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Chapter 8.

MICROBE-HUMAN INTERACTIONS:
INFECTION AND DISEASE

Tiana Milanda
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DEFINISI
• Patogen : organisme yg mampu menimbulkan
penyakit
• Patogenisitas : kemampuan organisme utk
menimbulkan penyakit
• Virulensi : derajat kemampuan organisme
menimbulkan penyakit
• Faktor-faktor virulensi : sifat organisme yang
menimbulkan patogenisitasnya
• Infeksi : peristiwa masuk dan berkembang
biaknya organisme dalam sel inang sampai
menimbulkan penyakit
• Penyakit : respons sel inang terhadap infeksi
MEKANISME INFEKSI
FAKTOR
VIRULENSI
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
MEKANISME ADHESI
MEKANISME ADHESI
pa
Penetration into Host Cells

• Invasins: Surface proteins that alter actin


filaments of host cell cytoskeleton, allowing
microbes to enter cells.
– Examples: Salmonella typhimurium and E.
coli.
• Cadherin: A glycoprotein that bridges
junctions between cells, allowing microbes to
move from one cell to another.
Antifagosit :
•Leukosidin : enzim yang merusak sel darah
putih
•Kapsul

pa
TOKSIN
• Toksin : zat beracun yg dihasilkan mikroorganisme
• Toksin terdiri dari
1. Eksotoksin : toksin yg diekskresikan
mikroorganisme ke medium atau jaringan di
sekitarnya
2. 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
EXOTOXINS
• Both Gram + and Gram – bacteria produce exotoxins.
• Exotoxins are secreted by bacterium or leak into
surrounding fluids following cell lysis.
• In most cases, the pathogen must colonize a body surface
or tissue to produce enough toxin to cause damage.
• Exotoxins can act locally, or they may be carried in the
bloodstream 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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EXOTOXINS
• The A-B toxins can be grouped into functional categories
as 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 13
EXOTOXINS
Neurotoxin : Botulinum toxin
 Clostridium botulinum causes botulism
is 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, if
heated to 80ºC for at least 10 minutes.
 Weakness and vertigo, followed by
double vision, difficulty in speaking,
swallowing and breathing, muscle
weakness, abdominal distention, and
constipation  paralysis and death
may follow

BC Yang
Neurotoxin : Tetanus toxin

Tetanus toxin:

Patient number in Canada


After antitoxin vaccine
1941-1995

BC Yang
Enterotoksin : Cholera toxins, cause
hyperactivation

Vibrio cholerae

BC Yang
Cytotoxin : diphteria toxins, inhibition of
protein synthesis
Subunit A

Corynebacterium diphtheriae
Beta-phage: lysogenic

BC Yang
EXOTOXINS
• Exotoxins are proteins, therefore, the immune
system can generally produce protective antibodies.
• Exotoxins can be inactivated and used to produce
antitoxins 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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MEMBRANE DAMAGING TOXINS
• 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.
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SUPERANTIGENS
• Superantigens short-circuit
normal control mechanisms of
antigen process and
presentation
• Superantigens also suspected in
contributing to autoimmune
disease
• Override specificity of T cell
response
• Causes toxic effects due to massive
release of cytokines by large number
of helper T cells
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ENDOTOXINS
• Endotoxins are
lipopolysaccharides, part of
the 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 toxic
properties of LPS.
• If the lipid A is systemic,
such as a septicemia, the
reactions can result in septic 22
shock or endotoxic shock.
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 the
magnitude of the reaction is small.
• Medical equipment that has been sterilized may still
contain endotoxins.
• Limulus amoebocyte assay (LAL) is a test used to
detect tiny amounts of endotoxin.

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Endotoxins and the Pyrogenic (Fever)
Response
COMPARISON OF EXOTOXINS
AND ENDOTOXINS

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COMPARISON OF EXOTOXINS
AND ENDOTOXINS

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ENZIM EKSTRASELULAR
• Hialuronidase : membantu bakteri patogen menembus
jaringan sel inang dgn menghidrolisis asam hialuronat
yg berfungsi melekatkan sel-sel menjadi satu 
dihasilkan Staphylococcus, Streptococcus dan
Clostridium

• Lesitinase : enzim yg menghancurkan berbagai


jaringan, terutama melisis sel-sel darah merah 
Clostridium perfringens penyebab gangrens gas
(kelemayuh), suatu infeksi jar disertai gas & nanah

• Kolagenase : enzim penghancur kolagen (serabut jar


pada otot, tulang & tulang rawan) serta membentuk
struktur jala  meningkatkan virulensi Clostridium
perfringens
ENZIM EKSTRASELULER
• Koagulase : enzim yg bekerja sama dgn aktivator pd
plasma utk mengubah fibrinogen mjd fibrin 
menyebabkan endapan fibrin di sekitar sel bakteri yg
melindunginya dari sel fagosit inang.
Contoh : pembentukan dinding pd bisul yg disebabkan
S. aureus

