Autoimmunity Flashcards
How do autoimmune diseases come about?
Self-Ag is recognized as foreign and there is a failure of regulatory mechanism to control that response
What are the three factors contributing to development of autoimmune diseases?
immune factors (breakdown of T or B tolerance), genetic factors, environmental factors
How do these factors contribute to the development of autoimmune disease?
Genetic susceptibility means they have genes that allow them to present self-Ag to the immune system, but usually autoimmune response is caused by the response to environmental trigger that is misdirected to self-Ag
How does B cell tolerance break down?
not all of self-reactive B cells in BM are deleted, defective B cell anergy (should apoptose but don’t, given T cell help)
How does T cell central tolerance break down?
defects in AIRE leads to production of variety of autoimmune B and T cell responses, self-Ag not expressed in thymus
How does T cell peripheral tolerance break down?
insufficient control of Tcell costimulation, lower threshold for costimulation activation, variants of CTLA-4 that bind less, variants of CD40/CD40L that allow easier activation
What does a deficiency of FoxP3 mean?
lack of regulatory T cells, potential cause of autoimmune disease
What are Th17 cells?
helper CD4+ T cells that secrete IL-17
What does IL-17 bind?
IL-17 receptors on fibroblasts, epithelial cells, and keratinocytes, leading to secretion of cytokines and recruitment of inflammatory cells
What is the dominant genetic factor affecting susceptibility to autoimmune diseases? What may cause this?
HLA, located in MHC region, may be due to role in Ag presentation
What other genes affect susceptibility to autoimmune diseases?
complotypes (variants of complements), CTLA-4, AIRE, Fas, FasL, bcl-2, TNF, FoxP3
What are cells with a high level of bcl-2 resistant to?
apoptosis
What are sites of immune privilege and how can they be related to autoimmune disorders?
Sites of immune privilege are normally isolated from naive lymphocytes so they are not tolerized to these self-Ag, trauma to these sites can release sequestered Ag into circulation and allow attack of self-Ag by effector cells
Why do most autoimmune diseases occur at higher incidence in women?
estrogen receptors on T cells, activates T cells in times of estrogen or estrogenic chemical (PCBs and doxins) flare
What is the mechanism of autoimmunity behind celiac disease?
self proteins are modified to appear foreign, activates CD4+ T cells
Infection of Group A Strep leads to what?
rheumatic fever, carditis, polyarthritis
Infection of chlamydia leads to what? What HLA is associated?
Reiter’s syndrome, reactive arthritis, HLA B-27
Infection of shigella, salmonella, yersinia, campylobacter leads to what? What HLA is associated?
reactive arthritis, HLA B27
Infection of B. burgdoerferi leads to what?
Chronic arthritis in lyme disease
Infection of coxsackie, echoviruses or rubella leads to what?
Type 1 diabetes
How does molecular mimicry instigate an autoimmune repsonse?
upon infection, pathogen-derived Ag presented are structurally similar to self-Ag and stimulate a T cell response against self-Ag
Infection may lead to increased antigen presentation. How does this occur?
IFNgamma induces class II expression on cells that don’t normally act as APCs and increases Class I and Class II expression on APCs
What is Hashimoto’s disease?
thyroid gland resembles secondary lymphoid tissue with B and T cells present due to induced expression of Class II HLA on thyroid epithelial cells
What autoimmune disease type is associated with type II hypersensitivity reaction?
antibody-mediated
