Immunology 3

Question 1

If every cell can express MHC Class 1 why is it that only cDCs can activate naive T cells?

Answer 1

• Naive CD8+ T cell require co-stimulation (via B7-CD28) + signal through TCR to become fully activated
• So requirement only satisfied by cDCs that express large amounts of B7

Question 2

How do CTL induce apoptosis in target cell?

Answer 2

Recognition of Class 1 peptide complexes =

1) Release of perforin + granzymes
2) Binding of Fas-ligand with Fas on target cell

Question 3

What are the 2 things naive CD4 T cells can be activated to become?

Answer 3

1) Virus-specific helper effector T cell (TH1)

2) Can remain within LN as follicular helper T cells (TH1FH)

Question 4

What is the role of CD4+ T cells in viral infection?

Answer 4

• CDC’s present MHC Class 2 complexes to naive CD4+ T cells
• Cytokine enviro will direct form of TH effector response
• Overall = prolif + diff
• Activated to become TH1 or remain in LN as TH1FH

IL12 + IFN y -> TH1 cells which exit LN and go help macrophages

Question 5

What happens to B cells circulating through lymphoid tissue?

Answer 5

When antigen of virus recognised by membrane-bound immunoglobulin, B cells stimulated to differentiate into plasma cells + start secreting IgM

Question 6

What happens to remaining B cells in LN?

Answer 6

• Some B cells remain in draining LN to interact with CD4TFH T cells at border of LN
• Interaction = critical:
  1) Allows B cells to undergo antibody class switching
  2) Allows for some hypermutation in immunoglobulin
  gene
• B cells endocytose virus within LN + present viral antigens to TFH

Question 7

Which cells are professional antigen presenting cells?

Answer 7

Dendritic
Macrophage
B cells

Question 8

How are B cells efficient at presenting antigens that bind to their surface?

Answer 8

• Internalised proteins processed into peptide fragments that bind to MHC Class 2
• Complexes appear on B cell surface
• B cells binds virus through viral coat protein (epitope)

Question 9

What is linked recognition?

Answer 9

B and T cells may recognise distinct epitopes of same molecular complex in order to interact (but have to be physically linked)

Question 10

Describe how B and T cells must recognise epitopes of the same molecular complex in order to interact

Answer 10

• Particular T cell receptor recognises peptide derived from viral internal protein
• But B cell Ig recognises protein from viral coat
  = fine if both found in same complex
• CDL40 on T cell interacting with CD40 on B cell = key to inducing critical changes in B cell

Question 11

What help can TFH provide to virus-specific B cell?

Answer 11

Helps B cell undergo antibody isotope change via class switching + somatic hyper-mutation to increase antibody affinity

Question 12

What is the molecular basis of CD4+ TFH cell help to B cell?

Answer 12

• Induction of activation-induces cytidine deaminase (AID) enzyme in B cell
• Catalyses some hypermutation of Ig genes = affinity maturation of antibodies in B cells
• Also catalyses class switching of Ig constant regions = isotype-switching of antibodies

Question 13

Why is there a selection for B cells with high affinity Ig?

Answer 13

• Able to compete more effectively for antigen binding, internalise antigen, process it + present to T cells

Question 14

What is immunoglobulin class switching?

Answer 14

• IgM = initial isotype of antibody produced by all B cells

- But depending on nature of infection + cytokine enviro B cells can switch to producing other isotypes

Question 15

Why are some vaccination given in 3 consecutive doses?

Answer 15

Every time. we boost - initiate another round of somatic hypermutations - stimulating B cells to produce higher affinity of antibody

Question 16

How can TFH interactions with antigen-primed B cell lead to antibody isotype-switching?

Answer 16

• Initial Ig always low affinity IgM
• Some B cells > plasmablasts + plasma cells producing antibodies
• Others remain in LN + have capacity to undergo further somatic hyper-mutation
• Cytokine enviro detects switch