Pathogenesis of infection Dieses

Done by :

Sara alomari

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Pathogenicity by definition means the ability to cause
disease .

Pathogenesis refers to the whole steps or mechanisms

involved in the development of a disease ..

infectious disease is a disease caused by a microbe, and

the microbes that cause infectious diseases are collectively
referred to as pathogens

many microbiologists , reseve use the word infection to

mean COLONIZATION by a pathogen ..
so the pathogen may or may not go on to cause disease;
in other words A person can be infected with a pathogen,
but not develop disease. Or not have the infectious disease
caused by pathogens ...

so Why Disease Does Not Always Occur ??

many people who exposed to pathogens not always get sick
... this is due to many reasons ..::
_ The microbe may land at an anatomic site where it is
unable to multiply ..

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 Ex : when a respiratory pathogens land in the skin it
can’t grow because the presence of fatty acid and lack of
moisture and nutrients ...

_ Many pathogens must attach to specific receptor sites

before they are able to multiply
and cause damage so if they land at a site where receptor
are absent they are unable to cause disease ...

_ Antibacterial factors may be present at the site where

the pathogen lands .that inhibit or destroy the growth of
bacteria ..
Ex > the lysozyme that is present in tears .. that is why
bacteria can not cause infection in eyes ..

_ Indigenous microflora of that site may inhibit growth of the

foreign microbe (i.e., microbial antagonism). That inhibit the
growth of foreign microbe by occupying space and using up
nutrients.. Or it can produce a Bacteriocins that kill the
newly arrived pathogens..

_ the person health status .. EX. The person who is in

good health with no medical problems would be less likely

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to become infected than that the person in poor health.. Or
the person may be immune to that pathogens by having
vaccinated for example...

_ the presence of WBC’s that destroy and engulf the

pathogens before multiply ..
Now once pathogen can enter the body the infectious
disease will has four periods ::
1- The Incubation period : the time between arrival of
pathogens and the symptoms start to appear ..
2- The prodromal period : the patient may feel they are
coming down with something but actually he don’t yet
know what ...
3- The period of Illness : the typical and actual symptoms
that associated with particular disease
4- The convalescent period :the time during the recovery
of the person ..

Now once the infectious process initiated may remain

localized such as boils abscess and pimples or it may
spread and carried to other part of the body and involve
the lymph and blood.. And this is we called Systemic

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disease Or generalized infection. ex >> Mycobacterium
tuberculosis. Spread to many internal organs..

The disease may be acute that has a rapid onset, and is

usually followed by a relatively rapid recovery
examples are measles, mumps, and influenza
or chronic which has a slow onset and last for a long time
examples are tuberculosis, leprosy, and syphilis.
Or A sub acute which is that comes on more suddenly
than a chronic disease, but less suddenly than an acute
disease; an example would be bacterial endocarditis.
Sometimes disease may go from symptomatic to
Asymptomatic and then after a time later will go back to
being symptomatic this is called Latent disease
Examples include syphilis and herpes virus infections such
as cold sores,
genital herpes, and shingles.
Now some evidence of a disease that is experienced by the
patient; something that is subjective is called A symptom of
a disease.
There are symptomatic and asymptomatic diseases. In a
symptomatic disease, the patient is experiencing symptoms.

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In an asymptomatic disease, the patient is not experiencing
any symptoms.
But A sign of a disease is defined as some type of
objective evidence of a disease; for example,elevated blood
pressure, abnormal heart sounds, abnormal pulse rate,
abnormal laboratory results
One infectious disease may commonly follow another; in
such cases, the first disease is referred to as a primary
infection and the second disease is referred to as a
secondary infection.
– Example: serious cases of bacterial pneumonia frequently
follow mild viral
respiratory infections.
•During the primary infection, the virus causes damage to
the ciliated epithelial
cells of the respiratory tract; these cells are then unable to
clear opportunistic
bacterial pathogens from the respiratory tract, leading to the
secondary infection (e.g. pneumonia).
In General the pathogenesis follows this sequence in order
to cause infectious disease

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1.Entry of the pathogen into the body. And penetrating the
skin and mucous membrane , provide the primary defense
against infection.
Frequent portals of entry of pathogenic bacteria:
_ Respiratory (upper and lower airways)
_ Gastrointestinal (primarily mouth)
_ Genital and urinary tracts.
_Abnormal areas of mucous membranes and
skin (e.g. cuts, burns, and other injuries) are
also frequent sites of entry.

