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180 Cards in this Set
- Front
- Back
What are the clinical uses of serology?
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-Screem for antibodies
-Identify infections agents and course of infection -Dx neoplastic disease -Dx of anti-body mediated AutoImmune or hypersensitivities |
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True or false:
For an imunodiagnostic assay, you don't need to know the antigen and antibody? |
Fsldr: either the antigen OR the antibody must be known
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What are the 4 diagnostic assays to test for AB or AG?
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Nephelometry
Precipitation reactions Agglutination reactios Labled Immuno assays |
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Describe nephelometry
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detection of immune complexes in a liquid form without precipitation
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Describe precipitation reactions
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soluble antigen and soluble antibody react, become insoluble and “fall out” of solution, allowing for visualization.
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Describe agglutination reactions
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soluble antibody reacts with antigen attached to a particle (or vice versa) and “clumps” together or aggregates, allowing for visualization
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Describe labled Immunoassays
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A label that can emit a measurable signal (radioactivity, color change, etc.) is attached to an antibody or antigen and an antigen-antibody interaction can be visualized.
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In nephelometry what serum consentrations are most frequentl being looked at?
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IgM, IgG and IgA (in the liquid phase)
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What is required for a percipitation reaction?
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A reaction between a soluble antigena nd antibody. The antigen must be either multivalent or polyvalent
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What is multivalent?
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2 or more copies of the same epitope
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What is polyvalent?
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different epitopes that will react with polyclonal antibodies, or mixed population of antibodies
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What is the equivalence zone?
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Area of optimal concentration of both antigen and antibody to achieve maximum precipitation
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What is radial immunodifusion?
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Antigen (or antibody) is placed in the center of an agar plate with antibody at the surrpound. If the antigen is in the sample placed in the center, it will difuse out to the agar/antibody zone and precipitate in the outer ring
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When is radial immunidiffusion generally used?
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certain viral infections and Ig isotypes:
Detects & QUANTIFIES antibody or antigen |
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What is Double immunodifusion used for?
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Diagnosis of various systemic fungal diseases
Detects & QUANTIFIES antibody or antigen |
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How is an double immunodiffusion test prefprmed?
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Antibody (patients serum) is placed in one well on one of the sides of an agar palet while the suspected antigen is placed on the opposite side. If the antibody to the know antigen is in the serum it will form and antige-antibody ineraction in the equivalence zone and precipitate
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How does an agglutiantion reaction occur?
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When antibodies crossluink either the surface andtigen of a target cell or a synthetically produced antigen coated particle and "clumps" them together
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What is required for an agglutination reaction?
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Soluble antibody and insoluble antigen
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What is agglutination between erythrocytes called?
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hemagglutination
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How are precioitation and agglutiantion reactions similar?
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They both require an optimal concentration of both antigen and antibody to acchieve max results and the optimal concentraion is know as the "equivalence sone in both
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What are the most common agglutiantion reactiosn?
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hemagglutination
bacterial agglutination latex agglutination |
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How are hemeagglutination tests preformed?
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Anti sera A or b are placed in a well. If the antibody is present in the serum, the blod will agglutinate (lage clumps) indicating a postiive test result.
Type AB aglutiante to antsera a & B Type O won't aggutiante at all sins it has no antibodies to A or B. It remains as a small "button" of blood |
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How are hemagglutination titers determined?
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By using a serial dilution of a patient sample to determine the quantity present
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What is an Antibody Titer?
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a relative [antibody] = the inverse of the greatest dilution (lowest concentration) of a patient’s serum that causes a detectable reaction (e.g. hemagglutination).
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When is hemagglutination titer commonly used clinically (to test for what?)
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Diagnosis of certain viral infections and autoimmunities.
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What is the antibody titer for a person who agglutinated at 1/64, but but not 1/128?
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64
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Following the rules for agglutination reactions what componets are soluble/not for bcaterial agglutination?
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Soluble antibody serum
Onsiluble bacterial cell particles (antigen) |
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When are laterx agglutination reactions used clinically?
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Diagnosis of various infections, including meningitis, strep throat, MRSA, toxoplasmosis, etc.
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When are bacterial agglutinatoin reactions most commonly preformed?
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Diagnosis of various bacterial infections, including Salmonella, Campylobacter, E. coli, etc.
