1. Non-Specific Host Defenses against Microbial Pathogens

2. Non specific defenses of the host The ability to ward off disease through body defenses is called resistance. Lack of resistance is called susceptibility. Nonspecific resistance refers to all body defenses that protect the body against any kind of pathogen. Specific resistance (immunity) refers to defenses (antibodies) against specific microorganisms.

3. An Overview of the body’s defenses

4. First line of defense : Skin and Mucous membranes Skin and Mucous Membrane: The skin and mucous membranes are the body's first line of defense against environmental pathogens. This function results from both physical and chemical factors. Whereas mechanical factors include barriers to entry or processes that remove microbes from the body's surface, chemical factors include substances made by the body that inhibit microbial growth or destroy them.

5. Mechanical factors associated with Skin Dermis: the skin's inner, thicker portion, is composed of connective tissue. Epidermis: the outer, thinner portion, is in direct contact with the external environment Keratin: The top layer of epidermal cells is dead and contains a protective protein called Keratin, provides resistance to microbial invasion.

6. A section through Human Skin

7. Mechanical factors associated with Mucous Membrane Some pathogens if present in large numbers can penetrate mucous membranes. Example: Treponema pallidum Mucus (slightly viscous fluid composed of glycoproteins secreted by goblet cells lining the epithelial layer of mucous membranes) traps traps many of the microorganisms that enter the respiratory and gastrointestinal tracts. The lacrimal apparatus protects the eyes from irritating substances and microorganisms. Saliva dilutes the number of microorganisms and washes them from teeth and gums.

8. The lacrimal apparatus

9. Mechanical factors associated with Mucous Membrane In the lower respiratory tract, the ciliary escalator moves mucus up and out. The flow of urine moves microorganisms out of the urinary tract and vaginal secretions move microorganisms out of the vagina. Microorganisms are also prevented from entering the lower respiratory tract by a small lid of cartilage called the epiglottis, which covers the larynx (voicebox) during swallowing

10. Chemical factors - Sebum contains unsaturated fatty acids which inhibit the growth of pathogenic bacteria. Low pH of skin (pH 3-5) discourages the growth of microorganisms. - Perspiration washes microorganisms off the skin. - Lysozyme, an enzyme that is capable of breaking down cell walls of gram-positive bacteria and to a lesser extent gram- negative bacteria is present in tears, saliva, nasal secretions and perspiration. - The high acidity (ph 1.2 -3) of gastric juice prevents microbial growth in the stomach. - Blood contains antimicrobial chemicals such as iron – binding proteins called transferrins that inhibits bacterial growth by reducing the amount of available iron. Iron is required for microbial growth and it suppresses chemotaxis and phagocytosis and so increases risk of infection.

11. First line of defense: Normal Microbiota Microbial antagonism: The normal microbiota prevent pathogens from colonizing the host by competing with them for nutrients (Compititive Exclusion). By producing substances that is harmful for the pathogens By altering conditions that affect the survival of the pathogens, such as pH and oxygen availa bility. Example: The presence of normal microbiota in the vagina, for example, alters pH, thus preventing overpopulation by Candida albicans, a pathogenic yeast that causes vaginitis. In the large intestine, E. coli bacteria produce bacteriocins that inhibit the growth of Salmonella and Shigella.

12. First line of defense: Normal Microbiota Commensalism: One organism uses the body of a larger organism as its physical environment and may make use of the body to obtain nutrien ts. Thus in commensalism, one organism benefits while the other is unaffected. Thus in commensalism, one organism benefits while the other is unaffected. Most microbes that are part of the commensal microbiota are found on the skin and in the gastrointestinal tract.

13. Second line of defense: Phagocytosis Phagocytosis : Phago: eat and Cyte: cell Phagocytosis is the ingestion of microorganisms or particulate matter by a cell. Phagocytosis is carried out by – phagocytes that are certain types of white blood cells (leukocytes) : neutrophils, eosinophils and macrophages.

14. Second line of defense: (Phagocytic white blood cell ) When an infection occurs both granulocytes (especially neutrophils) and monocytes migrate to the infected area. During this migration, monocytes enlarge and develop into actively phagocytic macrophages. These cells leave the blood and migrate into tissues where they enlarge and develop into macrophages (activated macrophages).

15. Mechanism of Phagocytosis : Phases of Phagocytosis : 1. Chemotaxis- Phagocytes are chemically attracted to site of infection. 2. Adherence- Phagocyte plasma membrane attaches to surface of pathogen or foreign material 3. Ingestion- Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called phagosome. 4. Digestion- Inside the cell, phagosome fuses with lysosome to form a phagolysosome initiate the digestion of target pathogen

16. Mechanism of Phagocytosis

17. Microbial Evasion of Phagocytosis MechanismOrganisms Inhibit adherence: M protein, capsules Streptococcus pyogenes, S. pneumoniae Kill phagocytes: LeukocidinsStaphylococcus aureus Lyse phagocytes: Membrane attack complex Listeria monocytogenes Escape phagosomeShigella Prevent phagosome-lysosome fusion HIV Survive in phagolysosomeCoxiella burnetti and Mycobacteria spp

18. Inflammation Inflammation is one of the first local responses of the immune system to infection. Injury can be caused by physical agents (heat, sharp objects), chemical agents( acids, bases, gases) or microbial infection. Inflammation is characterized by- 1. increased blood flow to the site of injury 2. increased temperature, 3. redness, 4. swelling, and 5. pain.

19. Destroy the agent causing injury or infection Limit the affect of injury or infection on rest of the part of body Repair and replacement of injured or infected tissue Objective of inflammation

20. The stages of Inflammation Tisssue Injury Vasodilation and Increased permeability of blood vessels Phagocyte migration and phagocytosis Tissue repair

22. Fever Fever is a systemic response of the body to injury, which is characterized by abnormally high body temperature.

23. Fever Body temperature is controlled by a part of the brain called the hypothalamus. The hypothalamus is sometimes called the body's thermostat, and it is normally set at 37°C (98.6°F). It is believed that certain substances affect the hypothalamus by setting it at a higher temperature. When phagocytes ingest gram-negative bacteria, the lipopolysaccharides (LPS) of the cell wall (endotoxins) are released, causing the phagocytes to release the cytokines interleukin- I (formerly called endogenous pyrogen), along with TNF- α. These cytokines cause the hypothalamus to release prostaglandins that reset the hypothalamic thermostat at a higher temperature, thereby causing fever

24. Fever

25. Assume that the body is invaded by pathogens and that the thermostat setting is increased to 39°C (I 02.2"F). To adjust to the new thermostat setting, the body responds by constricting blood vessels, increasing the rate of metabolism, and shivering, all of which raise body temperature. Even though body temperature is climbing higher than normal, the skin remains cold, and shivering occurs. This condition, called a chill, is a definite sign that body temperature is rising. When body temperature reaches the setting of the thermostat, the chill disappears. The body will continue to maintain its temperature at 39"C until the cytokines are eliminated. The thermostat is then reset to 37°e. As the infection subsides, heat- losing mechanisms such as vasodilation and sweating go into operation. The skin becomes warm, and the person begins to sweat. This phase of the fever, called the crisis, indicates that body temperature is falling.

26. Fever- a defense against disease Up to a certain point, fever is considered a defense against disease. Interleukin-I helps step up the production of T cells. High body temperature intensifies the effect of antiviral interferons and increases production of transferrins that decrease the iron available to microbes. Also, because the high temperature speeds up the body's reactions, it may help body tissues repair themselves more quickly.