ชุมพล สกลวสันต์ พบ. เกียรตินิยมอันดับ 1 วว. อายุ

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.