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What is the point of using lables in immunoassays? What are the 3 main lable types?
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It allows for visualization of the antibody or ANTIGENS
1)Radioactive 2) Enxymatic 3) Florescent Compounds |
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What is a clinical example of an RIA?
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the RAST = radioallergosorbent test used in allergy testing to detect allergen-specific IgE in patients.
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How do (RIA)Radioimmunoassays work?
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Antigen-antibody interactions are detected using radiolabeled secondary antibodies
1 antibody from patient 1 radiolable antibody from test kit 1 antigen from test kit persons antibody binds to antigen and radiolable anti-Ige binds to persons antibody |
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How does the ELISA work?
What does it stand for? |
Enzyme-Linked Immunosorbent Assays
An enzyme conjugated to an antibody reacts with a colorless substrate to generate a colored product. |
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Waht are the common enzymes for ELISA?
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horseradish peroxidase (HRP) or alkaline phosphatase (AP)
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What diseases are commonly detected fro by ELISA?
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HIV via indirect ELISA
PSA (prostate specific antigen) via Sandwitch elisa |
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What is the benifit of a Western Blot (over and ELISA)?
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it is more sensituve
and can further seperate out antibodies by seperating out specific proteins |
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What are some home testing kits that are immunosaasys?
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Pregnancy test (hCG) -ELISA
Oculation test (LH)-ELISA HIV-1 -IMMUNNOBLOT Hepatitis C Check-ELISA |
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What are Immunofluorescence Assays?
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Assays wehre the antibody is tagged with fluorochrome (vs radio). Can be Direct or indirect.
Direct uses 1* ntibody as labled, indirect uses a 2* antibody to idicate the presence of the 1* antibody |
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What is clincally tested for in a direct immunofluorescence?
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detect rabies virus or HSV antigens in tissue sample
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What is clincally tested for in an indirect immunofluorescence?
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detect antibodies to syphilis, some autoimmunities (RA, SLE, etc)
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When is Flow Cytpmetry used clinically?
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Analysis of T cell subsets in HIV patients
Diagnosis of types of leukemia Determine kind and number of WBC's |
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What markers does flwo cytometry use?
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Antibodies to cell specific markers like CD4, CD8, CD19, etc that is labled with a different fllourescent dye
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Label for RIA, ELISA, and WB are on what types of antibodies?
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Secondary
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True or False:
WB can only use secondary antibodies labeled with an enzyme. |
False. They can also use radioisotopes
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What is immunotherapy?
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strategies of treatment based on the concept of modulating the immune systemto achieve a prophylactic and/or therapeutic goal.
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Immunotherapies include the use of (5)
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Cytokines
LAK & TIL cells Antibodies Vassinations Hoposensitizations (allergy shots) |
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What is cytokin therapy most prequently used?
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in treating cancer as well as inflammatory diseases.
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What are th 6 cytokines discusses that are used in cytokin therapy?
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IL-2
INF-a GM-CSF INF-Beta INF-Gamma TNF-alpha |
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How does exogenous IL-2 work for caner patients? What types of cancers?
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(Proleukin)
Enhances Cell mediated Immunity, particularly Cytotoxic T cells and NK cells Renal cell carcinoma, melanoma, leukemias and lymphomas (& HIV infections) |
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How does exogenous INF-a work?
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Inhibits viral replication
Treatment of multiple myeloma (Intron), AIDS-related Kaposi’s sarcoma (Roferon-A), Hepatitis B and C (Infergen, Intron) |
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How does exogenous GM-CSF work for caner patients?
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Hematopoietic growth factors that regulate the commitment, proliferation, and maturation of myeloid cells
Treatment for chemotherapy induced neutropenia and also used in bone marrow transplantation and prevention of neutropenia in HIV infection |
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How does exogenous INF-B work?
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Helps fight viral infection
Common treatment for MS Prevents inflammation and demyelination in CNS |
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How does exogenous IFN-Y (gamma) work ?
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Promotes macrophage activation and enhances CMI responses
Used as treatment for chronic granulomatous disease (CGD) |
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How does exogenous TNF-a blocker work ?
What diesases is it indicated for? |
TNFareceptor blocks the proinflammatory activity
of TNFa Treatment for rheumatoid arthritis, psoriasis, and ankylosing spondylitis |
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Which cytokines are used for treating inflammation?
