Path & host

Question 1

Pathogenicity factors

Answer 1

How likely is an organism to cause an illness?

1. Infectivity, ability to become established on or within host
2. Virulence, ability to cause harmful effects once established

Question 2

Infectivity factors

Answer 2

• Attachment e.g. E.coli have P-fimbriae

- Acid resistance e.g. H.pylori, has urease which makes ammonia from urea

Question 3

Virulence factors

Answer 3

• Invasiveness, reproduces rapidly
• Toxin production, infects immune system
• Exotoxins released extracellularly by the microorganism
• Enterotoxins are exotoxins which act on the GI tract
• Endotoxin is structurally part of the Gram negative cell wall, Lipid A is the nasty bit
• Evasion of immune system
• These are specific to strains, not species

Question 4

Streptococcus pyogenes

Answer 4

• Highly invasive
• Enterotoxin, superantigen
• Necrotising fasciitis
• Cellulitis
• Connective tissue breakdown by enzymes
• Fibrinolysis - enzymatic breakdown of fibrin in blood clots
• Stimulate division of T cells in the absence of specific antigen
• Overwhelming cytokine production - toxic shock

Question 5

Tetanus

Answer 5

• Clostridium tetani
• High virulence
• Infects dirty wounds
• Toxin production, binds to nerve synapses, inhibits release of inhibitory NTs
• Death by respiratory paralysis
• Rx by debridement and abx and antitoxin

Question 6

Cholera

Answer 6

• Vibrio cholera
• High virulence
• Enterotoxins
• Colonises small intestine
• Toxin production, increases cAMP levels, inhibits uptake of Na+ and Cl- ions. Stimulates secretion of Cl- and HCO3- ions.
• Passive, massive outflow of H2O
• Death by dehydration
• Rx - rehydration

Question 7

Staph aureus

Answer 7

• Highly virulent
• Enterotoxin
• Stimulate division of T cells in the absence of specific antigen
• Overwhelming cytokine production - toxic shock

Question 8

E.coli

Answer 8

• O157 is the nasty one
• Induces severe uncontrolled host repose
• Cytokine production
• Fever, rigors, hypotension, tachycardia, collapse

Question 9

Mechanisms of viral pathogenesis

Answer 9

• Cell destruction following virus infection, death of T4 cells by HIV
• Virus-induced changes to cellular gene expression, cellular transformation by tumour viruses
• Immunopathogenic disease, Influenza A, induced myocarditis

Question 10

Sites of viral entry

Answer 10

• Conjunctiva
• Arthropod, insect bite
• Capillary
• Respiratory tract
• Alimentary tract
• Skin
• Urinogenital tract

Question 11

Types of viral infection

Answer 11

• Acute
• Latent
• Chronic
• Tumour virus infection
  NB: symptoms arise at peak of virus in body

Question 12

Acute viral infection

Answer 12

• Localised, specific to site

- Development of viraemia can go to other tissues

Question 13

Examples of acute viral infections

Answer 13

• Influenza A, resp. infection. Virus infects cells of respiratory tract, destruction of respiratory epithelium, altered cytokine expression leading to fever
• Enterovirus. Virus is normally excreted in faeces but if viraemia occurs then it can get into non-neuronal tissues and neuronal tissues.

Question 14

Enterovirus examples

Answer 14

Poliomyelitis, aseptic meningitis, myocarditis, pancreatitis, respiratory infections

Question 15

Latent viral infections example and life cycle

Answer 15

• Herpes simplex virus: primary infection in epithelium
• Virus migrates to ganglia and stays latent in nucleus, no virus replication
• Stimulus occurs e.g. stress, life events, immunosuppressants, sunlight
• Virus migrates back to epithelium and it is released, results in replication

Question 16

Tumour virus infections examples

Answer 16

• Papilloviruses: cervical carcinoma
• Retroviruses: lymphomas and leukaemieas, causes the cells to be transformed from normal:
  1. Virus infects cell, virus nucleic acid, as DNA, integrates into cellular genome
  2. Virus causes changes in cellular gene expression
  3. Uncontrolled cell multiplication and tumour formation

Question 17

Antigenic drift

Answer 17

Gradual evolution of viruses to generate antigenic variants

You might have partial immunity

Question 18

Antigenic shift

Answer 18

Significant changes in virus antigenic structure
Complete change, no immunity
Avian flu and swine flu are examples where non-human hosts for influenza A play a key role in new types of virus

