Autoimmunity Flashcards
Define autoimmunity
Immune response against the host due to the loss of immunological tolerance of self-antigen(s)
Define autoimmune disease
Disease caused by tissue damage or disturbed physiological responses due to an auto-immune response
How can autoimmune disease be classified?
Organ specific = 1/multiple self-Ag within 1 single organ or tissue
Non-organ specific = wide distribution of self-Ag throughout the body
What are the immune mechanisms of tissue damage?
Auto-Ab = complement, Ab-mediated cell cytotoxicity, neutrophils
Auto-reactive T cells = cytotoxic, macrophages
What is the set of criteria for diagnosing autoimmunity?
1) presence of auto-Ab/auto-reactive T cells
2) levels of Ab correlate with disease severity
3) auto-Ab/auto-reactive T cells found at site of tissue damage
4) transfer Ab/auto-reactive T cell to healthy host and induce autoimmune disease
5) clinical benefit provided by immunomodulatory therapy
6) Family history
Give some example of organ specific autoimmunity
Hashimotos = thyroid
T1DM = pancreas beta cells
Myasthenia gravis = block/destroy nicotinic ACh R
What techniques can be used for the detection of auto-Ab?
Coombs test
Indirect immunoflourescence radioimmunoassay
Can autoimmune disease be passed during pregnancy?
Yes = transfer of IgG
E.g. Haemolytic anaemia, neonatal myasthenia gravis, neonatal SLE
Outline the mechanism of induction of autoimmunity
1) failure to delete self-reactive immune cells
2) T cell defects, altered self-Ag
3) T cell independent activation of B cells
What can trigger autoimmunity?
Genetic = affect sibling, affected twin, AIRE mutation affect central tolerance
Environmental = hormones, infections, drugs
What infections can induce autoimmune disease?
Strep pyogenes M protein = similar to Ag in cardiac muscle, causing rheumatic fever damaging heart valves
Coxsakieviruse B4 nuclear protein = pancreatic islet cells
Can drugs induce autoimmunity?
Yes
What are the therapeutic options for autoimmune disease?
Monoclonal Ab = bind specific protein
Plasma exchange = remove auto-Ab
Immunosupressive drugs = suppress auto-reactive T cells
Anti-inflam drugs = aid tissue damage
Replacement therapy/surgery = tackle organ dysfunction
What are monoclonal Ab?
Monovalent Ab that bind to the same epitope
Harvest B cells from spleen of mouse
B cells fused with immortal myeloma cell line = hydridoma
Hybridoma cultured = cells that prod desired clonal Ab
How do monoclonal Ab work?
Bind cell surface = active/inhib cell signalling
Induce apoptosis
Active Ab-dependent cell mediated cytotoxicity
Active complement-dependent cytotoxicity
Internalisation delivering toxins into the cell
Block inhib effects on T cells
