuses with the endosome membrane ●Triggers uncoating Viral nucleocapsid released into cytoplasm Viral RNA is single stranded – negative sense mRNA translated in cytoplasm ●Early viral proteins, that is, those required for replication and transcription, are transported back to the nucleus. ●Late in the infection cycle, proteins facilitate the nuclear export of newly synthesized viral RNPs. RNA segments assembled within nucleocapsid ●The assembly and budding of progeny virions occurs at the plasma membrane.

Answer 203

Rota virus infects intestinal epithelium VP7 and VP4 are important for attachment and entry dsRNA replicates inside virus and leaves via VP6 channel Virus enters endoplasmic reticulum to acquire outer shell and be released

Answer 204

Initial Infection Replication in Parent Transmission to Offspring - Transovarial Transmission (In Ova) - Transplacental Transmission Replication in Offspring Continuation of the Cycle Such as Hepatitis B

Answer 205

positive-sense (also positive (+) or simply sense) if its nucleotide sequence corresponds directly to the sequence of an RNA transcript which is translated or translatable into a sequence of amino acids negative-sense (also negative (−) or antisense), and is reverse complementary to both the positive-sense strand

Answer 206

The surface antigens of Influenza A mutate rapidly because: ●Virus has an enzyme involved in virus replication - RNA polymerase ●This enzyme has low selectivity ●Enzyme has no proof reading mechanism

Answer 207

**Host Immune System:** The strength and effectiveness of the host's immune response. **Host Genetics:** Genetic factors that may affect susceptibility to certain viruses. **Age**: Infants, the elderly, and individuals with weakened immune systems are often more susceptible. **Health Status:** Pre-existing health conditions and nutritional status. **Viral Tropism:** The ability of the virus to infect specific cells or tissues. **Exposure and Transmission:** The frequency and type of contact with infected individuals or vectors. **Vaccination or Prior Infection:** Immunity acquired through vaccination or previous exposure. **Virus Strain:** Variability in viral strains and their ability to infect. **Environmental Factors**: Environmental conditions that may affect viral stability and transmission.

Answer 208

The first encounter between a host and a specific virus. Example: Primary infection with the varicella-zoster virus (VZV) causes chickenpox. A new infection with the same virus after the primary infection has resolved. Example: Secondary infection with VZV can occur as shingles (herpes zoster) after chickenpox.

Answer 209

Infection with the same virus strain after recovery from a prior infection. Example: Reinfection with the same strain of the common cold virus.

Answer 210

A dormant or latent virus becomes active again. Example: Reactivation of VZV from latency can cause shingles.

Answer 211

Direct Cell-to-Cell Spread: VZV can move directly between cells, often in neurons, to evade immune surveillance. Bloodstream Dissemination: The virus can enter the bloodstream, facilitating systemic spread. Neuronal Transport: VZV can use neurons to travel to different areas of the body, leading to latent infections and reactivation. Respiratory Spread: VZV can be expelled from the respiratory tract during infection, leading to transmission to other hosts.

Answer 212

Latency: Some viruses, like VZV and herpes simplex virus, establish latency in neurons, avoiding immune detection. Immune Evasion: Viruses can adapt to evade host immune responses. Cell-to-Cell Spread: Viruses can use cell-to-cell transmission, reducing exposure to the immune system. Antigenic Variation: Some viruses mutate their surface proteins, making them less recognizable to the immune system. Release decoy particles

Answer 213

* Papillomavirus has to override the cell cycle * Virus infects basal layers * Migrates to cell nucleus * Genome established as independent episome * Copies of viral DNA made E2 (Early 2) protein regulates HPV gene expression and replication; binds to the viral DNA and control the expression, including E6 and E7. E6 and E7 are the key oncoproteins involved in HPV-associated carcinogenesis. E6 targets the host protein p53 for degradation, preventing it from initiating apoptosis and cell cycle arrest. E7 interacts with the retinoblastoma (Rb) protein, disrupting its normal function. leads to the accumulation of genetic mutations in infected cells. if the viral oncoproteins are not cleared by the immune system, cancer

Answer 214

ability of pathogens to **alter their surface antigens** or markers to escape the host immune system's recognition

Answer 215

Bacteria alternately switch the expression of specific surface molecules, such as pili or adhesins, to evade the host immune system. This is a reversible change in surface structures

Answer 216

gradual genetic change in a pathogen that results in minor variations in surface antigens. reduced recognition by the immune system Needs updated vaccines.

Answer 217

sudden and major genetic change in a pathogen, often seen in influenza viruses. reassortment or exchange of genetic material between different strains, leading to the emergence of a completely new subtype.

Answer 218

The influenza virus has two major surface proteins: hemagglutinin (HA) and neuraminidase (NA), which are the target of the host immune response. Antigenic drift leads to gradual changes in HA and NA, making it challenging for the immune system to recognize the virus. This necessitates the development of updated vaccines each flu season.

