Professional Documents
Culture Documents
Immunopotent Part 1
Immunopotent Part 1
Immunopotentiation can be defined as the process which directly augments one or more specific immune functions or indirectly enhance it through modulating one or more of the complex regulatory networks that control the immune system. The process is generally manifested by an increase in the velocity and intensity of the immune response to different antigens, bacteria, viruses and tumor cells in particular.
Immunopotentiation
Prof. Dr. Mohammed-Samy Afifi
Head Immunology and Allergy Department Medical Research Institute, Alexandria University
Enhancement of the immune responses during immunization through the use of immunological adjuvants. Immunotherapy, malignant cells. directed at pathogenic microorganisms,
Prophylactic vaccination against infectious diseases remains the single most clear cut success of immunopotentiation in practical application of immunological principals to improvement of human and animal health
surprisingly, most of the highly successful vaccines currently available were developed before 1970.
STRATEGIES FOR THE POTENTIATION OF THE IMMUNE RESPONSE TO NEW VACCINES 1. Use of improved adjuvants suitable for clinical use.
2. Use of delivery systems which allow for sustained or controlled release of antigens and which induce prolonged immunity following a single dose. The delivery system has been modulated to potentiate the immune response either by delivering the antigen over a prolonged period of time or in a predetermined sequence or by incorporating substances with immunoadjuvant properties e.g..., lecithin and biodegradable polymers.
a. Microencapsulation
Involves the coating of the vaccine in a protective wall material that usually polymeric in nature e.g. poly DL-lactide-coglycolide (DL-PLG)
Advantages:
Substantial potentiation of the immune response Ability to construct formulations that release multiple discrete pulses of vaccine Effectively deliver vaccines to mucosal immune inductive tissues.
b. Liposomes:
Act as an agents for the presentation of antigen. Stimulate production of IL-2.
Vectors are organisms into whose genome has been introduced a foreign gene that codes for an antigen of the vaccine of interest. e.g.,. Vaccinia, Fowlpox, Adeno-and picornaviruses.
TUMOR VACCINES
The ideal approach to immunologic therapy for cancer would be surgical resection of the primary lesion and immunization of patient with their own tumor cells. The concept of memory is critical for this approach because it requires the development of antigen specific recognition by cells of the immune system.
Cytokines:
Rational: T cells from tumor bearing patients were observed to exhibit abnormalities in signal transduction that render them unresponsive to appropriate activation signals. Cytokines were observed to be capable of bypassing such defect and to enhance the antitumor vaccine effect. Therefore, it is used in conjunction with either viral or oncolysatebased vaccine.
CALCIUM PHOSPHATE PRECIPETATE ELECTROPERFORATION LIPOSOMES DIERECT MICROINJECTION INTEGRATION OF GENOME INTO VACCINIA VIRUS BIOLISTICS.
Routes of administration:
Systemic:
R/ advanced renal cell carcinoma, malignant lymphoma and hairy cell leukemia.
Local:
b. Peritumoral or intratumoral.
Gene Transfection
Hetrologous antibodies:
Immune serum globulin(ISG)are available for HBV, Vaccinia, Varicella, Tetanus and Rabies.
Antibody or Immunotoxin
Rituximab (Rituxan) Tositumomab(Bexxar) Ibritumomab tiuxetan (Zevalin) CAMPATH 1H HulD10 Apratuzumab (hLL2) LMB-2 (TAC) BL22 HuM291 HeFi-1 CTLA4-Ig
Target
CD20 CD20 CD20 CD25 HLA-DR variant CD22 CD25 receptor CD22 CD3 CD30 B7/CD28
Several clinical trials have shown that rituximto be an effective and relatively nontoxic therapy for patients with relapsed low-grade or follicular lymphomas. However, the data on its use in aggressive non-Hodgkins lymphoma histologic types are limited and do not allow definitive conclusions. As a single agent, rituximab appears to have significant activity in phase II and III trials in low- grade or follicular lymphoma. Beyond lymphoma, rituximab is being used in treatment of immunosuppression, multiple myeloma, immunethrombocytopeniaa, and HIV-NHL.
HuID10 is a humanized antibody that binds to a variant of an HLA-DR antigen expressed in B-cell malignancies. Benign toxicity profile, induce apoptosis and depletes B cells. Used in a variety of hematologic malignancies with variable response rates.
ADOPTIVE SPECIFIC IMMUNOPOTENTIATION: Refer to the transfer of immunologically active cells that can mediate immune enhancement. This strategy is mainly used in tumor immunotherapy. Tumor infiltrating lymphocytes (TIL):
Could be isolated from all human tumors. However, 1/3 exhibit specific cytolytic activity. Rosenbergs group at NCI observed that TILs + IL-2 are more effective than LAK.
NONSPECIFIC IMMUNOPOTENTIATION
ACTIVE NON SPECIFIC IMMUNOPOTENTIATION: IMMUNOADJUVANTS; CYTOKINES; SYNTHETIC CHEMICALS Purified (synthetic) antigen determinants relevant for induction of protective immunity against virulent organisms display only poor immunogenecity. Existence of a state of anergy in tumor bearing patients (defects in signal transduction).
Immunoadjuvants
Refer to compounds which act in nonspecific manner to augment specific immunity to antigen.
Mechanisms of action: activation of macrophages, improvement of antigen presentation , formation of depot ( delay Ag release, modyfing phagocytosis of particulate Ag), and selective activation of T cell subpopulation. Non-specific stimulation of host resistance against infections and cancer. Potentiation of vaccine immunogenecity. They serve to reduce the antigen dose required, the number of injections, and achieve an enhanced immune response.
Anionic polymers:
polynucleotid, and dextran sulphate
Miscellaneous:
Immunostimulating complexes (ISCOMs), bacterial products or derivatives, Schif-base forming compounds, vector adjuvant, and cytokines
SYNTHETIC CHEMICALS
Levamisole
Antihelminthic drug with immunomodulatory and anticancer effect.
Isoprinosine:
Act through a receptor for an inosin like compound on pre-T cells. Licensed for use in HSV, rhinovirus, early HIV, Measles- related Panencephalitis
Schiff-base
forming drugs
Selection of immune repertoires, a complex set of effects that may be observed in individuals receiving IVIG far beyond the half- life of the infused Ig.