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Chapter 8.MICROBE-HUMAN INTERACTIONS:
INFECTION AND DISEASE
Tiana Milanda
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DEFINISI
Patogen : organisme yg mampu menimbulkanpenyakit
Patogenisitas : kemampuan organisme utkmenimbulkan penyakit
Virulensi : derajat kemampuan organismemenimbulkan penyakit
Faktor-faktor virulensi : sifat organisme yangmenimbulkan patogenisitasnya
Infeksi : peristiwa masuk dan berkembangbiaknya organisme dalam sel inang sampaimenimbulkan penyakit
Penyakit : respons sel inang terhadap infeksi
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MEKANISME INFEKSI
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FAKTORVIRULENSI
Dapat berupa single
atau multiple factors :
1.Struktur permukaan
sel : fimbriae (pili),kapsul, spike (duri),
flagela, adhesin atau
antifagositosis
2.Produksi protein
toksin atau enzim
ekstraseluler
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MEKANISME ADHESI
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MEKANISME ADHESI
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pa
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Penetration into Host Cells
Invasins: Surface proteins that alter actinfilaments of host cell cytoskeleton, allowing
microbes to enter cells.
Examples: Salmonella typhimurium and E.coli.
Cadherin: A glycoprotein that bridgesjunctions between cells, allowing microbes to
move from one cell to another.
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pa
Antifagosit :
Leukosidin : enzim yang merusak sel darah
putihKapsul
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TOKSIN
Toksin : zat beracun yg dihasilkan mikroorganisme Toksin terdiri dari
1. Eksotoksin : toksin yg diekskresikan
mikroorganisme ke medium atau jaringan di
sekitarnya2. Endotoksin : toksin yang berupa bagian tubuh
mikroorganisme
Toksigenisitas : kemampuan produksi toksin pada saat
bakteri bermultiplikasi Toksinosis : kemampuan toksin merusak struktur atau
fungsi komponen sel inang
Toksikemia : adanya toksin ke dalam darah
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EXOTOXINS
Both Gram + and Gram bacteria produce exotoxins.
Exotoxins are secreted by bacterium or leak intosurrounding fluids following cell lysis.
In most cases, the pathogen must colonize a body surfaceor tissue to produce enough toxin to cause damage.
Exotoxins can act locally, or they may be carried in thebloodstream throughout the body, causing systemic
effects. Exotoxins have very specific damaging effects which are
disease specific.
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EXOTOXINS
Most exotoxins fall into 3 general categories that
reflect their structure and general mechanism of
action:
A-B toxins Membrane-damaging toxins
Superantigens
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The A-B toxins can be grouped into functional categoriesas well:
Neurotoxins
Cause damage to nervous system
Major symptom is paralysis
Enterotoxins
Damage to intestines and tissues of digestive tract
Major symptom is vomiting and diarrhea
Cytotoxins
Damage to variety of cells
Damage caused by interference with cell function
or cell lysis
EXOTOXINS
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EXOTOXINS
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Neurotoxin : Botulinum toxin
Clostridium botulinum causes botulismis a severe type of food poisoning
caused by the ingestion of foods
containing the neurotoxin formed
during growth of this bacteria
C. botulinum can be destroyed, ifheated to 80C for at least 10 minutes.
Weakness and vertigo, followed by
double vision, difficulty in speaking,
swallowing and breathing, muscleweakness, abdominal distention, and
constipation paralysis and death
may follow
BC Yang
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Neurotoxin : Tetanus toxin
Tetanus toxin:
Patient number in Canada
After antitoxin vaccine1941-1995
BC Yang
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Enterotoksin : Cholera toxins, causehyperactivation
Vibrio cholerae
BC Yang
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Cytotoxin : diphteria toxins, inhibition ofprotein synthesis
Corynebacterium diphtheriaeBeta-phage: lysogenic
Subunit A
BC Yang
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EXOTOXINS
Exotoxins are proteins, therefore, the immunesystem can generally produce protective antibodies.
Exotoxins can be inactivated and used to produceantitoxins called toxoids.
The body produces antibodies called antitoxins that
provide immunity to exotoxins. When toxoids are injected into the body as a
vaccine they stimulated antitoxins to be produced,diphtheria and tetanus are examples.
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Phospholipases are group of potent membrane-damaging
toxins
Remove polar heads of phospholipid
Destabilizes membrane
Clostridium perfringens which causes gas gangrene
is a phospholipase.
Disrupt plasma membrane
Cause cell lysis
Can be termed hemolysins or cytolysins.
Some membrane-damaging toxins produce pores that
allow fluids to enter causing cell destruction.
Streptococcus pyogenes on blood agar plates.
