Tolerance and Autoimmunity Flashcards
Clinical syndrome characterized by autoimmune adrenal and parathyroid disease.
Associated with fungal infections.
Due to a defect in the AIRE gene.
Induces expression of self antigens by the thymic medullary epithelial cells.
Failure of central tolerance.
APECED
Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
Presents with widespread lymphadenopathy, splenomegaly and autoimmune cytopenias.
Due to mutations in Fas or Fas ligand.
High IgG, IgA, IgM common. Increased percentages of CD4neg/CD8neg T cells.
Failure of peripheral tolerance.
ALPS
Autoimmune lymphoproliferative syndrome
Affects boys in infancy
Presents with IBS, sever eczema and food allergies, Type I DM, thyroiditis, autoimmune hemolytic anemia and thrombocytopenia
Hypergammaglobulinemia, very high IgE levels
Death if not treated aggressively
Due to mutation in Foxp3 and loss of Treg cells
IPEX
Immune dysregulation polyendocrinopathy, X-linked
JONES Criteria for acute rheumatic fever
Joints Heart Nodules Erythema marginatum Sydenham's chorea
2 major or 1 major and 2 minor to make diagnosis
What is the pathophysiology behind acute rheumatic fever?
M proteins expressed by S. progenies as virulence factors are structurally similar to heart muscle
Example of type II hypersensitivity
What are some treatments for antibody mediated diseases?
High dose intravenous immunoglobulin (IVIG)
Corticosteroids- prednisone
Rituximab (anti-B cell therapy)
Autoimmune disease characterized by auto-antibody production, particularly to DNA
Nephritis, rash, vasculitis common
Complement detents lead to early onset
Systemic Lupus Erythematosus
Pathogenesis of rheumatoid arthritis.
T cells in synovial space are oligoclonal.
Monocytes, macrophages, synovial fibroblasts activated by T cells that release IL-1, IL-6 and TNF (three main inflammatory cytokines).
B cells aggregate in synovium and autoantibodies are present in some.
What are some treatments for rheumatoid arthritis?
NSAIDs
Anti-metabolites
Glucocorticoids
Monoclonal Ab
Heliotropic rash–eyelids, bridge of nose, cheeks
Gottron’s papules–shiny, erythematous, scaly plaques
Proximal muscle weakness
Capillary changes
Perifascicular atrophy – necrosis of muscle occurs in periphery
Microvascular injury
Dermatomyositis
Diffuse muscle fiber death next to normal fibers
Mononuclear infiltrates through fascicle
Largely CD8 mediated
Polymyositis
Systemic autoimmune diseases
SLE
Rheumatoid arthritis
Rheumatic fever
Organ specific autoimmune diseases
Multiple sclerosis Thrombocytopenia Guillain-barre syndrome Hashimoto's thyroiditis Celiac disease
