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of infection
Entry of agents
pathogenic action
Portals of Entry
Skin
Mucous membrane
Respiratory, gastrointestinal, urinary,
reproductive tracts
Conjunctiva, the thin membrane covering
the surface of the eyeball and the
underside of each eyelid
Placenta
(Parenteral route)
Is not a portal entry, but instead a means by
which the portals of entry can be
circumvented
Colonization
To colonize a site populated by normal flora,
the new arrival must compete successfully
with:
established organisms for space and
nutrients (siderophores)
overcome their toxic product
counter the bodys defenses aimed at
protecting the surfaces (IgA proteases)
Adhesion / Attachment
The process by which microorganisms
attach themselves to cells
Adhesion factors:
Specialized structures
Adhesion disk (protozoa), suckers, hooks
(helminthes)
Ligands: Surface lipoprotein and
glycoprotein (bacteria, viruses)
Adhesin (bacteria): found on fimbrae,
flagella, glycocalyses
Attachment protein (viruses)
Adherence mechanism
factors support the adherence mechanism
Virulence
Degree of pathogenicity
Virulence factors
A variety of traits that interact with a host and enable the
pathogen to enter a host, adhere to host cells, gain
access to nutrients, and escape detection or removal
by the immune system
Virulence Factors
Extracellular Enzymes (Hyaluronidase and
collagenase, Coagulase, Kinase)
Toxin (Exotoxin, endotoxin)
Antiphagocytic factor (capsule, antiphagocytic chemical)
Invasion factor
Siderophore
Lipopolysacharides
Virulence Factors
Extracellular Enzymes
Hyaluronidase and
collagenase degrade specific
molecules to enable bacteria
to invade deeper tissue
Coagulase blood protein,
providing a hiding place for
bacteria within a clot
Kinase such as
staphylokinase and
streptokinase digest blood
clots
Virulence Factors
Toxins
Exotoxin
Cytotoxins: kills host cells in
general or affect their function
Neurotoxins: specifically interfere
with nerve cell function
Enterotoxins: affects cell lining the
gastrointestinal tract
Endotoxin
Lipid A, lipid portion of the
membranes lypopolysaccharide
Nomenclatur : has no systematic basis
Lyses cells
Capsules
Composed of chemicals that are normally
found in the body (including
polysaccharides) do not stimulate a
hosts immune response
Protect the bacteria from the host
inflammatory response (complement
activation and phagocyte mediated killing)
Capsules prevent formation of C3
convertase
Antiphagocytic chemicals
Prevent the fusion of lysosomes with
phagocytic vesicles, which allows the
bacteria to survive inside of phagocytes
S.pyogenes produces a protein on its cells
wall and fimbrae (M protein), that resist
phagocytosis and thus increases virulence
Virulence Factors
Invasion factors
Severity of disease
Cytopathic ability of virus
Immune status
Competence of immune system
Prior immunity to the virus
Immunopathology
Virus inoculum size
Length of time before resolution of infection
General health of the person
Nutrition
Other diseases influencing immune status
Host genetic makeup
Age
Tahap-tahap dalam patogenesis infeksi
virus
1. Masuknya virus dan replikasi primer
2. Tropisma dan penyebaran virus dalam tubuh
3. Kerusakan sel/ jaringan dan manifestasi
klinis
4. Pemulihan dari infeksi dan tipe infeksi
5. Penyebaran virus ke luar tubuh/ lingkungan
Virus spread in human body
Tahap-tahap dalam patogenesis infeksi
virus
1. Masuknya virus dan replikasi primer
- Jalan masuk
- replikasi primer pada tempat masuk
- masa inkubasi
2. Tropisma dan penyebaran virus dalam tubuh
- Mekanisme penyebaran dalam tubuh
bervariasi: aliran darah, limfatik, saraf
perifer, antar sel
- spesifik jaringan/ sel
- Faktor-faktor sel/ jaringan dan faktor-
faktor virus yang mempengaruhi tropisma
- reseptor spesifik
- ekspresi gen virus
- enzim yg diperlukan untuk replikasi virus
Tropisma
Receptor & co-receptor Hemaglutinin dan neuraminidase of
Of HIV influenza virus
Binding of a virus to its receptor on the host cell
surface result in penetration of the cell or the delivery
of virus nucleic acid to the cytoplasm of the cell
Cytopathic viruses
Ultimately kill the host cell, the result is often local necrosis
Can trigger apoptosis or programmed cell death
Noncytopathic viruses
Do not immediately produce cell death and result in latent or
persistent infections
Productive: virus produce persistent infection with the release of
only a few new viral particles at a time
Non-productive: viruses do not actively make virus at detectable
levels for a period of time (latent infection)
3. Kerusakan sel/ jaringan dan manifestasi klinis
- Iceberg concept of infection : tipe