Answer 219

Escape from Immune Recognition Reduced Cross-Immunity Viral Drift and Shift Antigenic Drift Antigenic Shift Prolonged Viral Shedding Enhanced Host Tropism Transmission Across Geographic Boundaries Challenges for Vaccination

Answer 220

**AVOID COMPLEMENT** **failure to trigger:** LPS, capsules **negative binding**: coating with non-fixing IgA Capsule blocks C3b binding Capsule prevents C3b receptor access **disrupt regulation** Factor H sequestration **block/expel MAC** C5a proteases , blebbing

Answer 221

Staphylococcus: leucocidins kill Mφ and protein A binds Fc of IgG to prevent opsonisation. Meningococcus and Hib: capsules block contact with immune cells. Intracellular pathogens: Promote own uptake (safe) - CR3; mannose lectin receptors Prepares cell for invasion - Shigella Inhibit Phagosome-lysosome fusion - M. tuberculosis Escape Phagosome-lysosome to cytoplasm - Listeria Resist oxidative killing - produce catalases/peroxidases

Answer 222

Bacterial Example (Phase Variation): Neisseria gonorrhoeae can alternate expression of pili and opacity-associated proteins (Opa) on its surface, allowing it to evade immune detection and facilitate host colonization. Viral Example (Antigenic Drift): Influenza viruses accumulate genetic mutations, leading to changes in HA and NA proteins, which allows the virus to evade pre-existing host immunity.

Answer 223

Bacterial capsular polysaccharides are components of the bacterial capsule that surrounds the cell acts as a physical barrier It prevents the recognition and binding of bacterial cells by immune cells Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, use capsular polysaccharides.

Answer 224

bacterium continuously alters the surface expression of specific proteins known as **pili** and **opacity-associated proteins (Opa proteins).** Pili facilitate adherence to host cells and tissues. Opa proteins, are involved in attachment to host cells and immune evasion. Variation in these proteins can result in evasion of immune system as the binding mechanisms are new and thus not "recognised"

Answer 225

Viral Culture Polymerase Chain Reaction (PCR) Serological Tests Antigen Detection Tests Next-Generation Sequencing (NGS) Immunofluorescence Assays (IFA) Enzyme-Linked Immunosorbent Assay (ELISA) Loop-Mediated Isothermal Amplification (LAMP) Direct immunofluorescence Immunochromatographic methods Nucleic acid amplification test (NAAT)

Answer 226

**Method**: Viral culture involves inoculating clinical samples onto specific cell lines or culture media to promote the growth of the virus. The growth is observed through the development of cytopathic effects (CPE) or other characteristic changes in the cultured cells. **Advantage**: Viral culture allows for the isolation and subsequent characterization of the virus, determining its sensitivity to antiviral drugs, and providing valuable information for epidemiological studies. **Disadvantage**: It is a time-consuming process, taking several days to weeks for results. It requires specific cell lines and expertise, and it may not be suitable for fast diagnosis or all types of viruses. | Influenza viruses, herpesviruses, noroviruses.

Answer 227

**Method**: PCR amplifies viral nucleic acids (DNA or RNA) by repeatedly cycling through a series of temperature changes, which leads to the exponential amplification of specific target sequences. It involves denaturation, annealing of primers, and extension by a DNA polymerase. **Advantage**: PCR is highly sensitive and specific, capable of detecting low viral loads, and can identify and subtype various viral strains. It is a well-established technique for viral diagnosis. **Disadvantage**: PCR requires specialized equipment, trained personnel, and knowledge of the viral sequence to design primers. It is susceptible to contamination and false positives. | SARS-CoV-2 (COVID-19), HIV, Hepatitis B and C viruses.

Answer 228

**Method**: Serological tests detect antibodies produced by the host's immune system in response to viral infection. This is typically done through ELISA, where viral antigens are immobilized, and antibodies from the patient's serum bind to them. **Advantage**: Serological tests are useful for diagnosing past infections, monitoring immune response, and seroprevalence studies. They are relatively simple and cost-effective. **Disadvantage**: These tests are not suitable for early infection detection and may give false negatives during the acute phase of the disease. Cross-reactivity with related viruses or previous vaccinations can occur. | HIV, Hepatitis B and C, Syphilis (Treponema pallidum).

Answer 229

**Method**: Antigen detection tests use antibodies that specifically bind to viral proteins or antigens in clinical samples, resulting in a visible signal, such as a colored line. **Advantage**: These tests provide rapid results, often within minutes, and are suitable for point-of-care testing. They don't require expensive equipment or specialized training. **Disadvantage**: Sensitivity can vary between different tests and may not detect all viral strains or mutants. False negatives are possible, especially with low viral loads. | SARS-CoV-2 (COVID-19), Influenza A and B viruses, Streptococcus pneumoni