2.Attachment of the pathogen to some tissue(s) within the

body
3.Multiplication of the pathogen.
4. Invasion or spread of the pathogen.
5.Evasion of host defenses.
6.Damage to host tissue(s)
so a common way for spreading is directly by invading the
tissue .. So some bacteria and viruses can enter and go
directly through a tissue and others basically will be carried
by a lymphatic tissue and from there will be carried to
blood circulation

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In the case of bacteria >> bacteremia

And viruses >> virimia

once it reach the blood it can wide spread or potentially

reach all tissue and organ of the body but usually pathogen
has specific tropism to specific tissue and organ .

that’s why hepatitis virus cause hepatitis and not for

example meningitis bcoz it likes to infects the liver cells and
not brain cells or meninges cells
now ..

to give u an idea about a general life cycle of a pathogen I

will told u the brief history or a brief description of a life
cycle of streptococcus pneumonia which can lead to
pneumonia and also other infection ..

so this is just for ur own info. And the next slide also for
ur info. About vibro colera which leads to colera which is
very sever form of watery diaria ...

A next important topic is virulence and virulence factor..

So the term virulence is sometimes used as a synonym for

pathogenic

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There may be virulent (pathogenic) strains and avirulent
(nonpathogenic) strains of a particular species.So when we
say we have a virulent bacteriam that means it’s a
pathogenic bacteriam that casing human dieses .. or more
likely to cause human disease than a non virulent or non-
pathogenic stage for the same bacteria or viruses ...
for example .we have a bacteria called
Corynebacterium diphtheriae some of these bacteria have a
gene for specific diphtheria toxin production .. so if u
colonies by this bacterium this bacteria will start to produce
toxin and will cause the disease so we called this type of
bacteria a pathogenic or a virulent bacterium ..

and also we have strains a similar that not contain a gene

of toxin production is considered to be a non pathogenic or
non virulent strain ..

so Virulent strains are capable of causing disease; avirulent

strains are not.
also Sometimes, the term virulence is used to express the
measure or degree of pathogenicity.
So we can compare 2 different pathogenic bacteria and
say this bacteria is more virulent or more pathogenic than
another type of bacteria ..

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For example..Salmonella need to ingest 100- 1000 cells to
cause salmonolosis.. Whereas shigella we need to
ingest only 10 cells to case shigellosis;So shigella is called
more virulent or more pathogenic than salmonella because
we need less cell to cause human disease; Also another
example is Streptococcus Pyogenes :Some strains can
produce enzyme toxin that allow them to destroy human
tissue so these strain are called fleshy strain and
considered to be more virulent than the strains that can't
produce this enzymes and toxin that destroy the human
tissue ...

So atrofiels that allow the bacteria to be virulent or non

virulent are called the virulence factor. So these are the
phenotypic characteristics for the pathogen .. and these are
basically an expression of a genotype ..

So virulence factor can't be express in air they need to

have specific gene within the genome of the virus or the
bacteria to express these virulence factor .

And here is a small list of some of the bacterial

virulence factor

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So in order to cause disease some bacteria contain one or
multiple of the following

We have tors that allow bacteria to adherence to host cell if

they can't adhere they can't cause disease

They can sometimes express factor or proteins that allow

them to invade inside host cell or invade tissue

They can also produce toxin

They can produce enzyme which usually are instructive

enzyme that allow them to destroyed the tissue.

They can produce Antiphagocytic factors that allow them

either to resist phagocytises all together ,,,, for example for
this .. capsule . That allow them to resist phagocytotic
killing So even if they get phagocytosis they will not be
killing.

Also some bacteria has specific factor that allow to survive

inside the host cell so basically becoming intracellular
pathogens.

And also they have factor to allow them to change the

antigenic structure in order to invade the immune system ..

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Also some virulent factor have relationship to human iron
levels

This allow them to be virulent inside human cell , inside

human body but not virulent outside .

And finally some bacteria can produce biofilm which

allow them to invade the immune system to resist the
antimicrobial drugs.

Slide 11 .

Here is a very short example

So some bacteria and viruses as we mention need to have

specific adhesions molecule under surface in order to bind
with specific receptor found in a specific host cell

So these are called (adherence ) Or ligand and they bind

specific receptor .And another example of adherence are
pili or the fimbiriae which we talked about it
previously ;and pili, one of the main function is which
allow the bacteria to attach the host cells surface ..

