Download Pathogenesis of bacterial infection Terms

现代医学导论
2012级食品安全与营养专业求是科学班
病原微生物的致病机理
及机体免疫调控机制
Infection and immunity
Dr. Jing Qian
Zhejiang University School of Medicine
April 09, 2014
Pathogenesis of bacterial infection
Terms
Pathogen: A microorganism enable to cause disease.
Nonpathogen: A microorganism that does not cause disease.
Opportunistic pathogen: A microorganism does not cause disease in normal
conditions, but is capable of causing disease in some special conditions.
Pathogenicity: The ability of a microorganism to cause disease.
Pathogenesis of bacterial infection
Terms
Virulence: The quantitative ability of a pathogen to cause disease. Virulent agents
cause disease when introduced into the host. It contains invasiveness and toxigenicity.
LD50: The number of pathogen required to cause lethal disease in half of the
exposed hosts.
ID50: The number of pathogens required to cause disease or infection in half of the
exposed hosts.
Pathogenesis of bacterial infection
Terms
• Adhesion (adherence, attachment): the process by which bacteria stick to the
surfaces of host cells. Adhesion is a key initial step during infection (then
invasion).
• Invasion: The process whereby microoganisms enter host cells or tissues as
well as spread in the body.
• Toxigenicity: The ability of a microorganism to produce a toxin that
contributes to the development of disease.
•
•
Pathogenesis of bacterial infection includes:
a) general process of infection
b) mechanisms of microbes causing disease
A bacterial infectious disease is a multi-factorial event which
depends on:
i.
Nature (virulence) of bacterial species or strain.
ii.
Number of invaded bacteria.
iii. Route of bacteria invading hosts.
Generally, infection process caused by a bacterial pathogen involves
the four steps as the following:
I.
Adhesion
II. Penetration and spread
III. Survival and propagation in the host
IV. Tissue injury
Any bacterial factors involved in the four steps determine the virulence
of bacteria.
Bacterial virulence is dependent on various virulent factors produced
by bacteria.
Degradative enzymes
• Collagenase: to destroy collagen. There are a lot of collagens in soft
tissue including connective tissue.
• Hyaluronidas: to destroy hyaluronic acid. Hyaluronic acid is a major
component in the matrix of connective tissue.
• Coagulase: to coagulate fibrinogen in tissue fluid and plasma into fibrin.
(to protect bacteria from damage by many agents)
• Streptokinase/fibrinolysin: The former activates fibrinogenase to
thrombin, which results in the degradation of fibrin. And the latter
directly lyse fibrin.
• Streptodornase: it is a DNase.
• Cytolysins:
1) hemolysins (to dissolve red blood cells)
2) Leoukocisins (to kill leukocytes or tissue cells )
Bacteria cause tissue injury by many factors or
some special mechanisms involving:
a) Exotoxin
b) Endotoxin
c) Inducement of Immunopathological reaction
Exotoxins
Cytotoxin: e.g. diphtheria toxin
Nuerotoxin: e.g. tetanospasmin
Enterotoxin: e.g. cholera enterotoxin
Cell surface
Toxic
Binding
A
B
Endotoxins (LPS)
Original and development of
Bacterial Infection
Source of infection
Exogenous infection
Infections caused by infectious agents that are come from the external
environment or other hosts (patient, carrier, diseased animal or animal
carrier).
Definition of “carrier”: individuals infected with infectious agents but no
clinical signs or symptoms.
Endogenous condition
Infections caused by normal flora under certain conditions (opportunistic
infection)
Transmission of bacteria
Bacteria can be transmitted in airborne droplets to the respiratory
tract, by ingestion of food or water or by sexual contact.
Specific bacterial species are being transmitted by different routes to
specific sites in the human body:
1. Respiratory
2. Gastroenteric
3. Genitourinary tract
4. Closely contact
5. Insect bite
6. Blood transfusion
7. Parenteral route
8. Skin and other mucosa (eye)
Types of bacterial infection
According to infectious state:
Inapparent or subclinical infection: The infection with
no
manifesting characteristic clinical signs and symptoms.
Latent infection: The infection is inactive but remains capable
of producing clinical signs and symptoms.
Apparent
infection :
The
infection
characteristic clinical signs and symptoms.
with
manifesting
Types of bacterial infection
According to infectious sites:
Local infection: The infection is limited to a small area of the body.
1.
2.
3.
4.
5.
Generalized or systemic infection:
Toxemia: Exotoxins enter bloodstream but no bacteria in the blood.
Endotoxemi: Endotoxins enter bloodstream but no bacteria in the blood.