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INF-B
INF-y (gamma) TNF-A Blocker |
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Which cytokines are used for treating cancer?
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IL-2
INF-a GM-CSF |
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What is Adoptive Cellular Immunotherapy?
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The transfer of cultured immune cells (mainly lymphocytes) that have anti-tumorreactivity into a tumor-bearing host.
Ex LAK, TIL |
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What is theh difference between LAK and TIL cells?
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Both are activate IL-2 Cells
LAK cells = lymphokine activated killer cells; obtained from peripheral blood TIL cells = tumor-infiltrating lymphocytes; obtained from the tumor infiltrate |
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What are monocolonal antibodies mAB?
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a homogenous prep od antibody in VITRO produces buy a single, immortalized clone of B cells that all have the same antigen specificity
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Waht are polycolonal antibodies?
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a mixture of antibodies produced by a variety of B cell clones that hace recognized the same antigen, but not the same epitope
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What is a HAMA response?
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undesirable immune response to the unique epitopes of the therapeutic antibody produced from murine (mouse) cells
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What are the 5 types of "Murine"/Human antibodies?
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Murine
Chimeric Humanized Human Bispecific –*can be any of the above |
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What is the nomenclature of monocolonal abntibodies?
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Virtually all monoclonal antibody generic names end with the suffix mab. Preceding this suffix is a one-or two-letter identifier of the animal source of the product.
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What is the identifier for a mouse antibody?
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O
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What is the identifier for a rat antibody?
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A
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What is the identifier for a hamster antibody?
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E
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What is the identifier for a primate antibody?
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I
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What is the identifier for a human antibody?
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U
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What is the identifier for a Chimera antibody?
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XI
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What is the identifier for a humanized antibody?
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ZU
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What is the makeup of Murnie Antibodies?
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They have mo human components
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What is the makeup of Chimeric Antibodies?
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contain murine Fab with human constant regions
ID = XImab |
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What are Bispecific antibodies? What are the two classifications?
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They have two distinct variable regions (specificities) and Can stimulate two receptors simultaneously
Trifunctional antibodies & Bispecific T cell Engagers |
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How do Trifunctional antibodies work?
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A trifunctional antibody is a monoclonal antibody with binding sites for two different antigens, typically CD3 and a tumor antigen, making it a type of bispecific monoclonal antibody. In addition, its heavy chains can bind to an Fc receptor like other antibodies. The net effect is that this type of drug links T cells (via CD3) and macrophages, natural killer cells or other Fc receptor expressing cells to the tumor cells, leading to their destruction
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What is the trifunctioanl antibody we learned in class and what are its regions?
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Catumaxomab (Removab®) –Fab regions are specific for CD3 & EpCAM, and Fc region binds to FcRs on various cells; indicated use for some cancers
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What is Blinatumomab used for?
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A Bispecific T Cell Engager (biTE) tht is fromed from teh fusion os toe FAB regions, one fore CD3 and othe other for CD19. This is used for tretmetn of B-cell cancers (CD19), spcifically indicated for non-Hodgkin’s lymphoma and acute lymphoblastic leukemia
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What are Naked Antibodies used for?
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to induce Antibody-Dependent Cell-Mediated Cytotoxicity
to activate compliment or to nutralize an organism |
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What are Conjugated monoclonal antibodies?
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immunoconjugates
-antibodies that are covalently bound to a radioactive nuclide, a toxin, or chemotherapy drug to deliver it to the target cell |
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What is Digibind?
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Polyclonal anti-digoxin Fab fragments that come from sheep IgG. It nutralizes the toxcicity of the frug by binding it without haveing reactive Fc fragment
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What are the drugs used in treating patients with Immmunodeficiency syndromes?
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Human Imminglobulins:
Gammagard Sandoglobulin Gamimune |
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What human immunoglobulins are used to treat Hep B?
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HyperHEP B
Hep-B-Gammagee |
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What is ATGAM?
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Animal imminoglobulin that is used to the management of allograft rejection in renal transplant patients
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What is OKT3?
