Assoc. Prof. Ma. Jennifer R.

Tiburcio,MSMT Chair, Department of Med Tech UST Faculty of Pharmacy

enhance Immune response suppress

Immunoenhancement/Immunopotentiation
1. Increasing the rate at w/c the response occurs
2. Elevating its magnitude 3. Increasing the duration of the response

Nonspecific potentiators

Adjuvants (Substances that enhance the immunogenicity of molecules without altering their chemical composition)

1. Increase the efficiency of the macrophage processing of antigen 2. Prolonging the exposure to an antigen 3. Amplifying the proliferation of IC lymphocyte by enhancing lymphokine activity

Freunds adjuvant A classic adjuvant used in experimental animals

Emulsion of paraffin or mineral oil (usually Bayol F) Lanolin or Arlacel A is used as emulsifying agent 1. Incomplete Freunds adjuvant (IFA) Water in oil w/ antigen Increases humoral Ab response about 100-fold Greatly reduced the required amount of antigen Prolongs the phase of active Ig synthesis by months

2. Complete Freunds adjuvant (CFA) An IFA plus mycobacteria /cell wall components Markedly enhance both Ab & CMI

Ex. Elevated IgE heat killed B. pertussis BCG causes macrophage activation & enhances NK cell activity

Class
Depot Water-in-oil

Mechanism of action
Delays release of Ag Prolongs lymphoid tissue exposure to antigen Same as above

Compound
Freunds adjuvant

Precipitants

Calcium alginate

Absorbents

Same as above

Alum, Aluminum hydroxide, Bentonite, Polyacrylamide, Methylated BSA

Foreign bodies, Mycobacteria (wax D) (muramyl dipeptide) LPS, PHA, Con A

Irritants

Induce inflammatory response w/c increases Ag exposure to macrophage, T and B cells Increase clonal expansion of T and B cells during an immune response

Mitogens

Class
Lymphokines

Mechanism of Action
Enhance proliferation and/or differentiation of T and B cells And macrophages Stimulate Ag processing and T helper cell activity

Compounds
IL-1, 2 and 3 MAF IFNs Polyadenylateuridylate

Synthetic polynucleotides

Specific potentiators Helper factors Secreted by T cells following interaction of Ag specific receptor w/ its homologous epitope Transfer factors An Ag specific dialyzable extract of immune T cells that is capable of transferring CMI Immunogenic RNA Extracted from the lymphoid tissues following Ag injection Appears to be an Ag receptor complexed w/ cellular RNA w/c greatly increases immunogenicity of a molecule

Immunosuppression
reduction in a large portion of immune responsiveness A. Physical means a. Surgical manipulation 1. Bursa of Fabricius & thymus In neonatal period immunologic competence not develop in the corresponding cell line After immunologic development, IC affected very little 2. Removal of peripheral lymphoid tissues actual tissues removed Lymph nodes & lymphoid cells in connective tissue little effect (too diffuse to be removed completely by surgical procedures) Spleen does not grossly impair Ab production b. Ionizing radiation damages the lymphoid organs & bone marrow

B. Chemical & Biologic means a. Lympholytic agents Can block the expression of the IR (cell lysis) but more effective in disrupting the initiation of the IR Types: ionizing radiation & Abs (ALS or ATS)
b. Lymphocytotoxic agents 1. Antimetabolites (purine & pyrimidine analogues & folic acid antagonists methotrexate) interfere w/ DNA synthesis 2. Alkylating agents (cyclophosphamide) interfere w/ cell division by altering guanine so DNA base pairing errors occur. Can crosslink the two DNA strands thus blocking replication

3. Antibiotics (cyclosporine) suppress graft rejection reactions. Exerts an inhibitory effect on IL-2 action thus blocking the expansion of the helper/inducer T cell population 4. Cortisone immunosuppressive & inflammatory. Lympholytic in animals but not in humans alter cell migration & cause lymphopenia & monocytopenia shortly after injection
c. Antibodies 1. Abs that react w/ lymphoid cells such as ALG or ALS particularly antithymocyte induces immune deficiency in transplant patients by suppression of CMI 2. Preformed Ab followed by injection of sp. antigen IR in the host will be blocked. The injected Ab binds up the Ag & prevents its access to the lymphoid tissue

3. If Abs that are specific for the Ag combining site (idiotype)specifically abort that particular response
C. Immunosuppression associated with diseases Congenital immunodeficiencies Brutons agammaglobulinemia failure of the development of the B Cell humoral immunity Ab production suffer from repeated bacterial infection

DiGeorge syndrome failure of the development of third & fourth pharyngeal pouches during embryogenesis recurrent viral diseases
Malignancies Lymphomas may disrupt normal lymphocyte functions directly or may crowd out normal lymphocytes from bone marrow & peripheral lymphoid tissues

Infections Measles & certain viral diseases cause a transient depression in CMIR HIV infection causes a profound IS w/c renders the host susceptible to fatal infection caused by opportunistic pathogens
Malnutrition CMI most sensitive to nutritional deprivation, HI, C and phagocytic functions are also affected

Tolerance
absence of specific immune responses in a fully competent person

A. Naturally acquired (Autotolerance, neonatal or natural tolerance)

Escape from this autoimmune diseases During fetal development, the ability to recognize ones own tissues is acquired. Theories:

Clonal deletion theory

It is probable that clone of cells capable of responding to own tissues arise throughout life. These clones (forbidden clones) are immediately deleted by encountering an overwhelming amount of self antigens or by the activity of antigen-sp T suppressor cells

B. Immune tolerance
1. Gradation of tolerance Partial unable to respond to some of the epitopes on the Ag but can respond to others Immune deviation/split tolerance one of the immune responses can be interfered with, but not another Ex. IgM response may be blocked but not IgG

2. Pathways to B cell tolerance As an immature B cell matures into Ab forming cell it becomes resistant to tolerization. At the same time the form of Ag presentation w/c will produce tolerance varies. The type of tolerance induced is dependent on the maturity of the cell, the Ag and the manner in which the antigen is presented to the cell A. Clonal abortion low concentrations of multivalent Ag may cause the immature clone to abort

B. Clonal exhaustion repeated antigenic challenge with T-independent Ag may remove all mature B cell clones C. Functional deletion absence of T helper cell with the presence of T-dependent Agt or an excess of T-independent Ag prevents mature B cell from functioning normally D. Antibody forming cell (AFC) blockade high concentrations of T-dependent Ag are blockading the receptors of the cell thereby interfering Ab secretion

3. Pathways to T cell Tolerance T cells do not show marked differences in their tolerizabiltiy. The Ag required to produce tolerance and in presentation is particular to each individual T cell subset. A. Clonal abortion immature T cell clones may be aborted in a similar manner to B cells B. Functional deletion the subsets of mature T cells may be individually deleted leading to the loss of only one of the functions of the T cell group

C. T suppression suppressor T cells actively suppress the actions of other T cell subsets or B cells

T and B cells differ in their susceptibility to in vivo tolerization with respectto the course of tolerance and also the levels of antigen required to tolerize the cells