Download Chpater 6 Pathogenesis of bacteria

Bacterial Pathogenesis
The term infection describes the process
that pathogenic microorganisms
multiply,release toxin within the body and
produce a change in the normal physiology
of the body.
Section 1 Normal flora and
opportunistic pathogens
 Definition: microorganisms that live on or in human
bodies, and ordinarily do not cause human diseases but
under certain condition can cause disease
pathogen
The distribution of normal flora
Normal flora
Skin
Staphylococcus epidermidis
Diphtheroids
Streptococci
Peptococcus
The significance of normal flora
constitute a protective host defense
mechanism: Competition of nutrients and receptors
Metabolic substances by normal flora: e.g., bacteriocins,
antibiotics, etc.
serve a nutritional function:several B vitamins
and vitamin K
keep our immune systems in tune
normal flora share many antigenic
determinants with pathogenic organisms
Opportunistic pathogens
Definition: normally nonpathogenic
microorganisms capable of causing infection
disease in an immunosuppressed host.
Conditions of causing diseases by opportunistic
pathogens:
o Alteration of colonization sites
o Declination of host immune system function
o Dysbacteriosis
Definition: the state in which the proportion of
bacterial species and the number of the normal
flora colonizing in certain site of a host present
large-scale alteration.
Nosocomial infections
Infectious diseases acquired as a result of a hospital
stay are known as nosocomial infections.
Surgical procedures and lower defenses permit
resident flora
Indwelling devices
Fomites ,medical equipment,other patients
Section 2 Bacterial pathogenesis
Immune status
of the host
Cause disease
inbody
outerbody
toxins
bacteria
bacteria
bacteria
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bacteria
bacteria
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Why do Animal get infectious diseases?
From the organism’s perspectives
The number of organisms
The virulence of these organisms
From the host’s perspective
Innate immunity
acquired immunity Antibody-mediated
cell-mediated
Pathogenicity of bacteria
Pathogenicity and virulence: refer to an organism's
ability to cause disease.
LD50 (median lethal dose) or ID50 (median
infectious dose): refers to the number of bacteria
or amount of bacterial products, such as toxins,
that cause death or bacterial disease in 50% of
animals in a defined period after the bacteria are
administrated by a designated route.
Pathogenicity of bacteria
 pathogenicity
（determined by):
virulence factors of the bacterium
the number of infecting bacteria
route of entry into the body
Virulence factors
Invasiveness
o Definition: the ability of a microorganism to invade
human cells or tissues,and to multiply on or within them.
o Capsules and slime layers: e.g.,
pneumococci
o Interfere with the ability of phagocytic
blood cells to engulf and destroy bacteria
and protect bacteria against some
antimicrobial substance
2.Adhesins
Bacterial infections are usually initiated by
adherence of the microbe to a specific
epithelial surface of the host,otherwise the
organism is removed
Peristalsis and defecation ciliary
action,coughing and sneezing or urination
A specific “stickiness”
(1)Finbrial adhesins
involved in mediating attachment of some
bacteria to mammalian cell surfaces
(2)Non-fimbrial adhesin
Including the filamentous haemagglutinin of
Bordetella pertussia,a mannose-resistant
haemagglutinin from Salmonella serotype
Typhimurium and a fibrillar haemagglutinin from
helecobacte pylori
Pili: e.g., Neisseria gonorrhoeae
Other surface structures of bacteria: LTA
Other extracelluar aggressins
o Invasive enzymes:
e.g.Coagulase:working in conjunction with
serum factors to coagulate plasma.contributes
to the formation of fibrin walls around
staphylococcal lesions.
Toxins
Exotoxin
o Definition: a soluble protein toxin
usually secreted from a living
bacterium.
o Origin and release: produced by Gram-positive
bacteria as well as Gram-negative cells
o Physical and chemical properties: proteins
and usually heat-labile.
Virulence factors
Toxins
Exotoxin
o Immunity: excellent antigens that elicit
specific antibodies called antitoxins.
Antitoxin:
Definition: a specific antibody capable of
neutralizing the exotoxin that stimulates its
production.
Toxoid:
Definition: a modified exotoxin that has been treated
to destroy its toxicity and remains immunogenicity.
Virulence factors
Exotoxin
o Component
characteristics: most
exotoxins consist of
two parts, an A (active)
component and a B
(binding) component.
Toxicity: high and even
fatal; highly tissue
specificity
o Categories:
Cytotoxins: exotoxins that destroy the target cells
directly by various mechanisms.
Neurotoxins: exotoxins that affect nerve
transmission of the nerve system.
Enterotoxins: exotoxins that stimulate hypersecretion
of water and electrolytes from the intestinal
epithelium and produce watery diarrhea.
Exotoxin
Neurotoxin
Tetanus toxin ,clostridium tetani
glycine spastic paralysis
Botulinum toxin, clostridium botulinum
acetylcholine flaccid paralysis
Cytotoxin diphtheria toxin inhibits
protein synthesis
Enterotoxins v. cholerae
perturb the processes that regulate ion
and water exchange across the intestinal
epithelium
Virulence factors
Endotoxins
o Origin and release:
produced only by Gramnegative bacteria and
released only when
bacteria lyze.
o Chemical and physical
properties:
lipopolysaccharide of the outer
membrane of Gram-negative
bacteria; heat-stable
Endotoxins
o Immunity: weakly immunogenic
o Biologic activity:
lipid A is the primary toxic component
all endotoxins present similar biologic effects.