So these the infection of the viruses ..

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So the viruses has specific molecule in surface adheres or
ligand that recognize by specific receptor found in
specific host cell ..

So if this interaction happens this viruses can then inter

the cell and causes the disease in that cell .But cannot
cause disease on a host cells that doesn’t have these
receptor on it’s surface ..

Slide 12 :

And this figure shows u basically some of the virulence

factor that are released or made by certain bacteria ..

As we mention

-pili : are the virulence factor because it allow attachment

- capsule : it considered to be a virulence factor because

it allow the cell to resist phagocytosis ..

- endotoxine : which is the lipopolysaccharide component

of the outer membrane of the gram negative bacteria .

Is considered to be a virulence factor because can

produce fever inside the host cell .

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 - Some bacteria can produce exotoxine such as :
neurotoxins . enterotoxins and cytotoxins which have
a varaytoabrose inside the human body ..

- Some bacteria can produce coagulase which leads

to angulation or to position of fibrin around the
bacteria which allow them to invade the immune
system .

- Some bacteria can produce hemolysis and

leukocidrins that allow them to lyses RBC’s and
WBC’s .

- Some bacteria can produce collagenase and

( hayalnurinases ) which allow them to destroy
and basically digest human tissue to allow the
bacteria to spread more easily within the tissue .

- And finally some bacteria produce kinase.

So a virulence factor are basically phenotypic representation

of particular virulence genes

So many of the virulent genes will found to be carried

extra chromosomal genetic human such as plasmid ,,
however some bacterial chromosome may contain some
virulent genes , however if they found chromosome the

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virulence gene are usually group together in the area
called a pathogenicity islands (PALs)

So the (PALs) are large group of genes are associated with

pathogenicity and are located in the bacterial chromosome

For example in (PALs) :

genes for toxins, adhesions, lytic enzymes, antibiotic

resistance, and iron uptake.
So a very important question is is how the bacteria know
when to express the particular virulence factor ??

The answer is very simple

- Bacteria are extremely adapted to their environments.

- Bacterial genes are only expressed when required to
conserve energy.
- Virulence Genes are usually expressed upon entry into the
host.
And the question now how does the bacteria know that it
entered a host ??

So the bacteria are very cleaver it can sense the

changes around it

So it can sense the multiple signals such as :

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Changes in Temperature so in environment the temp.
Maybe 20°C

But once inside the host the temp. Become 37 °C

They can also sense Iron availability even though the

human body has a lots of Iron most of this iron is not free
format usually most of this for pump protein , so basically
bacteria can sense the slow level of free sulphating Iron
and then can express virulent factor

They can check sense changing of osmolarity ph and

concentration of specific ion such as (Ca2+ ) Or also can
detect the present or absence of nutrients

All these of the sensor can detect when they enter the host
and when they outer the host and therefore know when
express the virulent factor or when not

Examples:
- Corynebacterium diphtheriae (having the gene for the
diphtheria toxin) will only express the toxin when iron levels
are low. Such as inside the human body
Bordetellapertussis which causes Whooping cough or in
Arabic ‫ السعال الديكي‬so this bacteria is produce or express
most of the virulence gene when the temp. Around 37°C

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Slide 14
So after attachment , multiplication and spread some
bacteria can invade or inter the host cell and become
intracellular pathogens and we have some example of this
we don’t have to memorize it .. 
Other bacteria do not become intracellular and they just
stay outside the cell but within the tissue and organ ..

So we called these basic or terminal invagenous tissue ex

( salmonella species )

So as the bacteria are growing and multiply and spreading

within the tissue some bacteria can produce one or two
type of the toxins

So we have something called :

Exotoxins can produce by gram +ve and –ve bacteria and

we have different type of these

And we have another type of toxin and this is made only

by gram –ve bacteria called endotoxin and specifically LPS
component of the cell wall

So the characteristic of these type of cytotoxin is very

important :

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Exotoxine : can made by Gram +ve and –ve bacteria they
are highly toxic so very small amount of exotoxine can kill
the human so usually 1microgram of exotoxin can kill the
human

These molecules are basically made up of protein so

protein are highly immunogenic inside the host so if u
get expose to an exotoxin agno-servived the toxin was
present in presentation for good amount of time the
immune system can produce antibodies against these toxin

Can neutralize the toxin and prevent them from functioning

inside the host ..

