Regulation of lymphocyte responses

Question 1

What are the 2 functions of immune regulation?

Answer 1

• stop there being too much immune response

- prevent reactions against self antigens

Question 2

What causes autoimmune disease?

Answer 2

imbalance between immune activation and control

Question 3

Define Immune- mediated inflammatory disease and what it is caused by

Answer 3

Chronic diseases with prominent inflammation, often caused by failure of tolerance or regulation.

• may result from pathogens expressing antigens that are similar to self antigens
• can be caused by T cells or antibodies
• can be systematic or organ-specific

Question 4

What is allergy

what can is it mediated by?

Answer 4

Harmful immune response to non- infectious agents that cause damage and disease.

• can be mediated by IgE and mast cells
• can be mediated by T cells- DELAYED TYPE HYPERSENSITIVITY
• When exposed to their antigen, mast cells degranulate and release their histamines causing local inflammation

Question 5

What is hypercytokinemia and sepsis?

Answer 5

TOO much immune response

• Positive feedback: triggers inflammation which damages locals cells leading to release of more inflammatory mediators
• Hypercytokinemia: too many cytokines in the blood - this is when you get too much immune response
• Sepsis: when bacteria crosses from the mucous into the blood stream- pathogens entering the wrong compartments
• sepsis can cause hypercytokinemia.

Question 6

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

Answer 6

• Responses against pathogens decline as the infection is eliminated – this is driven by apoptosis of lymphocytes
• Immunological tolerance to persistent antigens

Question 7

Define Immunological Tolerance.

Answer 7

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

Question 8

What are the two types of tolerance?

Answer 8

Central tolerance – destroy self-reactive B and T cells before they enter the circulation ( screening the newly developed T cells)
Peripheral tolerance – destroy self-reactive B and T cells that do reach the circulation

Question 9

What happens if the T cells and B cells react with self antigens?

Answer 9

• B cells may change their specificity ( affinity hypermutation)
• some T cells will turn into regulatory T cells

Question 10

What gene allows thymic expression of all the body’s gene products?

Answer 10

AIRE – autoimmune regulator

Question 11

What does the gene that allows for all genes to be expressed encode for?

Answer 11

Specialised transcription factor – allows thymic expression of all the body’s gene products

Question 12

What are the four main mechanisms of peripheral tolerance?

Answer 12

Anergy. 
Deletion .
Ignorance .
Regulation
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Question 13

Describe each of the four processes.

Answer 13

Anergy:
Naive T cells need COSTIMULATORY SIGNALS to become activated
-if an antigen is presented in the absence of costimulation you get apoptosis or anergy- which is unresppnsiveness ( sort of like increasing the activation energy)
Ignorance:
in some immunologically privileged areas the T cells cannot become activated because there are NO APCs. This is becuase the rsik of inflammation is greater than the risk of infection
Deletion: Antigen Induced Cell Death
- Activation through the T cell receptor can result in apoptosis
-in Peripheral T cells this is often caused by the expression of the death ligand- Fas Ligand
Regulation:
-regulated by T regulatory T cells (Treg)
-Treg produces cytokines ( IL-10) which inhibits other self-reactive T cells.

Question 14

What cytokine is frequently involved in shutting down dendritic cells?

Answer 14

IL-10 which shuts down other immune responses

Question 15

What transcription factor do Tregs express that is key to its function?

Answer 15

FoxP3

Question 16

What is the disease called when someone has a mutation in the gene in treg?

Answer 16

IPEX- immuno dysregulation, Polyendocinopathy, Enteropathy X-linked syndrome

Question 17

What are the two types of Treg?

Answer 17

Natural (nTreg):
-develop in the thymus
-reside in peripheral tissues to prevent harmful reactions against self
Inducible (iTreg):
-when exposed to APCs they turn from T helper function to Treg function

Question 18

what is the difference between resolution and repair?

Answer 18

Resolution - no tissue damage, returns to normal- phagocytosis of debris by macrophages
Repair- healing with scar tissue and regeneration- fibroblasts and collagen synthesis

Question 19

How can T cells be supressed metabolically?

Answer 19

By removing essential amino acids which leads to downregulation of responses

Question 20

Describe the cycle of T-B collaboration?

Answer 20

1. Both cells react to the same antigen
2. Specific interaction of antigen-binding B cell with eh T cells has BIDIRECTIONAL EFFECT
3. T cells are induced to express B cell costimulatory molecule CD40 which binds to CD40 on B cells, and secret cytokines
4. t cell derived cytokines drive proliferation and differentiation of B cells into antibody secreting plasma cells
5. the cytokines direct immunoglobin class-switching