Bacteremia : Bacteria enter bloodstream without
propagation in
bloodstream (bloodstream only used as a channel tool for bacteria to
spread)
Septicemia: Bacteria enter bloodstream with propagation and release
their virelent substances (e.g., toxins).
Pyemia : Pyogenic bacteria enter bloodstream with propagation and
release their virulent substances, and spread through bloodstream into
the target organs to form new pyogenic foci.
Pathogenesis of viruses infection
Steps in virus-host interaction
•Entry into the host
•Primary replication
•Spread
•Cell and tissue tropism
•Secondary replication
•Cell injury and persistence
•Host immune response
Viral pathogenesis
the seven steps from entry to disease
1 Replication at the
site of entry
2 Lymph node
HSV
VZV
3 Primary viremia
4 Replication sites
5 Secondary viremia
6 Replication sites
7 Transmission to
other hosts
Cytomegalovirus
Ganglion
Bone marrow
Sites of virus entry
Transmission of viruses
aerosols
parental
direct contacts
sexual
Outcomes of viral infections
acute, self limiting
chronic
Locally restricted
(z. B. Rhinitis, Enteritis)
Latent, reactivation (Phases
without viremia)
(eg Herpesviruses)
Chronic persistent
(permanent Virus production)
(eg Hepatitis B and C)
systemic
local replication => Viremia
(eg. Measles)
active progression
(eg HIV)
Patterns in acute and persistent infections
raute 7/2002
Pathogenesis of fungal infection
A. Superficial mycoses
B. Cutaneous mycoses
C. Subcutaneous mycoses
D. Systemic mycoses
Pathogenesis of fungal infection
A. Superficial mycoses
B. Cutaneous mycoses
Oral thrush
Host immune responses to infection
The two columns of immunity
immunity
innnate immunity
nonspecific immunity
constitutional, skin: defensins
aqcuired immunity
specific immunity
humoral
constitutional, blood : complement
reactive, blood: interferons
cellular
NK cells
cellular
cytotoxic
Early phase of immunity
Infectious agent
Infektions-Erreger
Epithelial
barrier
Epithel-Barriere
uns pezifis
che
Innate
immunity
Abwehr
polymorphkernige
polymorphonuclear Monozyten
Monocytes
Granulozyten (P MN)
Granulocytes (PMN)
N K-Zellen
NK cells ?
draining
drainierender
Lymphknoten
lymphnode
Interleukin/Cytokin
Interleukine/cytokine
Balance
balance
Polarization
of der
the
Polarisation
T Zell-Antwort
T-cell response
Time table
of innate and specific immunity
complement
interferon a/b
NK cells
CD4 lymphocytes
CD8 lymphocytes
antibodies
days after infection
Antimicrobial Defenses for Infectious Agents
Intracellular
Bacteria
Bacteria
Viruses
Fungi
Parasites
Complement
+
-
-
-
-
Interferon-α/β
-
-
++++
-
-
Neutrophils
++++
-
-
+
+
Macrophages
++
+++
++
++
+
NK cells
-
-
+++
-
-
CD4 TH1,
DTH
-
++
+++
+*
+
CD8 CTL
-
-
++++
-
-
Antibody
++
+
+
+
++(IgE)†
*CTL,
By activation of macrophages. †Immunoglubulin E and mast cells are especially important for worm infections.
Cytotoxic T lymphocytes; NK, natural killer.
Time table
of innate and specific immunity for bacteria infection
Effects of innate and specific immunity on viral infectionpositive part
Toll-like receptors
Surveillance systems for microbes
Surveillance systems for microbes
pathogen associated microbial patterns (PAMP)
pattern recognition receptors (PRR)
Toll-like receptor pathways
TLR4 has been reserved for
gramnegative bacteria
Interferons
Prevention and treatment of viral infection
human interferons
IFN-a
source
all cells
inductor
viral dsRNA
antiviral action
localization
number of subtypes
Function
IFN-b
all cells
viral dsRNA
+++
chromosome 9
22
Antiviral
infection
activation of
NK cell
IFN-g
T-lymphos
antigen/mitogen
+++
+
chromosome 12
chromosome 9
1
1
anti-tumor regulation of
enhancement of CMI
immunity
Interferon-inducing dsRNA: 30 bp
interferon a and b: gene products to remember
2‘,5‘-oligo adenylate cyclase
RNA dependent proteinkinase
Interferon
occupies receptors
on vicinal cells
30 bp dsRNA induces
production of
a & b Interferon
interferon activates > 100 genes
2‘, 5‘-oligo
adenylate synthetase
activation of an
endonuclease
degradation of
viral RNA
RNA dependent
proteinkinase (PKR)
phosphorylation &
inactivation of
elongationfactor EF-2
arrest of
proteinsynthesis
Inhibition of virus replication
raute 10/2002