Assoc. Prof. Ma. Jennifer R.

Tiburcio,MSMT
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
 Freund’s 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 Freund’s 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 Freund’s 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 Mechanism of action Compound
Depot Delays release of Ag Freund’s adjuvant
Water-in- Prolongs lymphoid tissue
oil exposure to antigen
Same as above Calcium alginate
Precipitants
Same as above Alum, Aluminum hydroxide,
Absorbents Bentonite, Polyacrylamide,
Methylated BSA

Irritants Induce inflammatory Foreign bodies,

response w/c increases Ag Mycobacteria (wax D)
exposure to macrophage, T (muramyl dipeptide)
and B cells
Mitogens Increase clonal expansion LPS, PHA, Con A
of T and B cells during an
immune response
 Class Mechanism of Action Compounds
Lymphokines Enhance proliferation IL-1, 2 and 3
and/or differentiation of T MAF
and B cells IFNs
And macrophages
Synthetic Stimulate Ag processing Polyadenylate-uridylate
polynucleotides and T helper cell activity
 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 one’s 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