respons sel/ pejamu terhadap infeksi
- Lokal, sistemik
- Jaringan tertentu lebih tahan thd
kerusakan dibandingkan lainnya (misal
jar.usus vs otak)
- Mekanisme pertahanan tubuh dan proses
imunopatologis
Syncytia in paramyxovirus infection
Neoplasia:
The phenomenon of uncontrolled cell division
Cell undergoing neoplasia are said to be neoplastic, and
a mass of neoplastic cells is a tumor
Tumor: benign and malignant
Protooncogenes: genes
that play a role in cell
division
VIRUS KANKER
Virus RNA
Virus Hepatitis C Karsinoma hepatoseluler
HTLV-1 ATL
Virus DNA
Virus hepatitis B Karsinoma hepatoseluler
Virus papilloma manusia Papilloma dan karsinoma
Herpes virus 8 Sarkoma Kaposi
Virus Epstein Barr Limfoma Burkitt,
ca nasofaring
Oncogenic viruses :
- Establish persistent infection
- Stimulate uncontrolled cell growth transformation and
immortalization
Usually the first step but not sufficient to cause oncogenesis / tumor
formation
Immortalization accumulation of mutations/
chromosomal rearrngement tumor
Immortalization more susceptible to co-factors tumor
Different oncogenic viruses have different mechanism of
cell transformation :
-Promoting or providing growth-stimulating genes
-Removing the inherent braking mechanism that limit DNA synthesis
and cell growth
- Preventing apoptosiss
- Indirectly : stimulation of cell growth and repair
-------- promote mutation
MEKANISME INDUKSI TUMOR OLEH VIRUS
Tidak langsung
1. Supresi sistem imun pejamu
(HTLV-1, HIV-1, CMV, avian reticuloendotheliosis virus,
feline leukemia virus, Mareks disease virus)
2. Stimulasi proliferasi sel, target perubahan neoplastik
lain bertambah.
a. Regenerasi sel setelah sitolisis oleh virus
(kemungkinan : HBV, HCV)
b. Mitogenesis sel imunokompeten atau sel lain
(kemungkinan : beberapa virus lekemia mencit,
HTLV-1, HIV-1)
MEKANISME INDUKSI TUMOR OLEH VIRUS
Langsung
1. Hit & run
- DNA atau fungsi virus bekerja sesaat
- Keberadaan gene atau struktur virus tidak perlu menetap
- Contoh : BPV, beberapa virus herpes (a.l. EBV)
2. Bagian gene virus yang penting tetap berada di sel
a. Virus memiliki gen yang produknya secara langsung
atau tidak langsung berfungsi dalam terjadinya tumor
(onkogen)
I. Onkogen telah berevolusi dari proto-onkogen sel
normal (RSV)
ii. Onkogen langsung ditransduksi dari protoonkogen
saat infeksi virus (FLV, ALV)
iii. Onkogen tidak mempunyai homolog gen sel normal
(SV40, polyomavirus, papillomavirus, adenovirus, EBV,
HTLV-1)
2.b. Mutagenesis dengan insersi
- Insersi DNA virus pada genome sel meningkatkan atau
menekan ekspresi gen normal
(a.l. ALV, beberapa virus papilloma)
Adenovirus E1A,
SV40-LT, HPV16&18 E7
-- bind to Rb-related proteins
Toksin??
Exotoxin and Endotoxin
Definition
Bacterial toxin :
A protein or protein complex that is toxic to
human cells and causes the symptoms of
diseases
Exotoxin : toxins are excreted from the cell
Endotoxin (LPS) : embedded in the bacterial
surface
Mycotoxin :
Low-molecular-weight natural products produce
as secondary metabolites by filamentous fungi
Exotoxin
Not all of toxins are directed at human
cells
Toxin produced by Bacillus thuringiensis is
used as an insecticide in agriculture
Chromosomal
Plasmid
Phage
These locations ensure that the
ability to produce toxin may
rapidly spread to non-toxigenic
bacteria
The property may also be lost
from the bacteria by curing the
cells of plasmids or prophage
Toxin production : When ?
A B Toxins
Membrane-disrupting toxins
Superantigens
A B Toxins
Portion of the toxin that binds a host cell
receptor (B=binding) is separate from the
portion that mediates the enzymatic
activity responsible for toxicity (A=active)
B portion B
B B A portion
ss B B
s B
A portion
B portion : multiple subunit
Lyses cells
Type I
Specialized proteins mediate excretion of toxin through pore-spanning
outer membrane and cytoplasmic membrane (Gram-negative bacteria)
Used by membrane disrupting (pore-forming) toxin
Type II
Gram-positive bacteria have only cytoplasmic membrane : exotoxins are
externalized by the general secretory pathway (Sec)
Toxin components secreted into periplasm; assembled there, usually
released by disrupting of outer membrane
Type III
Pore formed through cytoplasmic membrane of bacterial and
mammalian cells
Bacteria inject toxin directly into host cell cytoplasm
Type IV
Associated with the conjugal transfer of DNA
Most system : protein transferred directly into host cell. Some cases :
protein may be secreted into external environment
Endotoxin
LPS-LPS-binding protein
interact with CD14 receptors on
monocytes/macrophages/other
host cells such as endothelial
These clots :
Obstruct peripheral blood vessels
Restricting the normal flow of blood