Pyrogenicity
Leukocyte reaction
Endotoxemia and endotoxin shock
DIC (dissemiated intravascular coagulation)
Endotoxin
(especially lipid A))
Activates
macrophages
IL-1
Fever
TNF
Nitric oxide
Fever and
hypotension
hypotension
Activates
complement
C3a
Hypotension
Edema
Activates
Hageman fatcor
C5a
Neutrophil
chemotaxis
Coagulation
cascade
DIC
Endotoxins
o Detection of endotoxin:
The Limulus lysate test
The different between indotoxin and exotoxin
kinds
exotoxin
Endotoxin
source
G+or a few G-
G-
component protein
LPS
stability
good、160℃ 2-4h
Short of
destroyed
strong
weak
antigenicity strong
weak
virulence
Virulence of pathogenic bacterial
Ⅱ.Portals of Entry and the size of
the inoculum
If certain pathogen enter the wrong portal,they
will not be infectious.
Occasionally,an infective agent can enter by
more than one portal.e.g.mycobacterium
tuberculosis.
Portals of entry
skin
respiratory system
ingestion system
genitourinary system
C. tetani
The size of the inoculum
The quantity of microbes in the inoculating dose.
Ⅲ.the originate and progress of
infection
A.The source of the infection
B.routes of pathogen transmission
C.Patterns of infection
A.The source of the infection
Living reservoirs
Persons or animals with frank symptomatic
infection are obvious sources of infection
Nonliving reservoirs
Sources of infectious diseases
Exogenous infections:
o Patients
o Carriers: those in whom pathogens are present and
may be multiplying, but who shows no clinical
response to their presence.
o Contaminated animals
Endogenous infections
Carrier state
o Definition of carriers: those in whom pathogens are
present and may be multiplying, but who shows no
clinical response to their presence
o Definition of carrier state: a type of infections
causing no signs of symptoms, in which pathogens
multiply and may be transmitted to other individuals
two major types of carrier:
Convalescent carriers: those who recover from
infectious disease and in whom the pathogens remain
and multiply without causing overt symptoms.
Healthy carriers: those who do not have the clinical
symptoms but carry pathogens indeed.
Typhoid Mary (Mary Mallon)
B.routes of pathogen transmission
1.respiratory infections
the tiny particles of liquid released into the
air form aerosols or droplets
2.wound infectons:in soil and feces of
human and animal
3.intestinal infections: contaminate drinking
water and food or when used to fertilize
crops
4.contact infection:directly contact between
the skin and mucous membranes of the
infected person or animal and that of
healthy person
5.animal bites infections:the majority of
animal vectors are arthropods such as
fleas,mosquitos,flies,and ticks
C.Patterns of infection
Apparent infection
acute infection
chronic infection
1.apparent infection
When an infection causes pathological changes
leading to disease,it is often accompanied by a
variety of signs and symptoms
Infectons that come on rapidly,with severe but shortlived effects,are called acute infections
The infection persists several months to several
years called chronic infection
• Inapparent
infection: also called
subclinical infection that has no detectable
clinical symptoms
local infection
generalized/systemic infection
Localized infection stands for the case that the
microbe enters the body and remains confined to a
specific tissue
Generalized infection
Bacteremia
o Definition: a transitory disease in which bacteria present
in the blood are usually cleared from the vascular system
with no harmful effects.
Septicemia
o Definition: a disease in which the blood serves as a site of
bacterial multiplication as well as a means of transfer of
the infectious agent from one site to another.
Toxemia
o Definition: the presence of microbial toxins
in the blood
Pyemia
o Definition:
the presence of pyogenic
bacteria in the blood as they are being
spread from one site to another in the body
Local lesion
toxin
毒
素
血液
局局
部部
病病
灶灶
毒素
toxin
toxin
special toxic
symptom
Toxemia
Defense function↓↓
pathogenic
bacterium can
grow in blood
Organism is
seriously dadamaged,
toxic symptom all
over the body。
Bacteremia
Septicemia
e.g.tetanus
toxin
毒
素
局局
部部
病病
灶灶
毒素
toxin
blood
New pyosis
focus of
infection
Pyosepticemia
When Pyosis bacteria
cause Septicemia，
multiple pyosis focus
of infection will
happen.e.g.
staphylococci aureus
Section3 Antibacterial immunity
of host
Host resistance mechanisms
 Nonspecific host defenses
Anatomical defenses
o Skin and mucosal membrane
Mechanical barriers
Secretions
Normal flora
o Blood-brain barrier
o Placenta barrier
Cellular defenses: the reticuloendothelial system
Molecular defenses: complements, lysozymes, etc
Innate immunity
Skin & mucous membranes
Intact skin
Fatty acids
sebaceous glands
Mucous membrane of respiratory tract
1. ciliary action
2. traps many microorganisms
Lysozyme
Normal flora
Innate immunity
Inflammatory response & phagocytosis
(early host responses to bacteria infection)
Bacteria infection→vasoactive factors →
the increased permeability
Chemokines → Neutrophils and macrophages
Host resistance mechanisms
 Specific host of defenses
Humoral immunity: antibody-mediated immunity
Cellular immunity: cell-mediated immunity
Inflammatory response & phagocytosis
Host defences
Acquired immunity
Humoral immunity
antibody to aggressin
antibody to toxin
Cell-mediated immunity
T cells
lymphokines (IFN- γ)
macrophages