Answer 230

**Method**: NGS is a high-throughput sequencing technique that identifies viral genetic material through massively parallel sequencing, allowing for the analysis of millions of DNA or RNA fragments simultaneously. **Advantage**: NGS provides comprehensive genetic information, enabling the identification of novel or mutated viral strains and detailed epidemiological studies. **Disadvantage**: It requires expensive equipment, extensive bioinformatics expertise for data analysis, and may not be suitable for routine diagnostics due to time and resource constraints. | Mycobacterium tuberculosis (for drug resistance testing), Zika virus (f

Answer 231

**Method**: IFA uses fluorescently labeled antibodies to detect viral antigens in clinical samples. The sample is exposed to labeled antibodies, and if viral antigens are present, they will bind to the antibodies, producing a fluorescent signal. **Advantage**: IFA is useful for identifying viruses in tissue samples and is a valuable tool for direct detection. **Disadvantage**: It is less sensitive than PCR and can be labor-intensive. Additionally, it requires trained technicians and specialized equipment for interpretation. | Influenza A and B viruses (IFA for detecting viral antigens), Chlamydia

Answer 232

**Method**: ELISA detects viral antigens or antibodies through enzyme-linked reactions. Viral antigens or antibodies in the sample bind to immobilized molecules on the plate, and an enzyme-conjugated secondary antibody produces a color change. **Advantage**: ELISA is versatile and suitable for large-scale testing, as it can be automated. It's widely used for seroprevalence studies and diagnostic screening. **Disadvantage**: Sensitivity and specificity can vary between different ELISA assays, and cross-reactivity may occur. | HIV (ELISA for antibody detection), Rotavirus (ELISA for antigen detect

Answer 233

**Method**: Similar to IFA, direct immunofluorescence is used for the rapid detection of viruses in clinical samples. Fluorescently labeled antibodies bind to viral antigens in the sample. **Advantage**: It is faster than viral culture and is a valuable tool for rapid diagnosis. **Disadvantage**: Like IFA, it requires trained technicians and specialized equipment for interpretation. | Respiratory syncytial virus (RSV), Chlamydia trachomatis

Answer 234

**Method**: Immunochromatographic tests involve the use of specific antibodies bound to a strip. The sample, when applied, migrates along the strip and interacts with labeled antibodies or antigens, leading to the formation of visible lines. **Advantage**: Immunochromatographic tests provide quick results, often within minutes, and do not require specialized equipment or expertise. **Disadvantage**: They have limited sensitivity, primarily provide qualitative results (positive/negative), and may be subject to potential cross-reactivity. | SARS-CoV-2 (COVID-19 rapid antigen tests), Influenza A and B viruses, St

Answer 235

**Method**: NAAT is a broad category that includes various techniques like PCR and LAMP. It amplifies viral nucleic acids for detection, typically through the use of specific primers and probes. **Advantage**: NAATs are highly sensitive, specific, and provide rapid results. They are widely used for diagnosing various viral infections . **Disadvantage**: NAATs require specialized equipment and trained personnel, making them less suitable for point-of-care testing. They are also more expensive compared to some other tests. | SARS-CoV-2, Neisseria gonorrhoeae, Chlamydia .Viral load of HIV

Answer 236

**Method**: LAMP is an isothermal nucleic acid amplification technique that amplifies DNA at a constant temperature. It uses multiple primers and a DNA polymerase with strand-displacement activity. **Advantage**: LAMP provides quick results, requires less expensive equipment, and is well-suited for resource-limited settings. **Disadvantage**: It is limited to certain viruses, and specificity can be an issue, especially when dealing with closely related strains. | Human African Trypanosomiasis, various parasitic diseases.

Answer 237

The **antiviral** drugs target diverse group of viruses such as herpes, hepatitis, and influenza viruses. Whereas **antiretroviral** are the drugs that are used to fight retrovirus infections which mainly include HIV

Answer 238

**Adsorption** – virus binds to host cell Drugs that block or modify host receptor **Penetration/uptake**- uncoating and virus genome now in host cell **Inhibit transport of virus, prevent uncoating** **Virus genome replication** (interfere with viral RNA and DNA strand synthesis) Several different processes are possible depending on type of virus **Inhibit enzymes** and other factors involved in viral RNA and/or DNA synthesis Production of viral proteins and enzymes **Inhibit expression of gene/translation** **Inhibit action of formed enzyme** **Maturation** - assembly of virion Inhibit full assembly of the virus Release of mature virus If virus cannot leave cell, it cannot infect others

Answer 239

Obligate intracellular parasites Antiviral needs to be intracellular Viruses use host cell receptors to gain entry Receptor has important host functions Replicates in cell and may use some host enzymes/proteins These also have important functions for the host Genetic integration (HIV, HBV) ? Impossible target RNA viruses have high mutation rate (quasispecies) Rapid development of resistance Latency common (e.g. Herpes viruses) Metabolically relatively inert, thus difficult to target

Answer 240

NRTIs are antiviral drugs that interfere with the reverse transcription process of retroviruses, such as HIV. They are incorporated into the viral DNA chain, preventing further synthesis. Examples include zidovudine (AZT) and tenofovir.

