2. Although humoral (antibody-mediated
immunity) is an important host defense against
many bacterial and viral diseases,
in many other bacterial infections (especially
intracellular infections such as tuberculosis)
and viral infections, it is primarily the cell-
mediated arm that imparts resistance and aids
in recovery.
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3. Furthermore, cell-mediated immunity is important
in defense against
• fungi,
• parasites
• tumors
• rejection of organ transplants.
The strongest evidence for the importance of cell-
mediated immunity comes from clinical situations
in which its suppression (by immunosuppressive
drugs or disease, e.g., AIDS) results in
overwhelming infections or tumors.
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4. Constituents of the cell-mediated
immune system
The constituents of the cell-mediated immune system include
several cell types:
• (1) macrophages, which present the antigen to T cells;
• (2) helper T cells, which participate in antigen recognition
and in regulation (helper and suppressor) functions.
• (3) natural killer (NK) cells, which can inactivate pathogens
• (4) cytotoxic T cells, which can kill virus-infected cells with
or without antibody.
Macrophages and helper T cells produce cytokines that
activate helper and cytotoxic T cells, leading to the killing of
the pathogen or tumor cell.
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5. • The terms primary and secondary response are
associated primarily with antibody formation but
the timing of the T-cell response also follows the
same pattern.
• After the initial exposure to the antigen, the
specific T cell proliferates to form a small clone of
cells; i.e., a primary response occurs.
• Then, on subsequent exposure to the antigen,
the small clone expands and many more specific
T cells are formed. These cells constitute the
secondary response.
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6. • Although the interactions between various cells
and various cytokines are complex, the result is
relatively simple.
• In the person with competent cellular immunity,
opportunistic pathogens rarely or never cause
disease, and the spread of other agents—for
example, certain viruses (e.g., herpesviruses) or
tumors (e.g., Kaposi's sarcoma)—is limited.
• The assessment of the competence of cell-
mediated immunity is therefore important.
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7. Tests for Evaluation of Cell-Mediated
Immunity
• Evaluation of the immunocompetence of
persons depends either on the demonstration of
delayed-type hypersensitivity to commonly
present antigens (equating the ability to respond
with the competence of cell-mediated
immunity) or on laboratory assessments of T
cells.
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8. In Vivo Tests for Lymphoid Cell
Competence (Skin Tests)
Skin Tests for the Presence of Delayed-Type
Hypersensitivity
• Most normal persons respond with delayed-type
reactions to skin test antigens of Candida,
streptokinase-streptodornase, or mumps virus
because of past exposure to these antigens.
• Absence of reactions to several of these skin
tests suggests impairment of cell-mediated
immunity
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9. Delayed (cell-mediated) hypersensitivity
• Helper T lymphocytes sensitized by an antigen
release lymphokines upon second contact
with the same antigen.
• The lymphokines induce inflammation and
activate macrophages, which, in turn, release
various mediators.
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11. • The macrophage ingests the antigen,
processes it, and presents an epitope on its
surface in association with class II MHC
protein.
• The helper T (Th-1) cell is activated and
produces gamma interferon, which activates
macrophages.
• These two types of cells mediate delayed
hypersensitivity.
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13. Skin Tests for the Ability to Develop Delayed-Type
Hypersensitivity
• Most normal persons readily develop reactivity to
simple chemicals (e.g., dinitrochlorobenzene [DNCB])
applied to their skin in lipid solvents.
• When the same chemical is applied to the same area
7–14 days later, they respond with a delayed-type skin
reaction.
• Immunocompromised persons with incompetent cell-
mediated immunity fail to develop such delayed-type
hypersensitivity.
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14. In Vitro Tests for Lymphoid Cell
Competence
a)Lymphocyte Blast Transformation
• When sensitized T lymphocytes are exposed to the specific antigen,
they transform into large blast cells with greatly increased DNA
synthesis, as measured by incorporation of tritiated thymidine.
• This specific effect involves relatively few cells.
• A larger number of T cells undergo nonspecific blast transformation
when exposed to certain mitogens.
• The mitogens phytohemagglutinin and concanavalin A are plant
extracts that stimulate T cells specifically. (Bacterial endotoxin, a
lipopolysaccharide, stimulates B cells specifically.)
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15. b)Macrophage Migration Inhibitory Factor
• Macrophage migration inhibitory factor is
elaborated by cultured T cells when exposed
to the antigen to which they are sensitized.
• Its effect can be measured by observing the
reduced migration of macrophages in the
presence of the factor compared with the
level in controls.
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16. c)Enumeration of T Cells, B Cells, and
Subpopulations
• The number of each type of cell can be counted
by use of a machine called a fluorescence-
activated cell sorter (FACS).
• In this approach, cells are labeled with
monoclonal antibody tagged with a fluorescent
dye, such as fluorescein or rhodamine.
• Single cells are passed through a laser light
beam, and the number of cells that fluoresce is
registered.
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19. • B cells (and plasma cells) making different classes of
antibodies can be detected by using monoclonal
antibodies against the various heavy chains.
• The total number of B cells can be counted by using
fluorescein-labeled antibody against all
immunoglobulin classes.
• Specific monoclonal antibodies directed against T-cell
markers permit the enumeration of T-cells, CD4 helper
cells, CD8 suppressor cells, and others.
• The normal ratio of CD4 to CD8(cytotoxic t) cells is 1.5
or greater, whereas in some immunodeficiencies (e.g.,
AIDS) it is less than 1.
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20. Role of Adjuvants & Lipids in
Establishing Cell-Mediated Reactivity
• Weak antigens or simple chemicals tend not to elicit cell-
mediated hypersensitivity when administered alone, but
they do so when given as a mixture with an adjuvant.
• The role of the adjuvant is to enhance the uptake of the
antigen by antigen-presenting cells, e.g., macrophages, to
stimulate the expression of co-stimulators, such as B7, and
to enhance the production of cytokines, such as IL-12, that
promotes the development of Th-1 cells.
• A common experimental adjuvant is a mixture of mineral
oil, lanolin, and killed mycobacteria (Freund's adjuvant),
which stimulates the formation of local granulomas. It is
prohibited for human use.
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