Microbes and Human Diseases Microbial Mechanisms of Pathogenicity How microorganisms enter a host How microorganisms penetrate host defenses How microorganisms.

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


•Mycobacterium tuberculosis can even multiply inside phagocytes

• waxy lipid = mycolic acid

•Mycolic acid increase virulence by resisting digestion by phagocytes


• 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


•Coagulases = enzymes that coagulate (clot) the fibrinogen in blood

•Staphylococcus (some members)

protect the bacteria from phagocytosis


•Other enzymes•Kinases

•Fibrinolysin•Streptokinase

collagenase

IgA proteases = destroy IgA = antibody in mucosal surfacesNeisseria gonorrhaeaeNeisseria meningitidis


•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


•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


•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


•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


•The production of toxins = poisonous substance produced by bacteria

•Toxemia = the presence of toxins in the blood

•Toxigenicity = the ability to produce toxins


•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


•Toxins = can inhibit protein synthesis• destroy blood cells

• = = vessels• & disrupt the nervous system by

• causing spasms

•Exotoxins • &

• Endotoxins


•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


•Exotoxins = are soluble in body fluids

• = they can easily diffuse into the blood

• = are rapidly transported through the body

•Botulism


•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


•Types of exotoxins

•+++A-B toxins

•+++membrane-disrupting toxins

•+++superantigens

•A-B toxins=polypeptides = inhibits protein synthesis & kill the host cell

•Diphtheria toxin


•membrane-disrupting toxins =cause lysis of host cells by disrupting their plasma membranes

•Staphylococcus aureus= hemolysin

Destroy RBC


•Streptococci = hemolysin

•Streptolysins

• Streptolysin O )SLO( =is inactivated by

atmospheric O2

Streptolysin S (SLS) =is stable in an O2

environment

Lysis of RBC & WBC


•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•


•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


•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


•Shock = any life-threatening decrease in blood pressure

•Septic shock = shock caused by bacteria

•Endotoxic shock = Gram negative bacteria endotoxin


•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


•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

•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


•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•


•**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 PathogenicityMicrobial entryPenetration of host defensesDamage of the hostMicrobial 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


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


•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


•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


• 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


•There are many factors that determine the distribution & composition of the normal microbiota

•Nutrients

•Physical & chemical factors

•Defenses of the host

•Mechanical factors


•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


•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


•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


•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


•e.g.

•Lactobacilli & the yeast Candida albicans

•Vagina pH 4

•E.coli in the intestine produce bacteriocins , that inhibit the growth of salmonella & shigella


•Symbiosis==the relation between normal microbiota &the host ==means living together



•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.Good Luck

Microbes and Human Diseases Microbial Mechanisms of Pathogenicity How microorganisms enter a host How microorganisms penetrate host defenses How microorganisms.

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