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A monocolonal antibody used in the treatmetn of acute rejection in renal, hepatic & cardiac transplants
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Give and example of how Antibodies can be used as drugs to elicit phagocytic clearance of target cells
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RhoGAM-anti-D (anti-Rh) antibodies to clear fetal RBCs to prevent the development of erythroblastosis fetalis
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how does RhoGAM work?
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RhoGAM binds to the fetal RBCs and facilitates their clearance before the mother can generate an immune. It is given at 28 weeks and at delivery
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How does Cetuximab (Erbitux) work?
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It is a monoclonal antibody against the epidermal growth factor receptor inhibiting cell proliferation
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How does Rituximab (Rituxan) work?
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Chimeric monoclonal antibody against the CD20 antigen found on B cells
Used to treat B cell non-Hodgkin lymphoma (NHL) |
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How does Daclizumab (Zenepax) work?
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Humanized antibody against the IL-2 receptor which inhibits proliferation of antigen-activated T cells and thus the generation cytotoxic T cells
Use as an immunosuppressive agent after acute organ rejection in adults recovering from renal transplantation |
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How does Omalizumab (Xolair) work?
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Humanized anti-IgE antibody that binds to the constant region of IgE and blocks it from binding to FcRs and inducing degranulation
Relieves symptoms of asthma and allergic rhinitis |
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How does Ipilimumab (Yervoy) work?
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Human antibody against CTLA-4
Received FDA approval on March 25, 2011 for the treatment of late-stage melanoma; in trials for use in other cancers. |
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How do Immunotoxins work?
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Selective killing of tumor cells by linking a highly toxic agentto an anti-tumor antibody, such that the toxic agent will be delivered only to the tumor siteand not to normal tissues.
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What immunotoxic drug for treatment of acute myelogenous leukemia (AML) did we learn in class. How does it work
|
Gemtuzumab ozogamicin(Mylotarg)
Calicheamicin linked to an anti-CD33 antibody. Immunotoxin binds to cancerous CD33 cells and the complex is internalized. |
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What are the two Radiolabeled Antibodies for treatmetn of non-hodgkin lymphome?
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Ibritumomab (Zevalin)
Tositumomab (Bexxar) |
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What causes the tissue damage & sx of a hypersensitivity reaction?
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caused by the immune products that are released
from immune cells that recognize and react against the invading antigen |
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What are the four types of hypersensitivity reactions?
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Type I – Immediate hypersensitivity
Type II – Antibody mediated cytotoxicity Type III – Immune complex mediated cytotoxicity Type IV – Delayed-type hypersensitivity (I-III) Mediated by antibodies (IV) Mediated by T cells |
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Where is IL-4 released and what does it do?
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release from TH2 (CD4+) cells
-Induces naieve CD4+-> TH2 -Stimulates B cells to release IgE -Releases IFN-y to suppress macrophages |
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Describe the Sensitization Phase of a Type I Reaction...
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Antigen binds to b cell and activates->B cell presents to TH2 cell->TH2 cell releases IL4 & IL13-> signals for Bcells to release IgE which binds to FCeR receptor on Mast cells and Basophils
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Describe the Effector Phase of a Type I Reaction
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Bound IgE on mast cells cross links and causes:
1) Degranulation (premade particles) 2) Synthesis and secretion of prostaglandins and leukotrienes 3)Synthesis and secretion of cytokines |
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What mediators are being released with mast cell degranulation? What do they cause?
|
• Histamine
• Proteases • Heparin • TNFa -Vascular dilation, smooth muscle contration, & tissue damage |
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The specific results of histamine to H1 receptor causes what effects?
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Smooth muscle contraction
Ileum, bronchi and bronchioles, and uterus (But not of most blood vessels) Increased vascular permeability and vasodilation Increased mucus secretion |
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How do anti histamines work?
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They block the H1 receptors
First generation antihistamines enter the brain and are sedating Second generation antihistamines do not enter the brain well |
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Describe the Synthesis and secretion of prostaglandins and
leukotrienes with crosslinkinbg of IgE in to FceR receptor. |
Signaling from crosslinking induces Phospolipase A to release AA (Arachadonic acid) from the lipid membrane.
AA+ COX= cyclooxygenase pathway yeilding thromboxanes, prostacyclins and prostaglandins AA+ 5HPETE = lipooxegenase pathway to yeild leukotrienes |
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What is the effect of Prostaglandin D2 (PGD2)?
