You are on page 1of 23

Immunomodulation

Jardine Jade Albert C. Valdez, RMT


Lecturer/Clinical Instructor
Our Lady of Fatima University

Overview:

Suppression or enhancement of the immune response


to select antigen is sometimes desirable. The immune
modulation achieves this.

Objectives:

Further understand the immune response through the process if


immune regulation.
Explain the concept of immunosuppression and
immunopotentation.
Know the different immunosuppressive agents and their actions
Be aware of other factors and conditions that can lead to
suppression of the immune response.

Lesson:

1. Allergic conditions involving both immediate and delayed


hypersensitivities.
2. Autoimmune disease, in which the body destroys its own tissues,
may destroy normal tissue via an immune mechanism.
3. Prolongation of graft survival can be enhanced by suppressing
the patients immune response, because the rejection of grafted
tissues and organs has an immunologic basis.

Enhancement of immune response is advantageous in the


management of the immunodeficient patients.
Responsiveness is the key to immune regulation.
Unresponsiveness is the absence of an immune response to a
substance that would be immunogenic under ordinary
conditions: even though the substance has all the features
necessary for antigenicity, it elicits no immune response.

Classification
1. Immunosuppression refers to a reduction in a large portion of
the hosts immune responsiveness. The reduced responsiveness
may be caused by:
a. A congenital defect
b. An acquired immunocompromising condition.

2. Tolerance is more restrictive; it implies the absence of a


selected immune response and thus a state of specific
unresponsiveness (i.e, an immunotolerant state)

Enhancement of responsiveness

1.Immunopotentation, the enhancement of


responsiveness, can be specific or non specific.
2.Adjuvants are materials that possess the ability to
enhance or augment an immune response.

Natural processes control the


immune response:

1.Suppressor T (Ts) cells control the proliferation and


maturation of immunocompetent T and B cells
2.MHC restriction
3.Neuroendocrine control

Immunosuppression:
physical means of
immunosuppression

1.Surgical manipulation can have a major impact


on immune responsiveness.
2.Ionizing radiation damages the lymphoid organs
and bone marrow.

Chemical and biologic means of


immunosuppression

1.In transplantation procedures to suppress graftrejection reaction.


2.In autoimmune disease as therapeutic agents.
3.In cancer as chemotherapeutic agents.

Types of immunosuppressive
agents and their actions
1.Lymphatic agents can block the expression of the
immune response (through cell lysis) but are more
effective in disrupting the initiation of the immune
response.
a. Ionizing agent
b. Antibodies

2.Lymphocytotoxic agents agents are most efficient at


interrupting the induction of an immune response.
1.Antimetabolites
2.Alkylating agents
3.cyclosporine

3.Corticosteroids are both immunosuppressive and antiinflammatory. In addition to acting as an antiinflammatory agent, cortisone has several generalized
functions:
a. Decrease lymphocyte exposure to antigens.
b. Inhibits neutrophil immigration into areas of inflammation
c. Stabilizes lysosomal membranes so that exocytosis of
degradative lysosomes is lessened.
d. Influences T and B cell cycling, reducing inflammatory already
present.

4.Antibodies

Immunosuppression associated
with diseases and other conditions
1.Congenital immunodeficiencies
a. In Brutons hypogammaglobulinemia, B cell immunity fails to
develop. Patients form antibodies very poorly and suffer from
repeated bacterial infections.
b. In DiGeorge syndrome, T cell immunity is deficient because
the third and fourth phargyngeal pouches fail to develop
during embryogenesis. Patients are subject to recurrent viral
diseases.
c. In chronic granulomatous disease, phagocytes are unable to
kill ingested microorganisms. Patients have recurrent
bacterial infections.

2.Malignancies these are potentially


immunosuppressive, particularly if they involve
lymphoid tissues. Lymphomas may disrupt normal
lymphocyte functions directly or may crowd out
normal lymphocyte from bone marrow and peripheral
lymphoid tissues.

3.Infections
a. Measles and certain other viral diseases causes a transient
depression in cell-mediated immune responses.
b. Viral infections also have a negative effect on various
macrophage functions.
c. HIV infection causes a profound immunosuppression.
d. Specific anergy is seen in lepromatous leprosy and the terminal
sages of tuberculosis. In this conditions, delayed hypersensitivity
is impaired because amounts of antigen are excessive.

4. Malnutrition adequate nutrition is essential for proper


functioning of the immune system.
5. Chemicals various chemical can induce immunosuppression.
For example anesthetics and cannabinoids are compounds that
injure dividing cells and interfere with inflammatory process.

Tolerance

Tolerance is the absence of specific immunity responses


in an otherwise fully immunocompetent person. This
type of unresponsiveness can be either naturally
acquired (autolerance) or specifically induced (acquired
or immune tolerance).

Clinical importance. Tolerance is of importance in


clinical medicine in several ways:
1. Failure or autotolerance may result in autoimmune diseases.
2. Specifically induced tolerance could represent an avenue for
the therapy of autoimmune diseases, allergic conditions and
allograft rejection.

Autolerance and acquired tolerance


1. Autolerance (neonatal, natural or self-tolerance) autotolerance
s a tolerance to ones own antigens that is acquired early in life,
probably in utero.
Clonal deletion theory it is probable that clones of cells capable of
responding to a persons own tissue development throughout life. These
clones, called forbidden clones, are immediately deleted by encounters
with overwhelming numbers of self antigens or by the activity of antigen
specific suppressor cells. The cell that is most susceptible to deletion is the
Th cell, functional B cells that are potentially reactive against self-antigen
probably exist.

2.Acquired (immune) tolerance


a. Simulation autotelerance can be simulated by a simple
experiment. Unresponsiveness can be induced in a fetal
animal by the injection of a foreign substance.
b. Induction- acquired tolerance usually is induced by excessive
amounts of antigen. Tolerance involves each epitope of an
antigen. The antibody producing B cells or the T cells capable
of mounting a response are overwhelmed and deleted.

Immunopotentation
The immune response can be enhanced by increasing
the rate at which the response occurs, elevating its
magnitude, or increasing the duration of the response.
In some instances, one particular response can be
enhanced with no change in other responses. For
example, the presence of certain mycobacterial cell
wall components favor the development of cellmediated immunity.

Adjuvants

Adjuvants are nonspecific potentiators of immune


response. They are substances that enhance the
immunogenicity of molecules without altering their
chemical composition.

Mechanisms of potentiators

1.Increasing the efficiency of macrophages processing


antigen.
2.Prolonging the period of exposure to the antigen
3.Amplifying the proliferation of immunologically
committed lymphocytes by enhancing lymphokine
activity