MEMBRANE DAMAGING TOXINS
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SUPERANTIGENS
Superantigens short-circuitnormal control mechanisms of
antigen process and
presentation
Superantigens also suspected incontributing to autoimmune
disease
Override specificity of T cellresponse Causes toxic effects due to massive
release of cytokines by large numberof helper T cells
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ENDOTOXINS Endotoxins are
lipopolysaccharides, part ofthe outer leaflet of the outer
membrane of Gram negative
bacteria include Salmonella
typhi, Proteus spp.,Pseudomonas spp., Neisseria
spp.
The lipid A component is
responsible for the toxicproperties of LPS.
If the lipid A is systemic,
such as a septicemia, the
reactions can result in septic
shock or endotoxic shock.
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ENDOTOXINS
All endotoxins produce the same signs and symptoms,regardless of the species of microorganism, although
not to the same degree.
Responses by the host include fever, weakness, and
generalized. If the lipid A is in a localized region themagnitude of the reaction is small.
Medical equipment that has been sterilized may still
contain endotoxins.
Limulus amoebocyte assay (LAL) is a test used todetect tiny amounts of endotoxin.
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Endotoxins and the Pyrogenic (Fever)Response
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COMPARISON OF EXOTOXINS
AND ENDOTOXINS
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COMPARISON OF EXOTOXINS
AND ENDOTOXINS
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ENZIM EKSTRASELULAR
Hialuronidase : membantu bakteri patogen menembusjaringan sel inang dgn menghidrolisis asam hialuronatyg berfungsi melekatkan sel-sel menjadi satu dihasilkan Staphylococcus, Streptococcus danClostridium
Lesitinase : enzim yg menghancurkan berbagaijaringan, terutama melisis sel-sel darah merah Clostridium perfringens penyebab gangrens gas(kelemayuh), suatu infeksi jar disertai gas & nanah
Kolagenase : enzim penghancur kolagen (serabut jarpada otot, tulang & tulang rawan) serta membentukstruktur jala meningkatkan virulensi Clostridiumperfringens
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ENZIM EKSTRASELULER
Koagulase : enzim yg bekerja sama dgn aktivator pdplasma utk mengubah fibrinogen mjd fibrin
menyebabkan endapan fibrin di sekitar sel bakteri yg
melindunginya dari sel fagosit inang.
Contoh : pembentukan dinding pd bisul yg disebabkanS. aureus
Leukosidin : enzim yg menghancurkan leukosit
dihasilkan bbrp Staphylococcus dan Streptococcus
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ENZIM EKSTRASELULER
Hemolisin : enzim pelisis sel darah merah danmembebaskan hemoglobinnya.
Ada 2 tipe yaitu :
1. Hemolisin ekstraseluler
Contoh : Streptolisin O dan S yg dihasilkan bbrpStreptococcus
2. Hemolisin penyebab perubahan warna agar darah,
tdr dari :
- -hemolisis (merah tdk berwarna, krn sel drhmerah lisis & Hb diubah mjd senyawa tdk
berwarna)
- -hemolisis (merah hijau, krn sel drh
merah lisis & Hb diubah mjd metemoglobin
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FAKTOR-FAKTOR LAIN YGMEMPENGARUHI INFEKSI
Afinitas jaringan
Gerbang masuk (Portal of of entry)
Penyebarluasan (Transmisi)
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AFINITAS JARINGAN
Bbrp mikroorganisme mempunyai afinitas ttt thd sel &jar ttt dirusak timbul penyakit
Contoh :
Brucella penyebab bruselosis (keguguran) pada ternakmenyerang plasenta ternak, krn plasenta inimempunyai gula eritritol yg dibutuhkan Brucella
S. typhi menyerang jar limfoid dd usus
Virus polio menyerang sel syaraf
Bbrp protozoa spt parasit malaria menyerang eritrositmanusia, namun pada stadium ttt tumbuh dalam jarnyamuk
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GERBANG MASUK Gerbang masuk : rute tertentu
masuknya patogen ke dalamtubuh sel inang
Contoh :
Saluran pencernaan utk bakteri
tifoid, disentri dan kolera tahan thd enzim mulut dan cairanlambung
Saluran pernafasan : bakteri TBC,pneumokokus dan difteri
Saluran kemih-kelamin :gonokokus & spiroketa
Goresan/luka pada kulit :stafilokokus
Retakan kulit : basil antraks
Gigitan artropoda atau hewan-hewan besar : protozoa penyebabmalaria dan virus rabies
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GERBANG MASUK
Gerbang masuk racun menentukan kemampuanmenyebabkan penyakit pada sel inang
Contoh :
Toksin botulinum menyebabkan keracunanparah atau kematian, bila termakan
Toksin mikrokokus menyebabkan reaksigastrointestinal gawat, bila termakan
Toksin Clostridium tetani dan streptokokushemolitik yg masuk lwt sistem pencernaan tdkmenimbulkan penyakit, ttp menimbulkankejang parah bila melalui kulit atau otot
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Transmission
1. Contact transmission Direct (physical contact)
Indirect (via
contaminated objects)
Droplets2. Vehicle Transmission
Waterborne
Airborne
Foodborne
3. Vector transmission :
mechanical and biological
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CONTACT TRANSMISSION
DIRECT CONTACT reservoir to host
INDIRECT CONTACT contaminated object tohost.
