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Genetics > Immune Tolerance > Flashcards

Immune Tolerance Flashcards

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1
Q

What is the definition of immune regulation

A

Control of the immune response to prevent inappropriate reactions

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2
Q

Why is immune regulation needed

A

Avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections

Prevent inappropriate reactions against self antigens

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3
Q

What is the definition of autoimmunity

A

Immune response against self antigen leading to a pathologic disease

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4
Q

What are some examples of auto-immune disease

A

Rheumatoid Arthritis, Irritable Bowl Disease, Multiple Scelorosis, psoriasis

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5
Q

What are the features of autoimmune disease

A

Imbalance between immune activation and control

Failure of control mechaniscs

Underlying causative factos: susceptibility genes + influences

More prevalent in women

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6
Q

Immune mechanism of autoimmunity

A

Result from immune response against self antigens or microbial antigens

Immune response is inappropriately directed or controlled

May be caused by T cells and antibodies

Many immunological disease are chronic and self-perpetuating

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7
Q

Immune mechanism of allergy

A

Harmful immune response to non-infectious antigens that cause tissue damage

Mediated by antibody IgE and mast cells

Or T cells - delayed type hypersensitivity

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8
Q

What are acute condition of immune regulation

A

Hypercytokinemia and sepsis

Too much immune repsonse

Positive feedback loop

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

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9
Q

What is a self-limiting response of the immune system

A

All immune responses are self limiting, manifested by decline of immune response

Immuen response eliminates antigen that initiated response

First signal for lymphocyte activation is eliminated

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10
Q

What are the 3 signal model of licensing a response

A

Antigen Recognition

Co-stimulation

Cytokine release

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11
Q

Why does the response against pathogens decline as the infection is eliminated

A

Apoptosis of lymphocytes that lose their survival signals (antigens)

Memory cells are the survivors

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12
Q

What is the basis of cancer immunotherapy

A

Active control mechanisms function to limit responses to persistent antigens (self antigens)

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13
Q

Three possibel outcomes of an infection

A

Resolution - no tissue damage, returns to normal, damage due to phagocytosis

Repair - healing with scar tissue and regenration. Fibroblast and collagen synthesis

Chronic inflammation - active inflammation and attempts to repair damage

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14
Q

What is immune tolerance

A

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

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15
Q

What is the significance of immunological tolerance

A

All individuals are tolerant of their own antigens (self-tolerance); breakdown of self-tolerance results in autoimmunity

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16
Q

What are the two times tolerance can happen

A

Before T or B cells ever enter the circulation

Once in the circulation

17
Q

What is Central tolerance

A

Destroy self-reactive T or B cells before they enter the circulation

Lymphocytes that recognise self antigens are eliminated or made harmless as part of maturation process

18
Q

How is B cell central tolerance carried out

A

B cells mature in bone marrow

If immature B cell encounter antigen which can crosslink IgM, apoptosis is triggered

19
Q

How is T cell central tolerance controlled

A

Doesnt bind to any self-MHC - apoptosis due to death by neglet

Is T cell dangerous - binds to MHC too strongly, apoptosis triggered, negative selection

Is T cell useful - binds to self MHC weakly, signal to survive - postivie selection

20
Q

What is the autoimmune regulator

A

Transcription factor that allows the expression of antigen in the peripheral to be expressed in the thymus

Promotes self tolerance by allowign the thymic expression of genes from other tissue

Mutations have multi-organ autoimmunity

21
Q

What are the ways in which the shape of the B cell can change once activated

A

Affinity maturation - self reactive B cell can made here

Where change shape of antibody to better bind it

22
Q

How do you break tolerance with B cells

A

Somatic hyper mutations

Could become less tolerogenic and more reactogenic

Anti-streptococcus pyogenes - antigen that look like heart antigen

23
Q

Peripheral tolerance - anergy

A

T cells need co-stimulatory signals

Most cells lack co-stimulatory proteins and MHC

Becomes anergic, lack energy and higher activation energy

Less likely to be stimulated in the future

24
Q

Peripheral tolerance - ignorance

A

Antigen may be present in too low concentration to reach treshold for T cell triggering

Normally in eye and brain - T cell don’t really see antigen

Comparmentalisaiton of cells and antigens

25
Q

Peripheral tolerance - antigen induced cell death

A

Activation of T cell receptor results in apoptosis

Caused by interaction of other moelcules such as Fas ligand. death ligand

26
Q

What do Tregs do

A

Inhibit other T cells and other cells

27
Q

Role of T regs

A

Block T cell acitvation

Inhibit effector functions of T cells

28
Q

What does transcription factor FoxP3 syndrome

A

Have go Immune dysregulation, Polyendocrinopathy, Enterpathy X-linked syndrome (IPEX)

29
Q

What is the main way Treg regulate immune tolerance

A

IL-10 cytokine

Anti-inflammatory cytokine

Multifucntional

Acts on a range of cells

Blocks proinflammatory cytokine synthesis including TNF, IL-6, IL-8, IFNy

Down regulates Macrophage functions

30
Q

Why does T regs only exist in mammals

A

Mother is exposed to foreign MHC

Half from mum half from dad

31
Q

What is the natural regulatory T cells

A

Development in thymus requires

Recognise self antigen, begin to shut down harmful reactions against self

32
Q

What are inducible regulatory T cells

A

Develop in periphery - from mature CD4 T cells

Generate during immune response to limit collateral damage

33
Q

What are cytokines

A

Cytokines program immune response

Focus it for the right kind of response

Inflammatory

Anti-inflammatory

Interferon gamma, IL2, IL10

34
Q

What are cehmokines

A

Drive movement around the body

Act like address labels

Receptors profiles change with activation state of cell

35
Q

How is T cell help cross regulated

A

Different classes perpetuate themselves

They cross neutralise other T classes

36
Q

What does IL-21 in T cell do

A

Activates B cell and improves quality of B cell response

37
Q

How is the constant region of the antibody important

A

Differnet antibody classes have different constant regions

Differences in function reflect the different types of responses required to clear pathogens

38
Q

How do CD4 cells use cytokines on B cells

A

Cytokines to B cell to control gene editing and drop in and drop out different constant regions

Program B cells to make different antibodies

Genetics (9 decks)

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