Autoimmune Diseases Flashcards
1
Q
AI disease
A
- affect 5% of pop-incidence increased in women and developed countries
- self antigen is recognized as foreign by immune system and there is a failure of regulation
- effector mechanisms include types II, III, IV
- may be organ specific, affecting only a few cells or systemic, multiple organs
- no known cause or cure and treatment is aimed at controlling symptoms
2
Q
factors contributing to development of AI diseases
A
- immune factors-breakdown of T and B cell tolerance and the production of autoantibody/ IF autoreactive T cells
- genetic factors
- environmental factors
3
Q
development of AI
A
- trigger infection seems to be required- bacterial products required to induce autoimmune responses to injected self proteins
- also increase in disease incidence with industrialization supports role for environmental factors
4
Q
breakdown in B cell tolerance
A
- central B cell tolerance-clonal deletion of self reactive cells in marrow-not all deleted
- peripheral B cell tolerance-without T cell help, antigen activated B cells in the T cell zone die by apoptosis
- B cells may also become anergic after encounter with soluble (self) antigen, then will be eliminated by T cell via Fas
**this all doesn’t happen in AI-or at least some of it
5
Q
Breakdown in central T cell tolerance
A
- normally T cells that bind to self peptides presented by MHC on thymic cells are deleted
- defects in AIRE lead to the production of a variety of autoimmune B and T cell responses, and AI polyglandular disease
-even if negative selection works properly, some autoreactive cells do escape, theyre controlled by peripheral tolerance
6
Q
breakdown in peripheral T cell tolerance
A
- insufficient control of T cell costimulation
- need 2 signals, self signal usually no co stim and anergy develops
- autoreactive t cells may have low threshold for activation
- allelic variants of CTLA4 can cause AI
- CD40 of CD40L variants can mess up activation
7
Q
breakdown in peripheral 2
A
- lack of Tregs
- Tregs have CD4, CD25, CTLA4, produce IL4, IL 1- and TGFb
- require cell contact and CTLA4 to work
- defects in Foxp3 can cause AI mainly in boys
8
Q
TH17
A
- helper CD4 cells secrete
- activates fibroblasts, epithelial cells, keratinocytes, leads to secretion of cytokines and recruitment of IF cells
- may accumulate in affected tissues in crohns disease, RA, psoriasis, allergic asthma
- link between infection and AI?
9
Q
HLA
A
- dominant genetic factor affecting susceptibility to AI
- RR >150 down to 2 depending on HLA variations
- B27 big one
- also variants in AIRE, Fas, FasL, bcl2 (resistant to apoptosis) TNF, FoxP3, signalling molecules
10
Q
release of sequestered antigens
A
- trauma to sites of immune privilege, normally entry of naive lymphocytes prevented but self antigens exposed by wound or infection and effector cells can get in
- injury to eye releases eye antigens to blood, go to lymph nodes and activate T cells, effector cells come back and hurt other eye
11
Q
self protein modification
A
- gluten degraded to resistant fragment
- then deaminated
- then cd4 cell responds to peptide presented by HLA DQ
- IF effector cells cause villous atrophy
- leads to diarrhea and malabsorption
12
Q
lyme disease
A
-HLA DR2,4 can lead to chronic arthritis
13
Q
molecular mimicry
A
- self peptide looks enough like antigen than immune system gets confused and attacks
- T cell activated by actual antigen then thinks our protein is antigen
- also infection of APC, IF tissue damage/bystander, superantigens/LPS,
- neoantigens (penicillin)
14
Q
infection and antigen presentation
A
- thyroid cells don’t normally have HLA II (some of them)
- IFN gamma produced during infection or nonspecific IF induced HLA class II
- activated T cells recognize this and cause AI disease
15
Q
hashimoto’s disease
A
-thyroid gland resembles secondary lymphoid tissue with T and B cells present
