Flashcards in Autoimmunity Deck (20):
List the immunologically privileged sites:
-hamster cheek pouch
What constitutes peripheral tolerance?
-regulatory cytokines (IL-10, TGF-beta)
-immunoinhibitory molecules molecules (CTLA-4, PD-1)
What are the two main classes of autoimmune disease and give examples of each:
1. Systemic: SLE, rheumatoid arthritis, systemic sclerosis, mixed connective tissue disease
2. Organ specific: T1DM, multiple sclerosis, thyroiditis, Goodpasture, Guillain-Barre syndrome
What are the characteristics of autoimmune disease?
-evidence of autoantibodies and/or autoreactive Tcells
-some AI diseases are transmitted from mother to fetus by passage of IgG autoantibodies through placenta
-in animals the disease can be transferred by T cells or antibodies (adoptive or passive transfer)
List the postulated etiologies of ADs:
1. molecular mimicry with infectious agents --> rheumatic fever, Guillain-Barre
2. failure of Tregs
3. B cell or T cell polyclonal activation (especially SLE)
4. mutations to key regulatory molecules (AIRE, Foxp3) ex. PTPN-22 polymorphisms
5. tissue damage releasing hidden antigens (ex. sympathetic opthalmia, orchitis)
6. vitamin D deficiency ex. AD more common at high altitudes
7. Drugs and toxins (ex. autoimmune hemolytic anemia, SLE)
Name one reason we believe hormones influence ADs?
ADs are more common in females (estrogen related?). ex. SLE 10x more common in Females
List the 3 major types of Tregs:
-thymic derived (natural) Foxp3+ (nTreg)
-induced (adaptive) Foxp3+ (iTreg)
-Type 1 regulatory T cells (Tr1); produce IL-10 and TGF-beta
What lethal autoimmune/inflammatory condition do Foxp3+ mutations result in?
What Abs are present in SLE?
anti-nuclear antibodies (ANA)
What is more specific than ANA for diagnosing SLE?
what immune complex diseases are characteristic of SLE?
Can SLE be induced by drugs? What drugs?
Yes. By hydralazine and procainamide.
What are possible mechanisms of SLE?
-deficiency of compliment (ex. C2, C4, C1q)
-exposure to UV light exacerbates SLE
What is scleroderma (systemic sclerosis)?
-progressive fibrosis of skin and internal organs
-occlusive vascular disease
-renal disease with HTN
-can overlap with other ADs
Describe Rheumatoid Arthritis (RA):
-inflammation of synovium with pannus formation and destruction of cartilage
-not just about joints--> inflammation of lungs, heart, m etc possible
-characterized by RF= rheumatoid factors ie autoantibodies reactive to the Fc segment of IgG.
What are two examples of organ-specific ADs caused by T cell activity?
-MS (in mice model= EAE- experimental autoimmune encephalomyelitis)
What cells attack pancreatic beta cells in T1DM?
-CD4+ (Th cells)
What autoimmune conditions associated with cancer (PNS)
-neurological diseases: sensory neuropathy, Eaton-Lambert myesthenia syndrome
-systemic diseases (dermatomyositis/polymyositis)
-skin diseases (paraneoplastic pemphigus)
How do tumours initiate autoimmunity?
-anti-cancer immunity is often autoimmune
-mutated tumour antigens break tolerance
-tumours express antigens expressed during embryonic period or in immune-privileged sites
-tumours can secrete mediators that alter immune tolerance