Answer 241

These agents interfere with the replication of DNA viruses like herpesviruses. Examples include acyclovir, valacyclovir, and cidofovir.

Answer 242

NNRTIs inhibit the reverse transcriptase enzyme in HIV without being incorporated into the viral DNA. Efavirenz and nevirapine are examples of NNRTIs used in HIV treatment. | All have '-vir' in the middle of their name (exception: fusion inhibitor

Answer 243

Integrase is an enzyme that is crucial for the replication of retroviruses, such as HIV. Integrase inhibitors target this enzyme, preventing the integration of the viral DNA into the host cell's genome. | All have '- tegr' in the middle of their name like Raltegravir

Answer 244

block the fusion of the viral envelope with the host cell membrane, thus preventing the virus from entering interfering with the interaction between the viral envelope protein (gp41 in the case of HIV) and the host cell receptor (CD4 and CCR5 or CXCR4 co-receptors). Only two drugs: THINK - The tide (enfuvirtide) fuses with the rocks (maraviroc)

Answer 245

* exaggerated or inappropriate immune response * Result tissue damage * Types I-IV

Answer 246

* Pollen * Animal hair * House dust mite * Moulds * Insect bites * Food – peanuts * Latex * Medicine - penicillin

Answer 247

Protease Inhibitors: Inhibit HIV protease to prevent virus maturation (e.g., atazanavir, darunavir). CCR5 Inhibitors: Block host cell CCR5 co-receptor to prevent certain HIV strains from infecting cells (e.g., maraviroc). Fusion Inhibitors: Interfere with viral envelope-cell membrane fusion to prevent virus entry (e.g., enfuvirtide). Polymerase Inhibitors: Target viral RNA/DNA polymerase enzymes, used against various viral infections (e.g., sofosbuvir for hepatitis C). Maturation Inhibitors: Disrupt virion assembly to prevent mature virus release. Repurposed Drugs: Reuse drugs developed for other purposes to treat viral infections (e.g., remdesivir for COVID-19). Vaccines: Induce immunity by training the immune system to recognize and combat viruses.

Answer 248

* Immediate Hypersensitivity * B lymphocytes recognise the antigen and present to Th2 * Th2 cells secrete IL4 * IL4 induces B cells to switch class and produce IgE * IgE binds to mast cells by its tail end the Fc * region * On second exposure * Allergen binds to Antibody on Mast Cells * Mast Cells contain histamine * Histamine causes all effects.

Answer 249

* Cytotoxic Hypersensitivity * (IgG or IgM) targeting antigens on the surface of host cells * Antibody binding to self-antigens leads to cell destruction through complement activation or antibody-dependent cell-mediated cytotoxicity (ADCC) * Tissue damage occurs, and inflammation occurs.

Answer 250

Hemolytic disease of the newborn (HDN) due to Rh incompatibility. Autoimmune hemolytic anemia (AIHA), where antibodies attack red blood cells. Myasthenia gravis, where antibodies target acetylcholine receptors on muscle cells.

Answer 251

Immune Complex-Mediated Hypersensitivity Antigen can be own tissue or foreign material Immune complexes (antigen-antibody complexes) form in the circulation and deposit in various tissues, activating complement and recruiting inflammatory cells. This results in widespread inflammation, tissue damage, and vasculitis.

Answer 252

* Delayed-Type Hypersensitivity * T cell mediated –but dendritic cells, macrophages * and cytokines contribute to the disease process * * Antigen-presenting cells (APCs) present the antigen to CD4+ or CD8+ T cells. * CD4+ T cells release cytokines, activating macrophages and promoting inflammation. * CD8+ T cells directly attack and damage target cells.

Answer 253

* Contact dermatitis, like poison ivy rash, triggered by exposure to an allergen. * Mantoux test/tuberculin skin test is an example * Ulcerative colitis and Crohn’s disease * type I diabetes: * Beta cells in islets of Langerhans * Act as autoantigen

Answer 254

* Genetic Predisposition (such as HLA) * Loss of Immune Tolerance (such as MS) * Dysregulation of Regulatory T Cells (Tregs) (rheumatoid arthritis) * Immunologic Memory (SLE) * Chronic Inflammation and Cytokine Dysregulation: * Environmental Triggers (Hypothyroidism) * Specific autoantigens * Drugs (Patients on treatment for ventricular arrhythmia (procainamide) develop SLE) * Immunodeficiency (C1q inhibitor deficiency) *

Answer 255

Common Autoimmune Condition: Type 1 Diabetes (T1D) Genetic Predisposition: Inherited genetic factors, particularly HLA class II genes such as HLA-DR and HLA-DQ, increase susceptibility to T1D. Environmental Triggers: Viral infections, dietary factors, and early childhood exposures contribute to the initiation of autoimmune responses against pancreatic beta cells. Loss of Self-Tolerance: Autoimmune destruction of pancreatic beta cells occurs due to a breakdown in immune tolerance, leading to insulin deficiency. Role of Autoantibodies: Autoantibodies targeting pancreatic beta cell antigens, such as insulin, glutamic acid decarboxylase (GAD), and islet antigen-2 (IA-2), are detected in individuals with T1D. Inflammatory Cytokines: Pro-inflammatory cytokines, including interleukin-1 (IL-1), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), contribute to beta cell destruction and insulin deficiency.

