Autoimmune Disease Flashcards
What is the 2 hit mechanism contributing to autoimmune disease?
Immunoregulation and an environmental trigger in a genetically susceptible individual
What should happen to a self-reactive B cell?
It should be eliminated in clonal deletion
How can lack of T cell help control B cell activation?
Autoreactive B cells activated by antigen migrate to secondary lymph nodes. If there is no T cell help, B cell dies via apoptosis
How can B cell anergy occur?
B cell encounter with soluble self-antigen without costimulation
What two defects would allow an autoreactive T cell to escape into periphery?
Self-antigen not expressed in the thymus, or defects in (Autoimmune regulator [AIRE])
Describe the process in which clonal anergy is ineffective or overcome by T cell co-stim
Defects - insufficient levels of soluble CTLA-4 so it cannot compete with CD28 for binding to B7; Inappropriate co-stim: Cells express costim molecules and activate T cells
What markers and cytokines are expressed by regulatory T cells?
CD4, CD25, FoxP3, CTLA-4 secrete IL-4, 10 and TGF-Beta
What are several gene defects that can make one susceptible to autoimmune disease?
MHC region genes resulting in different allotypes, Complement, CTLA-4, AIRE, Fas and Fas Ligand
Why are autoimmune diseases found more frequently in women?
Changes in estrogen levels, or chemicals that have same effects as estrogen (PCBs, dioxin)
What are examples of environmental factors that can predispose a person to autoimmune disease?
Alteration of self antigen with drugs, chemicals/metals (PCBs, dioxins, pesticides, metals), breakdown of tissue integrity can result in release of antigen not normally presented to T cells, loss of oral tolerance to food proteins, infections
How can infections contribute to AI disease?
Molecular mimicry (pathogen peptide is presented on to T cell and looks like self antigen), production of high levels of interferon gamma (IF-gamma causes production of MHCII which can result in AA disease), damage to tissue to release self antigen
Characteristics of Antibody-mediated diseases
Single type of cell (organ) targeted by AutoAbs (organ specific); Type II hypersensitivity rxn
What is Autoimmune hemolytic anemia? What type of AI diease?
Loss of RBCs after fixation of complement by IgG and IgM Abs resulting in lysis or clearance via binding to Fc and complement receptors on phagocytes in spleen and liver; Type II hypersensitivity rxn
What is AI thrombocytopenia? Type of AI disease?
Platelet antigens are targets of autoAbs; Type II hypersensitivity rxn
What is Goodpasture’s syndrome? Type of AI disease?
IgG against Type IV colagen elicits inflamm response in renal tissue; Type II hypersensitivity response
What is Myasthenia Gravis? Type of AI disease?
Abs to AChR on muscle cells induce their endocytosis; Type II hypersensitivity rxn
What is Insulin-resistant diabetes? Hypoglycemia Syndrome?
Ab blocks insulin receptor binding so that insulin accumulates and hyperglycemia occurs (antagonist Abs); Agonist Abs deplete glucose to abnormally low levels resulting in hypoglycemia; Type II HR
What is Graves’ disease?
AutoAbs bind to TSH receptor of thyroid cells mimicking the action of TSH so more thyroid hormones are released (agonist Ab); Type II hypersensitivity rxn
What are some diseases that a fetus can acquire from a mother producing autoAbs? What autoimmune diseases can a fetus not get?
Graves’, Hemolytic disease, Myasthenia gravis, Trombocytopenic purpura, Neonatal Lupus; T cells cannot cross the placenta therefore child cannot acquire T cell mediated disease
What kind of AI diseases are Immune-complex mediated AI diseases? Mechanism? Examples?
Type III hypersensitivity rxn; ICs deposit in tissues, fix complement, leading to inflammatory cells and tissue damage; Subacute bac endocarditis resulting in glomerulonephritis; Mixed essential cryoglobulinemia - Rheumatoid factor leading to Systemic vasculitis, SLE - Glomerulonephritis, vasculitis, arthritis
What is the relationship between Type III hypersensitivity rxns and T cells?
T cells are important requirement for Ig production!
What type of HR is a T cell-mediated autoimmune disease? Mechanism? Examples?
Type IV hypersensitivity; Antigen-specific T cells activated by antigen lead to inflamm response and direct cytotoxic effects; Type 1 diabetes, Rheumatoid arthritis, Multiple sclerosis
Describe mechanism leading to juvenille diabetes
CD8 T cells attack Beta-cells in pancreas - target antigen is glutamic acid decarboxylase
Describe mechanism of rheumatoid arthritis
Production of Abs (Rheumatoid factor) that reacts with Fc region of other Abs and infiltration of joints with CD4 and CD8 T cells
