This document discusses cell-mediated immunity (CMI), which is mediated by T lymphocytes and is responsible for detecting and destroying intracellular pathogens like viruses or infected cells, graft rejection, and destroying tumor cells. CMI results in a delayed-type hypersensitivity reaction. Upon first exposure to an antigen, naive T-cells are sensitized and proliferate. Secondary exposures result in a faster and more effective response from memory T-cells. Lymphokines released by activated T-cells mediate immune responses. A positive tuberculin skin test indicates past tuberculosis infection. CMI differs from humoral immunity in its mechanisms, antigens recognized, and hypersensitivity responses.

1. Immunology
Cell-mediated immunity (CMI)
By
Ahmed Riyadh Abdul Rahman
Al-Noor University College
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Cell-mediated immunity (CMI)
 The term cell-mediated immunity (CMI) refers to protective mechanisms that are not
characterized by antibody.
 Cell-mediated immunity is mediated by T lymphocytes (T helper & T cytotoxic
lymphocytes).
CMI is responsible for:
 Detecting and destroying intracellular pathogens, e.g., cells infected with viruses or
bacteria.
 CMI is vital for graft rejection.
 Destruction of tumor cells.
 Delayed-type hypersensitivity reactions.

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The Timing of the T-Cell Response
First exposure to antigens:
 After the initial exposure to the antigen, the specific naive T- lymphocytes, sensitized by
an antigen.
 Then proliferates to form a small clone of cells (i.e., a primary response occurs).
 Numerous circulating (T8-memory cells and T4-memory cells) develop which possess
memory response or memory.

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Second or subsequent exposure to the same antigen:
 A subsequent exposure to that same antigen results in a more rapid, more
effective and longer production of cytotoxic T-lymphocytes (CTLs), and
T4-effector lymphocytes.
 The small clone expands, and many more specific T cells are formed.
These cells constitute the secondary response.
 The maximum CMI response occurring at 24-48 hours. This more rapid
response is due to the presence of memory cells.
 T-cells Release Lymphokines which act as mediators in the immune
response by activating macrophages and stimulating lymphocyte
production.

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Lymphokines: are polypeptide substances produced by activated
lymphocytes that participate in a variety of cellular immune reactions
including immune system regulation, For example, B cell
differentiating factor causes the activated B cells to differentiate into
antibody-producing cells, whereas T cell growth factor stimulates T
cell proliferation.
 After the termination of an infection the number of T-cells decreases but
a small number (T-memory cells) is maintained for years.

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An excellent example of cell-mediated immunity is the delayed
hypersensitivity response to the tuberculin skin test in people who have
been infected with Mycobacterium tuberculosis.
The TB skin test is also called the Mantoux tuberculin skin test (TST) or PPD
(purified protein derivative) test. The Mantoux tuberculin skin test (TST) is
the standard method of determining whether a person is infected with
Mycobacterium tuberculosis.
 The TB skin test is performed by injecting a small amount of fluid (called
tuberculin) into the skin on the lower part of the arm subcutaneously.
 A person given the tuberculin skin test must return within 24-48 or maybe
to 72 hours to look for a reaction on the arm.

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 Reaction in the skin to tuberculin PPD begins when specialized T cells,
sensitized by prior infection, are attracted by the immune system to the skin site
where they release chemical messengers called lymphokines upon second
contact with the same antigen. The Lymphokines induce inflammation and
activate macrophages.
 These lymphokines effects induce induration which is the key item of the detection
the test.
 The induration is a hard, raised, thickened local area of skin around the injection site
known as edema
 "Reading" the skin test result depends on the size of the raised, hard area or swelling.
 Read skin tests 24-48 hours after the injection when the size of the induration is
maximal. Tests read after 72 hours are not accurate.

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Positive skin test: This means the person’s body was infected with TB bacteria.
Additional tests are needed to determine if the person has latent TB infection or TB
disease.
Negative skin test: This means the person’s body did not react to the test, and that
latent TB infection or TB disease is not likely.
Some persons may react to the TST even though they are not infected with
M. tuberculosis. The causes of these false-positive reactions may include,
 Infection with no tuberculosis mycobacteria.
 Previous BCG vaccination

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Relationship between Cell-Mediated and Humoral Immunity
Antibody Production
T-Dependent Antigens:
 Antibody production requires help from T helper cells.
 A macrophage cells ingest antigen and presents it to T H cell.
 TH cell stimulates B cells specific for antigen to become plasma cells.
 Antigens are mainly proteins on viruses, bacteria, foreign red blood cells, and hapten-carrier
molecules.
T-Independent Antigens:
 Antibody production does not require help from T cells.
 Antigens are mainly polysaccharides or lipopolysaccharides with repeating subunits (bacterial
capsules).
 Weaker immune response than for T-dependent antigens.

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Major Differeces between
Cell-mediated Immunity
and
Humoral Immunity
Cell-mediated Immunity Humoral Immunity
It is mediated by T-cells. It is mediated by B-cells.
No formation of antibodies. Formation of antibodies.
Secretes lymphokines. No Secretion of lymphokines
Receptors are used to detect antigens. Antibodies are used to detect antigens.
T-cell receptors bind to the T-cell and bind
to the antigens.
The antibodies produced by B-cells
bind to the antigen.
It protects against virus, fungi and other
intracellular bacterial pathogens.
It protects against extracellular virus
and bacteria.
It can eliminate tumor cells and thus
protects against cancer.
It cannot eliminate tumor cells.
Both CD4+ and CD8+ cells are involved
in cell-mediated immunity.
Only TH cells are involved in humoral
immunity.
Mediates hypersensitivity type IV. Mediates hypersensitivity I, II and III.
It shows delayed response. It is quick in response.

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