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Flashcards in Autoimmunity Deck (47):

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?



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?



What are 2 examples of ab-mediate autoimmune diseases?

autoimmune hemolytic anemia, goodpasture's syndrome (glomerulonephritis, pulmonary hemorrhage)


What is the mechanism of hemolytic anemia?

IgG autoAb bind Rh or I antigens and activate complement for either phagocytosis or lysis of RBCs


What is the antigen, antibody and consequence of Grave's disease?

ag: thyroid stimulating hormone receptor
ab: agonist of TSH
consequence: hyperthyroidism


What is the antigen, antibody and consequence of myasthenia gravis?

ag: Ach receptor
ab: antagonist
consequence: progressive muscle weakness


What is the antigen, antibody and consequence of insulin-resistant diabetes?

ag: insulin receptor
ab: antagonist
consequence: hyperglycemia, ketoacidiosis


Why are endocrine glands affected by antibody-mediated autoimmunity?

well-vascularized so immune cells can gain access


How do anti-Ach receptor Ig cause myasthenia gravis?

antiAch receptor Ig binds receptor causing endocytosis and degradation, fewer receptors lead to decreased sensitivity to stimulation and progressive muscle weakening


Do IgG-mediated or Tcell-mediated autoimmune diseases present in newborns?

IgG-mediated, can be transferred in utero


How do you cure a newborn of autoimmune disorder transferred via IgG?

plasmapheresis to remove maternal Ab


What disease presents with anti-DNA and anti-nucleosome antibodies in immune complexes?



Why does the specificity of SLE response broaden over time?

the immune complex spreads and deposits elsewhere in body


What are 3 examples of T cell-mediated autoimmune diseases?

type 1 diabetes, RA, MS


What is the antigen in type 1 diabetes?

pancreatic b-cell antigen


Why is there hyperglycemia in type 1 diabetes?

B cells produce little to no insulin due to destruction by inflammatory cytotoxic CD8 T cells


What are the antigens of the autoantibodies in RA?

constant region of other antibodies (rheumatoid factor)


Is rheumatoid factor diagnostic for RA?

no, it can be found in other diseases too


What causes the joint damage in RA?

infiltration of inflammatory CD4 and CD8 cells that produce proteases and collagenases erode structures and damage cartilage


What are the antigens of the autoantibodies in MS?

myelin basic protein, proteolipid protein, myelin oligodendrocyte glycoprotein


How does MS occur?

autoimmune response to Ag in the myelin sheath of nerve cells involving Th1 CD4 T cells and macrophages resulting in the production of sclerotic plaques resulting in progressive paralysis


What are treatments for autoimmune disorders?

physical removal of Ag or immune complex, IV-IgG to remove antibody complex, NSAIDs, deplete immune cells, block activation of immune cells, replacement therapy, hormones


What is autoimmune thrombocytopenia?

platelet antigens are the targets of autoantibodies


What is Goodpasture's syndrome?

IgG against type IV collagen elicits inflammatory response in the renal tissue


Describe how SLE induces autoimmune disease.

circulating Ab specific for cell surface, cytoplasm, nucleus, nucleic acid, and nucleoproteins produced
autoAb and self-Ag form immune complexes that deposit in blood vessels, kidneys, and joints and initiate inflammatory reactions