Term describing situation in which there is no measurable immune response to specific (usually self) antigens
Describe “central tolerance”
self-reactive T and B lymphocytes are deleted during their maturation in the thymus and bone marrow
Describe “peripheral tolerance”
anergy, suppression and/or activation induced cell death of T cells that escape intrathymic negative selection
What are the five theories of autoimmunity?
Inaccessible self antigens Abnormal T cell function Molecular mimicry Polyclonal B cell activation Tissue Injury in Autoimmune disease
Basic idea of the “inaccessible self antigen” theory of autoimmunity?
An immune reaction develops to a self antigen that is not normally accessible to the immune system.
Principles of the “abnormal T-cell function” theory of autoimmunity?
Defects in T cells, especially suppressor T cells, are described in my autoimmune diseases. Abnormalities in helper T cells, where they become autoreactive, can also be present.
What is meant by “molecular mimicry” in autoimmune disease?
Antibodies again a foreign molecule (ex, streptococcal bacterial) cross react with with antigens from tissues (cardiac muscle), as in rheumatic heart disease
How can polyclonal B cell activation lead to autoimmunity?
B lymphocytes are directly activated by complex substances than contain many antigenic sites
What are the mechanisms by which autoimmune disease can cause tissue injury?
Immune complex formation and type II and III hypersensitivity reactions
ADCC (antibodies against an antigen expressed at the cell membrane lead to death of that cell)
Antireceptor antibody diseases (activate or inactivate receptor without killing cell)
Type III hypersinsitivity (immune complexes are depositied in tissues, induce inflammation and injury)
Difference between type II and type III hypersenditivity reactions?
Type III are immune complex diseases and are frequently systemic. Type II are cytotoxic and mostly organ specific.
What is Systemic Lupus Erythematosus?
SLE is a chronic, autoimmune, multisystem, inflammatory disease that may involve almost any organ but characteristically affects the soil, joints, serous membranes and kidneys.
High titers of what are nearly pathognomonic of SLE?
Two anti-nuclear antibodies or ANAs (double-stranded DNA and a soluble nuclear antigen complex called the Smith antigen that is part of the splicosome)
What is the most common manifestation of SLE?
Joint disease (polyarthralgia with inflammatory synovitis; joint destruction in unusual)
seven other manifestions of SLE, in addition to joint disease
Skin involvement, renal disease, serous membrane inflammation, disorders of respiratory system, cardiac involvement (including Libman-Sacks endocarditis), CNS disease, antiphospholibid antibodies and thrombotic events, vasculitis and other organ involvements.
What is Libman-Sacks endocarditis?
Usually not clinically significant; small non-bacterial vegetations on valve leaflets
What is drug induced lupus?
Certain medications may cause positive ANA tests and a SLE like syndrome, which involves immune complex deposition.
What is chronic discoid lupus?
The most common form of localized lupus erythematosus; a skin disorder
What is subacute cutaneous lupus?
Characterized by papular and annular lesions, principally on the trunk.
Characteristics of Sjogren syndrome?
Autoimmune disorder characterized by keratoconjunctivitis siccs (dry eyes) and zerostomia (dry mouth) without other connective tissue disease
Characteristics of scleroderma (progressive systemic sclerosis)?
Vasculopathy and excessive collagen deposition in the skin and internal organs. Organs most affected are the lung, GI tract, heart and kidneys.
What are the two distinct categories that scleroderma presents as clinically?
A generalized, progressive systemic form and a milder, limited variant
What is mixed connective tissue disease?
Combines features of SLE, scleroderma and dermatomyositis