Autoimmune disease Flashcards
What are the indicators that a disease is autimmune?
Presence of higher titer autoantibodies and/or autoreactive lymphocytes in vivo Autoantibody binding and/or T cell reactivity to autoantigen in vivo Tranfer of disease with autoreactive serum and/or autoreactive lymphocytes Immunopathology consistent with autimmune-mediated processes Beneficial effect of immunosuppressive interventions Exclusion of other possible causes of disease MHC association (defect of AIRE, or Foxp3) Animal model mirroring the human disease
What are autoimmune diseases?
Complex diseases with a genetic component (MHC)
What is the most common form of autoimmunity?
Autoimmunity of the thyroid gland is the most common form of autoimmune disease: Graves’ and Hashimoto’s disease
What organ does Graves’ disease affect?
the thyroid - the TSH receptor (TSH = thyroid stimulating hormone - controls metabolic rate throughout the body)
What does Hashimotos disease affect?
Targeting of thyroid peroxidase and thyroglobulin.
What determines whether an autoimmune disease is organ/non-organ specific?
It is dependent on the location of the antigen; if antigen is located throughout the body then is it non-organ specific; e.g. SLE immune complexes can be large with complement added, blocking small capullaries such as in the renal glomerulus and cutaneous blood supply.
How does autoimmune disease result?
The breakdown in immunological tolerance; can arise in any time point in life. Most commonly develop in adulthood. Aetiology of autoimmune disease is complex; i.e. combination of genes and environment (multifactorial) shows low concordance.
Which genes are normally involved in autoimmune disorders?
HLA; as certain HLA can present a given self-peptide. In Hasimoto’s disease = HLA DR5 3.2 relative risk. Type 1 diabetes; glutamic acid decarboxylase 65 (GAD65)
T/F autoimmune disease are more common in males?
False, they are more common in females; sex hormones implicated in aetiology.
What are the non-genetic factors of autoimmune diseases?
Infection; molecular mimicry
Stress; neuroendocrine pathways affecting the immune system
Environmental agents; immunological cross reactions due to sequence similarity/shape i.e. molecular mimicry between self-antigen and foreign immunogen.
For example; Hepatitis C virus has a similar peptide to GAD65; GAD65 is attacked by Tc cells.
How can harmful autoimmunity be prevented?
As T cell help is required for most immune responses, deletion or anergy of the relevant autoantigen-specific helper T cell is usually sufficient. Most autoimmune diseases involve contributions from both T and B cells.
Hashimotos thyroiditis is an example of what kind of autimmune disease?
An organ specific disease
Describe the presentation of Hashimotos.
swelling in neck; enlarged thyroid = goitre. Normal thyroids characterised by thyroglobulin with little thyroid epithelial cells. Hashimoto thyroid is infiltrated with lymphocytes causing destructive inflammation of thyroid; looking similar to germinal centre. Hypothyroidism appears. Serum from goitres mixed with agar = thyroglobulin binding to antibodies; immune complexes; precipitates out of solution due to size. Immunofluorescence staining of normal thyroid is another text. Antibody binding to thryoid peroxidase; thyroid specific auto-antigen.
What is the pathophysiology of SLE?
Anti-nuclear antibodies, making it non-organ specific autoimmune disease. Butterfly rash; deposition of immune complexes in capillaries of skin. Consequences of SLE; glomerulonephritis.
What are the autoimmune mechanisms?
Release of sequestered antigen; an antigen which has not been presented to any immune system
Inappropriate MHC expression on non-APCs
APC with cross-reacting Ag; molecular mimicry
Polyclonal activation; EBV. No T cell help.
