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

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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-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

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Hypotension

Edema

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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

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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↓↓

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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