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On the basis of life habitat, microorganisms can be classified into: 1- Saprophytes 2- Parasites 3- Commensals Definition of opportunistic pathogens -Pathogenic organisms: they are primary pathogens capable of establishing and causing disease in healthy person with intact immunological defenses. Virulence: is a measure for the degree of pathogenicity. Virulence depends on: a) Ability of entrance -colonize-invadeovercome host defenses- multiply and disseminate widely. b) toxigenicity: ability to produce toxins. Stages of bacterial pathogenesis: 1- transmission from an external source in to the portal of entry.( modes of transmission). 2- evasion of primary host defenses such as skin or stomach acid. 3- adherence to mucous membrane. 4- Colonization by growth the bacteria on the site of infection. 5- Disease symptoms caused by toxin production or extracellular enzymes. 6- Host responses, both specific and nonspecific (immunity). 7- Progression or resolution of the disease. Differences between Exotoxins and Endotoxins Properties Exotoxin Endotoxin Source Some +ve and –ve bacteria Part of cell wall of most –ve bacteria Chemical nature polypeptide L.P.S Location of genes plasmid Bacterial chromosome Toxicity high low Clinical effects various Fever, hypotension,shock Vaccines Toxoids No vaccine Heat stability thermolabile thermostable Extracellular enzymes: Many bacteria secrete a range of enzymes that involved in the pathogenic process e.g -Coagulase: it clots plasma and produce fibrin coat protects microorganisms from phagocytosis. Staphylococcus aureus - Collagenase: It breaks down collagen (which is the constituent of muscle, bone and cartilage) thus allow bacteria to spread. Clostridium perfringens -Lecithinase: It breaks down lecithin (main constituent of cell membranes) causes hemolysis, necrosis.Cl.perfringens -Leukocidin: it destroys host leukocytes Streptococci - Haemolysin: cause lysis of RBC. - Deoxyribonuclease: It breaks down host DNA Immunity Protection /defense . . . against whatever doesn’t belong Other pathogens Cancer Chemicals Damage/ injury Concept, Functions and Types of Immunity Concept and functions of Immunity Types of Immunity I- Concept of Immunity 1)Traditional concept: Immunity refers to protection against infectious diseases. 2) Modern concept-: Immunity is a function of which an individual recognizes and excludes antigenic foreign substances. It is normally beneficial, but sometimes, it is injurious. II- Concept of Immunology 1) Traditional concept: anti-infection immunity to different types of pathogenic microorganisms. 2) Modern concept: Immunology is an independent subject about - composition, - functions of immune system; - mechanism of immune response and the disease associated with immunity. III Functions of Immunity Immune defense: Immune homeostasis: eliminate injured and senile cells . Tolerate to self components . Immune surveillance: destroy transformed cells (anti-tumor ) . Types of Immunity I. Innate Immunity (or native immunity/ non-specific immunity /congenital immunity) II. Adaptive Immunity (or acquired immunity/specific immunity) Body defense against microbes Non-specific immunity First line (immediate) - Skin -Mucous membranes -- Chemicals Second line -Phagocytosis -Complement -Interferons -Inflamation -fever Specific immunity (delayed) -Lymphocytes -Antibodies Non- specific immunity Natural (innate) immunity - It is v. effective mechanisms present from birth which do not depend upon host having previous exposure to any M.O. - Acts immediately as the first line of defense or within several hours after exposure to antigen. -Innate immunity does not recognize every possible antigen. Innate immunity 1. Characteristics Exists naturally Non–specific No immune memory (innate immunity can’t be enhanced by the second stimulation of the same antigen). Immune memory: Exposure of the immune system to a foreign antigen enhances its ability to respond again to that antigen. 2. Composition (1) Barriers Physical barrier : skin and mucosa Chemical barrier: antimicrobial substances in secretion of skin and mucosa Biotic barrier: normal flora existing on the surface of skin and mucosa Anatomic barrier . blood- brain barrier . blood- placental barrier Physical Barriers - Skin - Mucous membranes - Hairs and mucus of respiratory system -Reflex flushing through coughing, sneezing, vomiting,, -Urinary flow -Blinking reflex of eyes. - digestive tract peristalsis. Chemical Defenses - Acids produced by sweat, sebaceous glands, and stomach - Lysozyme: in tears, saliva, mucus; cleaves peptidoglycan (G+) - Transferrin: in blood, binds free iron, thus inhibiting bacterial growth - Defensins: peptides disrupting cell membranes. (2) Humoral factors Complement system: Lysozyme: Basic protein found in microphage (PMN) as well as most tissue fluids except CSF, sweet and urine. It destroys the cell wall of bacteria. Interferons(IFN): C-reactive protein (CRP): Measure of inflammation produced in liver in response to inflammatory chemicals. 3) Cellular factors: - Normal flora ( Microbiota) -Natural killer cells: (NK), these are non-T, non-B lymphocytes, which have natural ability to kill foreign cell as tumor, viral cells and activated by interferon and interleukin 2. -Phagocytosis: - mononuclear phagocytes (Monocytes,Macrophages) - Professional phagocytes: microphages - Dendritic cells(DC) Macrophages NK cells Neutrophils Macrophages Macrophages excluding the pathogen Complement system -Is formed of heat labile proteins components present normally in an inactive form in serum and other body fluids except urine and CSF. -There are 9 major components termed C1-C9. -There activation proceed through: 1- Classical pathway or 2- Alternative pathway. 3-Lectin binding pathway. Role of skin in nonspecific defense: (first line of defense) Intact skin and mucous membranes of the body afford effective protection against M.O. Skin contains - Collagen: gives the skin strength and pliability to prevent skin scraps and introduce M.O - Dendritic cells . - The sweat and sebaceous secretions contain antimicrobial substances as F.A and lysozyme. Two major layers of skin: Epidermis -Outer layer composed of multiple layers of tightly packed cells. -Few pathogens can penetrate these layers. - Epidermal dendritic cells phagocytiz pathogens. Dermis: - Contains protein fibers called collagen - Give skin strength and pliability to resist abrasions that could introduce microorganisms. Mucous, secreted by the membranes lining the inner surfaces of the body acts as a protective barrier by trapping M.O. -Lysozyme -S IgA -Lactoferrin -Lactoperoxidase Role of normal microbiota in nonspecific microbial antagonism Many bacteria and other M.O reside in the human body. These normal body flora keep potentially harmful opportunistic pathogens and inhibit the colonization of M.O by: A- producing metabolic products( fatty acids, bacteriocins) . B- Can change the pH. C- adhering to target host cells thus covering them and preventing pathogens from colonizing. D- depleting nutrients essential for growth of pathogens. E- nonspecifically stimulating the immune system. For example: When protective commensals are disturbed by antibiotics, susceptibility to opportunistic infections such as Candida albicans and Clostridium difficile is increased. pathogen invasion of the vagina is limited by lactic acid produced by commensal organisms which metabolize glycogen secreted by the vaginal epithelium