• Leukosidin : enzim yg menghancurkan leukosit 


dihasilkan bbrp Staphylococcus dan Streptococcus
ENZIM EKSTRASELULER
• Hemolisin : enzim pelisis sel darah merah dan
membebaskan hemoglobinnya.
• Ada 2 tipe yaitu :
1. Hemolisin ekstraseluler
Contoh : Streptolisin O dan S yg dihasilkan bbrp
Streptococcus
2. Hemolisin penyebab perubahan warna agar darah,
tdr dari :
- -hemolisis (merah  tdk berwarna, krn sel drh
merah lisis & Hb diubah mjd senyawa tdk
berwarna)
- -hemolisis (merah  hijau, krn sel drh
merah lisis & Hb diubah mjd metemoglobin
FAKTOR-FAKTOR LAIN YG
MEMPENGARUHI INFEKSI
• Afinitas jaringan
• Gerbang masuk (Portal of of entry)
• Penyebarluasan (Transmisi)
AFINITAS JARINGAN
• Bbrp mikroorganisme mempunyai afinitas ttt thd sel &
jar ttt  dirusak  timbul penyakit

Contoh :
• Brucella penyebab bruselosis (keguguran) pada ternak
menyerang plasenta ternak, krn plasenta ini
mempunyai gula eritritol yg dibutuhkan Brucella
• S. typhi menyerang jar limfoid dd usus
• Virus polio menyerang sel syaraf
• Bbrp protozoa spt parasit malaria menyerang eritrosit
manusia, namun pada stadium ttt tumbuh dalam jar
nyamuk
GERBANG MASUK
• Gerbang masuk : rute tertentu
masuknya patogen ke dalam
tubuh sel inang

Contoh :
• Saluran pencernaan utk bakteri
tifoid, disentri dan kolera 
tahan thd enzim mulut dan cairan
lambung
• 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 penyebab
malaria dan virus rabies
GERBANG MASUK
• Gerbang masuk racun menentukan kemampuan
menyebabkan penyakit pada sel inang

Contoh :
• Toksin botulinum menyebabkan keracunan
parah atau kematian, bila termakan
• Toksin mikrokokus menyebabkan reaksi
gastrointestinal gawat, bila termakan
• Toksin Clostridium tetani dan streptokokus
hemolitik yg masuk lwt sistem pencernaan tdk
menimbulkan penyakit, ttp menimbulkan
kejang parah bila melalui kulit atau otot
Transmission
1. Contact transmission
• Direct (physical contact)
• Indirect (via
contaminated objects)
• Droplets
2. Vehicle Transmission
• Waterborne
• Airborne
• Foodborne
3. Vector transmission :
mechanical and biological
CONTACT TRANSMISSION
• DIRECT CONTACT —reservoir to host
• INDIRECT CONTACT —contaminated object to
host.
• DROPLET —reservoir to air (short distance)
to host

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Direct-Contact Transmission
Indirect-Contact Transmission
Influenza
virus?

Door knobs are


another good
example of a
fomite.
Droplet Transmission

Measles?
VEHICLE TRANSMISSION
• Common vehicle transmission
refers to the transmission of
disease agents by a common
inanimate reservoir (food,
drugs, blood) to an individual.

• Airborne transmission refers to


the spread of agents by droplet
nuclei or dust at a distance of
more than 1 meter from the
reservoir to host.

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Airborne Transmission

Mycobacterium
tuberculosis?
Airborne Transmission

Contact with air from clean, Contact with air from small
empty room. room containing 12 people.
Waterborne Transmission

parvum?
Cryptosporidium
Waterborne Transmission

from
water.
Giardiasis
Foodborne Transmission

Hepatitis A
Foodborne Transmission

Balantidium coli
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 INFECTIOUS
DISEASE
• An infection that results in disease is called
infectious disease.
• Diseases are characterized by symptoms and
signs.
• SYMPTOMS—subjective evidence of disease as
sensed by the patient.
• SIGNS—objective evidence of disease as noted by
an observer.
• SYNDROMES—a specific group of symptoms or
signs which accompany a particular disease. 48
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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. 50
PATTERN OF DISEASE

Fig. 13.p398
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 elicit
symptoms.
• Incubation periods range
between 2 and 30 days
usually. 52
PRODROMIAL STAGE
• The prodromial stage is the
period when symptoms
develop.
• The symptoms tend to be
vague 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 other
prominent and more specific
signs and symptoms.
• The length of this period is
extremely variable. 54
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 short
time
– Chronic
• Symptoms develop slowly
and persist
– Latent
• Infection never
completely eliminated
• Infection becomes
reactive 56
EXTENT OF HOST INVOLVEMENT

• A PRIMARY INFECTION—is
an acute infection that
causes the initial illness.
• A SECONDARY
INFECTION—is one caused
by an opportunist
microbe or is the result of
the primary infection.
• A SUBCLINICAL
INFECTION—is one that
does not cause any
noticeable illness. 57
EXTENT OF HOST INVOLVEMENT
• LOCALIZED INFECTION–
microbes enters body &
remains confined to a
specific tissue.
• FOCAL INFECTION– when
infectious agent breaks
loose from a local
infection and is carried
to other tissues.
• SYSTEMIC INFECTION–
infection spreads to
several sites and tissue
fluids usually in the
bloodstream. 58
EXTENT OF HOST INVOLVEMENT

• BACTEREMIA—the presence of bacteria


in the blood.
• SEPTICEMIA—if bacteria are multiply in
the blood.
• TOXEMIA—presence of toxins in the
blood.
• VIREMIA—presence 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 healthy
population.
• PREVALENCE – total number of existing
cases with respect to the entire
population usually represented by a
percentage of the population.
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OCCURRENCE OF DISEASE
• SPORADIC – when occasional
cases are reported at irregular
intervals.
• ENDEMIC – disease that exhibits
a relatively steady frequency
over a long period of time in a
particular geographic locale.
• EPIDEMIC – when prevalence of
a disease is increasing beyond
what is expected.
• PANDEMIC – epidemic across
continents
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