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Immunology > 8. Regulation of lymphocyte responses > Flashcards

8. Regulation of lymphocyte responses Flashcards

1
Q

Importance of immune regulation

A

Avoid excessive lymphocyte activation and tissue damage during normal protective responses against infections
Prevent inappropriate reactions against self-antigens (“tolerance”)

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2
Q

What is autoimmunity?

A

Immune response against self (auto-) antigen
Systemic or organ specific
Imbalance between immune activation and control

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3
Q

What are the underlying causative factors of autoimmune disease?

A

Susceptible genes

Environmental influences

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4
Q

Immune-mediated inflammatory diseases

A

Chronic diseases with prominent inflammation, often caused by failure of tolerance or regulation
e.g. RA, IBD, MS

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5
Q

What may immune-mediated inflammatory diseases result from?

A

Immune responses against self-antigens (autoimmunity) or microbial antigens
May be caused by T cells and antibodies

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6
Q

What is allergy?

A

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

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7
Q

What can allergy be mediated by?

A 
Antibody (IgE) and mast cells (acute anaphylactic shock)
T cells (delayed type hypersensitivity)
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8
Q

What is hypercytokinemia and sepsis?

A

When there is too much immune response
Too much cytokines in the blood
Sepsis: bacteria has crossed the mucosa and entered the blood stream

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9
Q

What is a cardinal feature of all immune responses and what is the mechanism for this?

A

Self-limitation
Manifested by decline in immune response
Removal of antigen means 1st signal for lymphocyte activation is eliminated

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10
Q

Describe the 3 signal model that licences a response

A

Antigen recognition
Co-stimulation
Cytokine release

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11
Q

What are the 2 general principles of regulating the immune response?

A

Responses against pathogens decline as infection is eliminated: driven by apoptosis of lymphocytes
Active control mechanisms limit responses to persistent antigens (self-antigens, tumours)

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12
Q

Define Immunological Tolerance.

A

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

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13
Q

What is self tolerance and what does breakdown result in?

A

All individuals are tolerant of their own antigens

Breakdown= Autoimmunity

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14
Q

Therapeutic potential of immunological tolerance

A

Inducing tolerance may be exploited to prevent graft rejection, treat autoimmune and allergic diseases

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15
Q

What is tolerance?

A

State of immune functional unresponsiveness

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16
Q

What are the 2 types of tolerance?

A

Central tolerance: destroy self-reactive B and T cells before they enter circulation
Peripheral tolerance: destroy/ control self-reactive B and T cells which do enter circulation

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17
Q

What happens to Lymphocytes that recognise self-antigens before maturation in the generative organs?

A

They’re eliminated (deletion) or made harmless

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18
Q

What gene allows thymic expression of all the body’s gene products and what does this allow?

A

AIRE: autoimmune regulator
Allows T cell developing in thymus to encounter MHC bearing peptides expressed in other parts of body
promotes self-tolerance

19
Q

What does this AIRE encode?

A

Specialised transcription factor

Allows thymic expression of all the body’s gene products

20
Q

What do mutations in AIRE result in?

A

Multi-organ autoimmunity

Self reactive T cells are released because they haven’t seen proteins from other tissue

21
Q

What are the 4 mechanisms of peripheral tolerance?

A

Anergy
Deletion
Ignorance
Regulation

22
Q

Describe Anergy

A

T cell sees antigen on DC, but no co-stimulation
Shuts down the T cell and makes it unresponsiveness
(like increasing the activation energy by denying it of co-stimulation)

23
Q

Describe Deletion

A

DC can induce cell death, removing T cell from circulation

24
Q

Describe Ignorance

A

In some immunologically privileged sites there aren’t any APCs for the T cells to bind with
No antigen
No co-stimulation
No activation of T cell

25
Q

Describe Regulation

A

Regulation of response by cytokines released by Treg

26
Q

What is often the cause of induced apoptosis of peripheral T cells?

A

Fas ligand (CD95)

27
Q

What transcription factor do Tregs express that is key to its function? What does mutation of this lead to?

A

FoxP3

Leads to severe autoimmune disorder: IPEX

28
Q

What cytokine is frequently involved in shutting down dendritic cells?

A

IL-10

29
Q

What are the multiple mechanisms of action of Tregs?

A

Secretion of immune-suppressive cytokines e.g. IL-10

Inactivation of DCs or responding lymphocytes

30
Q

What are the 2 types of Treg?

A

Natural

Induced

31
Q

Describe natural Tregs (nTreg)

A

Develop in the thymus
Development requires recognition of self-antigen during maturation
Reside in peripheral tissues to prevent harmful reactions against self

32
Q

Describe induced Tregs (iTreg)

A

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

33
Q

What do regulatory T cells turn off?

A

Immune response

34
Q

Why is regulation critical in pregnancy?

A

Pregnancy is a parasitic infection
1/2 MHCs on foetus are foreign
So need to be able to shut down immune response

35
Q

What occurs in resolution?

A

No tissue damage, returns to normal.

Phagocytosis of debris by macrophages.

36
Q

What occurs in repair?

A

Healing with scar tissue and regeneration.

Involves fibroblasts and collagen synthesis

37
Q

What occurs in chronic inflammation?

A

Ongoing inflammation and attempt to repair damage

38
Q

Breaking tolerance

A

Exposure to antigens which are similar to self-antigens can lead to lack of tolerance and autoimmune response

39
Q

Cross regulation by T cell cytokines

A

Each Th produce different cytokines
These cross regulate with each other: one becomes dominant and others shut down to focus immune response on a single Th subset

40
Q

Cross talk between Th and macrophages

A

T helper cells through production of cytokines, communicates to macrophages, change the output of macrophages

41
Q

What is the “master regulator”?

A

IL-10

42
Q

Describe IL-10

A 
Key inflammatory cytokine
Multi-functional
Acts on range of cells
"Turns off immune system"
Blocks pro-inflammatory cytokine synthesis
Down-regulates macrophages
43
Q

Influence of T cells on B cells

A

Ig Class switch: Cytokines made by T cells can change type of B cell output
Instruct B cells to make different qualities of antibody

Immunology (9 decks)

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