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Microbes and Human Diseases Microbial Mechanisms of Pathogenicity • How microorganisms enter a host • How microorganisms penetrate host • defenses How microorganisms damage host cells • Microbial Mechanisms of Pathogenicity Pathogenicity = is the ability of a pathogen • to produce a disease by overcoming the defenses of the host Virulence = is the degree of Pathogenicity • Incubation period = is the period between • the entry of the microbe till the appearance of disease symptoms Microbial Mechanisms of Pathogenicity To cause disease , most pathogens must • Enter the host • Adhere to host tissues • Penetrate or evade host defenses • Damage the host tissues • Exit from the host • Portals of entry Mucous membranes , conjunctiva , skin • Respiratory tract (inhalation) • (Common cold ,pneumonia ,tuberculosis ,influenza ,measles) • Gastrointestinal tract(food ,water, fingers) • (poliomyelitis ,hepatitis A ,typhoid fever ,amoebic dysentery • ,cholera ,giardiasis) Genitourinary tract (sexually transmitted diseases) • (HIV ,genital warts ,chlamydia ,herpes ,syphilis ,gonorrhea) • Portals of entry Skin • Intact skin = important defense • Hair follicles ,sweat gland ducts ,larvae of the • hookworm ,fungi Inoculation through the skin & mucous • membranes (injury) Bites = rabies • Injection =malaria • Wound • Parenteral route • Adhere to host tissues Adhesins or ligands == Surface • projections on a pathogen = glycoproteins or lipoproteins = associated with fimbriae Adhere to complementary receptors on • host cells = mannose How pathogen penetrate host defenses Capsules =some bacteria make • glycocalyx material that forms capsules around their cell wall This increase the virulence of species • ==prevent bacteria from being phagocytized Streptococcus pneumoniae • How pathogen penetrate host defenses Cell wall components = some bacteria • contain chemical substances that contribute to virulence Streptococcus pyogenes =produce a • heat-resistant & acid-resistant protein = Mprotein =present in cell surface & fimbriae =increase the virulence M-protein mediates attachment of the • bacteria to epithelial cells of the host & helps them resist phagocytosis by WBC How pathogen penetrate host defenses Mycobacterium tuberculosis can even • multiply inside phagocytes waxy lipid = mycolic acid • Mycolic acid increase virulence by • resisting digestion by phagocytes How pathogen penetrate host defenses Enzymes = the virulence of some • bacteria is thought to be aided by the production of extracellular enzymes =exoenzymes ==can digest materials between cells or • digest blood clot How pathogen penetrate host defenses Coagulases = enzymes that coagulate (clot) • the fibrinogen in blood Staphylococcus (some members) • protect the bacteria from phagocytosis How pathogen penetrate host defenses Other enzymes • Kinases • Fibrinolysin • Streptokinase • collagenase IgA proteases = destroy IgA = antibody in mucosal surfaces Neisseria gonorrhaeae Neisseria meningitidis How pathogen penetrate host defenses Antigenic variation =some pathogen alter • their surface antigens Adaptive immunity = acquired = specific • defensive response of the body to an infection or to antigen In the presence of antigen the body • produces protein called antibody = bind to antigen and inactivate or destroy them How pathogen penetrate host defenses by the time the body mounts an immune • response against a pathogen When the pathogen has altered its • antigens and is unaffected by the antibodies Neisseria gonorrhoeae • Influenza virus • Penetration into the host cell cytoskeleton Cytoskeleton =protein filaments • (microfilaments ,intermediate filaments & microtubules) that present in the cytoplasm of eukaryotic cells that provide support & movement Penetration into the host cell cytoskeleton ** when microbes attach host cell by • adhesins **this triggers signals in the host cell that • activate factors that can result in the entrance of bacteria **this mechanism is provided by the host • cell cytoskeleton How bacterial pathogen damage host cell Pathogen can damage host cell in four • basic ways: ## by using the host`s nutrients • ## by causing direct damage • ## by producing toxins • ## by inducing hypersensitivity • How bacterial pathogen damage host cell Using the host cell nutrients siderophores • =protein secreted by some bacteria in order to obtain free iron !!-iron is required for the growth of pathogenic • bacteria !!