Microbiology - Autoimmune diseases of the Musculoskeletal Sys Flashcards
What types of cells are specific for self antigens in an autoimmunity?
What sex gets more autoimmune disease?
- Autoreactive T-cells specific against self antigens.
- Female>males
What are the mechanisms of autoimmunity?
- Breakdown of tolerance (deletion, anergy, suppression)
- release of sequestered antigens
- Molecular mimicry
- Inappropriate expression of HLA
- Polyclonal B cell activators
- Genetics ( HLA association)
- AIRE ( autoimmune regulator)
What are the possible methods of tolerance?
- T cells bind with a high affinity to antigen in the thymus ensuring that any that might have an affinity for self are gotten rid of. Once made Tcells are protected from other tissues from barriers, DNA because they are in the cell, and T-cells do not express co-stimulatory molecules that might allow for easy activation.
What are the mechanisms for a breakdown of tolerance?
- There can be a missing self-antigen from the thymus/MHC can’t bind, autoreactive T cells are not deleted and escape the thymus, DNA leaks out of dying cells and are not cleared if complement is defective, physical barriers round cells may become defective, or infection initiates mimicry.
How does the lack of co-stimulatory signal result in anergy?
CTLA-4 binds B7 instead of (CD28 on the antigen presenting cell) thereby blocking activation signal. Soluble CTLA-4 also binds B7. Producing less sCTLA4 linked to autoimmunity diseases.
What type of cytokines are produced by T regulatory cells that suppress autoreactive CD4 T cells
- What specific gene acts as a transcriptional repressor on the Treg cells that a loss could result in autoimmunity?
IL-4 and IL-10 produced
- FoxP3 ** *crohns and inflammatory bowel disease
What is the main result of sequestered antigen released to T-cells that have have previously been sequestered?
What autoimmune disease does this occur in?
- They are activated becuase they were previously not seen during the priming stage in the thymus and can occur in trauma or with infectious agents
- SLE
What pathogens express proteins with regions that are similar to self, AKA molecular mimicry?
- Post rabies encephalities
- Rheumatic fever
- Viral peptides and MBP (Influenza, Polyoma, Adenovirus, Rous sarcoma, Abelson leukemia, Polio virus, Epstein Barr virus, Hep. B virus)
What disorders have pathogens that ectopically express MHC -II ?
- Insulin dependent Diabetes Mellitus- pancreatic Beta cells
- Grave’s disease - thyroid epithelial cells
What disorders show an increase in expression of IFN-y that induces MHC-II is normally seen in autoimmune disorders?
pancreatic beta cells intestinal epithelial cells melanoma cells thyroid acinar cells trauma in organ may trigger inflammatory response increase IFN-y SLE patients have an increase in IFN-y
What causes Polyclonal B cell activation and by what mechanism?
- Gram negatives, CMV, and EBV cause polyclonal B cell activation via non-specific polyclonal activation.
- The viruses get into the B cell and spark production of IgM
What is the HLA association and the relative risk of Ankylosing spondyilitis?
- HLA serotype is B27 and those with it have a relative risk of 87.4 (high) of getting ankylosing spondylitis.
What is an AIRE?
- AIRE (autoimmune regulator) is a transcriptional activator in the thymus responsible for inducing the expression of 200-1200 genes for organ specific antigens. Allow T cells to see “self antigens”. When AIRE is lacking, antigen are not present in the thymus possibly leading to the production of self reactive T cells.
- What disorder does AIRE cause?
- Autoimmune polyglandular syndrome, which affects individuals and develops a wide range of autoantibodies against endocrine glands, liver, and skin, blood cells, and platelets
What is Type II hypersensitivity?
It is a non-cytotoxic in which Abs binds to cells or tissues and does not kill cells, just changes its function
