Chapter 6 Guerin Lecture Part 2 Flashcards
Pathologic autoimmunity “confirmed” when… (3)
Presence of immune reaction specific for self
Evidence that reaction is not secondary to tissue damage
Absence of another well-defined disease
What are immune-mediated inflammatory diseases?
Disorders in which chronic inflammation is the prominent component
Systemic autoimmune diseaeses (4)
SLE
Rheumatoid arthritis
Systemic sclerosis
Sjogren syndrome
Organ-Specific autoimmune diseases (7)
Autoimmune hemolytic anemia Myasthenia gravis Graves disease Type 1 diabetes Mellitus Goodpasture syndrome Inflammatory Bowel Disease Multiple sclerosis
Why is type 1 diabetes mellitus an organ-specific autoimmune disease?
because it attacks the beta cells of the pancreatic islets
Why is muscle sclerosis an organ-specific autoimmune disease?
because it attacks the CNS myelin
Why is SLE a systemic autoimmune disease?
have diversity of antibodies directed against DNA, platelets, RBCs, and protein-phospholipid complexes
What is immunologic tolerance?
process where immune system has learned to tolerate our own self antigen
How does our body recognize self antigens?
through receptors made via somatic recombination of genes
How does our body make sure receptors that recognize self antigens are not present?
the cells with self recognizing receptors must be eliminated or inactivated as soon as they recognize self antigen
2 types of immunologic tolerance
central and peripheral
What occurs during central tolerance with T cells?
- APC presents self antigen to T cell
- T cells with high affinity TCR’s for self antigens are made
- Negative selection or deletion occurs
- Some CD4+ that see self antigens in the thymus do not die but turn into regulatory T cells
What is negative selection?
- Occurs in the thymus for central tolerance
2. Immature lymphocytes that encounter self antigens in the thymus and die via apoptosis
What occurs during central tolerance with B cells?
- Occurs in bone marrow
- B cells that strongly recognize self antigens may undergo receptor editing
- If receptor editing does not occur, self reactive cells undergo apoptosis
What is receptor editing?
Occurs with B cells in bone marrow
Rearrangement of genes on receptor to express new antigen receptor
What occurs during peripheral tolerance for T cells?
APC presents self antigen to T cell in periphery and there is no/weak costimulation
T cells undergo anergy (made inactive/unresponsive)
Or die via apoptosis
What occurs during peripheral tolerance for B cells?
B cells encounter self antigen in peripheral tissues and without a T helper cell, the B cells undergo anergy (made inactive/unresponsive)
Function of Regulatory T cells in peripheral tolerance
suppress and prevent immune reactions against self antigens
ex. play a role in mother’s acceptance of the fetus that has paternal antigens
Defects in regulatory T cells and accepting the fetus
can lead to recurrent spontaneous abortions
Immune-Privileged Sites
Testis, eye, brain
Where antigens do not communicate with blood and lymph
What if antigen occurs in immune-privileged site
antigens are released after trauma or infection
prolong tissue inflammation and injury
What general factors contribute to autoimmunity?
genetic susceptibility and environmental triggers
What changes can initiate autoimmunity? (3)
Defective tolerance or regulation
Abnormal display of self antigens
Inflammation or initial innate immune response
How can infections lead to autoimmunity? (2)
Induction of costimulators on APCs
Molecular mimicry
Classic example of molecular mimicry
Rheumatic heart disease
Antibodies against streptococcal proteins cross-react with myocardial proteins and cause myocarditis
How and what viruses can cause production of autoantibodies?
EBV and HIV cause polyclonal B-cell activation producing autoantibodies
What influence does the microbiome have on autoimmunity
Normal gut and skin microbe may provide us with non pathogenic microbes that dont hurt us
Help maintain proportions of effector and regulatory T cells
General Features of autoimmune diseases (4)
chronic, progressive, epitope spreading, excessive or abnormal Th1 and Th17 responses
What is epitope spreading?
An initial immune response occurs and causes tissue damage which releases other antigen and activated lymphocytes
What do systemic autoimmune diseases involve?
blood vessels and connective tissue
called “collagen vascular” or “connective tissue” diseases
