1
Q
Define the difference between class I and class II MHC molecules
A
Class I presents protein fragments to killer T cells whereas class II presents peptides to helper T cells Class I are expressed on almost every kind of cell whereas class II are expressed exclusively on cells of the immune system
2
Q
What can trigger a dendritic cell to activate?
A
When neutrophils and macrophages release tumour necrosis factor (TNF) when destroying an attacker
Interferon alpha and beta released by virus-infected cells
Pattern-recognition receptors on dendritic cells (e.g. TLR)
3
Q
Why is a short lifetime of a dendritic cell a good thing?
A
The shorter the lifespan encourages a proportionate response to the severity of the attack
4
Q
What do mature dendritic cells activate?
A
- Naïve T cells
* Activated tissue macrophages
5
Q
Why do activated tissue macrophages need activating?
A
- To re-stimulate experienced T cells
* If they are not re-stimulated, they will “rest” thinking the battle is over
6
Q
What molecules are involved in antigen recognition on T cells?
A
- T cell receptor (TCR)
* CD4 and CD8 co-receptors
7
Q
What class of MHC molecule does CD4 “clip onto”?
A
Class II MHC molecule
8
Q
What class of MHC molecule does CD8 “clip onto”?
A
Class I MHC molecule
9
Q
For a T cell to be activated what must occur?
A
- T cell receptors ligated by MHC-peptide
* Co-stimulation signals
10
Q
What does Toll-like receptor 4 (TLR4) recognise?
A
- LPS (component of Gram-negative bacteria)
* Proteins from specific viruses
11
Q
What does Toll-like receptor 2 (TLR”) recognise?
A
- Molecules that are “signatures” of Gram-positive bacteria
- Lipopeptides
- Lipoproteins
12
Q
What does toll-like receptor 3 (TLR3) recognise?
A
Double-stranded RNA produced during many viral infections
13
Q
What does Toll-like receptor 9 (TLR9) recognise?
A
Unmethylated DNA dinucleotides CpG (a characteristic of bacterial DNA)
14
Q
What does Th1 cells (helper T1 cells) protect against?
A
- Bacterial infection in tissues
* Virus in tissues
15
Q
What does Th2 cells (helper T2 cells) protect against?
A
- Parasites via digestive tract
* Pathogenic bacteria via digestive tract
16
Q
What does Th17 cells (helper T17 cells) protect against?
A
- Fungi
* Extracellular bacteria
17
Q
What are the organs of the secondary lymphoid organs?
A
- Lymph nodes
- Spleen
- Mucosal-associated lymphoid tissue (MALT)
18
Q
What are the steps of the movement of the immune system cells through the lymph node?
A
- Naïve B cell enter the node expressing chemokine CXCL13. They are attracted to where the follicular dendritic cells are displaying opsonized antigen.
- Once its cognate antigen is found, CXCL13 is downregulated and CCR7 (chemokine receptor) is upregulated
- CCR7 detects a chemokine where B and T cells meet (attracted by its “smell”). The B cell receives help from an activated helper T cell
- The activated helper T cell downregulates expression of chemokine receptors and upregulates CXCR5 chemokine receptors, which attract them to the border of the follicle
19
Q
What must occur before antibodies can be produced?
A
- APCs (antigen presenting cells) to present antigen to helper T cells (Th cells)
- Th cells with receptors that recognise the presented antigen
- Opsonized antigen displayed by follicular dendritic cells
- B cells with receptors that recognise the antigen
20
Q
Where in the lymph node is the killer T cell activated?
A
Paracortex
21
Q
Where do Peyer’s patches sample antigens from?
A
Intestines (small)
22
Q
Where does the spleen sample antigens from?
A
Resident dendritic cells in the marginal sinuses of the spleen
23
Q
What is pneumonia?
A
Consolidation of lung tissue by an inflammatory exudate effusion, usually caused by bacteria
24
Q
What is pleural effusion?
