Immune Regulation

Question 1

what is the central mode of regulation?

Answer 1

repertoire selection

Question 2

What is the peripheral mode of regulation?

Answer 2

peripheral deletion
anergy
regulatory receptors
regulatory T cells

Question 3

When does central tolerance take place?

Answer 3

during formation of T and B cells to remove auto reactive T and B cells

Question 4

How does deletion of T cells in periphery occur?

Answer 4

apoptosis of T cells
targets mitochondrial pathway of killing
extrinsic or intrinsic

Question 5

How does intrinsic deletion through apoptosis occur?

Answer 5

lack of IL-2 and IL-7 leads to upregulation of p53 - proapoptotic factors

Question 6

How does extrinsic deletion through apoptosis occur?

Answer 6

through Fas/FasL pathway

Question 7

What causes suppression of T cell responses/inhibition

Answer 7

response to chronic stress
tumours, viral infection

Question 8

How does inhibition via CTLA-4 occur?

Answer 8

cytotoxic T lymphocyte associated protein 4 (CD152) binds CD80 and CD86 on APCs. inhibits via decoy or intracellular activity

Question 9

How does inhibition via PD-1 occur?

Answer 9

programmed cell death 1
binding to PD-L1 and PD-L2
important in modulating immune responses

Question 10

What is exhaustion?

Answer 10

persistent stimulation of T cells

Question 11

What is stalemate?

Answer 11

virus/tumour-immune equilibrium

Question 12

What are 4 medications used to manipulate checkpoint blockades?

Answer 12

1. ipilimumab
2. involumab
3. pembrolizumab
4. atezolizumab

Question 13

What is the proposed role of PD1

Answer 13

suggested it can establish and reverse HIV latency

Question 14

Where does generation of Treg cells occur?

Answer 14

can occur in thymus or periphery

Question 15

What is the dual role of TGFb

Answer 15

TGFb is typically anti-inflammatory but can also stimulate naive T cells

Question 16

What are 2 effector functions of Treg cells

Answer 16

can act on other T cells or APCs
important balance in immune responses

Question 17

What are the suppressive cytokines of Treg cells

Answer 17

TGFb and IL-10
leads to alteration of transcription program

Question 18

How do Treg cells promote cell death?

Answer 18

express granzymes and perforin usually in CD8 T cells
requires Tregs to have long stimulation

Question 19

How do Treg cells disrupt function?

Answer 19

reduce metabolic capacity, which means less energy for effector functions
high affinity IL-2 receptor
displaced T cell interactions w DC

Question 20

Describe the role of granzyme B in inflammation and apoptosis

Answer 20

granzyme B triggers apoptosis but can also have other inflam effects

Question 21

What is tolerance?

Answer 21

process by which immune cells are made non-responsive to self-antigens

Question 22

What is AIRE?

Answer 22

an important regulator for -ve selection in thymus
eg. in presence of AIRE protein, thymic medullary cells express tissue-specific proteins leading to deletion of tissue-reactive T cells
eg. in absence of AIRE, T cells reactive to tissue-specific antigens mature and leave the thymus

Question 23

What is APS Type 1

Answer 23

lack of AIRE resulting in autoimmune reactions against endocrine glands

Question 24

What is peripheral tolerance for B cells?

Answer 24

second checkpoint, similar to central tolerance
receptor editing doesn’t happen bc these cells are mature and can’t rearrange light-chain loci

Question 25

Link between somatic hypermutation and auto reactive B cells?

Answer 25

auto reactive B cells can form during somatic hypermutation will be at a competitive disadvantage in GC reactions

Question 26

How does antigen sequestration/ignorance occur?

Answer 26

happens in situations where escaped cells don't ever see antigen can happen in sympathetic ophthalmia

Question 27

How does suppressing immune response lead to anergy?

Answer 27

inhibition of TCR signalling through Cbl-b which attaches to ZAP-70 ubiquitinatino of complex leads to degradation

Question 28

When does molecular mimicry occur?

Answer 28

when antigen is structurally similar to self-proteins

Question 29

How do auto reactive cells become anergic?

Answer 29

when stimulated with antigen under non-inflam conditions and made active again with sufficient stimulation

Question 30

What 2 situations break down tolerance mechanisms?

Answer 30

1. molecular mimicry 2. alloreactivity

Question 31

What are tolerogenic DCs?

Answer 31

DCs which still present Ag but down regulates co-stimulatory molecules and up regulates inhibitory molecules

Question 32

Use an examples to describe how gut microbiota can affect DCs

Answer 32

polysaccharide A of B.fragilis interacts with TLR2 of DCs to alter signalling and protects against experimental colitis cause disease and metabolic conditions

Question 33

What does central tolerance involve for T cells?

Answer 33

removing auto reactive T lymphocytes during development

Question 34

How does peripheral tolerance work in T cells?

Answer 34

occurs via self antigen presentation or antigen sequestration

Question 35

What are 3 ways that Tregs can become activated against auto antigen?

Answer 35

1. produce cytokines to dampen immune response 2. direct killing of auto reactive cells 3. disrupting function of auto reactive cells so its harder to exert effector functions