Immunology 2

Question 1

Which TLRs are specifically directed to endosome following synthesis?

Answer 1

3, 7, 8, 9

Never found on plasma membrane

Question 2

Describe how cDCs are extremely potent at internalising pathogens

Answer 2

• Immature DC’s in peripheral tissues activated by PAMPs
• Immature cDC great at probing enviro by phagocytosis or macropinocytosis
• Express high levels PRRs (esp. RLRs) for recognition of PAMPs
• Express no. of chemokine receptors

Question 3

How are cDCs activated to upregulate CCR7?

Answer 3

• Triggering of PRRs = upregulation of CCR7
• cDCs shift from antigen capturing mode > T cell sensitising mode
• Due to short fragments of proteins from viral antigens become bound to MHC class 1 receptors
• CCR7 directs CDC via lymphatics to nearest draining LN’s by allowing DC to follow trail of CCL21 chemokine

Question 4

How does HIV exploit the cDC mechanism?

Answer 4

Infects CDC then traffic to draining LN’s to infect CD4+ cells

Question 5

Describe the distribution of lymphoid tissues in the body

Answer 5

Lmyph moves through lymphatics + LNs before entering right lymphatic duct or thoracic duct before entering back into circulation at right + left subclavian veins

Question 6

Why is the lymphatic system a good way for viruses to move around body?

Answer 6

Lymphatic vessel capillaries = more permeable

Question 7

What is the role of the spleen?

Answer 7

Filters for blood borne viruses

Question 8

What happens in transplant rejection?

Answer 8

Mediated by immune cells

Involves major histocompatibility complex (MHC)

Question 9

What is the role of MHC molecules?

Answer 9

Allow display of virus derived peptides on surface of infected cell

Question 10

What do MHC Class 1 receptors do?

Answer 10

Stimulates TCRs found on CD8+ T cells

Question 11

What do MHC Class 2 receptors do?

Answer 11

Stimulates TCRs found on CD4+ T cells

Question 12

Which intracellular compartments do MHC Class 1 receptors act in?

Answer 12

• Peptides derived from viral antigens = proteolytically cleaves/processed in cytoplasm then shuttled > ER where they bind to MHC Class 1 - Once peptide binding groove filled MHC stable enough to traffic plasma membrane + display peptide to T Cell

Question 13

What intracellular compartments do MHC Class 2 receptors act in?

Answer 13

• Traffic to endosomal vesicle where they bind to peptide from proteins that have been endocytosed or phagocytosed
• Once groove filled can traffic to plasma membrane

Question 14

How do dendritic cells process antigens from viruses?

Answer 14

• Cross presentation = ability of endocytosed material to escape endosomal compartment + reach cytoplasm - acquiring ability to be presented by MHC Class 1
• Live attenuated vaccines = best way to achieve CTL response as only viruses have capacity to replicate intracellularly within cytosol + be presented by MHC Class 1

Question 15

What is lymphocyte recirculation?

Answer 15

• Constantly recirculating lymphocytes so immune system ensures encounter of T cell with cDC in LN
• Lymphocytes migrate across endothelium of unusual blood vessels into cortex of LN’s

Question 16

What happens when naive T cells (CD8+ and CD4+) traffic through secondary lymph nodes?

Answer 16

Antigen presenting cells (carried by lymph) encounter naive T cell from blood or upstream LN

Question 17

What happens to T cells not activated by antigen presented by DC’s?

Answer 17

Exit LN via cortical sinuses

Question 18

What happens to activated naive T cells?

Answer 18

Start to proliferate + differentiate + loose ability to exit LN

Question 19

How do viruses down regulate MHC Class 1?

Answer 19

e.g. Human cytomegalavirus - inhibits peptide loading of MHC Class 1

Question 20

How are naive CD8 T cells fully activated?

Answer 20

• Require 2 signals from cDC
• DC’s express high levels of B7 > activates CD8
• Activated CD8 T cells make IL-2 - driving its own proliferation + differentiation
• Signal 1 mediated by TCR upon recognition of peptide/MHC
• Signal 2 provided by co-stimulation ligand receptor B7 engaging with CD28 on T cell