FLORA NORMAL

EFRIDA WARGANEGARA
 Introduction
Many of m.o. this form what is
termed the indigenous or
normal flora of the body, a
collection of spesies routinely in the
normal, healthy individual
Some of this species are positively
benefecial to the host
M.O. that benefit from this
association without harming the
host are referred to as
commensals
 Introduction
Term flora is used because the
majority of the m.o. are bacteria.
Antibiotic therapi can eliminated
normal flora, but is not possible to
eliminate the normal flora of the skin
or intestine antibiotica can
drastically reduce their number to a
minimum
The host may then be overun by
introduce patogens or by overgrowth
of m.o. normally present in small
number
 Commensalism
The normal flora (commensals) is
aquired rapidly during and shortly after
birth and changes continously
throughout life.
It has been estimated that human have
approximately 1013 cells in the body and
something like 1014 bacteria associated
with them, the majority in the large
bowel.
Virus, fungi and protozoa can also be
found in healthy individuals, although
these form only a minor component of
the total population or resident organism
 Commensalism
Before birth the fetus is essentially in a
steril
environment, but at delivery m.o. come into
contact with the infantbaby is exposed to a
variety of m.o. that take up residence on its skins
and in the digestive tract.
Some of these m.o. are derived from the
mother or others who come into contact with
the infant.
Various m.o. in food, on other human, and

in the environment soon also become

established as residents on the newborn
 Constituent organism present at any given time
reflect the age, nutrition and environment of the
individual
concerned
 Commensalism
Most m.o. are transient paserby that are
destroyed
by conditions in the host, but others establish
themselves and produce microcolonies
colonized the host microflora
established (resident)
Not all area of the body are occupied

by commensal spesies
There are appreciable numbers of m.o. in the

: Upper Resp. Tract, lower intestinal tract,

and skin
 Esophagus, urinary tract and stomach
contain few m.o.
The blood, spinal fluid, urine and endothelial
tissues are normally steril
 Commensalism
Microflora remain with the host for life, with
only
minor changes resulting disease,
diatery alteration, or hormonal
changes
The factors that influence the kind and
number of m.o. at any body site are :
1. The availabiliy or unavailability
oxygen 2. The availability of
appropriate receptor
sites for
attachment 3. The pH
of the host site
4. The availability of nutrient
5. The influence exerted by other m.o. at the
site, 6. The immunological respone of the
host to the
presence of the m.o.
 Advantages of Flora
Normal
Many of the flora normal may be important
in
maintaining the health of the host, for
example : 1) some m.o. in intestinal capable
sinthesizing
vitamin (pathothenic acid, riboflavin, B12,
vit. k)
certain vitamine deficiencies in
human diet can be remedied by
bacterial vitamin synthesis in the
intestinal tract ;
2) some flora normal produce metabolic
product that are effective in
preventing invasion by parasites
(flora normal in intestinal tract produce
fatty acid that inhibit ingested bacteria
that attempt to colonize the host
 Advantages of Flora
Normal
3) Normal flora excludes patogen by :
a) covering binding sites that might
otherwise be used for attachment; b)
consuming available nutrients; and c)
producing compound toxic to other
bacteria
4) Gut bacteria release a number of factors
with antibacterial activity (bacteriocin,
colicin) and metabolic waste product,
which, together with lack of available
 oxygen, prevent the establishment of
other species
5) Vaginal lactobacilli maintain an acid
environment that supresses growth of
other organism
 Disadvantages of Flora
normal
Disadvantages of Flora normal lie
primarily in the potential for
spread into previously sterile parts of
the body.
This may happen under a
variety of circumstance :
- when intestine perforated
or - skin is broken,
- during extraction of teeth,
- E. coli from the perianal skin ascend
the urethra
Disadvantages of Flora
normal Overgrowth by potentially
pathogenic members of
the normal flora (Candida albicans,
Clostridium difficille) can occur when :
- the composition of the flora normal
changes (after antibiotics),
- when the local environment changes
(increases in stomach or vaginal pH) or
- when the immune system becomes
ineffective (AIDS)
Under these conditions, potential
pathogens take the opportunity to increase
their population size or invade tissues, so
becoming harmful to
the host
 The Dynamic Nature of
the
Flora Normal
Composition of normal flora is dynamic
can change change occur in
response to :
- Physiological variation within
the host ( hormonal changes),
and
- as direct result of the activities
of the human host (consuming
food)
 The intestinal m.o. of obese and
lean/thin is differ :
- Obese more members Clostridium
and Bacillus sp. and
- lean/thin more members Bacteroides
sp.
 Contoh Flora Normal
Flora Normal in Human
Site
Normal Flora
Nose Staphylococcus
Corynebacterium Mouth
Streptococcus Leptotrichia
Fusobacterium
Veillonella Actinomyces
Throat Streptococcus
Haemophillus Moraxella
Neisseria
Corynebacterium
Mycoplasma
Skin Staphylococcus
Propionibacterium Large -
Bacteroides Streptococcus
Intestine Escherichia Candida
 Proteus Clostridium
Klebsiella
Pseudomonas
Lactobacillus
Enterococcus Urethra
Streptococcus
Escherichia
Mycobacterium Bacteroides
Vagina Lactobacillus
PATHOGENESIS OF
INFECTION

