Immune Tolerance And Immune Recognition

Question 1

where do T cells develop? what is it like in there

Answer 1

thymus;
multi-lobar with organised zones
seeded by bone marrow derived precursors

Question 2

how do cd4 and cd8 cells form

Answer 2

at first, thymocyte expresses cd4 and cd8
positive selection: MHC I and II receptors present in thymic cortex, if thymocyte has affinity for MHCII-> stops cd8-> becomes cd4 t cell; if thymocyte has affinity for MHCI->stops cd4 expression-> CD8 cell; if no affinity at all-> apoptosis
negative selection: thymic medullary epithelial cells (TMEC) have MHC complexies-> if cell has low/moderate affinity, it is released; if it has high affinity-> apoptosis

Question 3

what happens in anergy? why is it important

Answer 3

t cell remains in circulation but is unresposnive to future stimulation;
TCR and MHC bind (signal 1)
no signal 2 (cd cluster of differentiation interaction is absent)
important as it confers tolerance to antigens not expressed in thymus
tolerance to food antigens
tolerance to commensal bacteria

Question 4

what do regulatory t cells do to?

Answer 4

prevent T cell proliferation 
prevent cytokine production
reduce co-stimulation 
alter cytokine production by APC-> reduced T cell attraction
suppress functions of NK and NKT cells

Question 5

types of regulatory T cells and their characteristics

Answer 5

nTreg: produced in thymus/responds to self-antigens/protection against autoimmunity
aTreg: develop from T cells in periphery/protection from autoimmunity/regulates responses to food antigens or commensal bacteria

Question 6

what are DAMPs ? what do they do? what are they produced by?

Answer 6

damage-associated molecular patterns
host biomolecules that initiate and perpetuate noninfectious noninflammatory response
produced by dead/dying cells-> dendritic cells activated

Question 7

what are HEVs

Answer 7

high endothelial venules: specialised bv that support migration of naive lymphocytes

Question 8

how are naive t cells recruited to site of activation

Answer 8

dendritic cell releases cytokines and chemokines-> upregulation of adhesion molecules on HEV-> naive T cells migrate to germinal centres in lymph nodes-> lymph node swells

Question 9

3 signals for activation of naive cd4 t cells

Answer 9

signal 1: TCR + MHC 2
signal 2: CD 28 + CD86
signal 3: cytokines

Question 10

th1, th2, th17, treg cytokines and type of pathogen they target

Answer 10

IL12 -> differentiation into th1-> intracellular pathogens (autoimmunity)
IL4-> Th2-> extracellular parasites (allergy/asthma)
TGF-beta+IL6-> differentiation into th17-> extracellular pathogens (autoimmunity)
TGF-beta + IL2-> Treg

Question 11

3 signals for activation of CD8 t cells

Answer 11

signal 1: TCR + MHC 1
Signal 2: CD 28 + CD86
signal 3: IFNgamma + IL2 from CD4

Question 12

3 things that can happen when t cells migrate out of lymph node

Answer 12

1. they dont encounter APC-> return to lymphatics
2. encounter APC-> effector function mode activated-> CD8 kills; CD4 releases TNFalpha/INF gamma
3. post infection-> t cells removed/become memory t cells

Question 13

cells responsible for immunological memory and their characteristics, sites of immunological memory

Answer 13

T memory cells (high fq/immediate response);
plasma cell (secrete high affinity antibodies/live for years)
B memory cells (high fq/develop into plasma cells)
lymphnodes/liver/spleen