Answer 256

Systemic Lupus Erythematosus (SLE) Genetic Predisposition: Multiple genetic variants, including those in genes involved in immune regulation and clearance of apoptotic cells, increase susceptibility to SLE. Environmental Triggers: Ultraviolet (UV) light exposure, infections, hormonal factors, and medications can trigger or exacerbate SLE flares. Loss of Self-Tolerance: Immune dysregulation leads to the production of autoantibodies against nuclear antigens, such as double-stranded DNA (dsDNA) and Smith (Sm) antigen. Immune Complex Formation: Autoantibodies form immune complexes with self-antigens, leading to tissue inflammation and organ damage, particularly in the kidneys, skin, joints, and cardiovascular system. Complement Activation: Dysregulated complement activation, including the classical pathway, contributes to tissue injury and inflammation in SLE.

Answer 257

Multiple Sclerosis (MS) Genetic Predisposition: Genetic factors, particularly within the major histocompatibility complex (MHC) region, influence susceptibility to MS. Environmental Triggers: Viral infections, vitamin D deficiency, smoking, and other environmental factors are implicated in triggering MS in genetically susceptible individuals. Loss of Self-Tolerance: Autoimmune attack against myelin proteins, such as myelin basic protein (MBP) and proteolipid protein (PLP), leads to demyelination and axonal damage in the central nervous system. Role of Autoantibodies: Autoantibodies targeting myelin proteins or components of the blood-brain barrier may contribute to the pathogenesis of MS. Inflammatory Cytokines: Pro-inflammatory cytokines, including interleukin-17 (IL-17), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α), drive inflammation and tissue damage in MS lesions.

Answer 258

**Complement" ** Immunodeficiency (C1q inhibitor deficiency) **Phagocyte:** Chediak-Higashi syndrome – failure of phagolysosome **B cell**: Severe combined immunodeficiency syndrome; Hyper IgM; B cells being unable to mature into plasma cells so low IgA/IgG ** T- cell**: Di George; **Secondary**: HIV, Malnutrition, Tumour, therapeis.,

Answer 259

**Secondary**: HIV, Malnutrition, Tumour, therapeis.,

Answer 260

Primary immunodeficiency is genetic, present from birth, and often requires specific treatments, while secondary immunodeficiency is acquired, can develop at any age, and is typically managed by addressing the underlying cause.

Answer 261

Skin Reactions: Hives (urticaria) or widespread skin redness. Swelling of the face, lips, or tongue (angioedema). Respiratory Symptoms: Difficulty breathing, including wheezing or coughing. Rapid, shallow breathing. Chest tightness or pain. Cardiovascular Symptoms: Rapid or irregular heartbeat (palpitations). Low blood pressure (hypotension). Feeling lightheaded or faint. Gastrointestinal Symptoms: Nausea and vomiting. Abdominal pain or cramps. Other Symptoms: Feeling of impending doom or extreme anxiety. Confusion. Weakness. Swelling of the throat, which can lead to difficulty swallowing.

Answer 262

May contain the same as anaphylaxis but is an acute reaction that is life threatening: Severe Hypotension: Profoundly low blood pressure, leading to circulatory collapse. Loss of Consciousness: Loss of consciousness or confusion due to inadequate blood flow to the brain. Cyanosis: Bluish or pale skin, lips, or extremities due to oxygen deprivation.

Answer 263

Type 1 Hypersensitivity (Immediate) * Immediate Hypersensitivity * B lymphocytes recognise the antigen and present to Th2 * Th2 cells secrete IL4 * IL4 induces B cells to switch class and produce IgE * IgE binds to mast cells by its tail end the Fc * region * On second exposure * Allergen binds to Antibody on Mast Cells * Mast Cells contain histamine * Histamine causes all effects.

Answer 264

Vasodilation: Histamine causes blood vessels to dilate, resulting in increased blood flow to the affected area. Increased Permeability: It increases the permeability of blood vessel walls, allowing plasma and immune cells to leak into tissues. Bronchoconstriction: In the airways, histamine can cause smooth muscle contraction, leading to bronchoconstriction and reduced airflow. Mucous Production: It stimulates the production of mucus, further narrowing airways and contributing to respiratory distress. Itch and Swelling: Histamine release leads to itching, hives (urticaria), and swelling (angioedema) of the skin. Cardiovascular Effects: Systemic histamine release can lead to hypotension and tachycardia due to vasodilation and increased vascular permeability. **H1 receptors are responsible for allergic symptoms such as itching and bronchoconstriction. H2 receptors are found in the stomach and are involved in gastric acid secretion. H3 receptors play a role in regulating neurotransmitter release.**

