Immunological tolerance and autoimmunity

self vs non self recognition

The immune system can distinguish from self and non self

immune receptors for self antigens are not excluded

self antigens are seen by the immune system

mechanisms must exist to prevent reactivity to self antigens

The immunological equilibrium: balancing lymphocyte activation

One side is activated and fights against pathogens

the other side is inactivated and tolerates anything. does not respond to self and other harmless antigens

Immunological tolerance

Unresponsiveness of the immune system to a specific antigen following prior to being exposed by that same antigen

Importance of immune regulation

To prevent innapropiate action towards self antigens (self tolerance)

To prevent immune responses against harmless environmental antigens, commensal microbes

to avoid excessive lymphoocytes activation, tissue damage during normal protective responses against infections

failure to control mechanisms is the underlying cause of immune mediated inflammatory diseases

Lymphocyte maturation

T cell maturation occurs in the thymus

B cell maturation occurs in the bone marrow

A common lymphoid progenitor cell—>pre B/T cell (if it is not expressed enough—>apoptosis

Pre B/T cell expresses ojne chain of antigen receptor—>proliferates

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2 stages of immunological tolerance

Central tolerance which is in the primary lymphoid organs

apoptosis (clonal deletion)

receptor editing to change specificty (B cells only)

development of regulatory T cells or treg (CD4+ T cells only)

Peripheral tolerenace

Anergy

apoptosis (clonal deletion)

AIRE (autoimmune regulator)

A regulator of gene expression which stimuklates thymic expression of many self-antigens which are restricted to peripheral tissues