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POM Block 2 > 16 Regulation of lymphocytes > Flashcards

16 Regulation of lymphocytes Flashcards

1
Q

What is immune regulation?

A

Control of the immune response to prevent inappropriate reactions

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2
Q

Why is immune regulation required?

A
  • To avoid excessive lymphocyte activation and tissue damage

- To prevent inappropriate reactions against self antigens (tolerance)

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3
Q

What is the underlying cause of immune-mediated inflammatory diseases?

A

Failure of control mechanisms

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4
Q

What is autoimmunity?

A

Immune response against self antigen

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5
Q

What is organ specific autoimmunity

A

Immune response only recognises an antigen present in one organ (e.g. Graves’ - eyes)

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6
Q

What is systemic autoimmunity?

A

Throughout the whole body

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7
Q

What are the underlying principles of autoimmunity?

A
  • Genetic susceptibility (self antigens presented in different ways)
  • Environmental receptors (trigger)
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8
Q

Why are many immunological diseases chronic and self-perpetuating?

A

More of the affected protein is being synthesised and thus immune cells continue to be activated

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9
Q

What is Crohn’s disease?

A

Inflammation of the gut

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10
Q

Failure of tolerance/regulation can also cause

A

Chronic diseases with prominent inflammation

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11
Q

Examples of chronic diseases with prominent inflammation

A
  • Rheumatoid arthritis
  • Irritable bowel disease
  • MS
  • Psoriasis
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12
Q

What is allergy?

A

Harmful immune response to non-infectious antigens causing tissue damage and disease

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13
Q

Allergies can be mediated by

A
  • IgE and mast cells (type I)

- T cells (delayed, type IV)

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14
Q

What is hypercytokinemia?

A

Too much immune response (often +ve feedback loop)

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15
Q

What triggers hypercytokinemia?

A
  • Pathogens entering the wrong compartment (sepsis)

- Failure to regulated response to correct level

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16
Q

What is the 3 signal, licensing model?

A
  1. Antigen recognition (activation)
  2. Co-stimulation (e.g. TCR + DC)
  3. Cytokine release
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17
Q

What is self-limitation?

A

Decline of immune response due to elimination of initiating antigen

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18
Q

What are the 3 phases of cell mediated immunity?

A
  • Induction
  • Effector
  • Memory
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19
Q

What happens in induction?

A

Cell infected DC collects material

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20
Q

What happens in the effector phase?

A
  • MHC peptide and TCR interact
  • Naïve T becomes effector
  • Effector cells sees MHC peptide on infected cell and functions
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21
Q

What happens in the memory phase?

A

Effector pool contracts to memory

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22
Q

What is resolution?

A
  • No tissue damage
  • Return to normal
  • Phagocytosis of debris by macrophages
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23
Q

What is repair?

A
  • Healing with scar tissue and regeneration

- Fibroblasts and collagen synthesis

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24
Q

What is chronic inflammation?

A

Active inflammation and attempts to repair damage ongoing

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25
Q

Why do responses against pathogens decline as the infection is eliminated?

A
  • Apoptosis of lymphocytes that lose their survival signals

memory cells left as survivors

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26
Q

How are responses to persistent antigens (tumours, self, chronic) limited?

A

Active control mechanisms (grouped under tolerance)

T cells become inert

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27
Q

What is the basis of cancer immunotherapy?

A

Reactivation of T cells, reversing inertness

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28
Q

What is PD-L1?

A

An inhibitory marker made by T cells making the cells inert over time

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29
Q

What is immunological tolerance?

A

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

30
Q

What is the importance of tolerance?

A
  • All individuals are tolerant of their own antigens (self-tolerance)
  • Inducing tolerance may prevent graft-rejection, treat autoimmune and allergic diseases
31
Q

What is central tolerance?

A

Destruction of self-reactive T or B cells before they enter circulation

32
Q

What is peripheral tolerance?

A

Destruction/control of any self reactive T or B cells entering circulation

33
Q

Central tolerance of B-cells

A

If immature B cells in bone marrow encounter a cognate antigen cross-linking their IgM, apoptosis is triggered

34
Q

How does tolerance work with T cells?

A

Need to select for TCRs which are able to bind to self MHC

35
Q

What is a useless T cell?

A

Doesn’t bind to any self MHC at all (apoptosis)

36
Q

What is a dangerous T cell

A

Binds self MHC too strongly causing activation (apoptosis - negative selection)

37
Q

What are useful T cells?

A

Bind to self MHC weakly (signal to survive - positive selection)

38
Q

What is Autoimmune Regulator (AIRE)?

