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Lecture Notes: Immune System (Part I: Innate Immune System) I. Parts of the Immune System A. Innate or Nonspecific system 1. External body membranes like skin and mucosae i. prevents physical entry of microorganisms ii. first line of defense 2. Phagocytes, antimicrobial proteins, inflammation i. activated by chemical signals when external defenses are penetrated ii. Second line of defense B. Adaptive or Specific system 1. Main components are the B and T lymphocytes i. B-lymphocytes involved in humoral or antibody-mediated immunity ii. T-lymphocytes involved in cellular or cell-mediated immunity 2. Takes considerable time but is highly specific i. this is the bodys third line of defense C. Functional System 1. has organs that are involved in the immune response but involves trillions of individual immune cells 2. the immune system confers immunity which is resistant to disease II. Innate defenses A. Function 1. combat pathogens which are harmful or disease-causing microorganisms 2. in a state of readiness and responds to protect the body from ALL foreign substances starting within minutes of invasion. B. Surface Barriers 1. Skin i. heavily keratinized epithelial membrane is a physical barrier ii. resistant to most weak acids, weak bases, bacterial enzymes and toxins. iii. secretions are acidic (pH 3-5) and inhibit bacterial growth iv. sebum contains chemicals that are toxic to bacteria 2. Mucous membranes i. line all body cavities that open to the exterior including the digestive, respiratory, urinary, and reproductive tracts. ii. stomach secretes HCl and protein-digesting enzymes which kill microorganisms. iii. Saliva and lacrimal fluid contains lysozyme, an enzyme that destroys bacteria. iv. Sticky mucus traps microorganism that enter the digestive and respiratory passageways. v. structure modifications such as the tiny mucus-coated hairs and ciliated mucosa of the respiratory tract which trap and sweep particles away from lower respiratory passages. 3. When surface barriers are breached by small nicks or cuts then the microorganisms invade deeper tissues and the internal innate defenses are important C. Internal Defenses 1. Nonspecific and consists of phagocytes, natural killer cells, antimicrobial proteins, fever, and the inflammatory response which includes macrophages, mast cells, and all types of white blood cells. 2. Phagocytes i. cells that engulf or eat pathogens ii. mainly macrophages a. derived from monocytes which leave the bloodstream and enter tissue and enlarge. b. can roam tissues search for cellular debris or foreign invaders like alveolar macrophages of the lungs or dendritic cells of the epidermis.

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c. can be fixed like Kupffer cells in the liver or microglia of the brain iii. neutrophils a. most abundant type of white blood cell b. may become phagocytic upon exposure to infectious material c. secrete defensins, which are antibiotic-like chemicals d. can release oxidizing and bleach-like chemicals which can destroy cells, including themselves e. prolonged activity may cause normal tissues to become cancerous iv. eosinophils a. weak phagocytes but are important against parasitic worms b. discharges destructive contents of cytoplasmic granules v. mast cells a. involved in allergies but have some phagocytic capabilities 3. Mechanism of Phagocytosis i. Ameoba-like digestion phagocyte engulfs particle using flowing cytoplasmic extensions the particle is enclosed within a membrane-lined vacuole called a phagosome a lysosome fuses with the phagosome to form a phagolysosome pathogen killed and digested within the phagolysosome indigestible waste is removed by exocytosis ii. requires adherence of the particle to the phagocyte a. carbohydrate signatures b. pneumococcus has a capsule which makes adherence difficult c. opsonization, which is the coating of foreign particles with complement proteins and antibodies, increases adherence iii. some pathogens can survive lysosomal enzymes and can multiply within the vacuole. a. respiratory burst can be activated by adaptive immune system chemicals that produce free radicals, like nitric oxide, which can kill cells. 4. Natural Killer Cells i. in the blood and lymph ii. can kill and lyse cancer cells and virus-infected body cells iii. belong to the group large granular lymphocytes iv. recognize surface sugars but are fairly nonspecific v. not phagocytic, but release cytolytic chemicals called perforins vi. secrete chemicals that enhance the inflammatory response 5. Inflammation i. triggered by body tissue injuries like physical trauma, heat, irritating chemicals, infection by viruses, fungi, and bacteria. ii. functions to: a. prevents spread of damaging agents b. disposes of cell debris and pathogens c. sets the stage for repair processes iii. signs of inflammation are redness (rubor), heat (calor), swelling (tumor), pain (dolor), and sometimes impairment of function (functio laesa). iv. begins with the release of inflammatory chemicals called inflammatory mediators into the extracellular fluid a. can come from injured tissue cells, phagocytes, lymphocytes, mast cells, and blood proteins v. main inflammatory mediators are histamine, kinins, prostaglandins, complement, and cytokines a. cause vasodilation and hyperemia, which is congestion with blood, that is responsible for the redness and heat b. increase permeability of local capillaries i. fluid containing proteins like clotting factors and antibodies, called exudates, flows from the bloodstream into tissue spaces

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ii. local edema occurs and pain is triggered vi. edema can be beneficial a. helps to dilute harmful substances that may be present b. brings in large quantities of oxygen and nutrients needed for repair. c. allows entry of clotting proteins which forms a fibrin mesh that prevents the spread of harmful agents. vii. increases the production of -defensins, which are antibiotic-like chemicals. 6. Phagocyte mobilization i. sequence: mast cells neutrophils macrophages ii. leukocytosis is first and chemicals called leukocytosis-inducing factors are released from injured cells to promote neutrophil release from red bone marrow. iii. margination is the process of cell adhesion molecules (CAMs) of neutrophils binding to cell adhesion molecules (CAMs) called selectins of the endothelial cells of capillary walls causing the neutrophils to cling to the capillary wall. iv. diapedesis is the process of neutrophils emigrating through the capillary walls to the site of inflammation. v. chemotaxis is the attraction of neutrophils and other white blood cells to the site of injury due to inflammatory chemicals called chemotactic agents. vi. monocytes become macrophages about 8-12 hours after entering the tissues. Macrophages are dominant at sites of chronic inflammation. 7. Pus is a mixture of dead or dying neutrophils, broken-down tissue cells, and living and dead pathogens. 8. Abscesses are sacs of pus walled off by collagen fibers 9. Infection granulomas are tumorlike growths containing macrophages infected by pathogens hiding within it surrounded by uninfected macrophages and an outer fibrous capsule. 10. Antimicrobial proteins i. attack microorganisms directly or inhibit their ability to reproduce ii. interferon a. different types like , , and -interferon b. are small proteins which interferes with viral replication. c. not virus specific d. comes from lymphocytes e. comes from most other leukocytes f. comes from fibroblasts g. activates macrophages and mobilizes natural killer cells h. play an anticancer role i. is used to treat genital warts and can combat Hep C 11. Complement system i. group of at least 20 plasma proteins that destroy foreign substances by lysis when activated. ii. amplifies the inflammatory process iii. there is a classical pathway and an alternative pathway that both lead to the activation of C3, one of the complement proteins, which is then cleaved into two subunits which can cause inflammation and opsonization. iv. MAC is the membrane attack complex which inserts into the membrane of the target cell and inhibits the cells ability to eject Ca+2 and causes lysis 12. Fever i. body temperature is controlled by hypothalamic neurons and is set to about 36.2 C ii. fever occurs when pyrogens, chemicals secreted by leukocytes and macrophages exposed to foreign matter, resets the neurons higher.

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iii. high fevers can denature enzymes iv. fevers are helpful because it speeds up the metabolic rate of tissue cells and cause the liver and spleen to contain iron and zinc, which bacteria require in large amounts to multiply