HUMORAL IMUNITY & CELLMEDIATED IMMUNITY Humoral Immunity and Cell-mediated immunity Both types of immunity work in concert and are interdependent Humoral immunity produces antibodies in response to extracellular pathogens and toxins. Depends on antibody-producing B-cells. Cell-mediated immunity responds to intracellular pathogens, transplanted tissues, and cancer cells. Depends on direct action of T-cytotoxic (Tc) cells instead of antibodies. Helper T lymphocytes function in both humoral and cell-mediated immunity Combats pathogens that have already invaded cells. Key components are helper T cells (Th) and cytotoxic T cells (Tc). These T cells mature in thymus and then migrate to lymphoid organs (spleen and lymph nodes). T cells respond only to antigenic epitopes displayed on surfaces of body’s own cells. Do not detect free antigens in body fluids CD4 is a cell surface molecule displayed by T cells which enhances the interaction between Th cells and antigen presenting cells (APC). Helper T cells stimulate other lymphocytes by receiving and sending cytokines. When Th cell binds to an antigen presenting macrophage, the macrophage releases interleukin-1 (a cytokine). Interleukin-1 stimulates Th cell to release interleukin-2. Interleukin-2 stimulates the Th cells to grow and divide rapidly resulting in the production of more Th cells and an increase in supply of interleukin-2. Because interleukin-2 and other cytokines secreted by the increasing numbers of Th cells activate B cells, the humoral response is enhanced. Increased level of cytokines also increases cell-mediated response by stimulating another class of T lymphocytes to differentiate into cytotoxic T cells (effector cells). The Humoral response Humoral response occurs when B-cells become activated by the exposure of antigen to helper T cells. The B cells differentiate into a clone of plasma cells that will secrete antibodies. Antibodies are most effective against pathogens circulating in blood or lymph. Memory cells are also involved and form basis of secondary immune response. Activation of B cells Selective activation of B cells to produce plasma cells and memory cells is actually a two-step process: 1. Binding of antigen on specific antigen-receptor on surface of B cell. 2. Involves macrophages and Th cells. This step results in production of plasma and memory cells. macrophage phagocytize pathogens. Pieces of partially digested antigen are presented on the surface of macrophage – APC A Th cell with receptor specific for the presented antigen binds to the antigen. Th cell is now activated and proliferates to produce a clone of activated Th cells specific for the presented antigen. These activated Th cells secrete cytokines which stimulate B cells. The B cells form clone of plasma cells. Each plasma cells (effector) then secretes antibodies for the specific antigen. Each effector cells can produce a many as 2,000 antibodies per second during its 4-5 day life span. Some antigens trigger humoral response without macrophage or Th cells involvement. This response is weaker and no memory is generated. Cell-mediated immunity cells destroy infected host cells Host cells infected by viruses and other pathogens display antigens on their surfaces. Tc cells have specific receptors which recognize and bind to antigen. Tc receptor can bind to any body cell. When Tc cell binds to an infected cell, it releases perforin, a protein that forms lesions in the infected cells membrane causing cell lysis. Cytotoxic T cells continue to live after destroying infected cell and go on to kill other cells. Cytotoxic T cells also function to destroy cancer cells which develop periodically in the body. Cancer cells possess distinctive markers not found in normal cells. These markers are recognized by Tc cells as non-self. Cancer develops primarily in individuals with defective or declining immune systems. Memory cells function in secondary immune responses Primary immune response = proliferation of lymphocytes to form clones of effector cells specific to an antigen during the body’s first exposure to the antigen. there’s lag time (5-10 days) between exposure and maximum production of effector cells. The lymphocytes selected by antigen are differentiating into effector T cells and plasma cells during this lag period. Secondary immune response = occurs when body exposed to a previously encountered antigen. Response faster and more prolonged than primary response. Antibodies are more effective at binding antigen. Ability to recognize previously encountered antigens known as Immunologic memory. Based on memory cells produced during primary immune response. Inactive during primary response. Long lived. When a previously encountered antigen enters body, it rapidly activates memory cells to divide and form new clones of effector cells and memory cells. These new effector cells constitute the secondary immune response. Types of immunity Natural passive immunity Antibodies made in one individual are passed into another individual of the same species. This only affords temporary protection, for, as the antibodies do their job, or are broken down by the body's natural processes, their number diminishes and protection is slowly lost. For example, antibodies from a mother can cross the placenta and enter her foetus. In this way they provide protection for the baby until its own immune system is fully functional. Passive immunity may also be conferred by colostrum (the mother’s first milk), from which antibodies are absorbed in the intestines of the baby. Acquired passive immunity antibodies which have been made in one individual are extracted and then injected into the blood of another individual which may, or may not, be of the same species. For example, specific antibodies used for combating tetanus and hepatitis B are cultured in horses and later injected into Man. They act to prevent tetanus and hepatitis respectively. This type of immunity is again short-lived – a matter of weeks only. Natural active immunity The body manufactures its own antibodies when exposed to an infectious agent. Since memory cells produced on exposure to the first infection are able to stimulate the production of massive quantities of antibody, when exposed to the same antigen again. This type of immunity is most effective and generally persists for a long time - sometimes even for life. Acquired active immunity This is achieved by injecting small amounts of antigen - the vaccine - into the body of an individual. The whole process is called vaccination or immunisation. The small dose of antigen is usually safe because the pathogen is either killed or attenuated (= crippled). This ensures that the individual does not contract the disease itself, but is stimulated to manufacture antibodies against the antigen. Often a second, booster, injection is given and this stimulates a much quicker production of antibody which is long lasting and which protects the individual from the disease for a considerable time.