Immuno 16: Autoimmunity Flashcards
Define autoimmunity.
adaptive immunity specific for self antigens
What is molecular mimicry, again?
When there is a clear connection between a normal immune response to infection and the autoimmune condition a pt is experiencing.
Type II autoimmunity is mediated by what immunoglobulin?
IgG
Type II autoimmunity is similar to Type II hypersensitivity in that they are mediated by Abs and are specific for determinants of _______/________.
cell surface structures/extracellular matrix
Type III autoimmune diseases are analogous to type III hypersensitivities because they are mediated primarily by ______ and result in _______ _______ disease.
IgG; immune complex disease
Type IV autoimmunities are analogous to Type IV hypersensitivities because they are mediated by ____ ____ specific for self determinants.
T cells
Are there any autoimmune diseases involving IgE?
Nope. That’s why there’s no autoimmune disease analogous to Type I hypersensitivity.
What’s going on in autoimmune hemolytic anemia?
The body has Abs (IgG and IgM) specific for surface antigens of erythrocytes. Results in activation of classical complement pathway»_space; cell lysis via MAC
There can also be uptake of opsonized RBCs by macrophages in the spleen. Either way, you get anemia, bc you have less RBCs circulating.
What test is used to detect if a pt has auto-antibodies to their own RBCs (as seen in autoimmune hemolytic anemia)?
Direct Coomb’s hemagglutination
What is the Tx for autoimmune hemolytic anemia?
corticosteroids
Describe the two ways Abs can lead to uptake of RBCs in the spleen as seen in autoimmune hemolytic anemia.
1) IgM or IgG can lead to activation of the classical complement cascade which will mark cells for phagocytosis by macrophages bearing CR1+ receptors in the spleen.
2) IgM or IgG can bind to the RBC and macrophages in the spleen with FcR+ will recognize the bound Abs and phagocytose the RBC.
Briefly describe how the Direct Coomb’s test leads to Dx of an autoimmune disease. Use autoimmune hemolytic anemia as an example.
Blood drawn from Pt.
Antigens are present on RBCs and host Abs are bound to those antigens.
Coomb’s reagent is added to sample, which if positive, will cause hemagglutination. (Coomb’s Rgt will bind to abs on surface of RBCs and cross-link them, causing hemagglutination)
Describe what is going on in autoimmune idiopathic thrombocytopenic purpura.
IgG binds to and inhibits an enzyme that would otherwise cleave vWF. This leads to over-aggregation of platelets»_space; excessive clotting. The excessive clotting in the microvasculature cuts up RBCs as they pass the clot and causes microangioplastic hemolytic anemia. The over use of platelets also leads to a deficiency of platelets and thus, bleeding, leading to the purpura.
How is autoimmune idiopathic thrombocytopenic purpura diagnosed?
observation of microangioplastic hemolytic anemia
What is the Tx for autoimmune idiopathic thrombocytopenic purpura?
plasmapheresis (exchange transfusion) with plasma from healthy donors.
Let’s play “Do You Remember from Block 1?”
Where is type IV collagen found?
Lines basement membranes all over the body
What is going on in Goodpasture’s syndrome?
IgG binds self type IV collagen. Initiates classical complement cascade, and then the alternative pathway, leading to phagocyte migration and resultant tissue damage.
The most important tissue damaged in Goodpasture’s syndrome is what?
Kidney, leads to glomerulonephritis
What are the symptoms of Goodpasture’s syndrome?
Loss of appetite, weakness, fatigue, progressive loss of kidney function.
How do you Dx Goodpasture’s syndrome?
Measurement of glomerular basement membrane-specific Abs (anti-GBM)
How do you treat Goodpasture’s syndrome?
can be by plasmapheresis and with anti-inflammatory drugs
What’s going on in Schleroderma?
IgG mediated autoimmune disease that results in damage to the vascular endothelium of arteriole and smooth muscle cells that results in replacement of damaged tissue with collagen. Results in skin thickening and hardening.
In addition to the damage to skin seen in Schleroderma, what other tissues are affected?
kidneys, blood vessels, liver, and brain
What is the treatment for schleroderma?
No standard treatment. Most treatments involve increasing blood flow to extremities.
How do you Dx Schleroderma?
presence of anti-nuclear Abs, anti-topoisomerase Abs, and anti-centromere Abs. These are all IgGs
What’s going on in acute rheumatic fever?
Autoimmune condition resulting from molecular mimicry. Normal IgG response to GAS infection cross-reacts with normal host tissue. Some GAS envelope components are very similar to determinants expressed on cardiac tissue. Damage to heart mediated by crossreactive IgG, and the resulting inflammatory response (myocarditis) becomes symptomatic due to scarring of heart valves.
List the symptoms of acute rheumatic fever.
chest pain, shortness of breath, fever, joint pain
What’s going on in Pemphigus vulgaris?
autoimmune disease where IgG is specific for desmoglein 1 and 3 (component of desmosomes that adhere cells to one another). Results in loss of cohesion in keratinocytes.
How do you Dx Pemphigus vulgaris?
immunofluorescent staining to identify IgG4 bound to tissue from a punch biopsy
What are the symptoms of Pemphigus vulgaris?
chronic painful skin blistering
How do you treat Pemphigus vulgaris?
corticosteroids and other anti-inflammatories; rituximab
What’s going on in Grave’s disease?
autoimmune condition in which thyroid stimulating hormone (TSH receptor)-specific IgG Abs cause over-production of thyroid hormone because the Abs serve as receptor agonists.
What are the symptoms of Grave’s disease?
bulging eye syndrome is hallmark. Also: enlarged thyroud, heat intolerance, nervousness, irritability, weight loss, and moist skin.
