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
