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71 Cards in this Set
- Front
- Back
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what recognizes class I MHC peptide complexes
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CD8 T cells; endogenously processed peptides
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what recognizes class II MHC peptide complexes
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CD4 T cells
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T cells are regulated via neg feedback loop involving what molecule
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T-lymphocyte-associated antigen 4 (CTLA-4); has higher affinity binding to CD80 and 86, displacing CD28 and results in T-cell supression of of activation and proliferation
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recombinant humanized antibody that binds CTLA-4
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ipilimumab; activates T cells
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Th1 subset produces
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IFN-gamma, IL-2, and IL-12 and induces cell mediated immunity by activation of macrophages, cytotoxic T cells, and NK cells
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Th2 subset produces
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IL-4, 5, 6, and 10; sometimes IL-13; induce B-cell proliferation and differentiation into antibody-secreting plasma cells
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IL-10
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inhibits cytokine production by Th1 cells via down-regulation of MHC expression by APCs
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IFN-gamma
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inhibits proliferation of Th2 cells
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extracellular bacteria typically cause elaboration of what T helper subset
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Th2-causes production of neutralizing or opsonic antibodies
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intracellular organisms typically cause elaboration of what T helper subset
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Th1-lead to activation of effector cells like macrophages
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how do CD8 T cells induce target cell death
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lytic granule enzymes, perforin, and Fas-Fas ligand apoptosis pathway
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4 types of hypersensitiviry
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types I-III are antibody mediated and type IV is cell mediated
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two phases of hypersensitivity
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sensitization and effector phases
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Type I hypersensitivity
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IgE mediated; symptoms occur within minutes of encounter; due to cross-linking of membrane-bound IgE on blood basophils or tissue mast cells by antigen
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Type II hypersensitivity
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formation of antigen-antibody complexes btwn forgein antigen and IgM or IgG; eg blood transfusion, drug-induced
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Type III hypersensitivity
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elevated levels of antigen-antibody complexes that deposit on BM in tissues and vessels
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Type IV hypersentivity
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delayed-type; antigen-specific DTH Th1 cells induce local inflammatory response that causes tissue damage by influx of antigen-nonspecific inflammatory cells; eg tuberculin and contact hypersensitivities, poison ivy
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rheumatoid arthritis cause
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IgM antibodies produced that react ith Fc portion of IgG and may form immune complexes that activate complement cascade causing chronic inflammation of joints and kidneys
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Multiple Sclerosis and type I diabetes cause
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cell-mediated autoimmune attack destroys myelin and insulin respectively
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X-linked agammaglobulinemia
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males; failure of immature B clymphocytes to mature into antibody-producing plasma cells; susceptable to recurrent bacterial infections
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administration of any glucocorticoid causes
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reduced size and lymphoid content of lymph nodes and spleen; although no toxic effect on proliferating myeloid or erythroid stem cells in marrow
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cyclosporine
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used in organ transplantation; acts in early sate of antigen receptor-induced differentiation of T cells and blocks activation; binds cyclophilin and inhibits calcineurin
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toxicities of cyclosporine
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nephrotoxicity, hypertension, hyperglycemia, luver dysfunction, hyperkalemia, altered mental status, seizures, hirsutism; very little bone marrow toxicity
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Tacrolimus
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immunosuppressant macrolide antibiotic; MOA similar to cyclosporine, but not chemically related; binds immunophilin FK-binding protein and inhibits calcineurin
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calcineurin
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necessary for activation of T-cell specific transcription factor NF-AT
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cyclosporine and tacrolimus metabolism
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primarily P450 enzymes in liver
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proliferation signal inhibitors (PSIs)
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bind circulating immunophilin FK 506-binding protein 13, resulting in active complex that blocks molecular targer of rapamycin (mTOR)
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mTOR
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key component of complex intracellular signaling pathway involved in cellular processes like cell growth and proliferation, angiogenesis, and metabolism
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examples of PSIs
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sirolimus and everolimus
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toxicities of PSIs
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profound myelosuppression (thrombocytopenia), hepatotoxicity, diarrhea, hypertriglyceridemia, pneumonitis, and headache; renal toxicity less common than in calcineurin inhibitors, but increased hemolytic-uremic syndrome
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mycophenolate mofetil (MMF) action
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inhibits T and B lymphocyte responses, including mitogen and mixed lymphocyte responses; may be due to inhibition of de novo synthesis of purines
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mycophenolate mofetil (MMF) toxicity
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GI disturbancesm, headache, hypertension, and reversible myelosuppression (primarily neutropenia)
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thalidomide MOA
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inhibits TNF-a, reduces phagocytosis by neutrophils, increases IL-10, alters adhesion molecule expression, and enhances cell-mediated immunity via interaction with T cells; sedative drug removed from market due to teratogenic effects-in clinical trials for several illnesses
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thalidomide current use
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myeloma
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toxicity of thalidomide
