A2. imm

Question 1

Define: Peripheral tolerance

Via which routes

Answer 1

Lymphocytes that encounter sufficient quantities of self-Ag for the first time in the periphery are eliminated or inactivated

• Activation-induced cell death
• Clonal anergy
• Clonal ignorance
• Suppression through regulatory cells

Question 2

Mechanisms of peripheral tolerance

Answer 2

1. Normal: B7.1 + CD28, CD4 –> activated Tc
2. Immunological ignorance: anatomical barrier –> Ignorant Tc
3. Deletion –> Apoptosis
4. Inhibition –> No activation
   Suppression –> No activation

Question 3

Define AICD

what type of regulator is AICD

What type of cells undergo deletion through AICD

Answer 3

(AICD) activation induced cell death = programmed cell death caused by the interaction of Fas receptors (Fas, CD95) and Fas ligands (FasL, CD95L)
AICD effector cells expressing FasL induce apoptosis of cells expressing Fas

AICD: -ve regulator of activated Tc - results from repeated stimulation of TCR

Both activated T & Bc express Fas therefore undergo clonal deletion via AICD

Question 4

How is anergy induced

Answer 4

Induced by co-stim inhibitory molecules e.g. CTLA-4

Question 5

What does a weak TCR stimulus result in

Answer 5

CD28:B7 predominates, resulting in net +ve activating signal & IL-2 production, proliferation & increased survival

Question 6

What does a strong TCR stimulus result in

Answer 6

CTLA-2 expression upregulated by increased transport to cell surface from intracellular stores & decreased internalisation

CTLA-4 competes w/CD28 for binding of B7 molecules….

Question 7

When does clonal ignorance occur

Name these sites

Answer 7

When Ag are sequestered in the immune privileged sites

Immune privileged sites:
brain (bloodbrainbarrier)
eye (bloodretinabarrier)
testis 
uterus (fetus) 
hamster cheek pouch