Immune Tolerance

Question 1

Define Immune regualtion

Answer 1

Control of the immune response to prevent inappropriate immune reactions

Question 2

Why is immune regulation important?

Answer 2

Prevents:
Responses against self
Tissue damage
Excessive lymphocyte activation

Question 3

What does failure in control result in?

Answer 3

Autoimmunity
Allergy
Hypercytokinemia and Sepsis

Question 4

Define autoimmunity

Answer 4

Immune response against self-antigen

Often classified under ‘immune-mediated inflammatory diseases’

Question 5

What are the two principles of autoimmunity?

Answer 5

Susceptibility genes and environmental trigger

Systemic or organ-specific

Question 6

What are the main features of autoimmune disease?

Answer 6

Imbalance between immune activation and control
Immune response is inappropriately directed/ controlled
Many are chronic and self-perpetuating

Question 7

What are the main features of immune-mediate inflammatory disease?

Answer 7

Chronic with prominent inflammation 
Can be autoimmune or response against microbial antigen 
(Crohn's)
May be caused by T-cells and antibodies
May be systemic or organ specific

Question 8

What are examples of immune-mediate inflammatory disease?

Answer 8

Rheumatoid arthritis
IBS
MS
Psoriasis

Question 9

What is Allergy?

Answer 9

Harmful response to non-infectious antigens that cause tissue damage and disease
Can be mediated by IgE and mast cells (acute anaphylactic shock)
Or mediated by T-cells- delayed type hypersensitivity

Question 10

What is Hypercytokinemia and Sepsis?

Answer 10

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

Question 11

How is a response licensed?

Answer 11

3 required signal model

1. Antigen recognition
2. Co-stimulation: cell-cell contact
3. Cytokine release

Question 12

What is self-limiting response?

Answer 12

Cardinal feature of all immune responses: SELF LIMITATION
Manifested by decline of immune response
Principle mechanism: immune responses eliminated antigen that initiated responses
First signal for lymphocyte removed

Question 13

What are the three phases of cell mediated immunity?

Answer 13

Induction
Effector
Memory

Question 14

What are the three options for the end of response?

Answer 14

Resolution
Repair
Chronic Inflammation

Question 15

What is resolution?

Answer 15

No tissue damage, returns to normal.

Phagocytosis of debris by macrophages

Question 16

What is repair?

Answer 16

Healing with scar tissue and regeneration

Fibroblast and collagen synthesis

Question 17

What is chronic inflammation?

Answer 17

Active inflammation and attempts to repair damage ongoing

Question 18

What is tolerance?

Answer 18

Specific unresponsiveness to an antigen that is induces by exposure to that antigen

Question 19

Why is tolerance important?

Answer 19

Therapeutic potential- inducing tolerance may be exploited to prevent graft rejection, treat allergy and auto-immune diseases

Question 20

What is Central tolerance?

Answer 20

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

Question 21

What is Peripheral tolerance?

Answer 21

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

Question 22

How does central tolerance happen with B-cells?

Answer 22

If immature B cells in bone marrow encounter antigen in a form which can crosslink their IgM
Apoptosis is triggers

Question 23

How does central tolerance happen with T-cells?

Answer 23

Need to select for T cell receptors which are capable of binding self MHC
Removed if useless or too dangerous

Question 24

What is AIRE?

Answer 24

AutoImmune REgulator
Transcription factor that allows expression of all human proteins
Enables self deselection

Question 25

What do mutations in AIRE result in?

Answer 25

Multi-organ autoimmunity

Question 26

How does peripheral tolerance work?

Answer 26

Removal of self-reactive cells already in circulation

Question 27

What is anergy?

Answer 27

Mechanism of peripheral tolerance Naive T-cells need co-stimulatory signals in order to become activated Most cells lack these proteins and MHC class II If naive T-cell sees MHC without appropriate co-stimulatory protein it becomes anergic

Question 28

What does anergic mean?

Answer 28

Less likely to be stimulate in future | Even is co-stimulation is then present

Question 29

What is ignorance?

Answer 29

Mechanism of peripheral tolerance Antigen may be present in too low a concentration to reach the threshold for T-cell receptor triggering Immunologically privileged sites e.g. eye Compartmentalisation of the cells and antigen control interactions

Question 30

What us antigen induced cell death?

Answer 30

Mechanism of peripheral tolerance | Activation through the T-cell receptor can result in apoptosis

Question 31

What are the three mechanism of peripheral tolerance?

Answer 31

Anergy Ignorance Antigen induces cell death

Question 32

What are the 5 types of T-helper cells?

Answer 32

``` T-helper 1 cells T-helper 2 cells Follicular helper T cells Th17 cells T-reg ```

Question 33

What do T helper 1 cells do?

Answer 33

Produce interferon gamma | Boost intracellular immune response

Question 34

What do T-helper 2 cells do?

Answer 34

Produce IL-4,5,13 | Boost anti-multicellular organism réponse

Question 35

What do follicular helper T cells do?

Answer 35

Produce IL-21 | Essential for generation of isotope-switched antibodies

Question 36

What do Th17 cells do?

Answer 36

Secrete IL-17 in autoimmune diseases such as arthritis | Important for the control of bacteria

Question 37

What do T-reg cells do?

Answer 37

Regulate the activation of effector functions of other T-cells Inhibit other T-cells Necessary to maintain tolerance to self-antigen Make FoxP3 transcription factor

Question 38

How are T-helpers defined?

Answer 38

Cytokines they release | Transcription factors they use

Question 39

Why is regulation key in pregnancy?

Answer 39

Pregnancy can be seen as a parasitic infection | Exposure to new antigen

Question 40

How can tolerance be lost?

Answer 40

Exposure to environmental antigens or self-antigens in the context of infection can alter the outcome

Question 41

What is IL-10?

Answer 41

Key anti-inflammatory cytokine Multi functional Acts on a range of cells Blocks pro-inflammatory cytokine synthesis