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Vasodilation
Bronchoconstriction Neutrophil and eosinophil chemotaxis |
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What is the effect of the Leukotrienes?
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1000x more potente than histamine!!!
Originally termed slow reacting substances of anaphylaxis (SRS-A) Prolonged smooth muscle contraction Increased vascular permeab |
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What are the Leukotrienes mentioned in class (how do you recognize them?)
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C4, D4, and E4 (LTC4, LTD4, LTE4)
|
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How do LT inhibitors work?
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LTD4-receptor antagonists
Oral administration (pill form) blocks airway hyperresponsiveness Montelukast (Singulair ® ), Zafirlukast (Accolate ® ), Pranlukast (Ultair ® ) |
|
How do mast cell stablizers work?
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They Inhibit mast cell activation
but Must be taken prophylactically because cannot reverse symptoms Administered using an inhaler to protect asthmatics Also used in nasal spray and eye drops to reduce symptoms of allergic rhinitis |
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What cytokines are signaled to be made upon histamine activation?
|
IL-1, IL-3, IL-4, IL-5, IL-6, TNFa, ECF (eosinophil chemotactic factor), NCF
(neutrophil chemotactic factor) TNF-a can also be prestored |
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What is the "late phase reaction?"
|
The response that occurs 2+ hours after onset of the mast cell signaling for Cytokines; lasts 1-2 days. Characterized by high levels of eosinophils (30%) and neurtophils (30%)
(as well as some Th2 cells, basophils and macrophages) |
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What about eosinphils and neutrophages causes tissue damage?
|
Eosinophils-enzymes release
neutrophils- ROS species |
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Distinguish early response from late response in type I hypersensitivities.
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Early: Vascular and smoothe muscle changes caused by histamines, prostaglandins and leukotrienes
Late: inflammation caused by cytokins signaling for leukocyte adhesion, migration and activation |
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How do corticosteroids work (biochemically)?
|
Inhibition of phospholipase A2
generation of arachidonic acid and metabolites. |
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In what ways do corticosteroids inhibit leukocytes? (5)
|
-Decrease cytokine production
-Decrease IL-1 production by macrophages -Decrease IL-2 production by T cells -Decrease chemotaxis of leukocytes -Decrease class II expression |
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Give examples of Localized anaphylaxis for type I reactions
|
Respiratory allergies: Allergic rhinitis (Hay fever), Bronchial asthma
Skin and mucosal allergies: Atopic dermatitis (Allergic eczema), Atopic urticaria (Hives) Gastrointestinal (GI) allergies, Food allergies |
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What are the four tests for Type I Hypersensitivies?
|
Skin testing (SPT, skin prick test)
Double-blind placebo-controlled food challenge (DBPCFC) Radioimmunosorbent test (RIST) (to look for IgE) Radioallergosorbent test (RAST) (IgE for aspecific antigen) |
|
What is a type I hypersensitivity reaction?
|
Called atopy. It is IgE mediated hypersensitvity
|
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What are teh typical manifestations of Type I hypersensitivities?
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Local or systemic anaphalyxix, hay fever asthma, hives food allergies, asthma, allergic rhinitis.
|
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What is a type II hypersensitivity?
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IgG or IgM mediated cytotoxic hypersensitiviy
|
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What is the mechanism for type II hypersens. reactions?
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Antibodies (IgG/IgM) are directed against cell surface antgens and mediate destruction via compliment of antibody-dependent cell-mediated immunity for distruction &/or phagocytosis via opsinosation
|
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What are the typical triggers/diseases associated with type II hs?
|
blood transfusion reactions
erythroblastosis fetalis Autoimmune or drug induced hemolytic anemia Hemolytic disease of the newborn Drug induced thrombocytopemia |
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What AI diseasea are classified as type II hs?
|
myasthenia gravis
graves disease hasimotos goodpasture |
|
How are Type II hypersensitivity tested for?
|
Coombs test
(detects antibodies on pts RBCs) |
|
What is a type III HS?
|
Immune complex mediated hypersensitivity
|
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What is the mechanism of activation for Type III HS?
|
Ag-Ab complexes deposited in various tissues induce compliment activation and ensuing inflammatour response mediated by massive NEUTROPHIL infiltration
|
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What are the typical manifestations/disease associated with type III HS?