A
Refers to the collection of fluid in one or both pleural cavities surrounding the lungs
25
What is the difference between plasma and cerebrospinal fluid?
* Cerebrospinal fluid has less protein and a lower concentration of protein-bound components (bilirubin)
* Cerebrospinal fluids electrolytes have more chloride and less potassium and calcium than plasma
26
How is xanthochromia seen?
The cerebrospinal fluid has yellow discolouration
27
When should a lumbar puncture not be performed?
When the patient has a raised intracranial pressure from
• Hypertension
• Bradycardia
• Papilloedema
28
What is chlye?
* Lymph found in the intestinal lymphatics during absorption of food
* Appears milky due to the presence of fats
29
What does CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and PD-1 (programmed death 1) function as?
* Checkpoint proteins which deactivate/“decommission” T cells as the battle winds down
* CTLA-4 makes it more difficult to reactivate T cells
* PD-1 make T cells function less well
30
What are the steps for activating a T cell?
* Cell-cell adhesion
* TCR clustering
* Co-stimulation
31
How does Bacteroides fragilis affect toll-like receptors on helper T cells?
The TLR recognises polysaccharide A and the T cell is instructed to produce IL-10 which dampens inflammation
32
What does Bifidobacterium breve affect?
Dendritic cells produce IL-10
33
Bacteroides fragilis and Bifidobacterium breve are examples of what?
Commensal bacteria
34
In response to a serious attack in the intestinal system, what is activated and what does it secrete?
• Th1 cells
o Secretes IFN-γ (enhances killing power of lamina propria macrophages)
• Th17 when in an environment of TGFβ and IL-6 or TGFβ and IL-23
o Produce IL-17 (to increase intestinal barriers effectiveness by strengthening the tight junctions between epithelial cells and facilitate transcytosis of IgA)
o Recruits neutrophils from blood stream
35
What does Toll-like receptor 5 (TLR5) indicate?
* Flagellin protein from which flagella are constructed
| * Used as a danger signal
36
What causes allergies?
Overproduction of IgE antibodies in response to otherwise innocuous environmental antigens (allergens)
37
What can cause autoimmune disorders?
* Genetic defects
| * Layer of tolerance-inducing mechanisms fail in eliminating self-reactive cells in genetically normal individuals
38
What must occur to a genetically normal individual for an autoimmune disorder to occur?
* MHC molecules that can present a self-antigen
* Lymphocytes with receptors that can recognise the self-antigen
* Environmental factors leading to the breakdown of the tolerance mechanisms designed to eliminate self-reactive lymphocytes
39
What is the molecular mimicry hypothesis?
During a microbial invasion, lymphocytes whose receptors recognise microbial antigens will be activated. The molecular mimicry hypothesis holds that sometimes these receptors also recognise a self-antigen, and if they do, an autoimmune response to that self-antigen may result
40
How are the self-reactive lymphocytes activated?
Simultaneously from molecular mimicry, the tissue undergoes inflammation by either the microbe itself, another, or an unrelated infection/trauma. This inflammation re-stimulates self-reactive T cells, and this upregulates Class I MHC molecules for a better target of self-reactive lymphocytes
41
What autoimmune disorder is not caused by molecular mimincry?
Celiac disease
42
How can a memory killer T cell be produced during a microbial attack?
* The microbe must infect an antigen presenting cell
* Killer T cells will recognise the virus’s proteins and activate
* If assistance of helper T cells is available, memory T cells are produced
43
What is a proto-oncogene?
A gene which, when mutated, can cause a cell to proliferate inappropriately
44
What does the safeguard system that monitors unrepaired mutations do?
* If mutations are not extensive, the system will stop the cell from proliferating to give the repair system more time to repair
* If the genetic damage is severe, the system will trigger the cell to commit suicide, eliminating the possibility that it will become a cancer cell
45
What is p53
* A protein of the safeguard system
* Safeguards against uncontrolled cell growth
* Known as tumour suppressors
46
What does cancer result from?
