8 - Regulation of Lymphocyte Responses

Question 1

What are the 2 parts of immune regulation?

Answer 1

• stop there from being too much of an immune response
• prevent reactions against self-antigens

NOTE: failure of these mechanisms is the underlying cause of immune-mediated inflammatory diseases

Question 2

What is autoimmunity?

Answer 2

immune response against self pathogens

Question 3

What causes autoimmunity?

Answer 3

can be due to genetic predisposition and/or environmental triggers
if the MHC can recognise a broad spectrum of antigens, it could include self antigens

FUNDAMENTAL PROBLEM:
IMBALANCE BETWEEN IMMUNE ACTIVATION AND CONTROL

Question 4

Define immune-mediated inflammatory diseases

What cells can cause it?

Answer 4

diseases with prominent inflammation, often cause by failure of tolerance or regulation
(can be autoimmune)

can be caused by T-cells and antibodies

Question 5

Define allergy

Answer 5

a harmful immune response to non-infectious agents that cause damage and disease

Question 6

What cells mediate allergy?

Answer 6

mast cells and IgE

Question 7

What cells mediate allergy to bring about delayed type hypersensitivity?

Answer 7

T cells

Question 8

What happens when mast cells are exposed to their antigens?

Answer 8

they degranulate and release histamine, causing local inflammation

Question 9

What causes hypercytokinemia and sepsis?

Answer 9

too much immune response

Question 10

What is the positive feedback mechanism in hypercytokinemia?

Answer 10

by triggering inflammation, you cause damage to local cells, leading to the release of more inflammatory mediators

Question 11

What happens in hypercytokinemia?

Answer 11

too many cytokines in the blood

Question 12

What happens in sepsis?

Answer 12

bacteria cross from the mucosa to into the bloodstream (pathogens in the blood)

NOTE: sepsis can cause hypercytokinemia

Question 13

What is a tolerogen?

Answer 13

A foreign antigen that suppresses immune response, or produces immune tolerance. In comparison with immunogen (that induces an immune response), a tolerogen evokes immune tolerance.

Question 14

breakdown of self tolerance leads to ___

Answer 14

autoimmunity

Question 15

What is therapeutic potential (with reference to tolerance)?

Answer 15

can turn T cells from being activated into tolerogenic - inducing tolerance by regular exposure

Question 16

What is considered when selecting T-cell receptors?

Answer 16

If the T-cell receptors can bind MHC
- if the binding is too weak, then it may not be enough to allow signalling when binding to MHC presenting a foreign antigen
if the binding it too strong, then it may result in signalling irrespective of whether a self antigen or foreign particle can be found in the groove

Question 17

Why is AIRE necessary?

the is a part of central tolerance

Answer 17

• the cells in the thymus can’t produce all all 250,000 gene products that your body can produce
• AIRE is a specialised TF that allows the thymus expression of genes that are expressed in peripheral tissues
  (THE THYMUS CAN EXPRESS ALL THE PROTEINS IN THE HUMAN BODY)
• therefore, all the proteins are presented on MHC to the developing T-cells
• you are negatively selecting against the entire peptide library
• PROMOTING SELF-TOLERANCE
  (people without AIRE are autoimmune)

Question 18

What is anergy?

Answer 18

unresponsiveness (impacts the activation energy)

if an antigen is presented in the absence of costimulation, you get apoptosis or anergy

Question 19

What is ignorance?

Answer 19

in come immunepriveged sites (where the risk of inflammation far outweighs the risk of infection), T cells cannot become activated because there are no APCs

Question 20

What is deletion (antigen-induced cell death)?

Answer 20

• activation through the TCR can lead to apoptosis of the T-cell
• in peripheral T-cells this can often be caused by the expression of the Fas ligand (death ligand)

Question 21

What is regulation?

Answer 21

• regulated by Treg cells

- produces cytokines (IL-10) which inhibits other self-reactive T-cells

Question 22

What gene drive Treg cells?

Answer 22

FoxP3

Question 23

What CDs do Treg have?

Answer 23

CD4 (a type of T-helper cell)

Question 24

Give the mechanism of action of regulatory T-cells?

Answer 24

• secrete immunosuppressive cytokines (e.g. TGFb, IL-10)
• they engage with other T cells and turn them off
• IL-10 has a role in shutting down DCs

Question 25

What are commensal organisms?

Answer 25

one organism derives food or other benefits from another organism which is unaffected (neither hurt nor help it)

Question 26

What is resolution?

Answer 26

no tissue repair, returns to normal by phagocytosis of debris by macrophages

Question 27

What is repair?

Answer 27

healing with scar tissue and regeneration

uses fibroblasts and collagen synthesis

Question 28

Why is regulation important in pregnancy?

Answer 28

the body needs to immunosuppressive, since it is like a parasitic infection

Question 29

What is self-limitation?

Answer 29

the immune response eliminates the antigen that first initiated the response, so the immune response shuts down

Question 30

What brings about the production of B regulatory cells?

Answer 30

CD40-CD40L interaction

Question 31

What is the function of regulatory macrophages?

Answer 31

to reduce inflammatory immune response and thereby limit tissue damage
(produces high levels of IL-10)