Transcript Lecture 7

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.
Good Luck