Pathogenesis of infection Dieses

Done by : Sara alomari

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Pathogenicity disease .

by definition means the ability to cause

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 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 ..

the microbes that cause infectious diseases are collectively

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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
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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. 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 – Example: serious cases of bacterial pneumonia frequently

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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 nonpathogenic 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 say this bacteria is more another type of bacteria ..
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and

virulent or more pathogenic than

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 virulence factor of some of the bacterial

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So in order to cause disease multiple of the following

some bacteria contain one or

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 ,,,, killing 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 .. this .. capsule . That allow them to resist phagocytotic So even if they get phagocytosis they will not be

for example for

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Also some virulent levels This allow them

factor

have

relationship to human iron

to be virulent inside human cell , inside

human body but not virulent outside . And allow finally some bacteria them to invade can produce biofilm which to resist the

the immune system

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

allow the bacteria So

attach the

these the infection of the viruses ..

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So the viruses has specific molecule in surface adheres or ligand that recognize specific host cell .. this viruses can that doesn’t then inter by specific receptor found in

So if this interaction happens the cell receptor Slide 12 : cause disease on it’s on a host cells surface ..

and causes the disease

in that cell .But

cannot

have these

And this figure shows u basically factor that are released or

some of the virulence by certain bacteria ..

made

As we mention -pili : are the virulence factor because it allow attachment factor because

- capsule : it considered to be a virulence it allow the cell to resist phagocytosis ..

- endotoxine : which is the lipopolysaccharide of the outer membrane of the gram

component bacteria . can

negative

Is considered to be a virulence factor because produce fever inside the host cell .

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- Some bacteria can produce exotoxine a varaytoabrose

such as : which have

neurotoxins . enterotoxins and cytotoxins

inside the human body .. which leads

- Some bacteria can produce coagulase to angulation or to position of fibrin bacteria system . - Some bacteria that can produce

around the

which allow them to invade the immune

hemolysis and RBC’s and

leukocidrins WBC’s .

allow them to lyses

- Some bacteria ( hayalnurinases and bacteria

can produce ) which

collagenase allow them

and to destroy

basically digest human

tissue to allow the within the tissue .

to spread more easily

- And finally some bacteria produce kinase. So a virulence factor are basically phenotypic representation of particular virulence genes found to be carried some the

So many of the virulent genes will extra chromosomal genetic virulent genes human

such as plasmid ,, may contain

however some bacterial chromosome

, however if they found chromosome
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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 For example located in the bacterial chromosome

in (PALs) :

genes for toxins, adhesions, lytic enzymes, antibiotic resistance, and iron uptake. when So a very important question is is how the bacteria know 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 changes So it can around it sense the

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 even though the

They can also sense Iron availability

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+ ) 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 Arabic ‫ السعال الديكي‬so this bacteria is produce or express most of the virulence gene when the temp. Around 37°C
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Or also can

which causes Whooping cough or in

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 and they just we don’t have to memorize it ..  Other bacteria do not become intracellular stay outside the cell but within the tissue and organ .. or terminal invagenous tissue ex

So we called these basic ( salmonella species )

So as the bacteria are growing and multiply and spreading within the tissue some bacteria type of the toxins So we have something called : Exotoxins can produce by gram +ve and –ve bacteria we have different type of these And we have another type of toxin and this is made only by gram –ve component bacteria called endotoxin and specifically LPS of the cell wall is very and can produce one or two

So the characteristic of these type of cytotoxin 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 inside the host so if u was the toxin

protein are highly immunogenic present in presentation

get expose to an exotoxin agno-servived

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 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 Some receptor took or these toxins and treated them with formaldahide

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basically later

will protect them from exposure with really toxin

in life exotoxin basically it’s made up of

The composition of the 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 u will feeling that this

deep wound with a dirty instrument

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 ,, bacteria found as a component gastric intestinal tract This bacteria is anaerobic so if u have a deep wound ( a deep wound is required because it provides anaerobic it can environment of the bacteria ) contain these bacteria so these of a normal flora of your

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 (LPS) of gram negative bacteria. Lipopolysaccharides

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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 so this is to constrict 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 ..??? heat it the bacteria will kill but the endotoxine will still be active . the exotoin which is heat lay bay so if u boil food which contain the exotoxion we can destroy

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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 enzymes Examples: such as exo-

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

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 they produce. pathogens cause disease are the exoenzymes or toxins that

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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 able to prevent infection to one pathogen u should be

in second time of the same that

pathogen but many bacteria and many other pathogens have a ways to keep changing there surface antigens 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 O1 So in the environment capsular or K Antigen So that is why u can infected with E.coli time and time again e.coli has up to 150 or more types that Antibodies is only specific for O7 not

for it’s O antigen and has more than 100 types for

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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 which (causes relapsing fever 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 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 high and Borrelia recurrentis can make frequent changes

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 surfaces and occur throughout nature. a slimy coat found on solid

So what is the significance of biofilms in pathogensis and the ability to bacteria to cause disease So biofilms by having that them polysaccharide capsule around

allow the bacteria to give protected from the also that covering or layer will not to

immune system so immune cells cannot penetrate and go inside the bacteria allow most trubile agent to pass through and kill the bacteria so medically speaking we will count the biofilm in narrower examples Staphylococcus epidermidis can contaminate and Staphylococcus aureus skin central

which are found in as normal flora of the epidermal catheters ex >> 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 .. .people with cystic fibrosis they

also the virulent example is had usually a problem anon easily

with Pseudomonas aeruginosa

which can form a biofilms that are very hard to remove and 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 ... <3

And Special hiiii to my sister Saja ALKhateeb

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PLZ 

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

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