Term
|
Definition
• Immunomodulators or biological response
modifiers
– Recombinant interferon and cytokines
• Enhance antitumor immunity
– Monoclonal antibodies
• Can be immunostimulants or
immunodepressants |
|
|
Term
|
Definition
-Glucocorticoids:
-Prednisone, dexamethasone, hydrocortisone
-Immunophilin ligands:
-Cyclosoprine, Tacrolimus (FK506), Sicrolimus (rapamycin)
-Cytotoxic agents:
-Cyclophosphamide, cisplatin, etc. |
|
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Term
|
Definition
• Cyclosoprine, Tacrolimus (FK506),
Sicrolimus (rapamycin)
– They are microbial derivatives
– They may not share a common mechanism(s) |
|
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Term
|
Definition
– Cyclosporin A and Tacrilimus
• inhibit T-cell receptor activation and induction of
cytokines
– Cyclosporin A
• inhibit IgE-stimulated mast cell degranulation and
stimulate TGF-β expression
– Sirolimus
• inhibit lymphocyte response to cytokines
• sensitize cancer cells to chemotherapeutic reagent |
|
|
Term
Cyclosporin A
• Mechanisms |
|
Definition
• inhibit T-cell receptor activation and induction of
cytokines
• inhibit IgE-stimulated mast cell degranulation and
stimulate TGF-β expression
• READ page 676 on effect on CD4+ Cells
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|
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Term
Cyclosporin A
• Clinical uses |
|
Definition
• Anti-rejection in organ transplants
• Autoimmune diseases: RA, bullous pemphigoid,
pemphigus, etc
• Topical agent for oral lichen plannus |
|
|
Term
• Cyclosporin A, Trcrolimus & Sirolimus
Adverse effects |
|
Definition
• Renal toxicity (dose related); hypertension
• CNS (headache, seizures); hirsutism,
• Gingival overgrowth |
|
|
Term
|
Definition
• Cytokines
– Interferon Alfa-2a; Interferon Alfa-2b
– Interleukin-2 (Aidesleukin)
– Colony-stimuating factors
• Levamisole (Ergamisol)
• BCG Vaccine
• Imidazoquinolinamines
– Imiquimod |
|
|
Term
|
Definition
• Cytokines secreted by virally infected
________ & macrophages
• Signals non-infected cells to synthesize and/
or secrete antiviral proteins
• Slow infection and enhance activity of
leukocytes
• Have antiviral, anticancer, and antiinflammatory
properties |
|
|
Term
|
Definition
• Have antiviral, anticancer, and antiinflammatory
properties.
• They modulate immune functions
– Increasing phagocytosis
– Enhance cytotoxic activity of T cells |
|
|
Term
|
Definition
• Several formulations
– IFN alfa-2a; pegIFN alfa-2a ; IFN alfa-2b;
pegIFN alfa-2b; IFN alfa-n3; IFN alfa-n1
– peg is polyethylene glycol
• Increases half-life, allows q24h dosing
|
|
|
Term
|
Definition
• Clinical uses
– Hairy cell leukemia, AIDs-related Kaposi’s
sarcoma, chronic myelogenous leukemia,
chronic hepatitis B & C |
|
|
Term
• Beta1a-IFN & Beta-1bIFN
– Clinical uses |
|
Definition
|
|
Term
IFN gamma-1b
– Clinical uses |
|
Definition
• Chronic granulomatous disease; severe osteopetrosis
(a rare congenital disorder) |
|
|
Term
|
Definition
• Cytokines synthesized by lymphocytes,
monocytes and macrophages
• Several types (> 20 types)
– IL-1 …… IL21 etc
• Wide spread effects on immune functions
– Stimulation of T cell activity against tumor cells
– Increase B cell & plasma cell production
– Promotes inflammation |
|
|
Term
• IL-1 Receptors (IL-1R)
– |
|
Definition
Two subtypes: IL-1RI & IL-1RII
– Exist as transmembrane receptor or a soluble form.
|
|
|
Term
|
Definition
– preferentially binding with IL-1α
– T cells, endothelial cells, keratinocytes, hepatocytes, fibroblasts
– More sensitive to IL-1Ra (than IL-1RII)
|
|
|
Term
|
Definition
– preferentially binding with IL-1β
– is expressed by neutrophils, monocytes, B cells and bone marrow
cells.
