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The Processes by which Organisms
Cause Disease to Host Tissue
(Pathogenesis)
Champa Ratnatunga
Department of Microbiology
Infection -1 2/4/2013
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Objectives
Define the term pathogenesis, immuno
pathogenesis
List currently known modes of transmission
microbial entry
Describe essential steps in microbial infection
attachment, invasion, mechanisms of damage
Explain how common clinical manifestations ofinfections reflect these mechanisms of damage in
various organs
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Pathogenesis-The mechanisms by which a disease
occurs
Pathogenthe organism causing the disease Pathogenicity the ability/ capacity to cause disease
Commensal/ Normal flora organism that lives on
or in the host/ human body normally without
causing disease
Colonizerorganism that colonizes the host /human
body but does not cause disease (these may be acquired
from new environments or be part of normal flora)
Colonizer PathogenChanges in the body defenses or flora
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To be a pathogen -
Transmissibility / communicability
Survival in the new host
Infectivity ability to breach the new hosts
defenses Virulence capacity of the pathogen to harm the
host.
2 types of pathogen Primary pathogen cause disease in healthy persons
Opportunistic pathogens - cause disease in impairedhost defenses
Strict pathogen ----------------------------------------
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Pathogenesis Important because-
.................................................................................
..
Infection- includes both the multiplication of theorganism within the host, invasion of a tissue byorganisms as well as the sequelae caused by theinfection even if the organism is no longer present
Signs and symptoms (disease) may or may not be seen
Natural history of a disease how the diseaseprogresses over time if not treated.
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Immuno - pathogenesis
Pathogen Invades Host/Human body
Immune system isactivated as defense
Immune system acts
against the pathogen
to destroy it
The immune reaction can cause damage
to the host tissue as well.
Ex: Wucheraria bancrofti - Elephantiasis
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Modes of Entry into the human body
Through respiratory tract aerosols / droplets
Direct contact with skin - intact or broken skin
Ingestion to GI tract
Genito urinary tract ascending infection
Exchange of body fluids (blood/ secretions) Injection by vectors
Sources
o Other humanso Animal reservoir
o Environment
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To cause disease
Colonization
Invasion
Avoidance of host defense mechanisms method/s of causing damage to tissue
Factors that help the bacterium to do these -
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Surface molecules and structural molecules
Many different molecules on the surface of bacteria/
viruses/fungi as well as on the surface of animal(human) cells.
Molecules are part of the normal (cell wall or internal)
structure of the organism.
have many functions including cell signaling ,binding to tissues/ organisms, activating
pathways, blocking pathways, identifying cell aspart of the body or from a different animal or asa pathogen by other cells.
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These can be proteins/ lipids/CHO or combinationsof them (glycopeptides/ lipoprotein).
Some of these molecules will play a part inpathogenesis.
They can also be useful in the identification ofbacteria with lab tests. (form the basis of someclassification systems of bacteria as the mostconvenient classification system for themicrobiologist is one that is based on the tests)
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Virulence factors - Virulence factors help bacteria to
(1) invade the host
(2) cause disease
(3) evade host defenses.
These can be surface molecules or structures of the organism thathelp it to cause disease by
help the organism attach to the cell it wants to infect
block host cells from identifying the microbe as a pathogen make the microbe motile
block the activation of our defense pathways etc.
- they can also be chemicals (enzymes, toxins) that the pathogenactively secretes in order to cause disease by damaging host tissue
-single organism can cause disease in different ways (tissueinfection/ toxin mediated/ immune mediated)
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Attachment / adhesion For colonization of mucosal surface adhesion
To avoid innate defenses Peristalsis of GIT
Flushing action mucus, saliva, urine
To acquire essential nutrient ex-Iron
Adhesion surface interactions between specificreceptors on the host cell membrane and ligands on thebacterial surface. contributes to tissue specificityof infection
Pathogenesis induces structural and functional changesin mucosal cells
exEntero pathogenic Escherichia coli (EPEC)
H pylori
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Invasion
Pathogenic effects can be by
Invasion bacterium invades host cell, multiplies,
lyses host cell and spreads to adjacent/ deeper
tissue.
Ex: Mycobacteria, Salmonella, Shigella, Escherichia,Neisseria
Without invasion toxins and induction of intra-
cellular signaling pathways mediate damage at
local or distant sites.
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Avoidance of host defenses Capsules polysaccharide capsules reduce efficiency of
phagocytosis
H influenzae, N meningitidis, S pneumoniae, Intracellular pathogens hide inside host cells
Leishmania, toxoplasma macrophages
PlasmodiumRBCs
Streptococcal M protien-..
Resistance to killing by phagocytic cells Mycobacteria prevents phago-lysosome fusion
S aureus produces catalase to neutralize effect of toxic O2radicals.
Immunoglobulin A proteases-.
Mimic host antigens Extracellular parasites
Keep changing antigens-host produces a lot of useless antibodies ex-Schistosomes
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Toxins
Endotoxin (LPS) component of the outer
membrane of gram negative bacteria Effects of endotoxin - .
Exotoxinsdiffusible proteins secreted into the
external medium by the pathogen. Cholera toxin promotes fluid and electrolyte excretion
from enterocytes without killing the cell.
Diptheria toxin mediates cell death
Tetanus toxin effect on skeletal muscle Shigella toxin Bacillary dysentry
Streptolysin O and S lysis of blood cells
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Enzymes
Mucinases
Phospholipases
Collagenases Hyaluronidases
Coagulase
Streptokinase
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Damage to cells and tissue
Damage to local tissue
Invasion and lysis of cells
Enzyme and toxin mediated destruction
Inflammatory reaction
Damage to distant tissue
Toxins -
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Pictures of microbial invasion of living tissue
(E coli invasion of renal tissue)
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Signs and symptoms in relation to the
mechanisms of pathogenesis
Pain, warmth, swelling, redness, loss of functionACUTE INFLAMMATION immune reaction
Nasal secretions when having a cold exudate dueto inflammation
Fever pyrexins
Diarrhoea toxin/ damage to gut epithelium Diarrhoea with blood indicates invasion of the gut
epithelium.
Abscess Pus formation due to large neutrophilresponse to some bacteria
Endotoxin toxin mediated shock
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Summary
Pathogenesis is the process/s by which
organisms cause disease.
Virulence factor factors that help the
organism to cause disease
Adherence , invasion, avoidance of host
defenses, toxins and enzymes
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When you learn about an organism
Name and type (classification)
Mode of transmission / reservoirs / hosts
Virulence factors Intra / extra cellular, capsule/
enzymes and toxins etc Types of disease and pathogenesis in relation to
signs and symptoms
Risk groups / opportunistic
http://www.life.umd.edu/classroom/bsci424/HostParasiteInteractions/HostParasiteSummary.htm
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