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52 Cards in this Set

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