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52 Cards in this Set
- Front
- Back
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What happens to Bcell tolerance in the absence of T cell help?
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It is quiescent - cells are simply anergic or ignorant.
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What type of antigen results in clonally ignorant mature B cells?
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Low concentrations of soluble Ag
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What do higher concentrations of soluble self Ag do to Bcells?
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Cause anergy
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What does self surface antigen do to Bcells?
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Causes clonal deletion or receptor editing
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What type of Ig is expressed on the surface of clonally ignorant Bcells?
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Normal IgM and IgD
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What type of Ig is expressed on the surface of anergic Bcells?
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Normal IgD, but low IgM
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When IgM pos Bcells interat with self cells with surface antigen, what is a mechanism for surviving apoptosis/deletion?
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Clonal deletion
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Where does Central Bcell Tolerance get established?
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In the bone marrow
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What happens when immature Bcells strongly recognize self antigens in the bone marrow?
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They undergo either:
-Negative selection or -Receptor editing |
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What is the result of receptor editing?
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The expression of a new antigen receptor that has a new light chain, but the same heavy chain.
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What happens to Bcells that survive negative selection?
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They go to the peripheral lymphoid tissues.
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What happens to mature B cells in lymphoid follicles if they recognize and bind self antigen there?
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Well the Tcell help required for CD40/CD40L interaction is missing, so the Bcells will go into anergy.
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What happens to mature Bcells in peripheral lymph nodes that bind self antigen and go into anergy?
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They leave the follicles and are subsequently excluded from lymphoid follicles.
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Autoimmunity is:
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an immune response against self antigens
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What are the 2 principal factors in the development of autoimmune disease?
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1. Susceptibility genes that contribute to self-tolerance failure
2. Environmental triggers that may activate self-reactive lymphocytes |
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How do we know that genetics play a large role in autoimmunity?
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Monozygotic twins are very likely to both have autoimmune disease if one has it
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What gene mutations are linked to many autoimmune diseases?
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MHC mutations
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How do MHC mutations cause defects in central tolerance?
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By messing up the process of self antigen presentation in the generative organs, so that negative selection is offkilter.
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How could an MHC mutation cause a defect in peripheral tolerance?
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By causing an abnormal antigen presentation that results in Treg cells not being stimulated.
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What autoimmune disease is very linked to the HLA allele B27?
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Ankylosing spondylitis
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In what sex is autoimmune disease more prevalent?
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Women
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What disease is associated with Complement protein gene mutations?
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Lupus-like disease
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What disease is associated with Fas, FasL protein gene mutations?
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ALPS
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What disease is associated with AIRE protein gene mutations?
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APECED
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How can bacteria cause autoimmunity?
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By "breaking" Tcell anergy - infection causes upregulation of B7, so that self-reactive Tcells survive.
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How does Mimicry cause autoimmunity?
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APC presents microbial antigen to a self-reactive Tcell which mistakes the microbe for self; because B7 is there, it results in proliferation of Self reactive Tcells.
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List 5 important organ-specific autoimmune diseases to know:
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CGHMT
Celiac disease Guillain-Barre syndrome Hashimoto's thyroiditis Multiple sclerosis Thrombocytopenia |
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What is the pathology in MS?
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Auto-reactive Tcells and activated macrophages specifically demyelinate the CNS motor and sensory neurons
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What is thought to initiate MS?
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A viral infection
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What is the cause of thrombocytopenia?
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Autoantibodies directed against platelets.
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What is the pathology in Guillain Barre syndrome?
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Autoantibodies to myelin basic protein
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What triggers Guillain Barre?
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Viral infections or Campylobacter Jejuni infections in genetically susceptible individuals
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What is the problem in Hashimoto's thyroiditis?
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An autoantibody to thyroglobulin
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What is the problem in Celiac disease?
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An autoantibody to Gliadin in food
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What are 3 important systemic autoimmune diseases to know?
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1. SLE
2. Rheumatoid arthritis 3. Rheumatic fever |
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What are the autoantibodies in SLE?
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-Anti-dsDNA
-Anti-Sm |
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Why are nuclear proteins susceptible to auto-Ab's forming?
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Because they are cryptic
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What are 2 drugs known to induce SLE?
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-Procainamide
-Hydralazine |
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What are the autoantibodies that cause Rheumatoid arthritis?
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Anti-IgG in joints (an Ab against an Ab!)
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What is the cause of Rheumatic fever?
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Autoantibody to myosin
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What infection triggers Rheumatic fever?
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Group A strep
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What protein in Group A Strep causes the autoantibody to myosin to develop?
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M protein
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What are 3 broad categories of methods to treat autoimmune diseases?
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-Systemic immune suppression
-Nonsystemic immune suppression -Plasmapheresis/Competitive FcR inhibition |
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What is the most common prescription for systemic immune suppression?
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Corticosteroids
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What is the danger of giving corticosteroids?
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Opportunistic infection
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What are 2 agents used for non-systemic immune suppression?
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-Infliximab
-Etanrecept |
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What is Infliximab?
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Antibody to TNF
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What is Etanrecept?
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Antibody to the soluble TNF receptor
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What is achieved by blocking TNF or its soluble receptor?
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Reduced inflammation
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How can competitive inhibition of the FcR be achieved?
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By giving high doses of IgG so that the receptor on neutrophils is blocked.
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What autoimmune disease is associated with HLA-DR4?
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Rheumatoid arthritis
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What autoimmune disease is associated with HLA-DR3/4?
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Insulin-dependent Diab. mellitus
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