Question 19

Define pathogen

Answer 19

Organism which can cause disease

Question 20

Define commensal

Answer 20

Organism which is part of the normal flora e.g. E.coli in gut, Staph aureus in nose, axilla

Question 21

Examples of innate immunity

Answer 21

• Skin, gastric acid, muco-ciliary escalator
• Phagocytic cells
• Other white cells (T cells, B cells, these aren’t phagocytic)
• Opsonisation

Question 22

Phagocytic cells examples

Answer 22

• Polymorphs (acute, short lived): neutrophils, eosinophils, basophils
• Macrophages (chronic, long lived): monocytes in blood mature into macrophages
• Fixed macrophages (liver, spleen, lymph nodes) of the mononuclear phagocytic system
• Free macrophages in the tissues
• Mononuclear phagocytic system

Question 23

Mononuclear phagocytic system examples

Answer 23

• Spleen clears blood (why you get overwhelming Strep pneumoniae infection in splenectomy)
• Liver clears entero-hepatic circulation
• Regional lymph node drain peripheral sites

Question 24

Opsonisation

Answer 24

• How a phagocyte recognises and destroys an antibody
• Phagocytic cell has receptors for both
• Efficiency of phagocytosis is greatly improved
• Important for capsulate bacteria as you can get around the problems with phagocytosis and intracellular killing e.g. Strep pneumoniae and haemophilus influenzae

Question 25

Process of phagocytosis

Answer 25

1. Phagocytosis (ingestion), cell engulfs particle in vesicle 2. Organism held in phagosome 3. Fusion with lysosome, in case of macrophage 4. Phagolysosome is formed 5. Intracellular killing

Question 26

Organisms resistant to phagocytosis

Answer 26

- Capsulate organisms e.g. strep pneumoniae | - Mycobacterium tuberculosis is resistant to intracellular killing

Question 27

Acquired immunity

Answer 27

- Specific response to antigen concerned - Immunological memory created - Humoral and cellular - Each organism is a complex mixture of antigens - Each antigen is a mixture of epitopes, bits that recognise immune system

Question 28

What do antibodies do?

Answer 28

1. Neutralise bacterial toxins 2. Neutralises viruses in viraemic stage 3. Prevent adherence of mircoorganisms 4. Opsonises capsulate organisms (Strep pneumoniae, Haemophilus influenzae) 5. Useful means of diagnosis with serology

Question 29

5 classes of immunoglobulins

Answer 29

- IgM: eliminates pathogens with B cells before there are any IgG cells - IgG: majority of antibody-based immunity against invading pathogens - IgA: mucosal immunity - IgE: allergy and helminth infection - IgD: antigen receptor on B cells that have not been exposed to B cells

Question 30

B-lymphocytes

Answer 30

- Differentiate into plasma cells when they recognise a specific epitope - B-lymphocytes require T cell help

Question 31

Monoclonal antibody vs polyclonal antibody

Answer 31

Monoclonal -from one clone of plasma cell which has specificity for a single epitope Polyclonal antibody - multiple specificity

Question 32

Antibody and complement in infection

Answer 32

1. Opsonisation by complement 2. Lysis of Gram negative organisms by complement 3. Complement cascade by-products are chemotactic (attract polymophs)

Question 33

Humoral immunity

Answer 33

- Found in body fluids - Mostly used in bacterial infection - Extracellular - Acute inflammation - Neutrophilia

Question 34

Cell mediated immunity

Answer 34

- Combats intracellular infection (viruses, certain bacteria and fungi) - Lymphocytosis - e.g. Mycobacterium tuberculosis is resistant to intracellular killing, Legionella pneumonphila and Candida albicans

Question 35

How cell mediated immunity works

Answer 35

- Macrophages 'present' the antigen and this stimulates the T-cells - Two T cells: CD4 helper and CD8 suppressor and cytotoxic cells - Cytokines are produced and control the response

Question 36

Define colonisation

Answer 36

- No signs or symptoms - MRSA can cause infection or colonisation - Infection is opposite as you get signs and symptoms

Question 37

Define asymptomatic infection

Answer 37

Infection without symptoms

Question 38

Define latent infection

Answer 38

Asymptomatic infection capable of manifesting symptoms under particular circumstances or if activated