Autoimmunity and Autoimmune Diseases Flashcards
Genetic factors associated with autoimmune disease?
Familial Incidence
Association with Specific HLA/MHC Haplotypes
Origins of autoimmune disease?
Genetics Failure to maintain self-tolerance Loss of Treg Expression of cryptic self epitopes Inappropriate MHC II molecules Antigen mimicry Polyclonal B activation Infectious Diseases Hormonal influences
Autoimmune hemolytic anemia.
Rxn Type, Autoantigen and Consequence?
Type II
Rh blood group antigens
RBC destruction, Anemia
Autoimmune thrombocytopenia purpura.
Rxn Type, Autoantigen and Consequence?
Type II
Platelet Integrin (gpIIb:IIIa)
Abnormal Bleeding
Goodpasture’s Syndrome.
Rxn Type, Autoantigen and Consequence?
Type II
Non-collagenous basement membrane, Type 4 collagen
Glomerulonephritis, Pulmonary Hemorrhage
Pemphigus Vulgaris.
Rxn Type, Autoantigen and Consequence?
Type II
Epidermal Cadherin
Blistering
Pemphigus foliaceus.
Rxn Type, Autoantigen and Consequence?
Type II
Desmoglein
Mild Blistering
Acute rheumatic fever.
Rxn Type, Autoantigen and Consequence?
Type II
Strep Wall antigens, cross react w/ cardiac
Arthritis, Myocarditis, Late Scarring of Heart
Grave’s Disease.
Rxn Type, Autoantigen and Consequence?
Type II
TSH receptor
Hyperthyroidism
Myasthenia Gravis.
Rxn Type, Autoantigen and Consequence?
Type II
Acetylcholine Receptor
Progressive weakness
Type II Diabetes.
Rxn Type, Autoantigen and Consequence?
Type II
Insulin Receptor
Hyperglycemia, Ketoacidosis
Subacute bacterial endocarditis.
Rxn Type, Autoantigen, and Consequence?
Type III
Bacterial Antigen
Glomerulonephritis
Mixed essential cryoglobulinemia.
Rxn Type, Autoantigen, and Consequence?
Type III
Rheumatoid Factor IgG complexes
Systemic Vasculitis
Systemic Lupus Erythematosus.
Rxn Type, Autoantigen, and Consequence?
Type III
DNA, Histones, Ribosomes, snRNPs
Glomerulonephritis, Vasculitis, Arthritis
Type I Diabetes.
Rxn Type, Autoantigen, and Consequence?
Type IV
Pancreatic beta cell antigen
beta cell destruction
Rheumatoid arthritis
Rxn Type, Autoantigen, and Consequence?
Type 4
Unknown synovial joint antigen
Joint inflammation, destruction
MS
Rxn Type, Autoantigen, and Consequence?
Type 4
Myelin basic protein, proteolipid protein
Brain degeneration, Paralysis
How do we normally prevent autoimmunity?
Positive/Negative Selection of B and T cells
Regulatory CD4CD25 T Cells
Physical Separation
Limited expression of MHC II and B7
Examples of physically separated from lymphocytes?
Brain, Eye, Testis
How are autoimmune cells repressed by Tregs?
IL10, TGFbeta
Five Major Susceptibility Factors in Autoimmune Disease?
HLA Genotype/Genetic Background Microbial Infection Injury Environmental Factors/Behavior Gender and Sex hormones
How might microbial infection promote autoimmunity
Adjuvant effect
Induction of higher MHC and B7
Molecular Mimicry
How might injury lead to an autoimmune response?
Reveals antigens from a previously immune priveledged organ
Environmental factors that affect autoimmune disease?
Smoking and hygiene
Which gender is more prone to autoimmune concerns?
Women
Describe the pathogenesis of Sympathetic Opthalmia
Injury in one eye releases eye antigen into local lymph nodes
Immune responses to antigen affect both eyes
Blindness in both damaged and undamaged eye
What does AIRE do?
Allows expression of peripheral antigen in the thymus
Mutation of AIRE leads to….
Wide range of autoimmune diseases