EFRIDA WARGANEGARA

 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’
 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
 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
 Before birth the fetus is essentially in a steril
environment, but at delivery m.o. come into contact
with the infant baby 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
 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

 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.
 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
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 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
 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 chabges (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
 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.
 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
EFRIDA WARGANEGARA
1. PATHOGENESIS OF BACTERIAL INFECTION

2. PATHOGENESIS OF VIRAL INFECTION

3. PATHOGENESIS OF FUNGAL INFECTION

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

 Some microoragnism :
- pathogenic
- mayority  harmless
- causes disease  under certains conditions:
* introduced into a normally steril body site
* infection of an immunocompromized host
 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
 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

 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
 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.
 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 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)

 Virulence factor are those characteristics of a

bacterium that enhance its patgogenicity, that
is, the ability to cause disease
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
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
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)
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)
 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
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 host’s 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.
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.
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)
 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.infl., and S.pneu.

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
 A succesfull pathogen must evade the host’s 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
 Transmission depends 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
 Transmission is at its most effective when it
takes place directly from human to human

 The commonest, 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
 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
1. Transmission from the respiratory tract

 Effectiveshedding 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
 During coughing, a smaller number of m.o. Are
expelled from the mouth, throat, larynx, and
lung
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
 The m.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
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.
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
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
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
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)
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