Autoimmunity Flashcards
autoimmunity
- downside to having acquired immunity
- developed defence system means that individual has ability to recognize any possible microbial antigenic determinant and potential for immune destruction
Autoimmune disease
The pathological conditions associated with ongoing tissue damage from self reactive antibodies and/or cytotoxic T cells
- spontaneous development
- predisposing causes are rarely observed
What causes autoimmune conditions?
- failures of immune tolerance and immunoregulation
**normal regulatory mechanisms do not function to prevent or to down-regulate the response to self antigens
What causes autoimmunity?
- exposure of hidden antigens
- new epitopes/antigens
- cross-reactive antigens
- bystander activation
Exposure of hidden antigens
- antigens are not normally exposed to the cells of the immune system (ex. eye, CNS, testes, cell cytoplasm) so no active tolerance
**Exposure of antigens leading to triggering of immune response and autoimmune disease= INFLAMMATION
New epitopes/antigens
Generated on self proteins by molecular changes
Example: Changes to IgG Fc after binding to antigen to create an immune complex (Rheumatoid factor)
Cross-reactive antigens
“molecular mimicry”
- immune response to an infectious agent which shares epitopes to self-antigens
(Self antigen and foreign antigen appear similar and are recognized as danger)
Rheumatic fever after streptococcus infection
- example of cross-reactive antigens
- Antibodies react to streptococcal cell wall, but antigen is similar to tissue in heart resulting in cross-reaction
Bystander activation
Once immune response is triggered, the antigen presenting cells in the area become activated and have enhanced interactions with Th cells. High levels of cytokines in the environment supply the co-stimulatory signals needed to trigger self-reactive cells
**Both bacteria and viruses have caused this
Two groups of autoimmune diseases
- organ specific
- Systemic
Organ specific autoimmune disease
Selective targeting of a single organ or cell type, and/or related cells/organs.
Immune response may be predominantly Th2
Systemic autoimmune diseases
Auto-reactivity to multiple self-antigens in unrelated tissues, cells, organs.
Immune response both Th1 and Th2
Examples of organ specific autoimmune diseases
- Endocrine: hypothyroidism, diabetes, addisons
- Neurological: polyneurotos, meningitis, myelopathy
- Ocular: uveitis, keratitis
- Skin: pemphigus, pemphoid
- Muscle: polymyositis
- Joints: polyarthritis
- Blood cells: RBCs, platelets
Systemic Lupus Erythematosus (SLE)
- systemic Autoimmune disease
- rheumatic, connective tissue, collagen diseases
- autoreactivity to multiple self-antigens, many of which are intracellular including components of the nucleus
- circulating immune complexes (antigens/antibodies) are important in pathogenesis of the lesions
Aire gene
- expressed by thymic epithelial cells
- autoimmune regulator gene which promotes the expression of many self-antigens in the thymus during T cell receptor selection
**defects associated with multiple autoimmune diseases
