4: Immune Tolerance

Question 1

Need for immune tolerance

Answer 1

Increased immune function - hypersensitivity
Decreased immune function - immunosupression

Question 2

Immunosuppression

Answer 2

reduced removal of unwanted cells or pathogens
immunocompromise (HIV, leukaemia, genetic disease)
Opportunistic infections
Cancer

Question 3

Hypersensitivity

Answer 3

attacks own tissues
trigger: often unknown, sometimes infection
genetic, environmental factors, female predisposition
mechanism often unclear

Question 4

Hypercytokinemia

Answer 4

Too much immune response
often in +ve feedback loop

Question 5

Autoimmunity

Answer 5

Immune response against self-antigen
-Immune mediated inflammatory diseases
Happens from imbalance of immune activation and control

Question 6

Allergy

Answer 6

Harmful immune responses to non-infectious antigens that can cause tissue damage and disease
Mediated by IgE/Mast cells/Tcells

Question 7

T cell response is controlled by

Answer 7

“licensing” of immune response

Question 8

T cell needs three signals to be activated:

Answer 8

Antigen (MCHI or MCHII)
Co-stimulation (receptors B7-CD28)
Cytokines (immune cells/infected cells)

Question 8

Tolerance is

Answer 8

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

Question 9

Tolerance occurs

Answer 9

before circulation - central tolerance
in circulation - peripheral tolerance

Question 10

B cell Central tolerance

Answer 10

bone marrow

• IgM antibodies on cell membranes
  -Tested for binding on stromal cells
  -Autoreactive B cells undergo apoptosis

easier than T cell central tolerance, no TCR:MHC activation

Question 11

B cell Peripheral Tolerance

Answer 11

picks up self-reactive B and T cells - important for B cells, which undergo somatic hypermutation

B cell stimulation - specific B cell divides=expansion

Gene transcription in B cell expansion, variable antibody region prone to errors - somatic hypermutation

Some cells antibodies with higher affinity , cells with more affinity survive, have stronger response to pathogen - affinity maturation

Question 12

T cell central tolerance

Answer 12

Thymus
T cells must bind MHC complexes, without response in absence antigen

2 STAGES:
1. positive selection - does T cell bind MHC at all. if not = apoptosis
2. Negative selection - does T cell react to self-antigens and MHC too strongly, if they do= apoptosis

T cells need exposure to all antigens of body

Question 13

What transcription factor do Thymic cells express

Answer 13

AIRE
- Autoimmune Regulator - antigens found in thymus

Question 14

What do mutations in AIRE lead to

Answer 14

Autoimmune disease

Question 15

What does negative selection determine the fate of

Answer 15

T cell - CD4 T-helper cell, CD8 cytotoxic T cell or T reg cell

Question 16

T cell peripheral tolerance mechanisms

Answer 16

Anergy
Ignorance
Deletion/Antigen Induced Cell Deat (AICD)

Question 17

Angery

Answer 17

T cell encounters specific antigen without co-stimulation :
most cells lack costimulatory receptors and MHCI
less likely response, even for antigen with co-stimulation later

Question 18

Ignorance

Answer 18

T cells separated from antigens or too low concentration;
potentially self-reactive Naive T cell kept out “immunoprivileged sites”
- anatomical barriers preventing migration - compartmentalisation
-anti-inflammatory cytokines and apoptotic signals

Question 19

Antigen induced cell dead / Deletion

Answer 19

Antigen presenting cell promotes apoptosis in presence of antigen:
- T cell binds to APC, encounters signal to undergo apoptosis often induced by- Fas ligand FasL/CD95 ligand

Question 20

T reg cells are formed in

Answer 20

thymus
- originate from T cells that bind self-antigen but not kill them

Question 21

Role of T reg cells

Answer 21

Start upregulating TF - FoxP3
helps develop into mature Treg cells

Question 22

Babies with mutation in FoxP3 gene develop

Answer 22

IPEX syndrome

Question 23

Function of Tregs in pregnancy

Answer 23

mother exposed to cells with different MCHI, immune response prevented

Question 24

Two types of T reg cells

Answer 24

nTreg - natural regulatory cells ; develop in thymus, reside in periphery
iTreg - inducible regulatory cells; develop during T cell immune response

Question 25

Tregs reflect the

Answer 25

Th subset seen in T effectors

Question 26

What helps T cells differentiate into different subtypes

Answer 26

Cytokines

Question 27

IL-10 Is the

Answer 27

master regulatory cytokine

Question 28

IL-10

Answer 28

Pleiotropic - multiple functions
Inhibits production of pro-inflammatory cytokines
Inhibits macrophage function

• some viruses can mimic IL-10 to escape immune system

Question 30

Costimulatory factors make T helper cells

Answer 30

develop into different subtypes
- produce cytokines= more subtype production
- downregulate formation of other subtypes

Question 31

Different T helper cells secrete

Answer 31

different types of interleukins

Question 32

What does the type of interleukin produced by T cells, determine

Answer 32

Type of antibodies produced
- different antibodies=different constant regions (important for Fc recognition)= different responses

Question 33

Follicular T helper cells (Tfh-cells)

Answer 33

help shape antibody response
activate naive B cells to become plasma cells

Question 34

Interaction between Tfh and B cell

Answer 34

1.B cell internalises antigen and presents on MHCII to Tfh
2.Co-stimulatory binding CD40L to CD40 activates B cell
3.T cell secretes cytokines that determine antibody class switch of B cell

Question 35

Function of T follicular helper cells

Answer 35

-Activate B cells that present antigens on MHC complexes
-Provide link between cellular and hormonal immune response
-Produce IL-21 to stimulate B cell activation

Question 36

Mutation in FoxP3 transcription factor results in

Answer 36

inability to allow T-reg cells to develop properly

in pregnancy; T-reg cells shut down immune response in womb because half antigens presented on foetus are non-self