IMMUNOTHERAPY ชุมพล สกลวสันต์ พบ. เกียรตินิยมอันดับ 1 วว. อายุรศาสตร์ Immunotherapy Treatment of disease by inducing, enhancing, or suppressing an immune response immunostimulation or immunopotentiation active immunization (vaccination) passive and adoptive immunization immunosuppression : autoimmunity, allergy, graft rejection Passive and Adoptive Immunization Passive Immunization ให้ antiserum หรื อ immune globulin เกิดภูมิคุม้ กันต่อโรคทันที ข้อบ่งชี้ : B-cell immunodeficiency disease ไม่มี active immunization หรื อต้องการภูมิคุม้ กันต่อ โรคทันที เช่น ให้ร่วมกับวัคซีน (rabies, tetanus) ควรให้ live virus vaccine หลัง immune globulin 6-12 สัปดาห์ รักษาการได้รับพิษหรื อน้ าพิษจากสัตว์ Passive Immunization ข้อบ่งชี้ อื่นๆ ป้ องกัน Rh immunization idiopathic thrombocytopenic purpura short half-life ผลข้างเคียง : ปวด, บวม, serum sickness, anaphylaxis Passive Immunization Human immune globulin prepared from pooled human plasma contains >95% IgG with small amounts of IgA and IgM given by IM injection used for prophylaxis in hepatitis A, measles, and rubella exposure during the 1st trimester of pregnancy Passive Immunization Human immune globulin IV immune globulin (IVIG) provide larger and repeated doses of human immune globulin used to treat or prevent severe bacterial and viral infections, autoimmune disorders, and immunodeficiency disorders hyperimmune globulin high titer of specific Ab, e.g., hepatitis B immune globulin (HBIG), rabies IG, tetanus IG, varicella-zoster IG Passive Immunization Heterologous antiserum and antitoxin hyperimmunized horse ตัวอย่าง : diphtheria antitoxin, tetanus antitoxin, rabies immunoglobulin, snake antivenin เกิด anaphylaxis, serum sickness ได้ Prophylaxis of Rh Immunization Serum sickness Injection of large doses of protein antigen into the blood e.g. horse antiserum Deposition of immune complexes in blood vessel walls, especially in the kidneys and joints Localized swelling at injection site about 8-12 days after injection A few days later : fever, rash, arthralgia, lymphadenopathy, splenomegaly Adoptive cellular therapy Immunopotentiator Cytokine Non-specific immunopotentiator Cytokine : Interferon (IFN) IFN-a (leukocyte interferon) produced by virus infected leukocytes IFN-b (fibroblast interferon) produced by virus infected fibroblasts or epithelial cells IFN-g (immune interferon) produced by certain activated T cells & NK cells Indications for Interferon IFN-a Hepatitis B & C, hairy cell leukemia, chronic myeloid leukemia, multiple myeloma, low grade lymphomas, Kaposi’s sarcoma, melanoma IFN-b Multiple sclerosis IFN-g Chronic granulomatous disease, chronic myeloid leukemia Non-specific Immunopotentiator Bacillus Calmette-Guerin (BCG) : activate macrophage, lymphocyte and NK cell – melanoma, bladder cancer Levamisole :- กระตุน ้ phagocytosis และ CMI, เพิม่ response และ proliferation ของ lymphocyte combined with fluorouracil for treatment of Dukes C adenocarcinoma of the colon (i.e., with regional lymph node involvement) Immunosuppression Extrinsic regulation of unwanted immune responses in autoimmune disease, transplant rejection, and allergy immunosuppressive drugs corticosteroids cytotoxic drugs, eg. azathioprine, cyclophosphamide fungal and bacterial derivatives, eg. cyclosporin A, FK506 (tacrolimus), rapamycin (sirolimus) passive immunotherapy Corticosteroids ทาลายเซลล์ lymphocyte ของผูป้ ่ วย ALL (acute lymphoblastic leukemia) ได้ดี ออกฤทธิ์ ปานกลางต่อ CLL (chronic lymphocytic leukemia) และ NHL (non-Hodgkin’s lymphoma) ไม่มีผลต่อ lymphocyte ปกติของคน Cytotoxic drugs purine - pyrimidine analog Azathioprine inhibit inosinic acid (purine precursor) synthesis มีผลต่อ T cell มากกว่า B cell transplantation rejection, chronic GVH reaction, autoimmune disease Cytotoxic drugs alkylating agent : - cyclophosphamide, chlorambucil Cyclophosphamide มีผลต่อ B cell มากกว่า T cell cross-link DNA strand Cyclophosphamide Cyclosporin A natural metabolite of fungus reduce the expression of several cytokine genes in T lymphocytes, e.g., IL-2, IL-3, IL-4, TNF-a reduce proliferation of T lymphocytes following decreased IL2 production ยับยั้ง allograft rejection ป้ องกัน GVH reaction Passive Immunotherapy Cytotoxic drugs kill all proliferating cells Cyclosporin A, tacrolimus, and rapamycin are more selective, but still inhibit most adaptive immune responses Antibodies against cell-surface molecules have been used to remove specific lymphocyte subsets or to inhibit cell function anti-lymphocyte globulin : used to treat acute graft rejection monoclonal anti-lymphocyte antibodies Monoclonal Anti-lymphocyte Antibodies suppress immune response by one of two mechanisms depleting antibodies : trigger the destruction of lymphocytes in vivo nondepleting antibodies : act by blocking the function of target protein, e.g., adhesion molecules, CD20, CD4, cytokines and cytokine receptors, etc.
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