Autoimmunity Flashcards
What are the 3 mechanisms that contribute to the development to autoimmune disease?
1- Defects in immunoregulation
2- Environmental triggers
3- genetic predisposition
What is an autoimmune disease?
“Self” antigen is recognized as foreign by immune system and there is a failure of regulatory mechanisms
What are the effector mechanisms of autoimmune disease?
Types II, III, or IV hypersensitivity reactions
What are the immune factors that contribute to autoimmune disease?
All autoimmune diseases involve the breakdown of T and B cell tolerance and the production of autoantibody and/or inflammatory autoreactive T cells
What are the genetic factors that contribute to autoimmune disease?
Genetic predisposition
Is a “trigger “ required to develop and autoimmune disease?
Yes– In the lab it is found that bacterial products are required to induce autoimmune response to injected self proteins
How does B cell tolerance breakdown?
No all reactive B cells are deleted during clonoal deletion in the boe marrow. As a result some autoreactive B cells remiain
How does T cell tolerance breakdown?
- Insufficient control of T cell co-stimulation (autoreactive T cells may have a lower threshold for activation)
2-Lack of Regulatory T cells (Treg) may contribute to autoimmune disease
How does the T cell tolerance breakdown lead to problems with B cells?
Since there are autoreactive T cells around, these T cells can activate B cells. Therefore Autoreactive B cells can have T cell help when they normally would not
Can decreased production of T regs lead to autoimmune disease? If so why?
Yes it can.
These cells secrete IL-4, IL-10 and TGF-beta, and these levels are reduced with there is decreased T regs.
These factors are needed to suppress autoreactive cells
What is the role does defects in AIRE play?
when have defects you have many autoimmune responses
What is the phenotype of T regs?
CD4+, CD25+, CTLA-4+
Th-17 role?
Connect infection to autoimmune disease?
What to Th-17 cells do?
T help secrete IL-17
Pro-inflammatory-binds to IL-17 receptor on fibroblasts epithelial cells and keratinocytes, leading to secretion of cytokines and recruitment of inflammatory cells
May accumulate in affected tissues in Crohn’s disease, RA, psoriasis, allergic asthma
How are Th17 cells regulated?
Reciprocally regulted with Tregs
What are some examples of geneitc factors that contribute to autoimmune disease?
HLA- class II (in higher frequency in patients)
varients of CTLA-4
varients of AIRE
varients of Fas and Fas ligand
What is the role of fas and fas ligand?
to destroy autoractive cells
What are some hormonal factors contributing to autoimmune disease?
estrogen (lupus)
estrogen like chemicals
Role of release of sequestered antigens in autoimmune disease?
Trauma to sites of immune privilege – normally entry of naïve lymphocytes is prevented but self antigens may be exposed to circulation by wound or infection, and effector cells can gain access
What is molecular minimcry? What is its significance?
Pathogen-derived peptides that are structurally similar to a self antigen.
These molecules can stimulate a T cell response direceted agains the self-antigen
What is the role of Interferon gamma?
Upregulate MHC calss II expression of cells that normally do not express it during an infection.
These cells can then express self antigen when this happens
Example is hotchimoto’s diseas
What are some environmental factors that lead to autoimmunity?
chemicals, loss of tolerance to food proteins, sunlight, aging, atrophy of thymus, nutrition, stree
What are the characteristics of autoimmune disease?
may be classifiedas organ-specific if only one organ or cell type is involved
sometimes classified by the immunological effector mechanism causing disease
Define antibody-mediated autoimmune diseases
a single type of cell (organ) is targeted by autoantbodies
this is an organ specific autoimmune disease
What type of hypersensitivity reaction does antibody mediated autoimmune disease correlate to?
Type II hypersensitivity (antibody mediated)
Please name some examples of antibody mediate autoimmune disease
1- autoimmune hemolytic anemia 2- autoimmune thrombocytopenia 3- goodpasture's syndrome 4- Grave's disease 5- Insulin resistant diabetes 6- Myasthenia gravis 7- Hashimoto's disease
Explain autoimmine hemolytic anemia
Loss of RBSs after fixation of compliment by IgG and IgM antibodies bound to components on RBCs
Lysis or phacocytosis results
Explain autoimmune thrombocytopenia
platelet antigens are the targets of antibodies
Explain goodpasture’s syndrome
IgG against Type IV collagen elicits an inflammatory response in renal tissues
Explain grave’s disease
antibodies that bind to the TSH receptor act as an agonist, so that the thyroid hormones are overproduced
Explain myasthenia gravis
antibodies to acetylcholamine receptors (AChR) on muscle cells unduce their endocytosis
antibodies also compete with acetylcholamine for binding to AChR. this results in progressive muscle weakening
Explain insulin-resistant diabetes
insulin binding to receptor is blcked by antibody so that insuuling accumulates causing hyperglycemia. this is characterized by resistance to insulin
in patients with agonist antibodies, cells deplete glucose to abnormally low levels resulting in hypoglycemia
Explain hashimoto’s disease
progressive destruction of normal thyroid tissue by antibodies and effector T cells, leading to hypothyroidism
What is mainly effected by antibody-mediated autoimmune diseases?
endocrine glands
Describe immune-complex-mediated autoimmune diseases
autoimmune response is directed at multiple cells of teh body, resulting in a systemic autoimmune response
What type of hypersensitivity reaction does immune-complex mediated autoimmune disease correlate to?
Type III Hypersensitivity
What is an example of immune-complex mediated autoimmune diseases?
Systemic lups Erythematosus
Explain SLE (immune complex mediated and T cell mediated):
Circulating antibodies that are specific for the constituents of cell surfaces, cytoplasm, and the nucleus indluding nucleic acids
autoantibodies and autoantigens form immune complexes that are deposited in he blood vessels, kidneys, and joints and initiate inflammatory reactions
There is also a T cell component
What is diagnostic of SLE?
antibodies to dsDNA
Describe T-cell mediated autoimmune diseases:
antigens in tissue are targeted by Th1- type T cells
What type of hypersensitivity reaction does T-cell mediated autoimmune disease correlate to?
Type IV hypersensitivity
What are examples of T-cell mediated autoimmune disease?
Insulin-dependent diabetes mellitus
rheumatoid arthritis
multiple sclerosis
SLE
Explain IDDM:
CD8+ T cells are cytotoxic to pancreatic beta cells so that insulin so tht insulin production is in sufficient to control glucose levels in the blood
Explain RA
Rheumatoid factors and cellular infiltrate contribute to inflammation in the joints
What are rheumatoid factors?
RF-IgM, IgG, and IgA antibodies specific for the Fc region of human IgG
What are cellular infiltrates?
CD4+, CD8+ T cells
Explain multiple sclerosis
anutoimmune resonse to antigens in the myelin sheath of nerve cells, involving Th1 CD4+ Tcells and macrophages
sclerotic plaques result and there is typically progressive paralysis
