Exam 3: Dr. Pinchuk Autoimmune Diseases Flashcards
In healthy individuals, what is the immune system tolerant?
Self antigens
What are autoimmune diseases cause by?
The loss of tolerance
What are the central tolerance mechanisms that contribute to immunological self-tolerance?
Negative selection in the bone marrow and thymus
Expression of tissue specific proteins in the thymus
What are the peripheral tolerance mechanisms that contribute to immunological self-tolerance?
No lymphocyte access to some tissues
Suppression of autoimmune responses by regulatory T cells
Induction of anergy in auto reactive B and T cells
What do the effector mechanisms of autoimmunity resemble?
Those causing hypersensitivity reactions
What are the auto antigens for lupus?
DNA Histones Ribosomes snRNP scRNP
What are the consequences for lupus?
Glomerulonephritis
Vasculitis
Arthritis
What are the 3 mechanisms that destroy erythrocytes in autoimmune hemolytic anemia?
FcR+ cells in spleen
Complement activation and CR1+ cells in spleen
Complement activation and intravascular hemolysis
What do FcR+ cells in spleen cause?
Phagocytosis and erthyrocyte destruction
What does complement activation and CR1+ cells in spleen cause?
Phagocytosis and erthyrocyte destruction
What does complement activation and intravascular hemolysis cause?
Lysis and erythrocyte destruction
What can autoantibodies against cell-surface receptors do?
Either stimulate or inhibit the receptor’s function
What causes myasthenia gravis?
Signaling from nerve to muscle across the neuromuscular junction is impaired
What is major example of rheumatic diseases caused by autoimmunity?
Systemic lupus erythematosus
What are the pathogenic mechanisms for lupus?
Type III hypersensitivity
A large amount of small immune complexes are formed due to the availability of autoantigen and autoantibody. Immune complexes deposit in the capillaries if various tissues. Immune complexes can either enter through the fenestrations of glomerular capillaries and become trapped in the basement membrane
What is the mechanism of autoantigen accumulation for lupus?
Possible defect in the clearance of apoptotic cells:
Macrophages from lupus patients have a reduced capacity to engulf apoptotic cells in vitro
Describe type I diabetes
T cell responses and antibodies are made against insulin and other specialized proteins of the pancreatic β cell islets of Langerhan’s
What can the two recently developed therapies that target different aspects of the rheumatoid arthritis do?
Eliminate B cells in a patient, which is okay because in theses patients most B cells are auto-reactive
What happens with ADCC in rheumatoid arthritis?
Lysis of B cells by NK cells and the therapeutic anti-CD20 antibody rituximab
What are the causes of rheumatoid arthritis?
Effector CD4 T cells and antibody
What is a feature of all autoimmune diseases?
Breaking T cell tolerance
Describe what happens in breaking T cell tolerance
Incomplete deletion of self-reactive T cells in the thymus, APECED
Insufficient control of T cell co-stimulation (CTLA-4 deficiency)
Lack of Treg cells, deficiency in FoxP3 is called immune dysregulation, polyendocrynopathy, enterophathy, and C-linked syndrome (IPEX)
What is HLA?
The dominant genetic factor affecting susceptibility to autoimmune disease
What is the HLA allotrope for ankylosing spondylitis?
B27 (MHC class I)
What is autoimmunity initiated by?
Disease-associate HLA allotypes presenting antigens to autoimmune T cells
What do animal models of autoimmune disease demonstrate?
That autoreactive T cell clones can transfer disease
What is an example of an infection as environmental facotrs that can trigger autoimmune disease?
Streptococcal cell wall stimulates antibody response
Some antibodies cross-react with hear tissue, causing rheumatic fever
How can autoimmune T cells be activated?
In a pathogen-specifc of non-specific manner by infection
What can predispose to autoimmune disease?
Genetic and environmental factors
