Regulation of Lymphocyte Responses

Question 1

define autoimmunity

Answer 1

immune response against self antigens, pathological

Question 2

What are the general principles of autoimmunity?

Answer 2

pathogenesis - susceptibility genes and environmental triggers
systemic or organ specific

Question 3

What are the features of autoimmunity?

Answer 3

chronic and self perpetuating
inflammation
T cell of antibody driven
imbalance beween immune activation and control

Question 4

define allergy

Answer 4

immune response to non-infectious agents

Question 5

What are the types of allergy?

Answer 5

anaphylaxis - mediated by IgE and mast cell

DTH - mediated by T cells

Question 6

define hypercytokinemia and sepsis

Answer 6

too much immune response due to positive feedback

Question 7

How do hypercytokinemia and sepsis differ?

Answer 7

sepsis = when pathogens enter wrong compartment such as blood
hypercytokinemia = failure to regulate response level

Question 8

What is self limitation? How is it done?

Answer 8

decline in immune response by eliminating antigen to decrease stimulation for T cell activation

Question 9

What is tolerance?

Answer 9

active control mechanisms function to limit responses to persistent pathogens

Question 10

define immunological tolerance

Answer 10

specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen

Question 11

How is immunological tolerance significant?

Answer 11

individuals are tolerant to their own antigens

can be used therapeutically to prevent rejection

Question 12

What is central tolerance?

Answer 12

destroy self reactive T/B cells before they enter the circulation

Question 13

Summarise the process of central tolerance

Answer 13

lymphocytes that recognise self antigens before maturation are apoptosed or changed
change:
-B cells change specificity
-T cells develop into Treg
apoptosis:
-B cells apoptosis triggered if IgM crosslinks with self antigen
-TCR and MHC binding can’t be too weak/not at all as no signal produced if peptide bound
-TCR and MHC binding can be too strong as signalling may happen without foreign peptide

Question 14

define peripheral tolerance

Answer 14

destroy self reactive T/B cells that enter circulation

Question 15

What is autoimmune regulator (AIRE)? Why is is important?

Answer 15

transcription factors allow transcription of proteins normally just expressed in peripheral tissues to be expressed in thymus to T cells encounter all self proteins

Question 16

What are the 4 mechanisms of peripheral tolerance?

Answer 16

anergy, ignorance, deletion, regulation

Question 17

What is anergy?

Answer 17

naive T cells need costimulatory signals to be activated
most cells lack costume. proteins and MHCII
naive T cell sees MHC?peptide without costim.
tells T cell to shut down and become anergia
less likely to be activated in future even if co stimulation present

Question 18

What is ignorance?

Answer 18

no antigen or costimulation so no activation

compartmentalisation means T cells and APC never in same tissue

Question 19

What is deletion?

Answer 19

APC drives apoptosis of T cell via TCR activation

Question 20

What is regulation?

Answer 20

block activation using Treg cells to inhibit T cells

Question 21

What is an immunologically privileged site? give examples

Answer 21

no APC so no reaction as risk of immune response damage greater than infection damage
e.g. brain, eye

Question 22

Give characteristics touristic of Treg cells

Answer 22

high IL-2 receptor levels
low IL-7 receptor levels
FoxP3 TF
secretes immunosuppressive cytokines to inactivate lymphocytes

Question 23

Why are Treg essential for pregnancy?

Answer 23

50% of MHC isn’t self

Question 24

What are the flavours of Treg?

Answer 24

natural Treg

inducible Treg

Question 25

What happens post infection?

Answer 25

resolution - no tissue damage, returns to norma phagocytosis of debris
repair - healing with scar tissue and regeneration with fibroblasts and collagen synthesis
chronic inflammation -active inflammation and attempts to repair damage ongoing

Question 26

Summarise cross regulation by T cell cytokines

Answer 26

Th cells produce cytokines which cross-regulate with each other
cytokines has diverse action on a wide range of cells
and influence outcome of immune response
focuses response of single subset and regulates macrophages

Question 27

Give characteristic of IL-10

Answer 27

master regulator
multifunctional
anti inflammatory cytokine 
shuts down IR
acts on may cells
down regulates macrophages

Question 28

Explain T-B cell collaboration

Answer 28

T cell recognises MHC:peptide
T cell expressed CD40L to activate B cell and CD28 to be activated
B cell expressed CD40 to be activated and B7 to activate T
T cell produces IL-4, IL-21, IFN-gamma