Module 5b

Question 1

What are some features of the LFA-1 and ICAM-1 binding synpase?

Answer 1

LFA-1 and ICAM-1 molecule interaction facilitates T-cell and APC to be close. Stabilises binding of the molecules involved, narrows the space for that binding, reorientation of cytoskeleton & delivery of molecules.

Question 2

What happens to CD8+ T cells when they recognise infected target cells?

Answer 2

Initially bind by LFA-ICAM (non-specific adhesion) and antigen-specific binding. CTL release granzymes and perforin into target cell and it undergoes apoptosis. CD8+ T cell detaches and moves onto to kill again.

Question 3

How does Th1 help naive CD8+ T cells become cytotoxic T lymphocytes (CTL)?

Answer 3

Th1 will provide IL-2 to support CD8+ proliferation. Naive CD8+ (CTL-P) needs both antigen on MHC I and help from Th1 for full activation. Memory CTL-P’s can be reactivated with just MHC I and costimulation (B7-CD28) producing their own IL-2

Question 4

How do cytotoxic T cells direct granule release specifically at target cell?

Answer 4

Initial contact by LFA-1 and ICAM-1. Upon antigen recognition, the MTOC reorients towards the target cell. Cytoskeleton and golgi reorient guilding cytotoxic granules to contact site. Granules are released precisely at the synapse.

Question 5

Why is cytokine production tightly regulated?

Answer 5

• They are short lived proteins & mRNA, degrade in minutes to hours.
• Regulated at TFs, RNA stability & protein processing levels.
• Act in high local concentration in microenvironments (lymph nodes).
• Effective at picomolar levels, extremely potent.
• Misregulation can lead to tissue damage due to overactivation.
• Produced as precursors and rapidly secreted when needed.

Question 6

How do cytokines show pleiotropy, redundancy, synergy and antagonism?

Answer 6

Pleiotropy - one cytokine, many effects. Such as IL-4 can go to B-cells, thymocytes and mast cells.
Redundancy - different cytokines cause the same effect. Such as IL-2, Il-4, IL-5 go to B-cells just for proliferation.
Synergy - Cytokines work together IL-4 + IL-5 will class switch IgE.
Antagonism - One cytokine blocks another (IFN-y blocks IL-4-induced IgE switch)

Question 7

What are some cytokines in the Th1 crowd? and their features.

Answer 7

Il-2: stimulates growth for B cells and T cells. Stimulates NK cell growth.
IFN-Y: Inhibits Th2 cell growth, activation of macrophages MHC I and II, activates NK cells.
TNF-B: Inhibits B-cells, kills T-cells induces NO production in macrophages, activates neutrophils

Question 8

What are some cytokines in the Th2 crowd? and their features.

Answer 8

IL-4: activates and growth of B-cells - igG1 and IgE; increased MHC class II induction, T-cell growth, inhibits macrophages activation.
IL-5: IgA synthesis for B cells.
IL-10: Increased MHC class II for B cells, inhibits Th1, inhibits macrophage cytokine release.

Question 9

What are some cytokines in the Th2/Th1 crowd? and their features.

Answer 10

1. Cytokine receptors consist of at least two chains (JAKs). Cytokine binding dimerizes the receptor, bringing together the JAKs which activate each other and phosphorylate the receptor.
2. Transcription factors (STATs) bind to phosphorylated receptors, and in turn are phosphorylated by JAKs.
3. Phosphorylated STATs form dimers and translocate to the nucleus to initiate gene transcription.

Question 11

What is the Th1 and Th2 dichtomy?

Answer 11

Naive Cd4 T cell -> proliferating T cell -> immature effector T cell (Th0) -> Th1 cell which activates macrophages. or Th2 cell which activates B cells to make neutralizing antibody