Immunology Cell-mediated immunity (CMI) By Ahmed Riyadh Abdul Rahman Al-Noor University College 1
2 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.
3 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.
4 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.
5 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.
6 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.
7 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.
8 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
9 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.
10 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.