EFRIDA WARGANEGARA
PATHOGENESIS OF
INFECTION

1. PATHOGENESIS OF BACTERIAL
INFECTION

2. 3. PATHOGENESIS
PATHOGENESIS
OF VIRAL
INFECTION OF FUNGAL INFECTION
1. PATHOGENESIS OF BACTERIAL
INFECTION

A Pathogenic microoragnism
- causes )
or - ) causing disease
capable
of

Some
microoragnism : -
pathogenic
- mayority harmless
- causes disease under certains
conditions: * introduced into a
normally steril body site * infection
of an immunocompromized host
1. PATHOGENESIS OF BACTERIAL
INFECTION

Bacterial Pathogenesis includes :

- initiation of the infectious process, and
- the mechanism that lead to the
development of signs and symptoms of
disease

Many infections caused by bacteria

that are commonly considered to the
pathogens are inapparent or
asymptomatic
 Disease occurs if the bacteria or
immunologic reactions to their presence
cause sufficient harm to the person
1. PATHOGENESIS OF BACTERIAL
INFECTION

The infectious prosses generaly :

1. entry into the host, with evasion of host
primary defences
2. adhesion of the m.o. to host cells
3. propagation of the organism ->
invasion of the host cells and tissues
4. damage to host cells by bacterial
toxins or an inflamatory response of
the host, and
5. evasion of host secondary defences

exit and transmission to another person

 Every Infection is a Race
Infection is a race : between the capasity of the
m.o. to
multiply, spread, and cause disease and the
ability of the host to control and finally terminate
the infection
Four type of infection :
1. M.o has spesific mechanism attaching, or
penetrating -> body surface of the normal
healthy host
2. M.o. is introduced into normal healthy host
biting arthropod
3. M.O. is introduce into an otherwise normal, healthy
host skin wound or animal bite
4. M.O. is unable infect a normal, healthy host
unless there is impairment of surface or
systemic defences
 Entry in the Host
All these body surface have : cleansing and
defence mechanism m.o.always face of
these natural mechanism
Succesfull m.o. possess efficient
mechanism for attaching, transversing these
body surface
M.o. have spesific molecules bind to
receptor molecules host (body surface,
tissues)
Receptor molecules benefit for infectious agents
thus critical determinant of cell susceptibility at
the body surface and all tissue
 After binding can multiply at the surface or
enter the cell and infect it.
 Entry in the Host
If m.o. to be transmitted to a fresh host must also exit
from the body.

