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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.

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slide2
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
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
normal flora
Normal flora

Skin

Staphylococcus epidermidis

Diphtheroids

Streptococci

Peptococcus

the significance of normal flora
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
Opportunistic pathogens
  • Definition: normally nonpathogenic microorganisms capable of causing infection disease in an immunosuppressed host.
  • Conditions of causing diseases by opportunistic pathogens:
  • Alteration of colonization sites
  • Declination of host immune system function
slide9
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
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

toxins

Cause disease

细菌

bacteria

bacteria

细菌

bacteria

bacteria

Section 2 Bacterial pathogenesis

bacteria

细菌

inbody

outerbody

Immune status of the host

why do animal get infectious diseases
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 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 bacteria1
Pathogenicity of bacteria
  • pathogenicity(determined by):
  • virulence factors of the bacterium
  • the number of infecting bacteria
  • route of entry into the body
virulence factors
Virulence factors
  • Invasiveness
  • Definition: the ability of a microorganism to invade human cells or tissues,and to multiply on or within them.
slide16
Capsules and slime layers: e.g., pneumococci
  • Interfere with the ability of phagocytic blood cells to engulf and destroy bacteria and protect bacteria against some antimicrobial substance
2 adhesins
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”
slide18
(1)Finbrial adhesins

involved in mediating attachment of some bacteria to mammalian cell surfaces

slide19
(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
Other extracelluar aggressins
  • Invasive enzymes:

e.g.Coagulase:working in conjunction with serum factors to coagulate plasma.contributes to the formation of fibrin walls around staphylococcal lesions.

slide21
Toxins
  • Exotoxin
  • Definition:a soluble protein toxin usually secreted from a living bacterium.
slide22
Origin and release:produced by Gram-positive bacteria as well as Gram-negative cells
  • Physical and chemical properties:proteins and usually heat-labile.
virulence factors1
Virulence factors
  • Toxins
  • Exotoxin
  • Immunity: excellent antigens that elicit specific antibodies called antitoxins.
slide24
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 factors2
Virulence factors

Exotoxin

  • 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

slide26
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
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 factors3
Virulence factors

Endotoxins

  • Origin and release:

produced only by Gram-negative bacteria and released only when bacteria lyze.

  • Chemical and physical properties:

lipopolysaccharide of the outer membrane of Gram-negative bacteria; heat-stable

endotoxins
Endotoxins
  • Immunity: weakly immunogenic
  • 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)

slide30

Endotoxin

(especially lipid A))

Activates

Hageman fatcor

Activates

complement

Activates

macrophages

C3a

Hypotension

Edema

TNF

Fever and hypotension

C5a

Neutrophil chemotaxis

Coagulation cascade

DIC

IL-1

Fever

Nitric oxide

hypotension

endotoxins1
Endotoxins
  • Detection of endotoxin: The Limulus lysate test
portals of entry and the size of the inoculum
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
Portals of entry
  • skin
  • respiratory system
  • ingestion system
  • genitourinary system

C. tetani

the size of the inoculum
The size of the inoculum
  • The quantity of microbes in the inoculating dose.
the originate and progress of infection
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
A.The source of the infection
  • Living reservoirs

Persons or animals with frank symptomatic infection are obvious sources of infection

  • Nonliving reservoirs
slide39

Sources of infectious diseases

  • Exogenous infections:
  • Patients
  • Carriers: those in whom pathogens are present and may be multiplying, but who shows no clinical response to their presence.
  • Contaminated animals
  • Endogenous infections
slide40
Carrier state
  • Definition of carriers: those in whom pathogens are present and may be multiplying, but who shows no clinical response to their presence
  • Definition of carrier state: a type of infections causing no signs of symptoms, in which pathogens multiply and may be transmitted to other individuals
slide41
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
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
slide43
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
slide44

acute infection

chronic infection

C.Patterns of infection

Apparent 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 short-lived effects,are called acute infections

The infection persists several months to several years called chronic infection

slide46
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
Generalized infection
  • Bacteremia
  • Definition: a transitory disease in which bacteria present in the blood are usually cleared from the vascular system with no harmful effects.
  • Septicemia
  • 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.
slide48
Toxemia
  • Definition: the presence of microbial toxins in the blood
  • Pyemia
  • Definition: the presence of pyogenic bacteria in the blood as they are being spread from one site to another in the body
slide49

Local lesion

毒素

毒素

毒素

毒素

毒素

毒素

toxin

血液

局部病灶

局部病灶

toxin

毒素

毒素

Defense function↓↓

toxin

special toxic symptom

pathogenic bacterium can grow in blood

Organism is seriously dadamaged, toxic symptom all over the body。

Toxemia

Bacteremia

Septicemia

e.g.tetanus

slide50

毒素

toxin

blood

局部病灶

局部病灶

toxin

毒素

毒素

When Pyosis bacteria cause Septicemia,multiple pyosis focus of infection will happen.e.g. staphylococci aureus

New pyosis focus of infection

Pyosepticemia

host resistance mechanisms
Host resistance mechanisms
  • Nonspecific host defenses
  • Anatomical defenses
  • Skin and mucosal membrane

Mechanical barriers

Secretions

Normal flora

slide53
Blood-brain barrier
  • Placenta barrier
  • Cellular defenses:the reticuloendothelial system
  • Molecular defenses:complements, lysozymes, etc
innate immunity
Innate immunity

Skin & mucous membranes

Intact skin

Fatty acids sebaceous glands

Mucous membrane of respiratory tract

  • ciliary action
  • traps many microorganisms

Lysozyme

Normal flora

innate immunity1
Innate immunity

Inflammatory response & phagocytosis

(early host responses to bacteria infection)

Bacteria infection→vasoactive factors →

the increased permeability

Chemokines → Neutrophils and macrophages

host resistance mechanisms1
Host resistance mechanisms
  • Specific host of defenses
  • Humoral immunity: antibody-mediated immunity
  • Cellular immunity: cell-mediated immunity

Inflammatory response & phagocytosis

acquired immunity
Acquired immunity

Humoral immunity

antibody to aggressin

antibody to toxin

Cell-mediated immunity

T cells

lymphokines (IFN- γ)

macrophages