Glossary of 2. Autoimmunity: Testing and Diseases

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Examples of autoimmunity:
-Organ specific
-general inflammation
-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.
-Sjogren's syndrome
Which HLA haplotype is assoc w/:
-Ankylosing spondylitis
-Rheumatoid arthritis
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
-Anti-intrinsic factor

-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
-Joint inflammation
-Pleural effusions
What are the pathophysiological manifestations of SLE?
-Nephritis/hematuria, leukocyturia, casts.
-Butterfly rash
-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
-joint deformities
-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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