They are either shed in :

- a large numbers in secretion, excretion, or
- available in blood for uptake by blood-
sucking artheropods, needles and so on

Body surface as sites of m.o. infection and

sheding : 1. Skin of a site of entry
2. Respiratory tract of a site of
entry 3. Intestinal tract of a site
of entry
4. Urogenital tract of a site of
entry 5.Oropharynx of a site of
entry
1. Skin as a site of entry
Skin (fatty acid, substances in
sebaceous/other gland, and material
producted by the normal flora of the
skin) inactive microorganism
Skin bacteria can introduce by : hair follicle,
sebaceous glands, teat canal, wounds,
aberasions or burns, a small break in the
skin, biting arthropoda (mosquitoes, ticks,
fleas and sandflies; penetrating the skin
during feeding, contaminating mouth,
saliva and feces)
 Conjunctiva, it is keep clean by flushing
action of tears, microorganism have
efficient attachment mechanism to infect
normal conjunctiva.
2. Respiratory tract as a site of
entry
In the upper or lower tract : inhaled
microorganism
like other particle entrapped in mucus
back of the throat by cilliary action and
swallowed (forming the mucocilliary
sheets).
Inhibiting ciliary activity invading
microorgansm establish themselves in the
respiratory tract
Inhaled microorganism the alveoli, encouter

alveolar macrophage (function is to remove

foreingn particle and keep these air space
clean) most are destroyed by macrophage
but one or two pathogens have learnt
either to avoid phagocytosis or to avois
destruction after phagocytosis.
3. Intestinal tract as a site of
entry
Infection in the intestinal tract affected
by the presence of mucus, acids,
enzymes and bile
Mucus :
* protect epithelial cell, perhaps acting
as a mechanical barrier to infection
* contain molecules that binding to microbial
adhesins, thus blocking attachment to host
cells
 * containing secretory IgA antibodies which
protect the immune individual against
infection
Motile m.o.( V.cho, Salm) can propel themselves
through the mucus layers and are thus likely
to reach epithelial cells to make spesific
attachment
4. Urogenital tract as a site of entry
The UGT is a continuum m.o. spread easily from
one part to another; nearly always invade from
the exterior, via the urethra.
* Urine in the bladder is sterile, succesfull invaders
(N.go, Chlamydia) have specialized attachment
mechanism
* Urinary infection (cystitis) in : a) male, rare, urethra
is 20 cm long, unless used catheter or flushing
activity is impaired; and b) female, urethra much
shorter (5 cm) but also suffers from anus, which
is a constant
source of intestinal bacteria
The invading bacteri : begin by colonizing the mucosa
around the urethra and probably have special
attachment mechanism to cells in this area and
invasion by mechanical deformation of the urethra
and surrounding region that occurs during sexual
intercourse
4. Urogenital tract as a site of entry
The vagina : no particular cleansing mechanism,
and
repeated introduction of a contaminated
pathogen-bearing foreign object (the penis)
make the vagina particularly vulnerable to
infection (STD)
* During reproductive life, the vaginal epithelium
contain glycogen, and certain lactobacilli
colonize the
vagina, metabolizing glycogen to produce lactic
acid pH : 5.0 inhibits colonization by all,
except the
 lactobacilli and certain Streptococci and
diphtherois If other m.o.are to colonize and invade
must either have
spesific mechanism (for attaching), or take
advantages of impaired defences (tampon,
oestrogen
imbalance) these are the m.o. Responsible
for STD
5. Oropharynx as a site of entry
A natural cleansing mechanism is : flushing action
of saliva, aided by masticatory and other
movement of the tongue, cheek and lips.
Additional defences : IgA and antimicrobial
substances (lysozyme, normal flora, leucocyte
present on mucosal surface and in saliva).
Factor that reduce mucosal resistance : Vitamine
C defeciency, or due to changed resident
flora after broad spectrum antibiotics
When salivary flow is decreased for 3-4 hours (as
between meals) or dehydrated patient, there is
a four-fold increase in the number of bacteria in
saliva
 Virulence and
Pathogenicity
Virulenceand Pathogenicity are
often interchangeably

Virulencecan quantified by how many m.o.

are required to cause disease in fifty
percent of those exposed to the pathogen (
ID50 and LD50)