|
localized arthus rxn
serum sickness necrotizing vasulitis glomerulnephretis Rheumatoid arthiris Lupus |
|
What is an Arthus reaction? What antibody?
|
(localized IgG that causes Local cutaneous vasculitis with necrosis)
|
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What causes serum sickness and what are the sx?
|
Antitoxins/antivenons & certain drugs
Rash (complex deposition in skin) Arthritis (complex deposition in synovial joints) Glomerulonephritis (complex deposition in kidney Fever |
|
What is a type IV HS reaction?
|
Cell-mediated HS
Takes 48-72 hrs to develop |
|
What is the mechanism of action for type IV reactions?
|
APC present to TH1 cells (TDTH/CD4+ cells) release cytokines (INF-y & TNF) that stimulate neutorphils, Cytotoxic T cells or/ and macrophages to mediate direct cellular damage
|
|
What are the common manifestations of type IV HS?
|
TB (and testing)
contact dermatitis graft rejection leprosy poision Ivy, oak, sumac |
|
Describe the role of T(DHT) cells in grauloma formation
|
T(DHT) = T helper 1 cells
When macrophages can't kill an organism, they secrete IL-12 to signal for TH1 cells to release more IFN-Y to enhnce macrophage activity. If macros still can't kill, after prolonged exposure, they turn into epitheloid cells and form granulomas. This is seen in TB & Leprocy |
|
How are Type IV Hypersensitivities detected/
|
Patch Testing
often metals, chemicals, topical drugs are haptens that compex with the skin and yeild a reaction in 24-48 hrs. (remember, posion ivy etc is also a hapten) |
|
How are type III HS tested for?
|
Use ELISA or Radioactive immunoassays to look for antibodies
|
|
What are some physical examination findings that allergic children exhibit?
|
Transvers nasal crease
Dennie Morgan lones Keratosis pilaris Xerosis |
|
What are the long term medications for asthma?
|
1) Inhaled
Corticosteroids, 2) Long-Acting β₂-Agonists, 3) Theophylline, 4) Omalizumab |
|
What are the short term medications for asthma?
|
1) Short-Acting β₂-Agonists,
2) Anticholinergic Agent, 3) Oral Corticosteroids |
|
Describe an Acute Asthmatic episode...
|
tachypnea, tachycardia, cough, wheezing, and a
prolonged expiratory phase. |
|
Hallmarks of Allergic rhinitis...
|
clear, thin
rhinorrhea; nasal congestion; paroxysms of sneezing; and pruritis of the eyes , nose, ears, and |
|
Atopic Dermaitis manifestations...
|
Hyperirratable skin... range from generalized xerosis (dry skin) to urticaria to the pruritic, erythematous papules. Can see hyperlinearity of the palms and soles, white dermatographism,
pityriasis alba, creases under the lower eyelids (Dennie-Morgan folds or Dennie lines), and keratosis pilaris |
|
What is puritis?
|
Itchiness
|
|
What is uticaria?
|
Hives: Swelling of the dermis
|
|
What is angeoedema?
|
Swelling extending deeper that the dermis
|
|
What can cause uticaria and angeoedima?
|
nflammatory mediators, including
histamine, leukotrienes, platelet-activating factor, prostaglandins, and cytokines from mast cells present in the skin |
|
What is anaphalyxis?
|
Anaphylaxis is a hypersensitivity type I, IgE-
mediated response |
|
What is an anaphalactoid reaction?
|
anaphylactoid
reactions result from mechanisms that are due to non-immunologic mechanisms. |
|
What medications are frequently implicated in serum sickness? What HS type is it?
|
Type III
penicillin, sulfonamides, minocycline, cefaclor, hydantoins, and thiazides. |
|
When does serum sickness occur?
|
7 to 21 days after the administration of drugs, foreign
proteins, or infection unless there was previous exposure in which case it can be as soon as 1-4 days |
|
What is an autograft?
|
Transplant from one individual to the same individual
|
|
What is an isograft?
|
Transplant between two genetically identical individuals
|
|
What is an allograft
|
Transplant between two genetically different individuals in the same species
-most common |
|
What is a xenograft?
|
Transplanted between individuals of different species
|
|
What are the two main types of transplants?