Answer 265

**Vasodilation and Hypotension:** Adrenaline constricts blood vessels, raising blood pressure. **Bronchoconstriction**: It relaxes airway smooth muscles, improving breathing. **Reduced Mucous Secretion**: Adrenaline decreases mucous production. Antihistamines compete with histamine for binding to H1 receptors, preventing or reducing the histamine-induced responses, alleviate skin reactions and itching Corticosteroids are used in anaphylaxis to mitigate the prolonged and delayed inflammatory response that can follow the initial release of mediators like histamine. Inhibit the production and release of various inflammatory mediators, such as cytokines and prostaglandins and supress delayed phases of immune system

Answer 266

* annual number of female deaths * from any cause related to or aggravated by pregnancy or its management (excluding accidental or incidental causes) * during pregnancy and childbirth * or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy. NICE: compared with white women (8/100,000), the risk of maternal death during pregnancy and up to 6 weeks after birth is: 4 times higher in black women (34/100,000) 3 times higher in women with mixed ethnic background (25/100,000) 2 times higher in Asian women (15/100,000; does not include Chinese women)

Answer 267

any health condition attributed to and/or aggravated by pregnancy and childbirth that has negative outcomes to the woman's well-being.

Answer 268

a group of diseases that cause congenital (present at birth) conditions if a fetus is exposed to them in the uterus. Toxoplasmosis Other Rubella Cytomegalovirus (CMV) Herpes simplex virus (HSV)

Answer 269

Syphilis Toxoplasmosis Other Rubella Cytomegalovirus (CMV) Herpes simplex virus (HSV) HIV

Answer 270

HIV Hepatitis B Syphilis Not Rubella

Answer 271

There is a difference in Immune Susceptibility when Pregnant ’The Government has accepted JCVI advice that the seasonal COVID-19 vaccine should be offered this autumn to all pregnant women – because they are at higher risk of severe COVID-19 infection. ’Wherever possible, vaccinations for flu, COVID-19 and pertussis should be offered at the same time

Answer 272

Characteristic scarring skin lesions known as cicatrix occur Limb abnormalities Typical ocular defects include chorioretinitis, cataracts Central nervous system abnormalities include microcephaly Birthing parent with vesicular rash in pregnancy Approach; VZV IgM(recent infection) and IgG(longstanding infection) tests on patient promptly and on booking blood Speak to on call microbiology May need treatment with VZV Immunoglobulin im

Answer 273

Slapped Cheek Also known as erythema infectiosum It is caused by human parvovirus B19 This is a tiny virus, 18 nanometers It can only replicate in rapidly dividing cells such as erythroid progenitor cells, bone marrow cells and fetal cells What is the presentation of parvovirus? Usually a non-specific viral illness for 5-7 days. Once the rash appears they are usually on the mend and not infectious. Birthing parent may have had contact with vesicular rash: Prompt blood tests for IgM (recent infection) and IgG (previous infection) of the relevant virus

Answer 274

The incidence of neonatal HSV infection is estimated to range between 1 in 3000 to 1 in 20,000 live births Symptoms of congenital herpes usually appear within the first month of the infant's life. Signs that your baby may have herpes are: irritability seizures trouble breathing, including grunting, blue appearance (cyanosis), rapid breathing and short periods of no breathing jaundice (yellow skin color) bleeding easily shock **RISK** Localized skin infection Encephalitis Disseminated herpes infection–the most dangerous type of herpes infection. The herpes virus is spread throughout the body and can affect multiple organs, including the liver, brain, lungs and kidney.

Answer 275

Decreased total IgG levels during pregnancy, especially in late pregnancy. Higher IgG1 levels in the three trimesters when compared to non-pregnant women. Since the 1918 influenza pandemic, it has been apparent that pregnant women suffer more severe complications from influenza infections than non-pregnant women Researchers have speculated that a shift to Th2 immunity is responsible for the altered responses in the periphery to respiratory viral infections [31] or autoantigens

Answer 276

Sepsis is a life-threatening reaction to an infection. It happens when your immune system overreacts to an infection and starts to damage your body's own tissues and organs. . 1.**Oxygen** to keep oxygen saturations above 95% 2.**Blood cultures**, also FBC, U&E, LFT, coagulations, glucose, other cultures 3. **Lactate measurement** 4 **.IV fluids bolus**20ml/Kg normal saline stat. If no response repeat unless there are signs of pulmonary oedema 5. **IV antibiotics**prescribe and commence within 60 minutes from triage/time of diagnosis. Do not wait for results of investigations. 6. **Monitoring;** respiratory rate, oxygen saturations, BP, heart rate, temperature, consciousness, fluid balance, **urinary output.**

Answer 277

Maternal sepsis is sepsis – a life-threatening condition – that develops during pregnancy, childbirth, or in the months following childbirth. It can also complicate abortions and miscarriages Pregnant women face a slightly higher risk of sepsis due to naturally occurring immunological changes, the need for procedures or surgery, and risks due to complications, such as premature rupture of membranes or gestational diabetes.  The most common cause is a severe bacterial infection of the uterus during pregnancy or immediately after childbirth. Maternal sepsis could also be caused by a urinary infection, or pneumonia.  Due to the physiological changes in pregnancy, the **National Early Warning Score (NEWS)** is not designed for use in pregnant patients. Use of a **Modified Obstetric Early Warning Score (MEOWS) **alongside the Maternal Sepsis screening tool is recommended to facilitate the early recognition and escalation of deteriorating maternal patients.  

