Glossary of 2. Autoimmunity: Testing and Diseases
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- Examples of autoimmunity:
-systemic lupus eryth.
- What 4 ways to Auto-Ab's develop?
- 1. Naturally, no disease.
2. Infection, Ag mimicry
3. Drug therapy
4. Chronic polyclonal Bcell activation
- Give an example of antigenic mimicry that causes auto-Ab disease.
- Rheumatic fever group A strep antigen cross-reacts wtih heart myosin.
- What are 3 immunologically privileged sites? what is the result?
-these self antigens do not undergo tolerance; auto-Ab can develop to these.
- What are 4 mechanisms for developing autoreactive T cells?
- 1. Self-Ag don't undergo tolerance - sequestration.
2. So low of [Ag] that it's ignored by the immune system.
3. Abnormal Ag processing
4. Inappropriate Ag presentation
- What are 4 more mechanisms for Tcell mediated autoimmun?
- 1. Tcells avoid negative selection of it's defective.
2. Large amts of cryptic Ag
3. Regulatory cells removed
4. MHC and TCR genes are genetically predisposed to disease
- What 4 methods are used to screen for autoantibody?
- 1. ANA antinuclear ab tests
2. RF rheumatoid factor
3. Complement fixation
4. Immunodiffusion assays
- What does complement fixation detect? Why?
- Detects the amt of free complement in the body. To detect the stage of disease.
- what is the best method for detecting and charactizing auto antibodies?
- ANA - antinuclear antibody
- Does a neg ANA rule out disease?
- no; but it does 99% in SLE
- how often are false pos results seen with ANA?
- 2-5% of normal people have a positive ANA with a titer of 1:4 or less.
- What type of antibody causes a homogenous result for ANA?
- Ab to histones and Deoxyribonucleoprotein.
- What will neg and pos cells look like in homogenous ANA?
- -neg cells are non-mitotic and their nuclei stain smooth.
-pos cells are mitotic and show a solid stain or peripheral.
- WhaWhat types of antigens are detected in homogenous pattern, and what do high titers suggest?
- -dsDNA, ssDNA, nDNA, histone and DNA.
- Name 6 organ specific autoimmune diseases, and the organ they're specific for:
- -Hashimoto's for thyroid -Grave's for thyroid
-Pernicious for gastric parietal cells
-IDDM for pancrs Bcells
-Myasthenia gravis, nerve muscle synapses
-Multiple sclerosis, myelin sheath of nerves
- Name 7 systemic autoimmune diseases.
- Which HLA haplotype is assoc w/:
- Addisons = DR3
Anklysng = B27
Rheum. A = DR4
- What microbial factor induces rheumatoid arthritis?
- Strep A
- What is the cause of myasthenia gravis?
- Anti-feceptor to Acetylcholine receptors; it binds/destroys them and prevents synapse.
- what is the cause of grave's disease? how does it compare to myasthenia gravis?
- anti-receptor antibodies to TSH receptors; but it doesn't destroy them like MG, it overstimulates it!
- what is hashimoto's thyroiditis and what is the cause?
How does it compare to mgravis or grave's?
- hypothyroidism, caused by antibodies formed to thyroglobulin, it ultimately destroys the thyroid.
Comparison: not antireceptor, but destroys tissue like MG.
- What antibodies cause pernicious anemia?
- -Anti-parietal cells of stomach
-Can't absorb Vit B12, so myelin sheath deteriorates.
- What is the pathophysiological process in MS?
- Myelin sheaths of axons are destroyed, and a plaque builds up in brain/spinal cord white matter.
- What CAUSES multiple sclerosis?
- -T cells infiltrate the CNS.
-Abnormal immunoglobulin develops within the plaques.
-Oligoclonal bands appear on SPE
- What are the clinical manifestations of SLE?
- -Fever, Skin rashes
- What are the pathophysiological manifestations of SLE?
-Nephritis/hematuria, leukocyturia, casts.
-Elevated serum creatinine
- What are the immunological manifestations of SLE?
- -Low levels of complement
-High levels of immune complexes in serum/glomerulus
- What genetic inheritance is associated with SLE?
- DR2 and DR3
- What drugs can induce SLE?
- What tests are useful in monitoring SLE?
- ANA (antinuclear antibody)
Anti-RF (rheumatoid factor)
VDRL (false positive)
C3/C4 level monitoring
- What ANAs are patients with SLE positive for?
- What are clinical manifestations of Rheumatoid arthritis?
- -Fatigue, anorexia, weight loss, transient joint and muscle pain
-skeletal muscle atrophy
- What mediates rheumatoid arthritis, and how does it affect Tcells?
- MHC class II, DR4
-may facilitate Ag presentation to Thelpers
-May prevent destruction of autoregulative Thelpers during thymic maturation.
-Results in Type II collagen response.
- What lab tests may help in diagnosing RA?
- -Rheumatoid factor - but neg doesn't rule it out.
-VRDL - may be false positive.
-ANA - may be positive.
- What occurs immunologically in RA?
- Increased Ig
Activated T helper cells
- What ANA pattern is seen in SLE?
- Homogenous and heterogenous
- What ANA pattern is seen in scleroderma?
- what ANA pattern is seen in MCTD?
- what else is seen in speckled?
- SLE, Scleroderma, Sjogren's and MCTD
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