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86 Cards in this Set
- Front
- Back
Type I, II, and III HSN all have what in common?
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Require the active production of antibody by plasma cells
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Antibody type involved in Type I HSN:
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IgE secreted by Bcells in response to antigen/IL-4 environment from Th cells
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Main factor released by Mast cell degranulation in Type I HSN upon subsequent Ag exposure:
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Histamine
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Effect of Histamine:
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Increased vascular permeability
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Major chemotactic factors released by mast cell degran in Type I HSN recruits:
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Eosinophils
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IL that activates eosinophils:
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IL-5
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3 Primary mediators released by mast cell degranulation:
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-Histamine
-Proteases -Chemotactic factors |
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Main effect of primary mediators of mast cell degranulation?
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-Bronchial Sm musc Contraction
-Vascular Dilation |
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3 Secondary mediators released in mast cell degranulation:
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-Cytokines
-Leukotrienes -Prostaglandin |
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Why do 2ndary mediators take longer to be released?
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They require gene transcription and expression
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Clinical example of disease of type I hsn:
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Bronchial asthma
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2 types of txmt for Bronchial asthma/what is each for?
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-PDE inhibitors - to relax bronchial smooth muscle
-Corticosteroids for inflammation (late phase) |
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Treatment for Anaphylaxis?
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Txmt: Epinephrine
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Type II HSN is also called:
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Antibody-mediated
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What are the antibodies involved in Type 2 HSN directed against??
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Antigens that are INTEGRAL components of the target cell!
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What are 3 distinct antibody-dependent mechanisms of type II HSN?
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a. Complement dependent
b. ADCC c. Ab-mediated cell dysfunction |
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What are 2 ways that Complement reactions can kill cells in type II HSN (a)?
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-Directly cause lysis
-Opsonization/phagocytosis |
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What does the interaction of complement with the target cell surface in type II hsn result in?
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Cell lysis and death or phagocytosis
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Where are the antigens involved in type II hsn reactions typically located?
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In basement membranes or in blood cell membranes
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What are 3 clinical examples of disorders of Type II mediated hypersensitivity where Ag is in RBC membranes?
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-Warm Ab Autoimmune HA
-Hemolytic Transfusion rxns -Hemolytic Disease of the Newborn |
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What is the Ig that mediates WAIHA?
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IgG
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What syndrome of Type II complement-mediated Ab-depend hypersensitivity targets Ag in the glomerular/alveolar basement membranes?
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Goodpastures syndrome
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How does ADCC type II HSN work?
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-Antibodies directly bind cell surfaces
-Fc receptors on killer cells bind the Ab-cell complexes |
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What is the most important killing cell that works in ADCC?
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NK cells
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What is the main distinction between type a/b Type II HSN?
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Complement is only involved in type II a
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What are 2 clinical examples of Type II HSN where there is antibody-mediated Cell Dysfunction?
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-Graves disease
-Myasthenia gravis |
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What is the antibody in Graves disease and what is it directed against?
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TSI - thyroid stimulating antibody; directed against the TSH receptor
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What is the antibody in Myasthenia gravis directed against and what is its effect?
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-Ab is against the NMJ receptor for Acetylcholine; result is inhibition of neurotransmission and destruction of the receptors.
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What are the 2 main effects of the TSI in Grave's disease?
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-Hyperplasia of the thyroid gland
-Overproduction of T3/T4 - hyperthyroidism |
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What are 6 other Type 2 HSN disorders in addition to Graves and Myasthenia gravis?
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Good Peanut Butter Tastes Very Awesome
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What are the Type II HSN disorders represented by Good Peanut Butter Tastes Very Awesome?
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-Goodpastures
-Pernicious anemia -Bullous pemphigoid -Thrombotic phenomena -Vasculitides -Acute rheumatic fever |
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Antibody specificity in:
-Goodpastures -Pernicious anemia -Acute rheumatic fever |
G = Type 4 collagen in BM
P = Anti-IF RF = Antistreptococcal Ab that cross reacts w/ heart |
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Type III HSN is aka:
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Immune complex
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Major difference of type III HSN from type II:
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Antigen in type III is NOT an integral component of target cells; it is CIRCULATING.
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What do Ag-Ab that are good sized normally do?
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Get eaten by MPS system cells
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What if the Ag-Ab complexes are insoluble aggregates?
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They deposit on serosal surfaces or in vessel walls.
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What happens when insoluble immune complexes in type III Hsn deposit in places?
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They activate COMPLEMENT which is highly chemotactic for NEUTROPHILS
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What happens when the neutrophils come flooding in to attack the immune complex depositions?
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They release their lysosomal enzymes and cause lots of TISSUE DAMAGE
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What are 4 substances that neutrophils release in type III hypersensitivity?
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-Lysosomal enzymes
-Prostaglandins -Kinins -Free radicals! |
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What other major important pathway is activated in type III hypersensitivity?
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Hageman factor 12 is activated
-Complement -Clotting cascade -Kinin system |
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Which pathway of coag is activated by Fx 12? Result?
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Intrinsic - nearby small vessels thrombose
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What does Kinin activation lead to?
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-Vasodilation (Bradykinin)
-Edema |
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What does platelet aggregation in type III HSN lead to?