Virulencefactor are those characteristics

of a bacterium that enhance its
patgogenicity, that is, the ability to cause
disease
 Virulence Factor
1. Entry into the Host the first step, by one of
several ports (resp. Tract, GI tract, urogenital
tract, and skin)
Once entry is achieved, m.o. must overcome a

diversity of host defences before it can establish

itself
These include : phagocytosis, the acidic

environments of the stomach and urogenital

tract, and various hydrolytic and proteolytic
enzyme found in tne saliva, stomach, and small
intestine
 Bacteria that have an outer polisacharida capsule
have a better chance of surviving these primary
host defences
 Virulence Factor
2. Adherence to Host Cells Some bacteria
use pilus/fimbrial adhesion (N.go; S.pyogenes), or
afimbrial/cell sutface adhesion molecule, or
hydrophobic adhesion (particularly hydrophobic
cell walls interaction)
Adherence enhance virulence by preventing the

bacteria from being carried away by mucus, or

washed from organs with significant fluid flow
(urinary and GI tract)
Adherence also allows each attached bacterial

cell to form a microcolony

 Virulence Factor
3. Invasion of Host Cells & Tissues is central
to the infectious process (for many disease-
causing bacteria)
Invasive bacteria are those that can enter host cells or
penetrate mucosal surface, spreading from the initial
site of infection
Invasiveness is facilitated by several bacterial enzyme,
the most of which are collagenase and hyaluronidase
degrade component of the extracellular matrix,
providing the bacteria with easier acces to host cell
surface
Invasion is followed by inflamation, which can be

either pyogenic or granulomatous, depending on

m.o. (pus -neutrophyl; granulomatous fibroblast,
lymphocyt, and macrophage)
 Virulence Factor
4. Bacterial toxin some bacteria cause disease by
producing toxins, of which there are two general type :
the exotoxin and (protein, secreted by both Gram pos.
and Gram neg. bacteria) the endotoxin (lipopolysacharida,
not secreted, but are integral component of the cell walls
of Gram neg. bacteria)
A. Exotoxin :
* Some of the most poisonous substance (tetanus)
* Exotoxin protein generaly have 2 polypeptide
component (for binding and for toxic effect)
* most are rapidly inactivated by moderate heating (60o C)
* treatment with dilute formaldehyd : destroyed the toxic
activity of most exotoxin but does not affect their
antigenicity (called toxoid, are usefull in preparing
vaccines)
 Virulence Factor
Some of the Exotoxin are :
a. Diphtheria toxin Coryn.
diphtheriae b. Tetanospasmin
Clost. tetani
c. Alpha toxin lecithinase C.
perfringens d. Toxic Shock Syndrome
Toxin-1 (TSST-1)
Staph.aureus
e. Pyrogenic exotoxin A, erythrogenic
toxin streptococcal
f. Enterotoxin : Vib. cholerae,
Staphylococcal, Clost. perfringens,
Yers. enterocolitica, Vib.
parahemolyticus
 Virulence Factor
B. Endotoxin These are heat stable,
lipopolysacharides (LPS) component of the outer
membrane of Gram Negatif Bacteria but not Gram
positive- bacteria
Molecular weight : 3000-5000 lipooligosacharides/LOS;