-in human body the concentration of free • iron is low = most of it is bound to iron transport protein (transferrin , ferritin & hemoglobin) **** = bacteria secrete siderophores in order • to obtain free iron How bacterial pathogen damage host cell Direct damage=pathogens metabolized & • multiply inside the host cell by using nutrients & produce waste products=destroyed = rupture • the microbe released & spread to other • tissues in greater number How bacterial pathogen damage host cell The production of toxins = poisonous • substance produced by bacteria Toxemia = the presence of toxins in the • blood Toxigenicity = the ability to produce toxins • How bacterial pathogen damage host cell Toxins=are primary factor contributing to • the pathogenic bacteria =when transported by blood or • lymph can cause serious & some times fatal effects fever • cardiovascular disturbances • diarrhea • & shock • How bacterial pathogen damage host cell Toxins = can inhibit protein synthesis • destroy blood cells • = = vessels • & disrupt the nervous system by • causing spasms • Exotoxins & • Endotoxins • • How bacterial pathogen damage host cell Exotoxins = are proteins = Gram • positive & Gram negative bacteria ====produced inside bacteria as a part of their growth & metabolism & are secreted into the surrounding medium or released following lysis How bacterial pathogen damage host cell Exotoxins = are soluble in body fluids • = they can easily diffuse into the blood • = are rapidly transported through the • body Botulism • How bacterial pathogen damage host cell Antitoxins = antibody to toxins = provide • immunity to exotoxins Toxoid = altered exotoxin = exotoxins are • inactivated by heat or by formaldehyde , iodine or other chemicals they no longer cause disease but can still stimulate the body to produce antibody (antitoxins) tetanus • vaccine How bacterial pathogen damage host cell Types of exotoxins • +++A-B toxins • +++membrane-disrupting toxins • +++superantigens • A-B toxins=polypeptides = inhibits protein • synthesis & kill the host cell Diphtheria toxin • How bacterial pathogen damage host cell membrane-disrupting toxins =cause • lysis of host cells by disrupting their plasma membranes hemolysin Staphylococcus aureus = • Destroy RBC How bacterial pathogen damage host cell Streptococci = hemolysin • Streptolysins • Streptolysin O (SLO) =is inactivated by • atmospheric O2 Streptolysin S (SLS) =is stable in an O2 environment Lysis of RBC & WBC How bacterial pathogen damage host cell Superantigens =bacterial proteins = antigen • that activate immune system ===electing a large immune response=====large amount of proteins (cytokines) ==== give rise to a number of symptoms *fever *diarrhea *nausea *vomiting • *some time shock & even • death Staphylococcal toxins • ==food poisoning • ==toxic shock syndrome • • How bacterial pathogen damage host cell Endotoxins = are lipopolysaccharides • **the lipid A component of the cell wall of • Gram negative bacteria ## are part of the outer portion of the cell • wall **are released when Gram negative • bacteria die & their cell walls undergo lysis How bacterial pathogen damage host cell Antibiotics used to treat diseases caused • by Gram negative bacteria can lyses the bacterial cell ===this reaction releases endotoxin • ====lead to an immediate worsening of • the symptoms Pyrogenic response caused by endotoxin == when gm – ve bacteria ingested by phagocytes – degradation & the release of toxin ==the endotoxin cause the macrophages to produce a cytokine = interleukin-1 ==carried via the blood to hypothalamus=a temp control center in the brain ==prostaglandins released = reset the thermostat = high temp = fever How bacterial pathogen damage host cell Shock = any life-threatening decrease in • blood pressure Septic shock = shock caused by bacteria • Endotoxic shock = Gram negative • bacteria endotoxin How bacterial pathogen damage host cell Phagocytosis of Gram negative bacteria • Phagocytes ---secrete polypeptide • (tumor necrosis • factor) bind to many tissues in the body & • alter the metabolism • Damage blood capillaries –their • permeability drop in blood • How bacterial pathogen damage host cell Salmonella typhi Proteus spp == typhoid • == urinary tract infection • == wound infection • Neisseria meningitidis == meningitis • exotoxins Naming – according to the system • that can be affected Neurotoxins = nervous system • Hepatotoxins = liver • Nephrotoxins = urinary tract • exotoxins According to the disease • Diphtheria toxin • Tetanus toxin • Vibrio toxin • Pathogenic properties of viruses **viruses evade destruction by the host s • immune response by: ---viruses can penetrate and grow inside of • host cell ---viruses have specific attachment sites • for receptors on their target cells CD4 for HIV • Pathogenic properties of viruses Cytopathic effects of viruses (CPE) = • destruction , killing & death of host cells **stop mitosis = cytocidal • **inclusion bodies =viral parts ,nucleic acid or • proteins in the cytoplasm or in the nucleus Negri bodies=rabies • • Pathogenic properties of viruses **syncytium=giant cell • **decrease immunity= measles • **interferon production • **chromosomal changes & contact inhibition • = oncogen =cancer causing genes • =transformation = malignant cell • Pathogenic properties of fungi Symptoms of fungal infections can be • caused by : Capsules • Toxins =inhibit protein synthesis • Ingestion of toxins cause headaches , • vomiting nausea Allergic responses = molds growing in • homes Pathogenic properties of protozoa & helminths Symptoms of protozoan & helminthic can • be caused by **damage to host tissue • **the metabolic waste products of the • parasite **some protozoan change their surface • antigen while growing in a host thus avoiding destruction by the host antibodies Portals of exit Pathogens have preferred portal of entry , • they also have definite portals of exit **respiratory tract = coughing ,sneezing • **gastrointestinal tract =saliva , feces • **genitourinary tract = genital secretions • Mechanisms of