IMMUNE REGULATION

Immunoenhancement/
Immunopotentiation
-the potentiating effect of immunoenhancers
-the augmentation of immune responsiveness
by immunization or other means

1. Increasing the rate at which 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
Emulsifying agent: paraffin or mineral oil

1. Incomplete Freund’s Adjuvant (IFA)

• Water in oil with 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
- An IFA plus mycobacterial cell wall components
- markedly enhance both HI and CMI

Ex.

BCG – causes macrophage activation and enhances NK

cell activity
 CLASS MECHANISM OF ACTION COMPOUND

Water in Oil Delays release of Ag Freund’s Adjuvant

Prolongs lymphoid tissue
exposure to Ag
Precipitants Same as Above Calcium Alginate

Absorbents Same As above Alum, Aluminum hydroxide,

Bentonite, Polyacrilamide
Methylated BSA
Irritants Induce inflammatory response Foreign bodies,
w/c increases Ag exposure to Mycobacteria (wax D)
macrophage ,T , and B Cells (muramyl dipeptide
Mitogens Increase clonal expansion of T/B LPS, PHA, Con A
cells during an immune response

Lymphokines Enhance proliferation and/or IL-1,2,3

differentiation of T/B cells MAF
and macrophages IFNs
Synthetic polynucleotides Stimulate Ag processing and Polyadenylate-uridylate
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
 Immunosupression
-reduction in a large portion of
immune responsiveness

• PHYSICAL MEANS
• CHEMICAL and BIOLOGIC MEANS
• IMMUNOSUPRESSION ASSOCIATED w/
DISEASES
Immunosupression
-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 dev’t– very little effect on IC

2. Removal of peripheral lymphoid tissue- actual tissues removed

Lymph nodes and lymphoid cells in connective tissue
– little effect

b. Ionizing radiation damages the lymphoid organs &

bone marrow
B. Chemical & Biologic Means

a. Lymphocytic Agents
-Can track the expression of the IR but more
effective in disrupting the initiation of the IR

b. Lymphocytotoxic Agents
1. antimetabolites (purine &pyrimidine, analogues and
folic acid antagonists) - interfere with DNA
synthesis
2. alkylating agents (cyclophosphamide) – interfere with
cell division by altering guanine so DNA base
pairing errors occur.
- Can crossllink the two DNA strands thus
blocking replication.
 3. Antibiotics (cyclosporin) – supress graft rejection reactions
-exerts an inhibitory effect on IL-2 action thus blocking
the expansion of the helper/inducer T cell population
4. Cortisone – immunosupressive & anti-inflammatory
--Lymphocytic in animals but not in humans
– alter cell migration & cause lymphopenia &
monocytopenia shortly after injection
c. Antibodies
1. Abs that react w/ lymphoid cells particularly thymocytes,
Induces immune deficiency in transplant patients by
supression of CMI
2. Preformed Abs followed by injection of specific antigen. IR
in the host will be blocked. The injected Ab binds up
the Ag & prevents its exits to the lymphoid tissues
3. Abs that are specific for the Ag combining site –
specifically abort that particular response
C. Immunosupression associated with Diseases

Congenital Immunodeficiencies
Bruton’s Agammaglobulinemia – failure of the
development of the B cell humoral immunity
– Ab Production is affected
– suffer from repeated bacterial infection

DiGeorge syndrome – failure of the development of third

& fourth pharyngeal pouches during embryogenesis
– recurrent viral disease

Malignancies
Lymphomas may disrupt normal lymphocyte functions
directly or may “crowd out” normal lymphocytes from bone marrow
& peripheral lymphoid tissues
Infections
-Measles & certain viral disease cause a transient
depression in CMI
-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

-Naturally acquired or Immune tolerance

 TOLERANCE
A. Naturally acquired (autotolerance,
neonatal or natural tolerance)
- Escape from this leads to autoimmune disease
- During fetal development, the ability to recognize
one’s own tissues is acquired

Clonal deletion theory

-It is probable that clone of cell capable of
responding to own tissues arise throughout life.
These clones are immediately deleted by
encountering an overwhelming amount of self
antigen or by the activity of antigen specific T
suppressor cell
Various
clones

Clone deletion

birth

Clone selection
 Clonal deletion theory

(1)There are various lymphocyte clones in

our body, each of them bears a unique
type of Ag receptor which can recognize
Ag specifically.
 Clonal deletion theory

(2)The clones of lymphocytes that can

recognize self-Ags will be destroyed or
learn to tolerance to self Ags (forbidden
clones) at the early stage of their
development.
----clone deletion
 Clonal selection theory

(3)The clones of lymphocytes that

can be interacted with
corresponding Ag will be selected
and lead to activation,
proliferation , produce Ab and
specific memory cells.
---- clone selection
(4) Forbidden clones can be revived and
cause antoimmunity.
B. Immune tolerance
-Gradation of tolerance
-Pathways of B tolerance
-Pathways of T tolerance
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. Cis nal 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 Ag or an excess of T independent Ag
prevents mature B cell from functioning normally

D. Antibody forming cell blockade

-high concentrations of T dependent Ag are
blocking the receptors of the cells hereby interfering Ab
secretions
3. Pathways to T cell Tolerance
-T-cells do not allow marked differences on their
tolerability. The Ag required to produce tolerance is
particular to each individual T cell subset

A. Clonal Abortion
-Immature T cell clones may be aborted in a
similar manner to B cell

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 the

T cell subsets or B cells

-T and B cells differ in their susceptibility to in vivo

tolerization with respect to the course of tolerance and
also the levels of antigen required to tolerize the cells.