DEFENSE MECHANISMS OF THE BODY INNATE SYSTEM: NON-SPECIFIC DEFENSES These are considered nonspecific defenses of the body given that they protect the body against ALL foreign substances. FIRST LINE OF DEFENSE (EXTERNAL INNATE) This line of defense includes the external body membranes and skin. The unique features of these two barriers offers further protection. BARRIER PROTECTION skin’s keratin protein acidic pH lacrimal glands: tears w/ lysozyme salivary glands: saliva w/ lysozyme sebaceous glands: sebum w/ antimicrobial chemicals respiratory tract: mucociliary escalator created by cilia actions defecation urination vomiting SECOND LINE OF DEFENSE (INTERNAL INNATE) This line of defense begins when the first defense has failed. The actions of antimicrobial proteins, phagocytes and assorted other cells collectively to manage the situation. As a result of these efforts, the site of penetration begins to exhibit the signs of inflammation. Two categories of actions operate here - cellular and chemical. CELLULAR PHAGOCYTES’ RESPIRATORY BURST: macrophages/monocytes, neutrophils, eisonophils, mast cells NATURAL KILLER (NK) CELLS: perforins perforate cancer & viral-infection cells, secretes interleukins (IL) for positive feedback in inflammatory response INFLAMMATION: initiated by histamine, kinins, prostaglandins, platelet-derived growth factor, complement proteins, cytokines . . . see flow chart next page for more details NATURAL FLORA: bacterial (E. coli), fungal (S. Cerevisiae) 1 2 CHEMICAL ANTIMICROBIAL PROTEINS CALLED INTERFERON (IFN): viral-infected cells release IFN which diffused to it neighbors . . . neighbors (1) produce protein PKR which shuts down protein synthesis at ribosome in these healthy cells and (2) positive feedback on macrophages & NK ANTIMICROBIAL PROTEINS CALLED COMPLEMENT: 20 plasma proteins acting in a cascade fashion with eventually lead to lysis of the infected cell (see photograph below for more details) HYPOTHALAMIC RESPONSE = Fever: secreted pyrogens trigger reset of thermostat to higher value; this new temperature results in (1) denaturing pathogen proteins and (2) liver’s sequestering of Fe and Zn NOTES < IFN varies include: gamma (lymphocytes), alpha interferon (other leukocytes), beta interferon (fibroblasts) < IFN directly acts on malignant cancer cells; pharmaceutical IFN available by biotechnology but are exceedingly cost prohibited to most individuals < Alpha IFN used to treat genital warts and hepatitis C 3 ADAPTIVE SYSTEM: (SPECIFIC) THIRD LINE OF DEFENSE: CELL MEDIATED AND ANTIBODY MEDIATED IMMUNITY How does the body must recognize a foreign substance. This is accomplished by two methods. < antigen (Ag) with antigenic determinate sites < major histocompatibility complex (MHC I or II) markers • MHC I . . . all body cells • MHC II . . . immune system cells 4 B AND T CELL CHARACTERISTICS COMPARED T B maturation site thymus bone marrow immunity type cell mediated antibody mediated subpopulation Th, Tc, Tnk Bp, Bm no yes surface antibodies CELL MEDIATED IMMUNITY (1) Phagocytosis of antigen (Ag) by antigen-presenting cell (APC) such as macrophage, PMN. (2) Antigen presented on the membrane of the APC along with MHC II marker. (3a) APC with Ag/MHC-II binds via CD4 & T cell receptor (TCR) to the T helper cell producing an activated T helper cell. (3b) Antigen-infected cell/MHC-I cell binds with via CD8 & TCR to T cytotoxic cell producing an activated T cytotoxic cell. (4a) Activated T helper cells serve in the co-stimulation of humoral (antibody) mediated immunity. (4b) Activated T cytotoxic cells lead to cellular lysis or phagocytosis. In both cases, activation of T helpers and T cytotoxic, (1) memory cells are produced with will allow for a faster response should the same antigen present itself in the future and (2) clones of the specific T cell in mass produced for a more enhanced response. 5 ANTIBODY MEDIATED IMMUNITY (A.K.A. HUMORAL IMMUNITY) What events(s) trigger an antibody mediated response? < correct THelper produces lymphokines which stimulate the correct B cell < correct B cell clones are produced < B cell binds to the presented antigen What events lead up to the production of antibodies? < correct B cell clones . . . takes about five days to produce antibodies de novo < memory and plasma cells produce antibodies by placing them on the cell membrane or secreting them into the serum 6 How does the presence of antibodies on a plasma cell membrane lead to the destruction of the antigen? < membrane bound antibodies stimulate the complement cascade which leads to cell lysis or phagocytosis of the Ag-containing cell < serum antibodies bind Ag in an agglutination reaction I Is there one kind of antibody? NO! There are several subclasses of antibodies. You should remember that Ig stands for immunoglobulins. Antibody come in different shapes. The IgG antibody is the typical one used for antibody structure; this is the one I will use. Please memorize figure 21.2. In addition, you are to memorize table 21.3 illustrating the detailed difference between the five types of antibodies. The table below will assist you in extracting the important information from table 21.3. ANTIBODY % CIRCULATING IgA 15 IgD 1 IgE 0.1 LOCATION saliva, sweat, intestinal juice, breast milk antigen receptor on B cell surface . . . aid in B cell activation 75 IgG IgM FUNCTION 5-10 7 The Th cell is the key player to both the cell mediated and antibody mediated immunities. There are several means by which immunity can be conferred. Active immunity is naturally acquired when you suffer from an bacterial or viral infection. In contrast, artificially acquired immunity occurs via vaccinations. April 6, 2009 (10:47am) C:\MyFiles\LCCC\a&p hybrid\lecture_136\notes.immune.wpd 8