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
SkinStaphylococcus 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 siteso Declination of host immune system function
o DysbacteriosisDefinition: 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
bacteriabacteria
Immune status of the host
inbodyouterbody
细菌细菌细菌细菌细菌细菌
bacteriabacteria
bbacteriaacteria
bacteriabacteria
bacteriabacteria
toxin
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isease
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-mediatedcell-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
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”
2.Adhesins
(1)Finbrial adhesins
involved in mediating attachment of some bacteria to mammalian cell surfaces
(2)Non-fimbrial adhesinIncluding 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
ToxinsExotoxin
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
Exotoxino 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 paralysisBotulinum 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 Gram-
negative 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))
Activatesmacrophage
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ActivatesHageman
fatcor
IL-1
Fever
TNF
Fever and hypotensio
n
Nitric oxide
hypotension
C3a
Hypotension
Edema
C5a
Neutrophil chemotaxi
s
Coagulation
cascade
DIC
Endotoxins
o Detection of endotoxin: The Limulus lysate test
The different between indotoxin and exotoxin
kinds exotoxin Endotoxinsource G+or a few G- G-
component protein LPS
stability Short of good 、 160 2-4h ℃
destroyed
virulence strong weak
antigenicity strong weak
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
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
Sources of infectious diseases
Carrier stateo 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
o 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 droplets2.wound infectons:in soil and feces of human and animal3.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
acute infection
chronic infection
C.Patterns of infection
Apparent infection
1.apparent infectionWhen an infection causes pathological changes leading to disease,it is often accompanied by a variety of signs and symptomsInfectons that come on rapidly,with severe but short-lived effects,are called acute infectionsThe 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
Bacteremiao Definition: a transitory disease in which bacteria present
in the blood are usually cleared from the vascular system with no harmful effects.
Septicemiao 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.
Toxemiao Definition: the presence of microbial toxins
in the blood
Pyemiao Definition: the presence of pyogenic
bacteria in the blood as they are being spread from one site to another in the body
毒素
血液
毒素
toxin
toxin
special toxic symptom
e.g.tetanus
Toxemia
局部病灶
局部病灶
pathogenic bacterium can grow in blood
BacteremiaBacteremia
Defense function↓↓
毒素毒素毒素毒素毒素毒素toxin
Organism is seriously
dadamaged, toxic symptom all over the body 。
Septicemia
Local lesion
blood
局部病灶
局部病灶
毒素 toxin
毒素 毒素
toxin
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 membranesIntact skin Fatty acids sebaceous glandsMucous membrane of respiratory tract 1. ciliary action 2. traps many microorganisms LysozymeNormal 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