Answer 278

Group A Streptococcal infection Streptococcus pyogenes Can cause post puerperal infection, tonsillitis, scarlet fever, erysipelas, rheumatic fever, endocarditis Colonies cause as beta-haemolysis on blood agar

Answer 279

A vaccine is a biological preparation that stimulates the immune system to recognize and fight specific pathogens, such as viruses or bacteria, without causing the disease itself.

Answer 280

Protective immunity can be achieved through natural infection or vaccination. It involves the production of antibodies and memory cells, which recognize and fight the pathogen upon exposure, preventing the disease from taking hold or reducing its severity.

Answer 281

Inactivated Vaccines: These vaccines use pathogens that have been killed or inactivated, so they cannot cause the disease. Live Attenuated Vaccines: These vaccines use weakened forms of the live virus or bacteria. They provide strong and long-lasting immunity. Subunit, Recombinant, or Conjugate Vaccines: These vaccines contain only specific antigens or protein subunits from the pathogen, not the whole pathogen. Viral Vector Vaccines: These vaccines use a harmless virus to carry genetic material from the target pathogen. Nucleic Acid (mRNA or DNA) Vaccines: These vaccines use genetic material to instruct cells to produce a harmless piece of the pathogen, triggering an immune response. Toxoid Vaccines: These vaccines target toxins produced by bacteria rather than the bacteria itself. Vector-borne Vaccines: These vaccines target diseases transmitted by vectors like mosquitoes. Multivalent or Combination Vaccines: These vaccines protect against multiple diseases in a single shot.

Answer 282

Inactivated Vaccines: polio vaccine (IPV) and hepatitis A vaccine. Live Attenuated Vaccines: (MMR) vaccine and the oral polio vaccine (OPV). Subunit, Recombinant, or Conjugate Vaccines: T hepatitis B vaccine and the Haemophilus influenzae type b (Hib) vaccine. Viral Vector Vaccines: J&J COVID-19 vaccine, which uses an adenovirus vector. Nucleic Acid (mRNA or DNA) Vaccines: Pfizer and Moderna COVID-19 vaccines, which are mRNA vaccines. Toxoid Vaccines: tetanus and diphtheria vaccines. Vector-borne Vaccines: yellow fever and Japanese encephalitis vaccines. Multivalent or Combination Vaccines: diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenzae type b. Live attenuated Tuberculosis (BCG), Oral polio vaccine (OPV), Measles, Rotavirus, Yellow fever, Varicella-Zoster virus, Influenzae (intranasal) Inactivated whole-cell (killed antigen) Whole cell pertussis, Inactivated polio virus, Hepatitis A, Influenza (injectable) Toxoid (inactivated toxins) Tetanus toxoid, Diphtheria toxoid Subunit (purified antigen) Acellular pertussis (aP), Haemophilus influenzae type b (Hib), Pneumococcal, Hepatitis B (HepB), Human papillomavirus (HPV) Viral vectored SARS-CoV-2 (adenoV), Ebola virus Nucleic acid vaccines SARS-CoV-2 (mRNA)

Answer 283

Age: Health Status: Risk Factors: Location: Travel

Answer 284

Reinforce Immunity Respond to New Threats Complete Initial Series

Answer 285

Fever Cough Fatigue Myalgia Arthralgia Dyspnea Altered sense of taste/smell Sore throat Headache Rhinorrhea Nasal congestion Sneezing Expectoration. Less common or uncommon symptoms include: Chest tightness/pain Malaise Dizziness Confusion Delirium Gastrointestinal symptoms Cutaneous symptoms Ocular symptoms Hemoptysis Audio-vestibular symptoms Oral mucosal lesions.

Answer 286

Blood tests - including Full Blood Count, Urea & Electrolytes, Liver Function Tests, CRP and Blood Cultures SARS-CoV-2 PCR swab Respiratory viral panel PCR swab - testing for alternative respiratory viruses including rhinovirus, influenza amongst others **Chest X-ray ** ECG (to screen for features of heart failure, pericarditis etc.) Urine dipstick (to exclude a urinary infection as the cause of his fevers/lethargy) CRP is raised (which is a non-specific marker of inflammation but is usually elevated in moderate-severe COVID), and the normal procalcitonin level makes a bacterial infection less likely.

