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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
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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
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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
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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)
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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
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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
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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
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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 = M-protein =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
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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
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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
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How pathogen penetrate host defenses
Coagulases = enzymes that coagulate (clot) the fibrinogen in blood Staphylococcus (some members) protect the bacteria from phagocytosis
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How pathogen penetrate host defenses
Other enzymes Kinases Fibrinolysin Streptokinase collagenase IgA proteases = destroy IgA = antibody in mucosal surfaces Neisseria gonorrhaeae Neisseria meningitidis
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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
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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
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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
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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
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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
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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
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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
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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
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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
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How bacterial pathogen damage host cell
Toxins = can inhibit protein synthesis destroy blood cells = = vessels & disrupt the nervous system by causing spasms Exotoxins & Endotoxins
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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
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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
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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
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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
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How bacterial pathogen damage host cell
membrane-disrupting toxins =cause lysis of host cells by disrupting their plasma membranes Staphylococcus aureus = hemolysin Destroy RBC
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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
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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
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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
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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
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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
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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
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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 pressure
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How bacterial pathogen damage host cell
Salmonella typhi == typhoid Proteus spp == urinary tract infection == wound infection Neisseria meningitidis == meningitis
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exotoxins Naming – according to the system that can be affected
Neurotoxins = nervous system Hepatotoxins = liver Nephrotoxins = urinary tract
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exotoxins Diphtheria toxin Tetanus toxin Vibrio toxin
According to the disease Diphtheria toxin Tetanus toxin Vibrio toxin
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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
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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
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Pathogenic properties of viruses
**syncytium=giant cell **decrease immunity= measles **interferon production **chromosomal changes & contact inhibition = oncogen =cancer causing genes =transformation = malignant cell
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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
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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
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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
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Mechanisms of Pathogenicity
Microbial entry Penetration of host defenses Damage of the host Microbial exit
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Microbes and Human Diseases
Normal Microbiota Biofilms Infectious diseases Emerging Infectious diseases
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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
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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 glycocalyx
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Relationship between the normal microbiota and the host
Symbiosis==the relation between normal microbiota &the host ==means living together
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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
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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
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Opportunistic microorganisms
==microorganisms that do not cause disease under normal conditions but cause disease under special conditions ***the symbiotic relationship can be changed
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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
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Opportunistic microorganisms
AIDS is often accompanied by a common opportunistic infections Because AIDS patients immune system is suppressed
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Second Term Exam. Good Luck
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