|
Hematopoietic Stem Cell (HSC)
Transplantation Solid Organ and Tissue Transplantatio |
|
What are the sources for Hematopoietic Stem Cell (HSC)
Transplantation? |
bone marrow, peripheral
blood, umbilical cord blood |
|
What are the indications for Hematopoietic Stem Cell (HSC)
Transplantation? |
Hematological malignancies
Primary hematological diseases (e.g. sickle-cell disease, thalassemias, aplastic anemia) Primary immunodeficiencies Rescue from marrow-ablating chemotherapy Autoimmune disorders (experimental) |
|
What are the sources for Solid Organ and Tissue
Transplantation? |
living and/or cadaveric
donors, autologous (skin), some xenographs |
|
What are the indications for Solid Organ and Tissue
Transplantation? |
Irreversible organ failure
Underlying condition with acceptable risk for recurrence Replacement of damaged tissue |
|
What are Foreign antigens on the surface of the transplanted cells/tissue?
|
Alloantigens
|
|
How can alloantigens be recognized by both T & B lymphocytes?
|
T cells recoginze the foreign MHC and B cells can recognize even small peptide fragments that are broken down
|
|
What is Histocompatibiliy?
|
The matching of Major MHC complexes
each person has 6. 1 set of 3 from mom 1 set of 3 from dad Siblings have a 25% chance of being histocompatible |
|
What is it called when Donor APCs can present donor antigens to
recipient T cells? |
Direct presentation
|
|
What is it called when Recipient APCs can present donor antigen
(peptides of donor MHC) to recipient T cells |
Indirect presentation
|
|
What are the four types of graft rejection?
|
Hyperacute
Acute Chronic GvHD |
|
What type of graft rejection occurs when Pre-existing antibodies
activate complement + ADCC |
Hyperacute
|
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What type of graft rejection occurs with B/T cell activation:
•T cells: CTL killing + Th1 cell-mediated inflammation •B cells: antibodies activate complement + ADCC |
acute
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What type of graft rejection occurs when Th1-mediated inflammation;
growth factors to increase proliferation of vascular smooth muscle |
Chronic
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What type of graft rejection occurs when donor immune
system attacking host |
Graft vs Host
|
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What is the time frame for a hyperacute vs acute graft rejection?
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HA: minutes-hours
Acute: 7-10 days, usually in 2-3 months |
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What is the time frame for a chronic graft rejection?
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Months to
years post- transplant |
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How can a hyperacute graft rejection be prevented?
|
Type blood, screen
for pre-existing antibodies |
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How can an acute graft rejection be prevented?
|
Blood type, antibody screen plus type and match MHCs
as best as possible Provide immuno thereapy during induction and for mantanience |
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How can a chronic graft rejection be prevented?
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Preventing acute
may slow development of chronic. No therapy to treat chronic once formed |
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What are the hallmarks for hyperacute, acute and chronic graft rejection?
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Hyper= thrombi
Acute= CTL killing of graft cells Chronic= loss of graft, fibrosis and occlusion |
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What can be done to prevent graft vs host?
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Partial donor T cell depletion
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What transplants are most common for Graft vs host?
|
bone marrow
liver, and intestinal transplants |
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What are the general immunosepressive therapies?
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Corticosteroids to minimize inflamation
Mitotic inhibitors to inhibit the biosynthesis of nucleic acid. |
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What do azathioprine,
mycophenolate mofetil, methotrexate do? |
inhibit biosynthesis of nuclei acids
|
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What are specific immunotheraputic agents?
|
Drungs that inhibit T-Cells by inhibitng the production of IL-2, IL-2 receptors and blocking IL-2 receptors
also Polyclonal anti-thymocyte antibodies Monoclonal antibodies |
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What is the finction of Muromonab-CD3 (OKT3 ® ) -
mouse (murine)? |
Specific for CD3; binds and
removes T cells |
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What are Basiliximab (Simulect ® ) and Daclizumab (Zenapax ® ) used for?
|
Specific for CD25 (=IL-
2R ); blocks effects of IL-2 |
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What is Alemtuzumab (Campath ® ) used for?
|
Specific for CD52; expressed
by mature lymphocytes (but not HSCs) [Mainly used in treatment of cancers] |