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teratogenesis; peripheral neuropathy, constipation, rash, fatigue, hypothyroidism, and increased DVT
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Immunomodulatory derivatives of thalidomide (IMiDs)
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lenalidomide, CC-4047 (actimid)
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selective cytokine inhibitory drugs (SelCIDs)
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thalidomide analogs; phosphodiesterase type 4 inhibitors with potent TNF-a activity, but no T-cell costimulatory activity
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Azathioprine and mercaptopurine
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cytotoxic agent; antimetabolite; interferes with purine nucleic acid metabolism-destroy stimulated lymphoid cells
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metabolism of azathioprine
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xanthine oxidase splits much of active material to 6-thiouric acid prior to excretion in urine
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toxicity of Azathioprine and mercaptopurine
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bone marrow suppression; skin rashes, fever, nausea, vomiting, diarrhea; hepatic dysfxn
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cyclophosphamide (cytotoxic agent)
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alkylating agent; destroys proliferating lymphoid cells and some resting cells
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leflunomide
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prodrug of an inhibitor of pyrimidine synthesis; approved only for RA; appears to have antiviral activity
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toxicity of leflunomide
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elevation of liver enzymes with some risk of liver damage, renal impairment, teratogenic effects; low frequency of cardiovascular events (angina, tachycardia)
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hydroxychloroquine
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antimalarial agent with immunosuppressive properties; supresses antigen processing and loading of peptides onto MHC II molecules by increasing pH of lysosomal and endosomal compartments, decreasing T-cell activation
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pentostatin
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adenosine deaminase inhibitor primarily used as an antineoplastic agents for lymphoid malignancies
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naming convention of monoclonal antibodies
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-umab' or '-zumab' for humanized and '-imab' or '-ximab' for chimeric products
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ALG and ATG
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antilymphocyte globulin and antithymocyte globulin
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muromonab-CD3 MOA
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blocks killing by cytotoxic T cells and several other T cell fxns
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possible MOA of immune globulin intravenous (IGIV)
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reduction of T helper cells, increase suppressor T cells, decreased spontaneous immunoglobulin production, Fc receptor blockade, increased antibody catabolism, and idiotypic-anti-idiotypic interactions with 'pathological' antibodies
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Rho(d) contains
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concentrated solution of human IgG containing higher titer of antibodies against Rho(D) antigen of the red cell
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alemtuzumab
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IgG with kappa chain that binds CD52 found on normal and malignant B and T lymphocytes, NK cells, monocytes, macrophages, and small population of granulocytes; B-cell chronic lymphcytic leukemia
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bevacizumab
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IgG; binds vascular endothelial GF and inhibits VEGF from binding to its receptor, especially on endothelial cells; antiangiogenic; metastatic colorectal treatment
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ranibizumab
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VEGF receptor antagonist antibody; use in neovascular macular degeneration
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cetuximab
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targets EGFR-inhibits tumor cell growth (decrease kinase activity, matric metalloproteinase activity, GF production, increased apoptosis); use with metastatic colorectal cancer with overexpression of EGFR
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gemtuzumab
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kappa light chain specific for CD33 (sialoadhesion protein on leukemic blast cells in AML)
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trastuzumab
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recombinant DNA0derived; bind extracellular domain of HER-2/neu
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4 types of rejection in solid organ transplant
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hyperacute, accelerated, acute, and chronic
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hyperacute
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preformed antibodies within hours; can't be stopped by immunosuppressive drugs
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accelerated rejection
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antibody and T cell mediated; can't be stopped by immunosuppressive drugs
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acute rejection
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days to months; mainly cellylar immunity; reversal possible
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chronic rejection
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months/years; thickening, fibrosis of vasculature; cellular and humoral immunity
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graft-vs host disease
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usually within first 100 days; skin rash, severe diarrhea, or hepatotoxicity; usually resolces 102 yrs after transplant (unlike solid organs)
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common toxicity of IFN-a, IFN-B, IL-2, and TNF-a
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induce fever, flu-like symptoms, anorexia, fatigue, and malaise
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Type I interfurons
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IFN-a and B; acid-stable proteins that act on same receptor on target cells; usually induced by virus infections
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type II interferons
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IFN-gamma; acid-labile and acts on separate receptor on target cells
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what usually produces IFN-a
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leukocytes
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what usually produces IFN-B
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fibroblasts and epithelial cells; induce class I MHC expression
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what usually produces IFN-gamma
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product of activated T cells; induced class II MHC along with class I
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drugs and type II hypersensitivity
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drugs often modify host proteins eliciting antibody responses; IgG and IgM in which antibody becomes fixed to a host cell, which is then subject to complement-dependent lysis or antibody-dependent cellular cytotoxicity
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type III hypersensitivity and drugs
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serum sickness via immune complexes containing IgG
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prednisone
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blocks proliferation of IgE-producing clones and inhibits IL-4 production by T helper cells in IgE response
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