Tolerance

Question 1

Tolerance definition

Answer 1

Tolerance prevents the immune system from reacting to self-antigens, preventing autoimmunity

Question 2

Central tolerance

Answer 2

Central tolerance occurs during lymphocyte development (bone marrow & thymus)

Question 3

Peripheral tolerance

Answer 3

Peripheral tolerance occurs in tissues

Question 4

Central tolerance: T-cells

Answer 4

T-cells undergo a round of positive and negative selection during their education in the thymus

There are some limitations of this process

• Not all self-antigens can be expressed in the thymus
• Environmental antigens are not accounted for
• Not all self-reactive cells are deleted (would impact immune cell repertoire)

Question 5

Central tolerance: B-cells

Answer 5

B-cells undergo positive and negative selection in the bone marrow

Self-reactive B-cells have 3 possible fates:

1. High affinity BCRs undergo receptor editing
2. Deletion
3. Low affinity BCRs can undergo receptor editing or become anergic

Question 6

T-cell ignorance

Answer 6

A type of peripheral tolerance

Some antigens are only expressed at certain times or hidden in immunologically privileged sites

Some antigens may also be at a dose too low to activate the TCR

Question 7

T-cell lack of co-stimulation

Answer 7

A mechanism of peripheral tolerance

The absence of co-stimulatory molecules leads to anergy

Question 8

T-cell death

Answer 8

A mechanism of peripheral tolerance

Some self-reactive T-cells are deleted in the periphery by activation-induced cell death (AICD)

Occurs when the TCR is repeatedly activated which induces the expression of death receptors and pro-apoptotic proteins (bax, bad, bid)

Question 9

Regulatory T-cells

Answer 9

Aid peripheral tolerance

Can express CD8 or CD4 but all express FoxP3

Express high levels of CTLA-4 and so cause APCs to become tolerogenic

Can directly kill APCs

Secrete anti-inflammatory cytokines

Question 10

B-cell exhaustion

Answer 10

A mechanism of peripheral tolerance

Chronic, low level B-cell cross-linkage and a lack of co-stimulation results in anergy

Question 11

Partial activation of B-cells

Answer 11

A mechanism of peripheral tolerance

Partially activated B-cells do not express the right chemokine receptor and so are excluded from lymphoid follicles

Question 12

B-cell lack of co-stimualtion

Answer 12

A mechanism of peripheral tolerance

Acute, high level B-cell cross-linkage and a lack of co-stimulation results in apoptosis of the cells

Question 13

Autoimmune disorders

Answer 13

Inflammatory responses towards self-antigens

Mediated by hypersensitivity reactions I, II & III

Question 14

Hypersensitivity disorders

Answer 14

Inappropriate or uncontrolled responses towards environmental antigens