DROPLET reservoir to air (short distance)to host
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Direct-C
ontactTransmission
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Indirect-Contact Transmission
Door knobs areanother goodexample of a
fomite.
Influenzavirus?
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Droplet Transmission
Measles?
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VEHICLE TRANSMISSION
Common vehicle transmissionrefers to the transmission ofdisease agents by a commoninanimate reservoir (food,
drugs, blood) to an individual.
Airborne transmission refers tothe spread of agents by droplet
nuclei or dust at a distance ofmore than 1 meter from thereservoir to host.
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Airborne Transmission
Mycobacteriumtuberculosis?
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Airborne Transmission
Contact with air from small
room containing 12 people.
Contact with air from clean,
empty room.
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Waterb
orneTransmission
Cryptosporidium
parvum?
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Waterb
orneTransmission
Giardiasis
from
water.
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FoodborneTr
ansmission
Hepatitis A
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FoodborneTr
ansmission
Balantidium coli
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VECTORS
A vector, animals that
carry pathogens from
one host to another.
Biological: bite or feces
Mechanical:transported
on feet
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CHARACTERISTICS OF INFECTIOUSDISEASE
An infection that results in disease is called
infectious disease.
Diseases are characterized by symptoms and
signs.
SYMPTOMSsubjective evidence of disease as
sensed by the patient.
SIGNSobjective evidence of disease as noted byan observer.
SYNDROMESa specific group of symptoms or
signs which accompany a particular disease.
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CHARACTERISTICS OF INFECTIOUS
DISEASE Infectious diseases that spread from one host
to another are called communicable or
contagious diseases.
The ease of spread of a contagious disease
partly reflects the infectious dose, or the
number of microbes necessary to establish
an infection. The infectious dose is expressed as the ID50 ,
which indicates the number of microbes that
results in disease in 50% of the population.
PATTERN OF DISEASE
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Fig. 13.p398
PATTERN OF DISEASE
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INCUBATION PERIOD Incubation period is the time
from initial contact with the
infectious agent to the
appearance of the first
symptoms. During this period the agent is
multiplying at the portal of
entry but has not yet caused
enough damage to elicitsymptoms.
Incubation periods range
between 2 and 30 days
usually.
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PRODROMIAL STAGE
The prodromial stage is the
period when symptoms
develop.
The symptoms tend to bevague feelings of discomfort
such as head and muscle
aches, fatigue, and general
malaise.
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PERIOD OF INVASION
During the period of invasion
the infectious agent
multiplies at high levels,
exhibits its greatest toxicity,and becomes well
established.
This period is often marked
by fever and otherprominent and more specific
signs and symptoms.
The length of this period is
extremely variable.
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PERIOD OF CONVALESCENT
The period of convalescent is the time when
the patient recovers his strength and health
gradually returns.
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PRINCIPLES OF INFECTIOUS
DISEASE Duration of symptoms
Acute
Symptoms have rapid
onset and last only shorttime
Chronic
Symptoms develop slowly
and persist
Latent
Infection never
completely eliminated
Infection becomes
reactive
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EXTENT OF HOST INVOLVEMENT
A PRIMARY INFECTIONis
an acute infection that
causes the initial illness.
A SECONDARYINFECTIONis one caused
by an opportunist
microbe or is the result of
the primary infection. A SUBCLINICAL
INFECTIONis one that
does not cause any
noticeable illness.
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EXTENT OF HOST INVOLVEMENT
LOCALIZED INFECTION
microbes enters body &
remains confined to a
specific tissue.
FOCAL INFECTION when
infectious agent breaksloose from a local
infection and is carried
to other tissues.
SYSTEMIC INFECTION
infection spreads to
several sites and tissue
fluids usually in the
bloodstream.
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EXTENT OF HOST INVOLVEMENT
BACTEREMIAthe presence of bacteria
in the blood.
SEPTICEMIAif bacteria are multiply inthe blood.
TOXEMIApresence of toxins in the
blood. VIREMIApresence of viruses in the
blood.
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OCCURRENCE OF DISEASE
INCIDENCE measures the number of
new cases over a certain time period,
as compared with the general healthypopulation.
PREVALENCE total number of existing
cases with respect to the entirepopulation usually represented by a
percentage of the population.
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OCCURRENCE OF DISEASE
SPORADIC when occasionalcases are reported at irregular
intervals.
ENDEMIC disease that exhibits
a relatively steady frequencyover a long period of time in a
particular geographic locale.
EPIDEMIC when prevalence of
a disease is increasing beyondwhat is expected.
PANDEMIC epidemic across
continents