When multiple systems, both growth-promoting and safeguard, are corrupted within a single cell, cancer results
47
How can PD-1 become impaired by a cancer cell?
* Many types of cancer cells express ligands for PD-1
* PD-1 is ligated to the cancer cell and supresses the T cells effector function (ability to kill their target cells) and the ability to proliferate
48
Checkpoint blockage cancer treatment only works if a patient is doing what?
If the patient's immune system is producing anti-tumour T cells whose effectiveness is limited wither because there are too few of them or because they do not function well
49
What is an important point of checkpoint blockade cancer treatment?
It does not work for all cancers, only for tumour-specific T cell cancers
50
What are some cancer immunotherapies using T cells?
* Adoptive cell transfer
| * Engineered T cells (CAR T cell therapy)
51
What are some typical causes of necrosis?
* Tissue trauma
* Burns
* Certain toxins
* Non-physiological stimuli
52
What are some differences between apoptosis and necrosis?
* DAMPs are released in necrosis where in apoptosis DAMPs are hidden
* Necrosis is uncontrolled cell death where apoptosis is regulated cell death
* Necrosis encourages an immune response where apoptosis does not active the immune system
* Necrosis ruptures cells where apoptosis is removed by phagocytosis of macrophages
53
What cells do cytokines effect?
* Endothelium
* Macrophages
* Dendritic cell
54
How do cytokines effect the endothelium?
* Cell contraction
| * Cytokine secretion
55
How do cytokines effect macrophages?
Cell activation
56
How do cytokines effect dendritic cells?
Cell differentiation
57
What cells do chemokines effect?
Phagocytes
58
How do chemokines effect phagocytes?
Cell migration
59
What does Toll-like receptor 1 (TLR1) recognize?
* Lipopeptides
| * Lipoproteins
60
What does Toll-like receptor 6 (TLR6) recognize?
* Lipopeptides
| * Lipoproteins
61
What does Toll-like receptor 10 (TLR10) recognize?
Unknown
62
What does Toll-like receptor 11 (TLR11) recognize?
Profilin (Toxoplasma gondii)
63
What must a phagocyte be able to do to complete phagocytosis completely?
* “home onto” the microorganism
* Adhere to it
* Respond by the membrane activation that initiates engulfment
64
What is inflammation?
The term given to the series of events that surround an immune response and display a number of characteristic features that are collective consequence of the release of cytokines, chemokines, complement fragments and vasoactive amines from macrophages and mast cells upon the initial encounter with a pathogen
65
What are the characteristic features of inflammation?
* Local swelling (oedema)
* Redness (due to capillary dilation)
* Pain
* Heat
66
What is a lysozyme?
Also known as muramidase, it is an antimicrobial enzyme that splits the exposed peptidoglycan wall of susceptible bacteria
67
What induces type I interferons (IFNα and IFNβ)?
Viral and bacterial infections
68
What immune cell deals with infections within a cell?
Natural killer (NK) cells
69
What pathways does natural killer cells kill their target cells?
* Death receptor pathway
| * Granule-dependent pathway
70
What do both pathways of killing the target cell of a natural killer cell lead to?
Apoptosis
71
What granules does natural killer cells have?
* Serine proteases called granzymes
| * Pore-forming protein called perforin
72
Why cannot macrophages phagocytose parasites?
Parasites are much bigger than macrophages, making it physically impossible for the macrophage to engulf the parasite
73
What immune cell attacks a parasite?
Eosinophil
74
Why does an eosinophil attack against parasites?
• Most helminths (parasite) can active the alternative complement pathway allowing C3b to coat them. This coat of C3b allows the adherence of eosinophils at the C3b receptor. If the contact of eosinophils leads to their activation, they will launch an extracellular attack with their granules (cationic protein damaging the parasite membrane)
Clinical Immunology
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