Answer 287

Dexamethasone is a corticosteroid which is now standard-of-care (Recovery trial) many of the adverse outcomes from COVID-19 are related to a hyper-inflammatory response to the virus (particularly in the lungs). Low molecular weight heparin (LMWH) is a subcutaneous anticoagulant COVID-19 is a prothrombotic condition and all patients admitted to hospital with COVID-19 should be considered for treatment with LMWH Remdesivir is an anti-viral medication which has been shown in the Recovery trial to quicken recovery time . Tocilizumab is an interleukin-6 inhibitor, . It has been shown as part of the Recovery and REMAP-CAP trials to shorten the duration of hospital stay and ICU admission in patients with severe COVID-19, as well as reducing mortality. Nirmatrelvir/ritonavir (brandname Paxlovid) is the first-line option of a number of antiviral medications which are used to reduce the risk of severe COVID-19 in patients who are extremely vulnerable. This may include those who are immunosuppressed (solid-organ transplant, haematological malignancy) or with severe underlying respiratory disease. It should only be initiated in accordance with local guidance or on specialist advice. Paxlovid is a proetase inhibitor - it aims to suppress viral replication - and is therefore most useful early on in the disease course.

Answer 288

Patients with COVID-19 are at increased risk of VTE, particularly PE Hypoxia bilateral pulmonary emboli (PEs) post-intensive care syndrome thrombosis cardiovascular complications acute kidney injury post-COVID-19 syndrome (long COVID) post COVID-19 vaccination: myocarditis/pericarditis acute liver injury neurologic complications cardiac arrest

Answer 289

* Lymphoedema * Elephantiasis skin changes * Infection * Increased risk of local malignant changes * Lymphoedema fluid promotes fat deposition in affected limb

Answer 290

* drainage system of interstitial fluid * Protein and fluid homeostasis * Cellular drainage from tissues * Immune surveillance * Regulation of inflammation * Fat homeostasis

Answer 291

drainage because of: 1) increased filtration e.g. venous hypertension. 2) impaired flow of lymph e.g. abnormal development of lymphatic vessels (primary lymphoedema); or interruption of lymphatic pathways (secondary lymphoedema).

Answer 292

* Lymphoedema is pitting (initially) * Lymphoedema causes skin thickening and hyperkeratosis * Lymphoedema may improve overnight (initially) * Diuretics have no longterm impact on lymphoedema * More than one attack of cellulitis has occurred

Answer 293

Secondary Lymphoedema * Malignancy (disease / treatment) * Infection (incl. Filariasis) * Inflammation (RA / psoriasis / eczema / acne / cutaneous Crohn’s) * Medications (e.g. calcium channel blockers) * Trauma * Venous disease * Immobility / Dependency * Obesity

Answer 294

developmental abnormality of the lymphatic system, * It is not just one disease. Phenotypes vary in age of onset, site, inheritance patterns, associated features. * Multiple causal genes identified Classified * Associated with other genetic syndromes. * Associated with systemic lymphatic problems. * Congenital (swelling present at birth). * Late-onset (onset after 1 year of age). * Lymphatic malformations +/- overgrowth disorders.

Answer 295

* Congenital lymphoedema of lower legs * Autosomal dominant inheritance * Large calibre veins with venous reflux confirmed on ultrasound examination

Answer 296

Pubertal onset of lower limb lymphoedema * Distichiasis * Ptosis, cleft palate, congenital heart disease, scoliosis * Autosomal dominant inheritance

Answer 297

Late onset lymphoedema of lower limbs * +/- Genital lymphoedema * Mutations in GATA2 are causative * Autosomal dominant inheritance * Sensorineural hearing loss * Cutaneous warts * Predisposition to AML leukaemia

Answer 298

Extensive congenital lymphoedema with visceral involvement * Mutations in CCBE1 are causative * Autosomal recessive inheritance * Learning difficulties, unusual facial features

Answer 299

Differences between metabolic pathways between normal and tumouric cells High degree of discrimination (ratio of therapeutic to toxic effect)

Answer 300

Side chain from the βlactam ring determins the properties of different penicillin but: penicillin binds to PBP (penicillin binding proteins) which inhibits peptide cross links in the microbial cell wall. Essentially inhibits transpeptidation- which prevents peptide bridge forming. (NAG and NAM)

Answer 301

Binds to essential portions at the transcription process. Streptomycin changes 30S: mRNA incorrectly read Tetracyclin changes how tRNA and mRNA bind

Answer 302

Interacts hydrophobically with ergosterol in fungal cell membrane and forms pores within it – binds avidly to ergosterol * Creates transmembrane channel and cell contents (electrolytes) leak out * Selectively toxic – humans have cholesterol instead of ergosterol

Answer 303

Therapeutic index = 1 it means that the concentration that causes toxicity is = conc. that causes cancer cell death Therapeutic index should be wide not narrow Many anticancer agents affect all dividing cells which causes side effects.

Answer 304

ZDV synthesised in 964, inhibits HIV 1984 Thymine analogue Prodrug which must be phosphorylated to activate Causes comeptition as used instead of thymine in the same reverse transcription enzyme Causes selective inhibition Inhibits infection of new cells

I & I Flashcards

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