Pathogenicity Microbial entry Penetration of host defenses Damage of the host Microbial exit Microbes and Human Diseases Normal Microbiota • Biofilms • Infectious diseases • Emerging Infectious diseases • Biofilms Masses of microbes & their extracellular products • attach to living & non living surfaces == biofilms Dental plaque on teeth • Algae on walls of swimming pools • Scum accumulates on shower doors • Biofilms provide attachment & resistance to • antimicrobial agents Biofilms Microbes adhere to particular surface that • is typically moist & contain organic matter Microbes multiply & secrete a glycocalyx • glycocalyx = enzyme produced by bacteria convert glucose • into sticky • polysaccharide Normal microbiota = normal flora Pathology = is the science of diseases • Etiology = the causes of the disease • Pathogenesis & Pathogenicity • Virulence • Infection = invasion or colonization of the • body by pathogenic microorganism = the presence of a particular type of microorganism in a part of the body where it is not normally found E.coli = normally in intestine ** urinary tract • infection Normal microbiota = normal flora disease = an abnormal state in the body , in which part or all of the body is not properly adjusted , or incapable of performing normal functions ====any change from a state of health Infectious disease = caused by a microbe • Normal microbiota = normal flora Microorganisms -----few are pathogenic • -----some are benefit • Humans are generally free of microbes in • utero Microbes being colonization in & on the • surface of the body soon after birth Normal microbiota = normal flora The first contact is during delivery • Lactobacilli ==become the predominant • organism in the newborn E.coli == acquired from foods begin to • inhibit large intestine & remain there throughout life Normal microbiota = normal flora 14 • The number of bacteria on the body =1x10 • 13 • The number of body cells =1x10 • Bacteria which are establish permanent residence • inside or on the body without producing disease is called === normal microbiota or normal flora Transient microbiota ==present for various • periods & then disappear Normal microbiota = normal flora There are many factors that determine the • distribution & composition of the normal microbiota Nutrients • Physical & chemical factors • Defenses of the host • Mechanical factors • Normal microbiota = normal flora Nutrients== bacteria can colonize only those • body sites that can supply the appropriate nutrients Nutrients may be derived from • secretary products of cells • Body fluids • Dead cells • food in gastrointestinal tract • Normal microbiota = normal flora Physical & chemical factors === • temperature pH, O2 , CO2 • Defenses=immune response=variety of • molecules & activated cells that kill microbes or inhibit their growth or prevent adhesion & neutralize toxins Normal microbiota = normal flora Mechanical factors=may affect • colonization by normal flora e.g. • Chewing action of the teeth remove • microorganism attachment G.I.T. – flow of saliva & digestive • secretions R.T –mucus membrane • Normal microbiota = normal flora Other factors that also affect the normal • microbiota Age • Nutritional status • Diet • Health status • Disability • Climate\geography • Personal hygiene • Life style • Relationship between the normal microbiota and the host Microbial antagonism ===competitive exclusion ====normal microbiota prevent pathogen from colonization === protect the host By----Competing for nutrients Producing harmful substance affecting the growth of the pathogen Relationship between the normal microbiota and the host e.g. • Lactobacilli & the yeast Candida albicans • Vagina pH 4 • E.coli in the intestine produce bacteriocins • , that inhibit the growth of salmonella & shigella Relationship between the normal microbiota and the host Symbiosis==the relation between normal • microbiota &the host ==means living together Relationship between the normal microbiota and the host commensalism • One of the organism is benefited &the other is unaffected • Corynebacteria- eye---mycobacteria-ear no apparent benefit or harm to the host mutualism • Both are benefits • E.coli in intestine synthesize vitamins K ?& some B vitamins parasitism • One organism Is benefited by deriving nutrients at the expense of the other • disease Relationship between the normal microbiota and the host Probiotics==are live culture application to • exert beneficial effect Microbes produce CD4 --- HIV • The relationship (symbiosis) can change • under certain condition Opportunistic microorganisms ==microorganisms that do not cause • disease under normal conditions but cause disease under special conditions ***the symbiotic relationship can be • changed Opportunistic microorganisms e.g. • E.coli=harmless as long as it remains in • the large intestine – but if it gains access to other body sites it may cause disease Urinary bladder===urinary tract infection • Lung===pulmonary infection • Spinal cord===meningitis • Wounds===abscesses • Opportunistic pathogen • Opportunistic microorganisms AIDS is often accompanied by a common • opportunistic infections Because AIDS patients immune system is • suppressed Second Term Exam. 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