and severa million - lipopolysacharides/LPS

They are released into the hosts circulation

following bacterial cell lysis

LPS consist of polysacharide O (somatic antigen, core

polysacharide) and lipid A (responsibility for the

toxixity)
Gram pos. do not contain LPS, their cell wall

peptidoglycan can elicit shock syndrome but not

severe, because so different and also less potent
generally not considered to be endotoxin
 The main physiologic effects of LPS endotoxins
are : 1. fever, after 60-90 minutes for the body to
release IL-1
2. early leucopenia, as does bacteriemia with Gram neg
org., secondary leucocytosis occurs later.
3. hypoglycemia because LPS enhances glycolysis in many cell
types 4. Hypotension - peripheral vascular dilatation, increaed
vascular
permeability, decrease venous return, lowerd cardiac out
put, stagnation in the microcirculation, peripheral
vasoconstrictie, shock, and impaired organ perfusion and
its consequences. hypotension, and thrombosis
collectively referred to as Septic Shock
5. Disseminated intravascular coagulation (DIC), is a
frequent complication of Gram neg bacteria and can
also occur in the other infection
6. LPS causes platellet to adhere to vascular
endothelium and occlusion of small blood vessel
causing ischemic or hemorrhagic necrosis in various
organ.
 Virulence Factor
5. Enzymes : many species of bacteria produce
enzyme that are not intrinsically toxic but do play
important role in the infectious process.
a). Tissue-degrading Enzymes :
- lecithinace damages cell membranes by
splitting lecithin Clost. perfringens
- collagenase (proteolytic) degrades collagen,
the mayor protein of fibrous connective tissue ,
and promotes spread of infection in tissue
Clost. Perfr.
- coagulase contribute to the a) formation of
fibrin walls around Staph. lesions, which helps
them persist in tissues; b) causes deposition of
fibrin on the surface of Staph., which may help
protect them from phago-cytosis or from
destruction within phagocytic cells.
 Virulence Factor
a). Tissue-degrading Enzymes :
- hyaluronidase enzyme that hydrolyze
hyaluronic acid constituent of the ground
substance of
connective tissue aid in their spread through
tissues. - Streptokinase (fibrinolysin) a
substance that activates
a proteolytic enzyme of plasma able to
dissolve coagulated plasma and probably aids
in in the rapid spread of Strept. Through tissues
 (in treatment myocardial infarction to dissolve
fibrin clots)
- Cytolysins are hemolysin (dissolve
RBC) or leucocidins (kill tissue cell or
leucocyte)
 Virulence Factor
b). IgA 1 Proteases is the secretory
antibody on mucosal surface, it has 2
primary forms (IgA 1 and IgA 2)
Some bacteria that causes disease,
produce enzyme Ig A 1 proteases
that split IgA 1 and to inactive the
primary antibody found on mucosal
surface and thereby eliminate
protection of the host by the antibody
 IgA 1 is an important virulence factor of
the N.go, N.meningitidis, H.inf., and
S.pneu.
 Virulence Factor
6. Antiphagocytic Factor many bacterial
pathogens are rapidly killed once they are
ingested by poly-morphonuclear cells or
macrophages
- some pathogen evade phagocytosis or
leucocyte microbicidal mechanism by
adsorbing normal host components to
their surface protein A Stap. aureus
- Other pathogens have surface factors that
impade phagocytosis, have : polysacharide
capsules Strep. pneu; N.meningitis;
protein M Strep. pyogenes; pili N.go
 Antigenic Switching
A succesfull pathogen must evade the hosts
immune system that recognized bacterial
surface antigens one important evasive
strategy for the pathogen is to change its
surface antigens
This is accomplished by several mechanism :

a. Phase variation is the genetically reversible

ability of certain bacteria to turn off and turn
on the expression of genes coding for surface
antigens
b. Antigenic variation involves the modification
of the gene for an expressed surface
antigen can assume many different antigenic
structure
 Exit and Transmission
Transmissiondepends in the first
place on three factors :

1. Number of m.o. shed

2. Stability in the environment

3. The number of m.o. required to

infect a fresh host
 Types of Transmission
Transmission is at its most effective when
it takes place directly from human to
human

Thecommonest, world-wide infectiopns

are spread by the respiratory, fecal-
oral, or veneral route
A separated set of infection acquired from
animal, either directly from
verteberates or from biting arthropods
 Types of Transmission
Type of transmission are :
1. Transmission from the respiratory
tract 2. Transmission from the
intestinal tract 3. Transmission from
the urogenital tract
4. Transmission from the oropharynx tract
5. Transmission from the skin and skin glands
tract 6. Transmission from blood
7. Vertical and Horizontal
Transmission 8. Transmission from
animal
 Type of transmission
1. Transmission from the respiratory
tract

