Autoimmunity 4 Flashcards
Describe the process of anergy in peripheral tolerance.
described as prolonged or irreversible inactivation of lymphocytes, due to interaction of autoreactive T cell presents to an APC and APC does not provide costimulatory signal which causes anergy
Describe how regulatory T cells act in surveilance of self-proteins.
When an autoreactive T cell binds to self protein, it releases inhibitory cytokines (IL-10 and TFG-B)
What marker could you use to identify a regulatory T cell and what gene is required for their development?
regulatory T-cells are CD4+ cells with CD25; development is controled by Foxp3, mutation can cause IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked
Describe the two proposed mechanisms for clonal deletion by activation of induced cell death (peripheral tolerance mechanism).
pro-apoptic gene Bim triggers apoptosis via the mitochondrial pathway in T cells (intrinsic) or Fas-Fasligand system triggers apoptosis in T and B cells by the death receptor pathway
What CD molecule is Fas receptor and why is its expression important?
CD 95, expression of its ligand FasL is upregulated with repeated autoreactive activation and binding with Fas receptor induces apoptosis
Fas mutation results in which conditition?
autoimmune lyphoproliferative syndrome, a lupus like disorder
What is an immune privileged site?
parts of the body where antigen is sequestered from the immune cells, although antigens may be released in trauma or infection
Name genes that are commonly assoicated with autoimmune function .
HLA genes, AIRE, Foxp3, Fas mutation and PTPN-22 (#1 single gene mutation in autoimmunity, mutation in tyrosine phosphatase leading to excess lymphocyte activity)
List two ways in which infection can induce an autoimmunity disorder.
infections can : upregulate expression of costimulatory molecules; infection antigens may mimic the body’s proteins and mount an immune response to that structure
Give an example of molecular mimicry causing an autoimmune disease in the case of a group A strep infection.
strep antigens mimic self antigens of the ehart and antibodies can “cross-react” and damage the heart causing carditis and rheumatic heart disease
What is the fundemental defect that leads to Systemic Lupus Erythematosis?
failure of self tolerance due to cross reaction of antinuclear antibodies (ANAs which can include DNA, histones, non histone proteins bound to RNA, nucleolar antigens)
What different patterns of forescent staining would you expect to see for antibodies against different nuclear proteins?
homogenous/diffuse (chromatin, histones); rim/peripheral (dsDNA); speckled pattern (non-specific); few discrete spots/ nucleolar pattern (RNA)
Name two other structures in the body that are commonly targeted for autoantibodies.
antibodies agains blood elements or proteins complexed with phospholipids
Describe the antiphospholipid antibodies that can develop due to SLE.
present in 40-50% of SLE patients, antigens can include plasma proteins as the epitope is revealed when protein binds phopholipid, these antibodies can lso bind cardiolipin and can cause a false positive syphilis test or also APTT may indicate bleeding risk when really the patient is hypercoagulable
Describe the grouping of symptoms for classification of SLE.
3 skin (malar rash, discoid rash, photosensitivity), 3 system specific (oral ulcers, arthritis and serositis) and 3 systemwide (renal, neurological and hematological)
What symptoms are most likely of a Lupus patient and which are the greatest cause of mortality.
common: hematologic disorder, artritis, rash; renal disease causes significant mobidity and mortality
What is the mechanism for renal disease in SLE?
immune complex deposition leads to type III hypersenstivity, causing inflammation and resulting in a granular pattern immunoflorecence of the glomerular basement membrane
