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 = 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

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 Staphylococcus aureus = hemolysin 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 pressure

How bacterial pathogen damage host cell Salmonella typhi == typhoid Proteus spp == 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 Diphtheria toxin Tetanus toxin Vibrio toxin 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 glycocalyx

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

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