antigen presentation and T lymphocytes

Question 1

what does immune regulation prevent

Answer 1

excessive immunity and inappropriate reactions vs self antigen

Question 2

what principally controls immune regulation

Answer 2

Treg

Question 3

define autoimmunity

Answer 3

immune response against self antigens by the same mechanism as against a pathogen, caused by an imbalance between immune activation and control

Question 4

what is the pathogenesis of autoimmunity

Answer 4

susceptibility genes and environmental triggers

Question 5

2 areas of autoimmunity

Answer 5

systemic or organ-specific

Question 6

why are many autoimmune diseases chronic and self-perpetuating

Answer 6

over time more immune cells are produced and exhausted

Question 7

what is the principle feature of immune-mediated inflammatory diseases

Answer 7

failure of tolerance and regulation

Question 8

2 examples of immune-mediated inflammatory diseases

Answer 8

rheumatoid arthritis, multiple sclerosis

Question 9

2 causes of immune-mediated inflammatory diseases

Answer 9

inappropriate immune response (T cells, antibodies) or microbial antigens (e.g. Crohn’s)

Question 10

define allergy

Answer 10

harmful immune response to non-infectious antigens, causing tissue damage

Question 11

what antibody and cell is the allergic response mediated by to produce an acute anaphylactic shock

Answer 11

IgE and mast cells

Question 12

what cell is the allergic response mediated by to produce delayed type hypersensitivity

Answer 12

T cell

Question 13

define hypercytokinemia

Answer 13

excessive immune response caused by positive feedback loop between cytokines and immune cells

Question 14

what triggers hypercytokinemia

Answer 14

pathogens entering wrong compartment (sepsis) or failure to regulate response to correct level

Question 15

what is the cardinal feature of the immune response

Answer 15

self-limitation

Question 16

what is the principle mechanism of self-limitation

Answer 16

immune response eliminates antigen, eliminating first signal of lymphocyte activation

Question 17

what are the 3 signals to stimulate naive T cells

Answer 17

antigen, co-stimulation, cytokine release

Question 18

how does the response of lymphocytes vs pathogens decline as pathogens are eliminated

Answer 18

apoptosis of lymphocytes lose survival signals, with only memory cells surviving

Question 19

3 examples of persistent antigens which active control mechanisms function to limit responses to

Answer 19

self, tumours, chronic

Question 20

define tolerance

Answer 20

specific unresponsiveness to antigen, induced by exposure to lymphocytes of that antigen

Question 21

what is the significance of tolerance

Answer 21

ensures tolerance of own antigens, with the therapeutic potential exploited to prevent GVHD, and treat autoimmune and allergic diseases

Question 22

what is the central active process

Answer 22

destruction of self-reactive T/B cells before entering circulation

Question 23

what is the peripheral active process

Answer 23

destruction or control of any self-reactive T/B cells which do not enter circulation

Question 24

with B cell central tolerance, what happens if TCR detects self antigen

Answer 24

instead of proliferating it will die and collapse

Question 25

with T cell central tolerance, what is the ideal capacity of binding to self MHC for postive selection, and mention fates of negative selection

Answer 25

weak binding; if too weak to be useful, undergoes apoptosis; if too strong and will generate signal irrespective of pathogen antigen present, undergoes apoptosis

Question 26

AutoImmune REgulator (AIRE): location and function

Answer 26

thymus and recognises all possible proteins in all cells, screening for those which target self antigens

Question 27

AutoImmune REgulator (AIRE): consequence of mutations

Answer 27

multi-organ autoimmunity

Question 28

when does peripheral tolerance occur in relation to circulation

Answer 28

after circulation

Question 29

define anergy

Answer 29

absence of normal immune response to an antigen

Question 30

significance of peripheral tolerance

Answer 30

T cell meets antigen on APC but no/wrong co-stimulation, causing it to shut down; it is less lilely to be stimulated in the future even if co-stimulation is present

Question 31

when does ignorance occur in peripheral tolerance

Answer 31

no antigen or low [antigen] and no co-stimulation, or in immunologically priveleged sites

Question 32

when does deletion occur in peripheral tolerance

Answer 32

instead of shutting down T cell, APC tells T cell to kill itself; become more sensitive to FasL-mediated apoptosis

Question 33

which cell blocks activation of other cells in peripheral tolerance

Answer 33

Treg

Question 34

what CD is Treg

Answer 34

CD4

Question 35

which IL receptor is significant on Treg

Answer 35

IL-2

Question 36

what transcription factor drives Treg

Answer 36

Foxp3

Question 37

how does Treg shut down APC or responding lymphocytes

Answer 37

driven by Foxp3 → makes IL-10 → releases → shut down other cells

Question 38

where do natural Treg develop

Answer 38

thymus

Question 39

what does natural Treg development require

Answer 39

recognition of self-antigen during T cell maturatoin

Question 40

where do natural Treg reside

Answer 40

peripheral tissues

Question 41

what do inducible Treg develop from

Answer 41

mature CD4 T cells

Question 42

what responses are Treg cells generated in

Answer 42

all responses to limit collateral damage

Question 43

where are inducible Treg exposed to antigen

Answer 43

peripheral tissues

Question 44

define resolution and fate of debris

Answer 44

end of response where no tissue damage and functions return to normal; phagocytosis of debris by macrophages

Question 45

define repair

Answer 45

end of response with healing using scar tissue; fibroblasts and collagen synthesis

Question 46

fate of chronic inflammation as an end of response

Answer 46

active inflammation and attempts to repair damage ongoing (cyclical, and positive feedback can escalate)

Question 47

what can trigger a lack of tolerance

Answer 47

exposure to environmental antigens/self-antigens in context of infection, inflammation (e.g. due to exposure in wrong place)

Question 48

what is cross regulation achieved by

Answer 48

T cell cytokines

Question 49

what can cytokines shut down

Answer 49

different T cells, macrophages

Question 50

bidirectional effects of specific interaction between antigen-binding B cell and T cell

Answer 50

T cell induced to express B cell CD40 ligand → binds to CD40 on B cell → cytokine secretion

Question 51

what can T derived cytokines drive in B cells

Answer 51

proliferation and differentiation of B cells into plasma cells or direct Ig class switching

Question 52

what is the master IL regulator

Answer 52

IL-10

Question 53

features of IL-10

Answer 53

anti-inflammatory, acts on range of cells, blocks pro-inflammatory IL synthesis, downregulates macrophages, viral mimics, shuts down immune response

Question 54

T-B cell collaboration

Answer 54

dendritic cell licenses T cell → cytokine release → licenses B cell → production of different Ig