Effective shedding from the nasal cavity

depends on an increase in nasal
secretion, and is helped by sneezing and
coughing
In sneezing up to 20000 droplets are
produced and during a common cold
many of them will contain virus particles
 Duringcoughing, a smaller number of m.o.
Are expelled from the mouth, throat,
larynx, and lung
 Type of
transmission 2. Transmission
from the intestinal tract

During most of human, there has been a large

scale recycling of fecal material back into
the mouth and this continues in developing
country
Intestinal infection are still spread in
developed countries but via food and
fingers, rather than water and flies
 Them.o.that appear in feces have generally
multiplied in the lumen or wall of the
intestinal tarct, but there are a few that
are shed into bile
 Type of
transmission 3. Transmission
from the urogenital tract
Urine can contaminate food, drink and living space, but UTI are
common, most are not spread via urine
M.O. Shed from the UGT are generally transmitted as a result of
mucosal contact with susceptible individuals (sexual activity
and cause STD)
If there is a discharge some of the most succesfull STD
transmitted m.o. induce dischage
Other are transmitted effectively from mucosal sore/ulcers T.pall
or HS The Human Papilloma Virus are transmitted from genital
warts or from foci
of infection in the cervix where the epithelium, although
apparently normal, shows displasia and contain infected cells
 It may be expected thar semen is involved in the transmission of
infection (human cytomegalo virus, hepatitis B, HIV)
The female genital tract can also be a source of infection for the
newborn child. During passage down an infected birth canal
m.o. can be wiped onto the conjuctiva of the infant or
inhaled, leading to conjuctivitis, penumonia, bacterial
meningitis and so on.
 Type of transmission
4. Transmission from the Oropharynx

Saliva is often the vehicle of transmission

m.o.reach saliva during upper and
lower respiratory tract infection, but
certain virus infect salivary glands and
are transmitted in this way.
In young children fingers and the other
objects are regularly contaminated
by saliva and each of these
infection is aquired via this route
 Type of transmission
5. Transmission from the Skin
and the Skin glands

M.O. From the skin are generally

transmitted by direct contact
rather than folowing release into
the environment (Staphylococci
and HPV)
 Dermatophyte are shed from skin
and also from hair and nails
 Type of
transmission 6.
Transmission from Blood

Blood is often the vehicle of transmission m.o.

Spread by blood-sucking athropod can be said to
have been
shed into the blood.
Infectious agents present in blood (hepatitis

virus,HIV) are transmissible also by needles,

 either in transfused blood or when contaminated
needles are used.
The blood is also the source of infection in
transplacental t ransmission and yhis generally
involves initial infection of the placenta
 Type of
transmission 7. Vertical and
Horizontal Transmission
When transmission is direct from parents to
offspring via sperm, ovum, placenta, milk, blood
etc VERTICAL
Other infection, in contrast, HORIZONTALLY
transmitted, an individual infecting unrelated
individuals by contact, respiratory or fecal-oral
spread
Vertical transmitted infection, subdivided as in
type : a) prenatal (route placenta -> Lues);
b) perinatal (infected birth canal -> Go, Chlam.
conjuctivitis); c) postnatal (milk or direct contact ->
hepatitis B,CMV);
d) germline (viral DNA sequences in human genom ->
many retrovirus)
 Type of
transmission 8. Transmission
from Animals
Animal-tansmission infections can be divided into two
categories : 1) involving arthropod and other intervertebrate
vectors, and
2) transmitted directly from vertebrates (zoonoses)

Arthropod (Mosquitoes, ticks and mites) a mayor source of

infection bloodsuckers
Other invertebrate vector (shellfish : moluscs and crustacea)
food poisoning and GE
Zoonosis (infection transmitted to humans from infected animal),
wether this is : - direct (by contact or eating) or
- indirect (via intervertebrate vector)
 A very large number of pathogens are transmitted in this way by a
veriety of different routes : contact, inhalation, bites, scratch,
contamination of food or water, or ingestion as food
Dogs and cats are the commonest domestic pets both are
reservoir of infection for their owner m.o. are spread by :
contact, bites and scratches, vectors and contamination with
fecal material
Terima
Kasih