– Has a short cytoplasmic domain .. “decoy receptor” |
|
|
Term
|
Definition
– a protein with structural homology to IL-1α and IL-1β.
– Secreted by monocytes
– Competes with IL-1α and IL-1β for the IL-1 receptor.
– Blocks the IL-1 receptor events, a means of blocking excessive
IL-1 inflammatory events
» Shock, arthritis, osteoporosis, colitis, leukemia, diabetes,
wasting, atherosclerosis |
|
|
Term
| – Interleukin-1RI (IL-1RI)- (Anakinra) [Kineret®] |
|
Definition
• Category: Interleukin-1 receptor antagonist
• Recombinant form of IL-1R1
• Tx of rheumatoid arthritis not responding to DMARDs.
– Subcu injections, daily
• ADRx
– Cutaneous reactions; lichenoid reactions’ neutropenia
• Drug InterX
– No significant interaction reported |
|
|
Term
| – Interleukin-2 (Aidesleukin; Proleukin) |
|
Definition
• Aka T cell growth factor
• Promotes proliferations of T lymphocytes and
activated B lymphocytes
• Metastatic renal carcinoma
|
|
|
Term
– Interleukin-11 (Oprelvekin, Neumega)
|
|
Definition
• growth factor with multiple hematopoietic
(hemopoiesis) effects
• Stimulates platelet production in immunosuppressed
patients |
|
|
Term
|
Definition
• Granulocyte colony stimulating factors
– G-CSF (filgrastin, Neupogen)
• Granulocyte-macrophage colony stimulating
factors
– GM-CSF-leukine (Leucomax) |
|
|
Term
|
Definition
• An antihelmintic agent
• Acts on multiple cell types, restoring
fucntions
– Neutrophils, macrophages, T cells
– Thymomimetic agent,
• stimulates cell-mediated immunity
|
|
|
Term
Levamisole (Ergamisole)
• Clinical uses |
|
Definition
– Cancers;
– Autoimmune diseases: Rheumatoid arthritis;
Crohn’s Diseases
– Dental: Aphthous tomatitis |
|
|
Term
| BCG Vaccine (Tice, TheraCys) |
|
Definition
• Is an attenuated strain of Mycobacterium bovis
• Once in the bladder,
– the organisms are taken up by macrophages,
– Initiate an immunologic reaction as in tuberculosis.
– BCG vaccine also targets bladder cancer cells,
• This induces a cytokine and direct cell-to-cell
cytotoxicity response, which targets these cells for
destruction. |
|
|
Term
|
Definition
– Imiquimod (Zyclara , Aldara): Topical
– Resiquimod : Topical & Oral
|
|
|
Term
Imidazoquinolinamines
Clinical Uses:
|
|
Definition
Basal Cell carcinoma, Actinic Keratoses, anogenital
and non-genital warts and other skin lesions |
|
|
Term
| Imiquimod (Zyclara , Aldara) |
|
Definition
• Nucleoside analog
• First developed as an antiviral agent …. but
found to have no direct antiviral properties
• Have antiviral properties via an indirect
mechanism |
|
|
Term
Imiquimod (Zyclara , Aldara)
• Mechanism: stimulating the Innate immunity |
|
Definition
• Mechanism: stimulating the Innate immunity
– Macrophages, neutrophils; basophils, mast cells,
eosinophils and NK cells
• Release cytokines such as TNF-α; IL (1,6,10, 12, 15,18); IFN-α and chemokines
– Imiquimod binds to cell-surface Toll-like receptors (TLR) leading the the activation of NFkB signaling, and subsequent gene expression of proinflammatory cytokines {IL (1, 6 and 8); TNF-α; IFN-α ; etc] |
|
|
Term
Imiquimod (Zyclara , Aldara)
• Mechanism:stimulating the Adaptive immunity (B and T lymphocyte, APC) |
|
Definition
• Mechanism:stimulating the Adaptive immunity (B and T lymphocyte, APC)
– No direct evidence showing imiquimod directly
stimulated lymphocyte proliferation or cytokines
release
– Some evidence that imiquimod may activate
Th1(activate cellular responses to pathogens –
macrophages, cytotoxic T cells) and Th2 cells
(activate humoral response by stimulating B
cells) |
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