So in order to protect the human from exotoxin such as

(“tetanospasmin” and Diphtheria toxin Some receptor took
these toxins and treated them with formaldahide or
formaline .

If u do this side of treatment the toxic properties of the

toxin would be inoculated but it’s antigenisity will not change
..

So you can take this formaldahide in antibiotic toxin or

which equal toxoil and ejected inside the humans and that

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basically will protect them from exposure with really toxin
later in life

The composition of the exotoxin basically it’s made up of

two subunit :

We have a subunite called A (activity subunit ) has a toxic

activity of the toxine .. the A subunite is usually associated
with a B (Binding ) subunit and a B subunit allows the toxin
to attach to specific host cell

So examples of these toxin :

The Diphtheria toxin” produce by C. Diphtheria this toxin

enter host cell and prevent cell protein synthesis leading to
cell death

tetanospasmin” or tetanostoxin produce by (Clostridium

tetani):

for example if u puncture your foot or hand and become a

deep wound with a dirty instrument u will feeling that this
bacteria will produce tetanospasmin that prevent the muscle
from relaxing so all ur muscle will continue to be in an
Exciting contractive state ..

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so we have something called “Spastic paralysis another
example is “Botulinum toxin produce by Clostridium
botulinum
so this is a toxin that we found in a swelling cans food
..this bacteria make the swelling in cans and leading to
death
And finally we have Clostridium perfringens ,, so these
bacteria found as a component of a normal flora of your
gastric intestinal tract
This bacteria is anaerobic so if u have a deep wound ( a
deep wound is required because it provides anaerobic
environment of the bacteria ) contain these bacteria it can
start growing and producing lots of toxin and enzymes that
destroy the tissue so end up basically of something called
Gas gangrene ;) ;) ;) 
Due to the toxin and enzyme produce by this bacteria ..
And some toxin are called alpha toxin and theta toxin. And
these basically destroy RBC’s and destroy lots of host
tissue ..
Slide 16 :
Endotoxins: so Endotoxins are basically Lipopolysaccharides
(LPS) of gram negative bacteria.

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So if u see an example asking u endotoxine can made by
gram +ve bacteria so the answer is no 
Only gram –ve bacteria
So these LPS are usually released upon death or destroy
the cell so once the cell die the cell wall component will
diffuse away and it can end up with effect of endotoxin
and the important properties of endotoxin is the heat-stable
so if u have a solution and u want heat it the bacteria will
kill but the endotoxine will still be active .
so this is to constrict the exotoin which is heat lay bay so
if u boil food which contain the exotoxion we can destroy
the toxin

now LPS is composed of three main parts ::

O-specific polysaccharide and Common core polysaccharide
, lipid A and finally KDO so the structure within the LPS
that responsible for endotoxine properties is lipid A and
KDO
So general speaking that considered LPS as endotoxin but
if u want to be very accurate and specific lipid A and KDO
that responsible for primary toxicity of the endotoxine
So now how does the endotoxin work ..???

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The pathophisiology of endotoxine is regardless of the type
of the gram –ve bacteria all endotoxine will function in the
same way once inside the circulation except of this rule
Bacteroides species this is gram negative bacteria found in
GI tract these have slightly deferent structure of LPS are
slightly less toxic than other type of LPS
So once u have LPS in bloodstream interact with receptor
found in microphages and monocytes and other cells of
the reticuloendothelial system need to release cytokines
most important cytokines is IL-1 which induce fever also we
have realise of Tubular Necrosis Factor (TNF) and other
Cytokines also we end up of activating the complement and
coagulation cascades so attractive of all these will introduce
fever so end up also we end up of hypotension and shock
and these invention will end up with more serious problem
impaired blood flow to essential organs (e.g, brain, heart,
kidney. the activation of coagulation; cascade will lead to
intravascular coagulation; and death from massive organ
failure or dysfunction
Now the important virulence are enzyme such as exo-
enzymes
Examples:

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- C. perfringens produces two toxin alpha interotoxin it can
also produce a lecithinase and a collagenase that degrade
tissues thus promoting
bacterial spread inside the tissues
-Staph. Aureus if enters the blood it will use its enzyme
called a coagulase to clot of plasma and formation of fibrin
forming a shell of fibrin to hide bacteria from the immune
system and thus protect the bacteria from phagocytosis ..

