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35 Cards in this Set
- Front
- Back
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Discuss role of the following in autoimmunity
a.genetics, b. hormones, c. diet, d. drugs e. infections |
a.Mutations in one gene (certain genes more susceptible) to certain autoimmune
When have one more likely to have 2 b.Women- estrogen= SLE c. d. PCN= bind to RBC and make neoAg that causes hemolytic anemia TNF-a – SLE/MS unknown how e. Reheumatic fever- strep Multiple sclerosis- from Epstein Barr, influenza A, HPV |
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What are the three big picture reasons self tolerance is important...
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i. Transplantation
ii. Treatment of autoimmune and allergic disease iii. Preventative stem cell/gene therapy |
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Describe central tolerance and peripheral tolerance...give examples of when these processes go wrong...
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central- when T-cells and B-cells go through negative selection any reaction to self Ags will go through apoptosis sometimes T-cells released that should not be released
peripheral- Tcells that do not bind to specific Ag are not activated (immunologic ignorance) - Fas (CD95) receive signal from FasL- (causes apoptosis, and deletion) - CTLA4 (CD152) binds CD80 (inhibits activation) - |
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Describe the concept known as immunodominance and its role in epitope spreading...
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describes an initial focusing activity of host immune system against 1-2 epitopes of proteins
- self Epitopes may not be seen as dominant and remain cryptic |
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What is example of systemic and of organ specific autoimmune diseases?
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systemic- SLE Systemic Lupus Erythematosus
organ-specific- T1D mellitus |
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What are specific ways in which the following autoimmune disease occur?
a. Gullain-Barre b. Inflammatory Bowel Disease c. SLE |
a. loss of B-cell tolerance
b. genetic alteration of function of regulatory T-cell or cytokine production c. Problems in TNF-a, something that lowered threshold of # of Ags for immune response |
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What is an example of deficiencies caused by the following problems...
a. impaired clearance and tolerance induction by apoptotic cells b. impaired production of regulatory T-cells (FoxP3) |
a. C1q and C4
b. IPEX syndrome |
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What is an example of deficiencies caused by the following problems...
a. incomplete induction tolerance in thymus (AIRE deficiency) b. Immune signaling threshold (CTLA-4 polymorphisms) |
a. APECED syndrome
b. type I diabetes, thyroid disease, primary billary cirrhosis |
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Explain CTLA-4's importance and how it is used...
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helps send signals for immune system to stop responding...
- if not with CD8 cells then the CTLs will keep responding (autoimmune) |
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Discuss drugs associated with myosytis
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D penicilamine
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Compare dermomyositis and polymyositis
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a. subacute onset of skin changes that also accompany or precede muscle weakness
i. Heliotrope rash ii. Symmetrical pattern iii. Skin lesions iv. Infrequent overlap with other autoimmune v. 15% associated with cancer B. Polymyositis i. mainly adults ii. positive family history iii. HIV, HTLV-1 infections iv. overlaps with other autoimmune diseases v. drug induced vi. signs of IBM |
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What are unique clues something is Inclusion body myositis (IBM)?
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a. distal muscle weakness
b. assymetric weakness and atrophy c. no response to steroid treatment |
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What is only true way to diagnose a myopathy?
What Ab- is usually represented more in DM? |
a correctly interpretation of a muscle biopsy
b. HLA DR3 with DM |
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What are specific Abs found in blood that are indicative of Myositis (mostly DM)?
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i.Aminoacyl transfer RNA (tRNA) synthetases
ii.Histidyl tRNA synthetases (Anti-Jo-1) |
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What histological findings distinguish DM from PM and IBM?
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1. CD4 and Bcells
2. Endothelial swelling 3. hyperplasia in capillaries with necrosis 4. compliment activated |
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What are unique IBM histological findings?
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a. vacuoles that contain membranous debris
b. Eosinophillic inclusion bodies have 3 proteins: i. B-amyloid protein (BAPP) ii. Ubiquitin iii. Apolipoprotein E (APOE) |
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What are the most 4 common treatments of myositis?
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1. Rehab/physiotherapy
2. Steroid therapy 3. IV methyl prednisolone 4. Immuno suppressive therapy (if resistant to steroids) |
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What are the most commonly used immuno suppressive agents to treat myositis?
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a. Methotrexate and azathioprine
b. Cyclosporin or cyclphosphamide c. Tacrolimus and mycophenolate |
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Discuss the mechanisms and outlined processes of antibody-mediated and cell-mediated damage in pathogenic mechanisms of autoimmune diseases.
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1. Th1 cells are activated after pathogen invades and activate macrophages
2. Molecular mimicry occurs- - Cross reactive Th1 recognize (mTH1 and sTh1) release cytokines,, macrophages produce tissue damage--- Self Ags are released from damage and are later seen as bad. |
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What is epitope spreading?
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autoimmune response caused after repeated infections causes that left damaged tissue...
Damaged tissue seen as part of microbe and spread throughout and reacted on by self Th1 |
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What is bystander activation?
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non-specific activation of Th1 cells that are self-reactive
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What are cryptic antigens?
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After cytokines activate APC, protease can be produced that makes processing of self-Ags different...
Some are not processed correctly called cyptic, which can activate self-reactive Th1 |
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What are the pathological findings in myonecrosis (rhabdomyolysis)?
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a. elevated CK (MM for skeletal muscle, MB for cardiac)
b. Elevated serum myoglobin c. Monocytic infiltrate and myofiber necrosis d. Abnormal ECG or EMG |
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What type of infection most commonly shows peripheral eosinophila?
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metazoal infections (worms)
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Describe the process of infection for trichinosis give and example of one...
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- it encrusts its larvae in striated muscle and is ingested from undercooked meat.
- larvae are released in small intestine and goes to circulation Trichinella (tissue round worm)- |
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This type of parasite eventually migrates into skeletal muscle and produce, myalgia, eosinophila...
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trichinella
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What kind of parasitic diagnoses fits- conjunctivitis and edema and splinter hemorrhages?
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trichinosis
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The parasite trypanosoma cruzi causes what disease of the muscle?
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Chagas
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Describe the findings in Chagas disease...
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caused by parasite..
a. cardiomegaly b. Right bundle branch block c. dilated esophagus d. endemic area |
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What disease shows the following findings...
a. lives in endemic area, cardiomegaly, 20-40 years of age, dilated esophogus |
Chagas disease
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If people infected with toxoplasmosis, what would they show and how do u diagnose it?
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a. headache, CT or MRI
or biopsy |
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What is molecular mimicry?
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some virus or bacterias activate autoreactive T or B cells
- due to viral or bacterial mimicing normal bodily function. |
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If there is a problem involving the following what is the mechanism of failure or tolerance? (from midterm)
a. CTLA-4 - what diseases? b. Fas/FasL- what disease? c. FOXP3 d. IL-2, IL2Ra/B |
a. failure of anergy in CD4+ T cells (several diseases)
b. defective deletion of anergic self-reactive B-cells, reduced deletion of mature CD4 T cells (ALPS) c. Defeciency of regulatory T cells d. Defective development survival function, or function of regulatory T cells |
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Blockage of TNF-a can induce what dieases?
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a. SLE
b. MS |
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Regulatory T cells can inhibit the production of which inhibitory cytokines?
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IL-10 and TGFB
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