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MCD > Immunology 8 - Regulation of lymphocyte responses > Flashcards

Immunology 8 - Regulation of lymphocyte responses Flashcards

1
Q

Why is immune regulation important?

A
  • To avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
  • To prevent inappropriate reactions against self antigens (‘tolerance’)
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2
Q

Define autoimmunity

A

Immune response against self (auto-) antigen = pathologic

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3
Q

What are the general principles of the autoimmune response?

A
  • Pathogenesis: Susceptibility genes + environmental triggers
  • Systemic (relating to a system) or organ-specific
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4
Q

What can cause an immune-mediated inflammatory disease?

A
  • Immune responses against self antigens (autoimmunity) or microbial antigens (Crohn’s disease?)
  • T cells and antibodies
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5
Q

What is allergy?

A

Harmful immune responses to non-infectious antigens that cause tissue damage and disease

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6
Q

What is allergy mediated by?

A
  • Antibody (IgE)
  • Mast cells (acute anaphylactic shock)
  • T cells (delayed type hypersensitivity)
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7
Q

What cases hypercytokinemia and sepsis?

A
  • Too much immune response
  • Often in a positive feedback loop
  • Triggered by pathogens entering the wrong compartment (sepsis) or failure to regulate response to correct level
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8
Q

How does self limitation occur in regard to immune responses?

A

There is a decline of the immune response as the antigen is eliminated, meaning the signal for lymphocyte action is eliminated.

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9
Q

What occurs to lymphocytes when the infection is eliminated?

A
  • There is apoptosis of lymphocytes that lose their survival signals
  • Memory cells are the survivors
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10
Q

Define immunological tolerance.

A

Specific unresponsiveness to an antigen that is induced by exposure of lymphocytes to that antigen (tolerogen vs immunogen)

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11
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
  • Therapeutic potential: Inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases
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12
Q

What are the two types of tolerance

A
  • Central tolerance

- Peripheral tolerance

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13
Q

What is central tolerance?

A

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

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14
Q

What is peripheral tolerance?

A

Destroy or control any self reactive T or B cells which do enter the circulation

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15
Q

What happens in central tolerance to suppress the immune response?

A
  • Apoptosis
  • Editing of B cell receptors
  • Development of regulatory lymphocytes (only in CD4+ T cells)
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16
Q

What happens in peripheral tolerance to suppress the immune response?

A
  • Anergy (lymphocyte doesnt react to their antigen)
  • Apoptosis
  • Suppression
17
Q

How is apoptosis of B cells triggered in the bone marrow?

A

When immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM.

18
Q

How are T cells selected in the thymus?

A
  • If the t cell cant bind to any self-MHC there is death by neglect (apoptosis)
  • If the T cell binds to self MHC too strongly, there is negative selection (apotosis)
  • If the T cells binds to MHC weaky there is a signal to survive (positive selection)
19
Q

How do T cells in the thymus encounter MHCs with petides expressed in other parts of the body?

A
  • A specialised transcription factor (AIRE) allows thymic expression of genes that are expressed in peripheral tissues
  • Promotes self tolerance by allowing the thymic expression of genes from other tissues
20
Q

What do mutations in AIRE cause?

A

Multi-organ autoimmunity

21
Q

What are the 4 possible outcomes in peripheral tolerance when there is an abnormal T cell response?

A
  • Anergy
  • Ignorance
  • Deletion
  • Regulation
22
Q

Describe the process of anergy

A
  • When naive T cells are activated there are costimulatory signals
  • If a naive T cells sees an MHC without the right costimulatory protein it will be less likely to be stimulated in the future
  • This is true even when costimulation is present
23
Q

Describe the process of ignorance in T cells

A
  • The antigen is present in such a low concentration the threshold is not reached for T cell activation
  • Occurs in the brain and eyes, where infection is unlikely
  • Can occur by compartmentalisation of cells
24
Q

Describe the process of antigen induced cell death in T cells

A
  • Activation through the T cell receptor results in apoptosis
  • In peripheral cells this is caused by Fas ligand (FasL)
25
Q

Describe the process of regulation in T cells

A
  • T regulatory cells (Treg) inhibit other cells
  • Secrete immune-supressive cytokines
  • Inactivate dendric cells/responding lymphocytes
26
Q

What are the types of Treg cells?

A
  • Natural regulatory T cells (nTreg)

- Inducible regilatory T cells (iTreg)

27
Q

How do nTreg cells develop and where do they reside?

A
  • Development requires recognition of self antigens during T cell maturation
  • Reside in peripheral tissues to prevent harmful reactions against self.
28
Q

How do iTreg cells develop and when are they generated?

A
  • Develop from mature CD4 T cells that are exposed to antigen in the periphery; no role for thymus
  • May be generated in all immune responses, to limit collateral damage
29
Q

Why is regulation important in pregnancy?

A
  • Pregnancy is like a parasitic infection
  • Half of the antigens present are from the husband, so are non-self
  • Therefore, there is foreign MHC I
30
Q

What is resolution after the immune response?

A

Where there is no tissue damage, everything returns to normal

31
Q

What is repair after the immune response?

A

Healing with scar tissue and regeneration - involving fibroblasts and collagen synthesis.

32
Q

What is chronic inflammation after the immune response?

A

Active inflammation and attempts to repair damage ongoing.

33
Q

What can cause tolerance to end?

A
  • Exposure to environmental antigens or self antigens in the context of infections can alter the outcome
  • Antibodies can cross react with heart muscle
  • Exposure in the wrong place - e.g. peanut oil onto broken skin can induce inflammation
  • Exposure + inflammation may trigger lack of tolerance
34
Q

How does cross regulation of T cells occur?

A
  • The T helper cell that is dominating the immune response produces cytokines to inhibit the other T helper cell types.
  • This focuses the immune response so that unnecessary responses don’t occur (eg. you don’t want a fungal response to a virus)
35
Q

Why is IL-10 reffered to as the master regulator?

A
  • Key anti-inflammatory cytokine
  • Multi-functional (pleiotropic)
  • Acts on a range of cells
  • Blocks pro-inflammatory cytokine synthesis
  • Downregulates Macrophages
  • Mimicked by some viruses
36
Q

Summarise T and B cell collaboration and the mechanisms governing the generation of antibody classes

A
  • B cells are selected for by T cells which bind to processed antibodies on their cell surface
  • T cells then produce cytokines to activate the B cells
  • B cells can bind to soluble antigens¬ T cells cant.
  • T cells cause the Ig class switch by different classes producing different types of cytokines.

MCD (56 decks)

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