Also other enzymes that can destroy the cell for example
hemolysis can lyses or destroy RBC’s also some cytolysins
can produce kill typical host cells and some cytolysis called
leukocidins) are produce specifically to kill WBC’s
(leukocytis)

EX “Streptolysin O produce by group A streptococci such

as streptocoocus phygens this one can destroy RBC’s of
human and other animals as mice

So the key point when ether we talked about virulence

factor or virulence mechanism in pathogens is The major
mechanisms by which
pathogens cause disease are the exoenzymes or toxins that
they produce.

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So as we mention some bacteria have a virulence
mechanism that can allow them to either evade
phagocytosis or avoid the killing of phagosomes and the
base example of this Polysaccharide capsules of S.
pneumoniae, and N. meningitidis.
The next intracellular factor is Intracellular Pathogenicity:

Intracellular Pathogenicity: have a virulence factor that allow

them to survive inside the host cells

Example of intracellular bacteria is:

- Mycobacterium tuberculosis that cause human tuberculosis

Antigenic Heterogeneity so as we now if u introduce an

organism in a host the immune system will respond to
that pathogen and will produce antibody against cell.

So in theory if u get expose to one pathogen u should be

able to prevent infection in second time of the same
pathogen but many bacteria and many other pathogens
have a ways to keep changing there surface antigens that
are immunogenic inside the host cells

So Bacteria have three types of surface antigens That the

immune system pathogens respond to :

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O antigen which is part of LPS of gram –ve bacteria so
these antigens only present in gram –ve bacteria

Bacteria that have flagella that able to move so motile

bacteria have antigens in their flagella structure called F
antigens

And bacteria that contain a capsule will have capsule

Antigens called K antigen

So if u get expose for example to E. Coli have an O

antigen type 7 your body will respond to this antigen by
produce neutralizing antibodies and if u get expose of E.coli
O type 7 second time in future u will protective but E.coli
can perform many types of O Antigen

So if u get expose of E.coli O1 after O7 we will infected

again because that Antibodies is only specific for O7 not
O1

So in the environment e.coli has up to 150 or more types

for it’s O antigen and has more than 100 types for
capsular or K Antigen

So that is why u can infected with E.coli time and time

again

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Most likely u get infected with E.coli carried with different
type of antigens

In addition to this some bacteria will actively change the

antigen while inside the host so even as a immune system
is recognize this antigen this antigen are changing over time


For example : N. Gonorrhoeae and Borrelia recurrentis

which (causes relapsing fever can make frequent changes
in their surface antigens
to evade the immune system.

Finally ..

The last virulence factor is Ability to form “Biofilms”:

So basically bacteria not always present as single cell in

the environment some bacteria have basically develop high
order structures called biofilms

So biofilms are aggregate or accumulation of interactive

bacteria usually attached to a solid surface or to each other
and encased in an exopolysaccharide matrix

so basically bacteria can grow forming a large mass and

then will secret some type of polysaccharide covering or

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layer around them protect them from the outside
environment so this called a biofilm

Biofilms basically are a slimy coat found on solid

surfaces and
occur throughout nature.

So what is the significance of biofilms in pathogensis and

the ability to bacteria to cause disease

So biofilms by having that polysaccharide capsule around

them allow the bacteria to give protected from the
immune system so immune cells cannot penetrate and go
inside the bacteria also that covering or layer will not to
allow most trubile agent to pass through and kill the
bacteria so medically speaking we will count the biofilm in
narrower examples

Staphylococcus epidermidis and Staphylococcus aureus

which are found in as normal flora of the epidermal skin
can contaminate catheters ex >> central
venous catheters can follow by this bacteria and this
bacteria will grow form a biofilm that is very hard to
remove leading to bide infection inside the host

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also people who work contact lenses has an eye infection
because some bacteria produce biofilms or contact lenses

and also dental plaque some of plaque involve the

formation of biofilms by bacteria within the plaque ..

also the virulent example is .people with cystic fibrosis they

had usually a problem with Pseudomonas aeruginosa
which can form a biofilms that are very hard to remove and
anon easily clear by trouble agent

sorry for any mistake ,

‫لتحسبن المجد تمرا ً انت أكله لن تبغ المجد حتى تلعق الصبرا‬
Done BY :

SARA ALOMARI 

Special thx to my lovely Friends (RUBA RABE,,, DALIA

SHUNAQ ,,, YASMIN ABU ZAID ) <3 <3 <3

And Special hiiii to my sister Saja ALKhateeb ... <3

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PLZ Forgive me if there is mistakes i really do the best ..


GOOD LUCK ... 

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