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More microthrombus formation and release of dense granule contents - Vasoactive amines!
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What are 3 general conditions that result from deposition of immune complexes in small vessels and type III HSN?
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-Vasculitis
-Glomerulonephritis -Arthritis |
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What SIZE of immune complex is more likely to be deposited in vessel walls? Why?
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SMALLER - less likely to precipitate locally and be removed by the MPS
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5 clinical examples of Type III hypersensitivity:
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-Serum sickness
-Arthus reaction -SLE -Polyarteritis nodosa -Glomerular diseases |
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What was Serum sickness characterized by?
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Deposition of immune complexes in multiple sites - heart/joints/kidneys
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What causes serum sickness?
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Injections of large amounts of foreign protein (horse serum)
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What is the most common cause of serum sickness if it is seen today, and how is it treated?
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Cause: Antibiotics - Penicillin
Treat: Corticosteroids |
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What is Arthus reaction?
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A LOCALIZED immune complex reaction
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What is Arthus reaction caused by?
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Introduction of an exogenous antigen in the presence of a EXCESS of PREFORMED antibodies
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Type IV HSN is aka?
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Cell-mediated hypersensitivity
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What are 2 subtypes of Type IV cell mediated HSN?
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1. Delayed type
2. CTL mediated |
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What are the cells that act in DTH type IV HSN?
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-CD4+ Thelper cells
-Macrophages |
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What is the 1st step in DTH?
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APC processing and presentation of antigen to CD4+ cell
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What does the CD4+ Th cell do in response to Ag presentation?
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Secrete cytokines to stimulate inflammation and get rid of the antigen, and REMEMBER the antigen
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What cytokine especially is produced by CD4 Thelpers on subsequent exposure to the same antigen? What does it do?
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IL-2 - stimulates macrophages to phagocytose the antigen.
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What are 2 clinical examples of DTH cell-mediated HSN involving CD4+ Thelpers and macrophages?
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-Tuberculin reaction (PPD)
-Contact dermatitis |
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How does the PPD test work in positive patients?
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1. First TB exposure produced Th1 cells with MEMORY
2. Intracutaneous shot of PPD causes activation and proliferation of the Th1 cells |
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What is induration?
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Firming of the site of the PPD shot due to fibrin formation
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What is the other type of cell-mediated HSN?
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CTL-mediated
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Other than involving CD8+ CTLs instead of CD4 Th's, what is the major difference between the 2 types of cell mediated type IV HSN?
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CD4 Th1 mediated involves cytokines; CD8 CTL does NOT involve cytokines
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What are the 2 mechanisms of direct killing by CTL's in that type of cell-mediated HSN?
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-Fas-fasL mediated
-Perforin/granzyme mediated |
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What do Granzymes trigger?
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Apoptosis
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What does Fas-FasL interaction trigger?
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Apoptosis as well
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What type of target cells are generally killed in Type IV CTL mediated hypersensitivity?
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-Tumor cells
-Virus infected cells |
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What MHC presents the antigen of target cells to CTLs?
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MHC I
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What are the 3 EARLY histologic findings in Cell-mediated hypersensitivity?
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-Perivascular cuffing of Tcells
-Edema -Fibrin deposition (induration) |
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What are the LATER events of Cell-mediated histology?
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Granuloma formation
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What is a Granuloma a type of?
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Chronic inflammation
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What IS a granuloma?
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A nodular collection of EPITHELIOID cells surrounded by a rim of lymphocytes
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What are Epithelioid cells?
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Special macrophages that have been activated to transform into Epithelioid cells.
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What starts off the formation of a Granuloma?
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Presentation of antigen by an APC (macrophage) to a naive but Ag-specific CD4+ Th cell.
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What interleukin does the APC secrete as it presents the Ag to the Th cell?
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IL-12
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What effect does IL-12 have?
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It helps convert the CD4+ Th cell into an active Th1
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What are 2 interleukins secreted by the activated Th1 cell? What effect does each have
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-IL-2: stim autoproliferation of Th1 cells
-IFN-y: activates macrophages to transform into Epithelioid and Giant cells |
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How do more monocytes get recruited to add to the formation of a granuloma?
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By endothelial cell changes in the vasculature in response to TNF-a secreted by Th1 cell
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Do granulomas develop from a PPD skin test?
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I don't think so.
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But what do Granulomas develop in?
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A number of infections
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What are 4 infections in which granulomatous inflammation is characteristic?
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-Mycobacterial (TB/leprae)
-Fungal - Blast/Histo/Cocci -Treponema pallidum (syph) -Bartonela henselae (cat scr) |
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What disease of unknown etiology is characterized by granulomatous inflammation?
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Sarcoidosis
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What is the predominant difference in granulomas seen in TB vs sarcoidosis?
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TB - caseating
Sarcoid - noncaseating |
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What is caseation?
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Death of macrophages in the center of a granuloma due to the actions of peripheral lymphocytes.
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What are 2 types of Giant cells based on morphologic appearance?
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-Langhans
-Foreign body giant cells |
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What do Langhans giant cells look like and what are they classic in?
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Nuclei in HORSESHOE pattern at the PERIPHERY of cell
-Tuberculosis |
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What do Foreign body Giant cells look like?
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Nuclei are just scattered everywhere.
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