A

A specialised transcription factor allowing thymic expression of genes expressed in peripheral tissues

39
Q

What does AIRE do?

A

Promotes self tolerance (allows thymic expression of genes from other tissues)

40
Q

What can happen if there are mutation in AIRE?

A

Multi-organ autoimmunity

41
Q

What is a potential benefit of mutated AIRE?

A

May not be affected by several pathogens as viruses have evolved to have similar proteins to self

42
Q

What are the 4 mechanisms of peripheral tolerance?

A
  • Anergy
  • Ignorance
  • Deletion
  • Regulation
43
Q

What is anergy?

A
  • Naive T cells need co-stimulatory signals to be activated

- If the T cells sees the MHC peptide ligand without appropriate costimulatory protein, it becomes anergic

44
Q

What does anergic mean?

A

Less likely to be stimulated in future, even if co-stimulation is then present

45
Q

What is ignorance?

A
  • Antigen may be present in too low a concentration to reach T cell activation threshold
46
Q

What is an immunologically privileged site?

A

Where T are cells unable enter (e.g. eyes, nerves , brain)

47
Q

What is antigen induced cell death (AICD)?

A
  • Activation through T-cell receptor can result in apoptosis

- Often caused by expression of death ligand Fas (CD95 ligand, FasL)

48
Q

What does Th1 do?

A
  • Produce interferon gamma
  • Boos intracellular response
    (viral infection)
49
Q

What does Th2 do?

A
  • Produce Il-4, Il-5, Il-13
  • Boost anti-multicellular organism response
    (parasite/worm)
50
Q

What do follicular helper cells do (Tfh)?

A
  • Produce IL-21, reside in B cell follicles
  • Essential for generation of isotype-switching antibodies
    (communicate + activate B cells)
51
Q

What does Th17 do?

A
  • Secrete IL-17 in autoimmune diseases such as arthritis
  • Control of bacteria, activate neutrophils, macrophages
  • Pro-inflammatory
52
Q

What do Treg cells do (Th0)?

A
  • Regulate the activation or effector functions of other T cells
  • Maintain tolerance to self antigens
  • IL-10, TGFB
53
Q

How are T helper cells defined?

A
  • Cytokines they produce

- Transrciption factors they use

54
Q

What is cross regulation?

A

If one type of cytokine is being produced, other pathways are shutdown
- Cannot have 2 types of CD4 responses at the same time

55
Q

How do Treg cells inhibit other cells?

A

They produce the cytokine IL-10 which is anti-flammatory making the immune response less aggressive

56
Q

What other important molecule is encoded by Treg cells?

A

Foxp3 - transcription factor drives IL-10 production

Specifies how T cell responds

57
Q

What does a mutation in Foxp3 lead to?

A

Broad systemic autoimmunity

58
Q

What is scurfy?

A

A condition in mice associated with Foxp3

59
Q

What is IPEX syndrome?

A
  • Immune dysregulation
  • Polyendocrinopathy
  • Enteropathy
  • X-linked
60
Q

What are natural Treg cells (nTreg)?

A
  • Develop in thymus
  • Require recognition of self antigen during T cell maturation
  • Reside in peripheral tissues
61
Q

What are inducible Treg cells (iTreg)?

A
  • Develop from mature CD4 cells exposed to antigen in periphery
  • May be generated in all immune responses
62
Q

Why is regulation critical in pregnancy?

A
  • Exposure to new antigen (paternal antigens)
  • Expressed in the context of foreign MHC I
  • T regs only exist in mammals
63
Q

How can tolerance be lost?

A

Exposure to environmental antigens or self antigens in infections

64
Q

Example of tolerance being lost

A

Post strep pyogenes

  • B cells made against bacteria
  • Antibodies cross react with auto-antigen
  • React with heart muscle
65
Q

What is IL-10?

A
  • Key anti-inflammatory cytokine that acts on a range of cell
66
Q

What does IL-10 do?

A
  • Blocks pro-inflammatory cytokine synthesis (TNF, IL-6, IL-8, IFNy)
  • Down-regulates macrophages
67
Q

Co-stimulation - T cells

A
  • Express CD40L to activate B

- Express CD28 to be activated

68
Q

Co-stimulation - B cell

A
  • Express CD40 to be activated by T

- Express B7 to activated T

69
Q

What shapes the B cell response?

A

Production of cytokines by T cells

70
Q

What is class switching?

A
  • Variable region remains same
  • Antibody type changes
  • Depends on type of T helper cell

POM Block 2 (9 decks)

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