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Flashcards in Tolerance Deck (14)
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Tolerance definition

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


Central tolerance

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


Peripheral tolerance

Peripheral tolerance occurs in tissues


Central tolerance: T-cells

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)


Central tolerance: B-cells

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


T-cell ignorance

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


T-cell lack of co-stimulation

A mechanism of peripheral tolerance

The absence of co-stimulatory molecules leads to anergy


T-cell death

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)


Regulatory T-cells

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


B-cell exhaustion

A mechanism of peripheral tolerance

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


Partial activation of B-cells

A mechanism of peripheral tolerance

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


B-cell lack of co-stimualtion

A mechanism of peripheral tolerance

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


Autoimmune disorders

Inflammatory responses towards self-antigens

Mediated by hypersensitivity reactions I, II & III


Hypersensitivity disorders

Inappropriate or uncontrolled responses towards environmental antigens