Ch. 9 Immunologic Tolerance and Autoimmunity Practice Flashcards

A comprehensive set of vocabulary flashcards covering the definitions, cell types, mechanisms, and specific diseases associated with immunologic tolerance and autoimmunity.

Central tolerance

A process occurring in the bone marrow for B cells and thymus for T cells where immature lymphocytes specific for self-antigens are deleted by apoptosis, B cells undergo receptor editing, or T cells develop into regulatory T cells.

Peripheral tolerance

A process where mature lymphocytes encounter self-antigens in secondary lymphoid organs or peripheral tissues and are inactivated, deleted, or suppressed by Treg cells.

Anergy

A state of long-lived functional unresponsiveness to antigen stimulation where cells survive but are incapable of responding; in B cells, this is often accompanied by reduced antigen receptor expression and exclusion from follicles.

Rheumatoid factor

Plasma cells making IgM, IgG, and IgA autoantibodies specific for the Fc portion of IgG; these immune complexes can deposit in joints and recruit complement.

Molecular mimicry

A condition where microbial antigens contain epitopes similar to self-antigens, causing an immune response against microbes to cross-react with self-cells and tissues.

Receptor editing

A central tolerance mechanism in B cells where recognition of self-antigen triggers the re-expression of RAG genes and resumption of Ig light chain (LC) gene recombination to form a new receptor.

FoxP3

A transcription factor that controls the development and function of regulatory T cells (Tregs); mutations in this gene result in IPEX.

Negative selection

A form of central tolerance where developing thymocytes die by apoptosis if their TCR is ligated by a self-peptide:MHC complex in the thymus.

Treg (Regulatory T cells)

A subset of cells, typically $CD4^{+} CD25^{+} CTLA-4^{+}$, that suppress the activation of other T cells through contact-dependent mechanisms or the secretion of inhibitory cytokines.

Cell-intrinsic anergy

A peripheral tolerance mechanism resulting from the recognition of antigens without costimulators, leading to a block in TCR signaling and engagement of inhibitory receptors.

CTLA-4

An inhibitory receptor expressed on Treg cells that competitively inhibits the B7-CD28 interaction to prevent T cell activation.

RAG genes

Genes that encode for the VDJ recombinase; they are re-expressed during B cell receptor editing to allow for light chain (LC) gene rearrangement.

Rheumatic fever

A transient autoimmune disease where anti-streptococcal antibodies cross-react with myocardial protein, causing inflammation until the bacterial antigen is cleared.

Rheumatoid arthritis

An autoimmune disease causing chronic joint inflammation characterized by the infiltration of leukocytes into the synovium and the recognition of citrullinated proteins as non-self.

Citrullination

The enzymatic conversion of arginine to citrulline in self-proteins, which creates neoantigens that elicit an adaptive immune response in rheumatoid arthritis.

Sympathetic ophthalmia

An autoimmune reaction in both eyes following physical trauma to one eye, caused by the release of previously sequestered or "cryptic" eye antigens.

Cryptic antigens

Sequestered antigens not normally seen by the immune system that may initiate an autoimmune reaction if released due to tissue damage.

Systemic lupus erythematosus (SLE)

A multi-organ autoimmune disease where IgG is produced against nuclear antigens (like dsDNA), forming immune complexes that deposit on basement membranes.

Antinuclear antibodies (ANAs)

Autoantibodies directed against nuclear antigens, found in nearly all individuals with active Systemic lupus erythematosus (SLE).

IPEX

Immune dysregulation, X-linked polyendocrinopathy and enteropathy; a systemic autoimmune disease caused by a mutation in the $FOXP3$ gene.

AIRE

A gene encoding a transcriptional regulatory protein that allows thymic epithelial cells to express peripheral tissue self-antigens for the elimination of self-reactive T cells.

APS-1 (Autoimmune polyendrocrine syndrome)

Also known as APEDED; a disease caused by mutations in $AIRE$, leading to a failure in eliminating self-reactive T cells or developing them into Tregs.

ALPS (Autoimmune lymphoproliferative syndrome)

A collection of diseases characterized by defective apoptosis of self-reactive T and B cells in the periphery, often due to mutations in the $FAS$ gene or caspase-8 or 10.