Autoimmunity Flashcards
What do all autoimmune diseases involve?
Self peptide recognized as foreign; breakdown of T and B cell tolerance; loss of regulatory mechanisms
Which plays a role in autoimmune disease: environment or genetics?
Both- genetics can predispose, environmental can trigger
Generally a trigger leads to an autoimmune disease, what is meant by this trigger and how does it lead to the autoimmune disease?
Trigger such as an infection- get reactive T/B cells that then get misdirected to self-Ag
If a B cell gets out of the bone marrow but is found to be autoreactive in the periphery, how is it regulated so that it doesn’t autoreact?
Anergy- doesn’t receive the second costimulatory signal from T cells, or eliminated by T cells by Fas binding
What will a defect in AIRE result in? Why?
Autoimmune disease because don’t get peripheral protein presentation in the thymus
If a T cell that is autoreactive makes it into the periphery, how is it normally regulated so that autoimmune diseases don’t occur?
Anergized- doesn’t receive the costim signal (B7 to CD28)
What population that is important in turning off the immune response might be missing when there’s autoimmune diseases?
Tregs (CTLA4 binding to B7) turning off the cell
What cytokine released by T cells is believed to be the link between infection and autoimmunity? To which cells does it bind?
IL-17- binds to fibroblasts, epithelial cells, and keratinocytes initiating inflammation
What is the dominant genetic factor that make you susceptible to autoimmune diseases?
HLA
What are immune privileged sites? If these are damaged then what might happen?
Places where antigens are sequestered or hidden from the immune system (such as in the brain/eye); trauma can cause T cells to see these proteins that aren’t normally seen and therefore get an autoimmune reaction
How is autoimmunity generated with Celiac’s disease?
Alter the self protein so that it looks foreign; do this by digesting the gluten to produce fragments that are then deaminated and activate CD4 cells
Group A strep infection can lead to what autoimmune disease?
Rheumatic fever (carditis/ polyarthritis)
Enteric bacteria (Salmonella/Shigella/Yersinia) can lead to what autoimmune disease ? What MHC makes them susceptible?
Reactive arthritis; HLA-B27
Chlamydia can induce what autoimmune disease? What MHC makes them susceptible?
Reiter’s arthritis; HLA -B27
Coxsackie viruses, echoviruses and rubella can lead to what autoimmune disease?
Type I diabetes
What is the concept of molecular mimicry? How does this lead to autoimmune disease?
Pathogen invades that looks similar to self; body mounts a response to the pathogen and after being cleared reacts with self
Inflammatory tissue damage can lead to the bystander effect, what is the bystander effect?
Autoreactive cells are stimulated because of inflammation
One of the first cytokines released following infection causes increased expression of MHC Class I and II on cells that do not normally express MHC. What is this cytokine?
IFN-gamma
What environmental factors might increase the predisposition to autoimmune diseases?
Diet, chemical exposure, stress, hormones
What type of hypersensitivity is responsible to antibody mediated autoimmune diseases?
Type II
What are some antibody mediated autoimmune diseases?
Goodpasture’s, Acute rheumatic fever, autoimmune hemolytic anemia, autoimmune thrombocytopenia, myasenthia gravis, insulin resistant diabetes
What are some autoimmune diseases where antibody binding stimulates the antigen?
Graves disease, hypoglycemia
In Graves disease where do antibodies bind? How does this lead to autoimmune disease?
TSH receptor, leads to overproduction of T3/T4 because mimics TSH
In Myasthenia gravis what do antibodies bind to? How does this lead to the symptoms?
Binds to Anti-ACh receptors; leads the destruction of anti-ACh receptors so have decreased sensitivity and muscle weakening
What autoimmune diseases can be transmitted from a mother to a fetus?
Antibody mediated since IgG can pass through the placenta
What type of hypersensitivity is associated with immune-complex autoimmune disease?
Type III
What are some immune-complex autoimmune diseases?
Lupus, subacute bacterial endocarditis, mixed essential cryoglobinemia
What is diagnostic of SLE?
High anti-dsDNA titer, butterfly rash on face, fatigue, headaches
What are some T cell mediated autoimmune diseases?
MS, Rheumatoid arthritis(may also be classified as immune complex), Type I diabetes
What cells are responsible for killing the pancreatic beta cells in type I diabetes?
CD8+
Do the symptoms arise immediately for Type I diabetes?
No- don’t occur until there are too few cells to produce insulin
In Rheumatoid arthritis, what are antibodies made against?
The constant regions of other antibodies (the rheumatoid factor)
Why can Rheumatoid arthritis be considering both an immune complex mediate and a T cell mediated autoimmune disease?
Have both antibodies and T cells- the antibodies are against rheumatoid factor and the T cells infiltrate the joint synovium
What is attacked with MS? What cells are responsible?
Myelin sheath; TH1 cells secrete IFN-gamma which activates macrophages and mast cell/complement activation
Normally the brain is an immune privileged site. How do cells attack the myelin within the brain with MS?
Inflammation may act as a trigger resulting in increased permeability of the BBB and giving T cells access to the brain
What are some potential treatments for autoimmune disease? Have they been effective?
Physical removal of the antigen. Ab, Ag:Ab complexes, IV IgG, anti-inflammatory drugs, block cytokines, replacement therapy- not very successful
