Immune

Question 1

Mechanisms of T cell mediated autoimmunity

Answer 1

Cytokine mediated inflammation

• APC presenting self-tissue antigen binds to CD4+ T cell
• Release of cytokines which trigger inflammation
• Neutrophil degranulates and releases enzymes, reactive oxygen species etc
• Resulting in tissue injury

Cytotoxic killing

Question 2

Mechanisms involved in affinity maturation - Cytokine secretion

Answer 2

IFN-gamma, TGF-β, IL2, IL4, IL5 → bind to B cells and mediate growth and differentiation signals

Question 3

Activation and MOA of defensins

Answer 3

Natural antibody peptides found in phagocytes and epithelial cells

Mode of action - targets bacteria, yeast, enveloped viruses

• Electrostatic attraction to pathogenic cell surface
• Inhibits bacterial cell wall synthesis
• Penetrate microbial membrane by forming pores
• Lysis

Question 4

Affinity maturation occurs in ?

Answer 4

Germinal centre of secondary follicle

Question 5

Viruses/bacteria induce IL-12 secretion by DCs that can activate NK cells to produce IFN-gamma →

Answer 5

naive CD4 T cell population is activated in the presence of IL-12 and IFN-gamma → committed to differentiate into TH1 cells

Activated TH1 cells secrete IFN-gamma → acts on TH2 cells to inhibit proliferation

Question 6

Other pathogens (eg worms) do not induce IL-12 secretion by DCs but may cause the synthesis and secretion of IL-4 →

Answer 6

Naive CD4 T cells are activated in the presence of IL-4 → committed to differentiate into TH2 cells
activated TH2 secrete TGF-β and IL-10 which act to inhibit the activation and growth of TH1 cells

Question 7

Pathophysiology of systemic lupus erythematous (SLE) -

Pathological deposition of immune complexes within tissues → complement clearance

Answer 7

Immune complex disease (type III hypersensitivity)

• C3a: complement mediated inflammation and tissue injury
• C3a (anaphylatoxins): neutrophil activation and recruitment → opsonisation → frustrated phagocytosis (when target cell is too big for phagocytes to engulf, lysosomal enzymes get released into the environment → tissue damage as collateral damage)
• C3b: opsonisation on cells which leads to frustrated phagocytosis
• Leads to complement consumption: decreased levels of intact C3 and C4 reflect disease activity

Question 8

How to treat pts with anti-IgA antibodies of the IgE isotype in selective IgA deficiency

Answer 8

Some may produce anti-IgA antibodies of the IgE isotype → present with anaphylaxis during infusion of IgA in blood transfusion → treat with washed red blood cells and blood from an IgA deficient donor/their own pre-stored blood

Question 9

What does the activation of TLRs induce

Answer 9

Changes in expression of molecules involved in T cell activation by antigen presenting cell

Question 10

How does the mucous membrane act as a physical barrier

Answer 10

Blocks attachment sites on epithelial cells (negative charge which will repel microbes that seek to form stable attachments to the epithelial cells which line our mucosa)

Contains antimicrobial proteins (Eg. lysozymes, defensins, lactoferins) which degrade bacteria

Question 11

Molecules involved in triggering T cell recirculation after encountering the pathogen

Answer 11

CCR7 and L-selectin receptors: Signals to naive T cells which enter the lymph node across a high endothelial venule that it is in the lymph node; decreases in expression once activated

S1PR1 receptor: Interacts with S1P on the efferent lymphatic vessels; increases in expression once activated
the S1P gradient on the efferent lymphatic vessels will lead the activated T cell out of the lymph nodes to the effector site

Question 12

Generation of TCR ligands from different pathogens and subsequent activation of cells

Answer 12

Cytosolic pathogens: captured by any cell in the body → presented on MHC I molecules → presented to CD8 T cells for activation → leads to cell death for the presenting cell

Intravesicular pathogens: captured by macrophages → presented on MHC II molecules → presented to CD4 T cells for activation → leads to activation of macrophage to kill intravesicular bacteria and parasites

Extracellular pathogens: captured by B cells → presented on MHC II molecules → presented to CD4 T cells for activation → leads to activation of B cells to secrete Ig to eliminate extracellular bacteria/toxins

Question 13

Lab tests for SLE

Answer 13

ANA test: Detects presence of serum autoantibodies that bind to components of cellular nuclei (non specific test for SLE)

Anti-dsDNA test: a specific type of ANA antibody found in a subset of patients with SLE
More specific for SLE than the ANA test

Question 14

Function of IgG- Opsonisation

Answer 14

Opsonisation

• coating of pathogen with antibodies → becomes signals which recruit phagocytes (macrophages/neutrophils)
• mediated by antibody receptors (FcRs) expressed on the surface of phagocytes (macrophages and neutrophils) binding to antibodies that have attached to pathogens

Question 15

Function of IgG

Antibody dependent cellular cytotoxicity (ADCC)

Answer 15

Antibody dependent cellular cytotoxicity (ADCC)

when bound to infected host cell, it can recruit natural killer cells that express CD16 FcRs

Question 16

Requirements for differentiation and proliferation of activated CD8 T cells - Requires the help of activated CD4 T cells

Answer 16

Further activate APCs (increasing expression of CD40 and 4-IBBL) to better activate CD8+ T cells by co-stimulation

Question 17

Process of positive and negative selection of T cells

Answer 17

T cell starts off as double negative for CD4 and CD8

Becomes double positive for CD4 and CD8, coincident with successful expression of a folded TCR on their surface (CD3)

Question 18

Positive selection of T cells

Answer 18

at double positive level, determines if cell becomes CD4 or CD8

• Allows for robust detection and response to foreign antigens
• epithelial cells express MHC I and II → preferential binding to MHC I/II molecules will cause upregulation of CD8/CD4 respectively

Question 19

negative selection of T cells

Answer 19

at single positive level, detection of potentially autoreactive cells

• prevents autoimmine response
• TCRs which bind too strongly to MHC molecules on thymic epithelium which displays host cell peptides will be induced to undergo apoptosis
• the cells which emerge bind weakly to MHC molecules displaying self peptides (when switched to pathogenic peptide there will be stronger binding)