Lymphatic System and Immunity
Innate defenses antimicrobial proteins
B-Lymphocytes antibody mediated immunity
T-Lymphocytes cellular immunity
Innate defenses cellular defense
Macrophages: "big eaters". Clean up crew that arrives late to the infected or injured scene and stays longer. Destroy pathogens via phagocytosis. APC.
Neutrophils: the first to arrive at the site of infection. Destroy pathogens via phagocytosis.
Dendritic cells: destroy infectious agents and then present fragments of the microbe on its cell surface to T-lymphocytes. APC.
Basophils: proinflammatory chemical-secreting cell. Circulate in the blood. Secretions include histamine, a vasodilator and heparin, an anticoagulant. Eicosanoids are also secreted and increase inflammation.
Mast cells: serve a similar function to basophils. Unlike basophils, mast cells can be found in the CT of the skin, mucosal linings, and various internal organs.
Natural killer cells: destroy a wide a variety of unwanted cells, including virus-infected cells, bacteria-infected cells, tumor cells and cells of transplanted tissue.
Immune surveillance: NK cells patrol the body in an effort to detect unhealthy cells. NK cells make physical contact with unhealthy cells and destroy them by releasing cytotoxic chemicals; perforins and granzymes.
Eosinophils: target parasites. They attack via degranulation and the release of enzymes that are lethal to the parasite. Like NK cells, they release proteins that perforate the membrane of multicellular organisms.
Both serve as chemotactic chemicals which attract immune cells as part of the inflammatory response. Secretions from both cells increase fluid movement form the blood to an injured tissue.
Interferon: cytokines produced by leukocytes, virus-infected cells, T-lymphocytes, and NK cells. A virus-infected cell helps prevent further spread of the virus by releasing IFN.
Alpha and beta interferons bind to receptors of neighboring cells, preventing them from becoming infected by triggering synthesis of enzymes that both destroy viral RNA or DNA and inhibit synthesis of viral proteins. Stimulate NK cells to destroy virus-infected cells.
Gamma interferon is released from NK cells to stimulate macrophages to also destroy virus-infected cells.
Complement: composed of at least 30 plasma proteins that make up approx. 10% of the blood serum protein. Work with antibodies. Activation occurs following entry of a pathogen into the body. Once activated, the complement system mediates several important defense mechanisms, and it is especially potent against bacterial infections.
Opsonization is the binding of protein to a portion of bacteria or other cell type that enhances phagocytosis.
Inflammation. Complement increases the inflammatory response through the activation of mast cells and basophils and by attracting neutrophils and macrophages.
Cytolysis. Some complement components trigger direct killing of a target by forming a protein channel (a hole) in the plasma membrane of target cell called a membrane attack complex.
Elimination of immune complexes. Complement links immune complexes to RBCs so they may be transported to the liver and spleen. RBCs are stripped of these complexes by macrophages within these organs.
Innate defenses inflammation and fever
Inflammation: a multi-step process. One of the most important outcomes of inflammation is a net movement of additional fluid from the blood through the infected or injured area and then into the lymph.
First step involves the release of various chemicals. Damaged cells of injured tissue, basophils, dendritic cells, macrophages, mast cells, and infectious organisms release numerous chemicals including histamine, leukotrienes, prostaglandins, interleukins, TNFs, and chemotactic factors.
Step two involves vascular changes, including vasodilation, increase in capillary permeability, and stimulation of the capillary endothelium to provide molecules for leukocyte adhesion.
Step three involves the recruitment of leukocytes. Leukocytes make their way to the infected tissue via: margination, diapedesis, and chemotaxis.
Delivery of plasma proteins occurs in the fourth step. Immunoglobulins, complement, clotting proteins, and kinins are brought to the injured or affected site.
Margination is the process by which CAMs in the leukocytes adhere to CAMs on the endothelial cells of capillaries within the tissue.
Diapedesis is the process by which cells exit the blood by squeezing out between vessel wall cells and migrate to site of infection.
Chemotaxis is migration of cells along a chemical gradient. Chemicals released from damaged cells, dead cells, or invading pathogens diffuse outward and form a chemical gradient that attracts immune cells.
Fever: an abnormal elevation of body temperature (pyrexia) of at least one degree celcius. Results from the release of fever-inducing molecules called pyrogens. Fever inhibits replication of bacteria and viruses, promotes interferon activity, increases activity of adaptive immunity, and accelerates tissue repair.
Onset of fever; hypothalamus stimulates blood vessels in the dermis of the skin to vasoconstrict to decrease heat loss through the skin, and a person shivers to increase heat production through muscle contraction.
Stadium is the period of time where the elevated temperature is maintained. The metabolic rate increases to promote physiologic processes involved in eliminating the harmful substance.
Defervescence occurs when the temperature returns to its normal set point. The hypothalamus is no longer stimulated by pyrogens.
Cell mediated immunity by T-lymphocytes doesn't require antibodies to activate. Instead it requires the help of specific cells called APCs to activate them.
APCs include dendritic cells, macrophages, and B-lymphocytes.
Helper T-lymphocytes: coordinate the immune response by helping both cell-mediated immunity and humoral immunity, as well as enhancing certain aspects of innate immunity such as activating NK cells and macrophages.
Healthy helper T-lymphocytes play a central role in a normal functioning immune system. HIV attacks these cells.
Cytotoxic T-lymphocytes: release chemicals that are toxic to cells. It secretes perforins and granzymes.
Humoral immunity by B-lymphocytes can be activated by direct contact with an antigen.
Upon activation, B-lymphocytes proliferate and differentiate into antibody producing plasma cells and memory B-lymphocytes.
Memory B-lymphocytes: activated upon reexposure to the same antigen.
B-lymphocytes have the ability to act as APCs. They recognize and respond to antigens outside cells.
They can engulf, process and present the antigen to the helper T-lymphocyte that recognizes that antigen.
Naïve T-lymphocytes will not recognize an antigen on its own.
An antigen bound to an MHC I or II protein on the surface of an APC will trigger the activation of a T-lymphocyte if it recognizes the antigen. Upon activation, T-lymphocytes proliferate and differentiate into helper T-lymphocytes and cytotoxic T-lymphocytes.
Plasma cells: produce antibodies. More specifically, they produce immunoglobulin proteins.
These antibodies can bind to antigens and mark them for destruction by other immune cells.
Perforins puncture the cells plasma membrane.
Granzymes move in and induce cell death by apoptosis, limiting the spread of the infectious agent.
These cells have a much longer life span than plasma cells. Usually months to years compared to five to seven days.