Chapter 16 Host Defenses Against Microbes NONSPECIFIC 1 Nonspecific Defenses What are Nonspecific Defenses? Defenses that protect against any pathogen, regardless of species. two nonspecific lines of defense: first: skin and mucous membranes second: phagocytes, inflammation, fever, and antimicrobial substances Specific resistance (immunity) - third line of defense… Effective against particular pathogens (covered in Ch. 17) 2 3 Mechanical Barriers - Skin largest organ of human body consists of dermis, thick inner portion made of connective tissue; and epidermis, thinner outer portion which contains sheets of tightly packed epithelial cells covered with outer layer of dead epidermal cells and waterproofing protein, keratin provides a barrier against penetration by microorganisms 4 5 Mechanical Barriers - Mucous Membranes Mucous membranes line gastrointestinal, respiratory, & genitourinary tracts. also have epithelial layer over connective tissue secrete mucous (prevents drying) less protective than skin (thinner barrier) 6 Lacrimal Apparatus group of structures which manufacture and drain away tears continual washing keeps microorganisms from settling on the surface of the eye 7 Saliva dilutes microbes in mouth… washes microbes from surface of teeth 8 9 Ciliary Escalator in respiratory tract, cilia move mucous toward the throat, physically removes microorganisms 10 11 Genitourinary Tract Two methods of nonspecific protection urine flow helps prevent colonization by microbes vaginal secretions move microorganisms out of the body 12 Chemical Factors Sebum produced by sebaceous (oil) glands forms protective film over surface of skin, and fatty acids in it lowers the pH of the skin low pH discourages bacterial growth perspiration from sweat glands not only helps maintain body temperature, but also flush microorganisms from the skin Sweat contains lysozyme an enzyme which can breakdown the Grampositive cell wall (less effective against Gram-negatives) Lysozyme is also found in tears, saliva, nasal secretions and tissue fluids & gastric juice in stomach 13 Phagocytosis "cell eating", any cells which do this are called phagocytes 14 Macrophage phagocytizing bacteria 15 16 Let’s Meet the Phagocytes! Components of Blood plasma is the fluid portion formed elements: cells and cell fragments (Table 16.1) 17 White Blood Cells Phagocytic & Non-Phagocytic 18 19 20 Phagocytes are White Blood Cells Leukocytes - white blood cells changes in WBCs detected by differential white blood cell count three categories of WBCs include” granulocytes (grainy cytoplasm) agranulocytes (non-grainy cytoplasm) monocytes lymphocytes 21 Actions of Phagocytic Cells Granulocytes and monocytes migrate to the site of the infection Monocytes enlarge and become macrophages Some leave the blood and migrate into surrounding tissues are known as wandering macrophages some, called fixed macrophages, are located in specific tissues and organs Together, these macrophages constitute the mononuclear phagocytic (reticuloendothelial) system 22 Order of Battle for Phagocytes Granulocytes (esp. neutrophils) dominate phagocytic role in the initial phase of a bacterial infection – extremely active phagocytes Later in the infectious process macrophages (agranulocytes) become dominant as the infection progresses 23 Mechanisms of Phagocytosis Four Steps of Phagocytosis Chemotaxis - chemical attraction of phagocytes to microorganisms Adherence - attachment of the phagocyte’s plasma membrane to the surface of the microorganism Ingestion - engulfment by pseudopods, produces phagosome Digestion - phagosome fuses with lysosome (containing digestinve enzymes) to form a phagolysosome 24 Bacterial Digestion in Phagolysome digestive enzymes are activated at low pH of about 4 and, along with other toxic compounds, kill and digest the bacteria The residual body is the phagolysome containing the remaining undigestible material after digestion, which is then ejected from the cell 25 26 Inflammation functions (3) of inflammation… Destroy infections agent & remove its toxic by-products If destruction not possible – isolate the organism & its products to prevent spread Repair tissue damage 27 Inflammation …a defensive response triggered by damage to body tissues symptoms include redness pain heat swelling 28 29 30 Process of Inflammation Damage occurs Vasodilation (blood vessels expand) Blood vessel permeability increases (become leaky so phagocytic cells can leave bloodstream & enter tissues) Phagocytes migrate to damaged area & begin cleaning up bacteria & cellular debris Damage tissue repaired 31 Vasodilation Vasodilation is the increase in diameter of blood vessels increases blood flow to damaged areas responsible for redness and heat associated with inflammation increase permeability of blood vessels permits fluid and other elements of blood to enter the injured area responsible for edema (swelling) of inflammation these effects caused by chemicals released by damaged cells 32 Vasodilation Causing Substances Substances which lead to vasodilation/permeability histamine - released by injured cells, also a part of the complement system kinins - present in blood plasma, when active also play a role in chemotaxis of phagocytic granulocytes prostaglandins - released by damaged cells, intensifies effects of histamines and kinins, helps phagocytes move through capillary walls leukotrienes - produced by mast cells - increase permeablility of blood vessels and help attach phagocytes to pathogens 33 Phagocyte Migration within 1 hour of initiation of inflammation, phagocytes arrive on the scene phagocytes stick to inner surface of lining of blood vessels (called margination) collected phagocytes squeeze between endothelial cells to reach the damaged area (migration) monocytes follow the granulocytes into the affected area once in the tissue, the monocytes transform into macrophages & actively phagocytize 34 Tissue Repair the final stage of inflammation dead or damaged cells are replaced by new cells in stroma (connective tissue) and parenchyma (functioning portion of tissue) 35 Fever abnormally high body temperature most frequently caused by bacterial infection (or toxins) or viruses Interleukin-1 (IL-1) – produced by phagocytes resets hypothalamic thermostat to a higher temperature (may also be induced by endotoxins) blood vessel constriction, increased rate of metabolism, and shivering all contribute to temperature rise - maintained until IL-1 is eliminated Higher body temperature makes some antiviral proteins (interferons) more effective & may inhibit growth of some microbes crisis: period of sweating, indicates that temperature is falling 36 Antimicrobial Substances Complement System Interferons both to be discussed in some detail in following slides… 37 Complement System Complement is a defensive system of blood serum proteins that participate in lysis of foreign cells, inflammation, and phagocytosis activated in two ways: immune reaction of antibodies to antigens (classical pathway) direct interaction of certain proteins with polysaccharides (alternative pathway) 38 components: at least 20 interacting proteins major components labeled by numbering system from C1 to C9 alternative pathway consists of proteins called factor B, D, and P, along with C3, C5-C9 39 Common Link in Pathways The factor in common between the Classical & Alternate pathway Production of the activating factor C3b 40 41 42 Inflammation & Complement Inflammation can be induced by the complement system… When C5a & C3a bind to mast cells, histamine is released C5a acts as a chemical signal to call in phagocytes (chemotaxis) 43 44 Consequences Of Complement Activation Cytolysis - complement system components damage the plasma membranes of the foreign cells, causing them to leak Inflammation - cleavage products from C3 and C5 can contribute to the development of acute inflammation, C5a also a powerful chemotactic factor Opsonization - immune adherence -- binding of C3b to the microbe can interact with receptors on phagocytes Inactivation of complement -regulatory proteins quickly inactivate 45 Interferons Interferons (IFNs) - class of similar antiviral proteins produced by certain animal cells in response to viral infection How do they function? Interferons interfere with viral multiplication Where do they come from? Excreted by host cell What do they do? Stimulate production of antiviral proteins (AVPs) by neighboring cells AVPs are enzymes that disrupt various stages of viral multiplication IFNs are effective for short times, and do not affect viral multiplication in cells already infected 46 47 48