Bacterial infection and immunity

Xiao-Kui Guo PhD

Content:

Normal microbial flora and opportunistic bacteria

Bacteria pathogenesis Host defense against bacteria infection The initiation and courses of infection

The battle between body and bacteria

T cell

B cell

Macrophage

PMN

Skin

The normal microbial flora

Mucousmembrane

Immuno-cells and antibody

Hostile agents

Body defense

Section A

Normal microbial flora and opportunistic bacteria

The definition of the normal flora

The normal microbial flora:The population of microorganisms that inhabit

the skin and mucous membranes of health normal persons

The normal flora under microscope

The contribution of the normal flora

Immunocells

No, it is so crowded here and the environment is in great harmony, you have

no permission to live here!

We want to live here!

Stimulating the immuno-cells constantly and kee

ping them awaken.Producing the

essential nutrient for human body

Opportunistic bacteria Sometimes, the normal flora will rebel the host if they are

not properly treated

Intestinal mucous Bladder mucous

Immunocells

Immunocells

Long term usage of antibiotics Long term usage of antibiotics

Immuno-compromise

Causing diseases

Dysbacteriosis

Relocated by force

免疫功能低下免疫功能低下

定位转移定位转移

菌群失调菌群失调

Section B

Bacteria pathogenesis

Pathogenesis

Pathogenesis is a multi-factorial process which depends on the immune status of the host, the nature of the species or strain (virulence) , the number of organisms in the initial exposure and Routes of infection.

Virulence Virulence Amount of invasive bactAmount of invasive bacteriaeria

Pathway of invasive bacteriaPathway of invasive bacteria

The virulence of bacteria consists following parts

The virulence of the bacteria

Adherence Factor

Invasive of host cells and tissues

ToxinsEndotoxin

Exotoxin

Enzymes

Antiphagocytic Factors

Bacterial biofilms

inva

siv

en

ess

Adherence factor

The mechanism of the adherence between bacteria and tissue consists of two parts as following:Surface hydrophobicity and net surfaceThe combination between de ligands and rece

ptors

Surface hydrophobicity and net surface

DNA

- - - - - - - - - - - - -

- - - - - - - - - - - - - - - - - - The bacteria and

host cells have net negative surface.

It exists repulsive electrostatic

forces, but it’s very slight

The hydrophobicity power is much powerful than the electrostatic force and causes the a

dhesion

The mechanism of adhesion

adhesinadhesin

EPITHELIUMEPITHELIUM

receptorreceptor

BACTERIUMBACTERIUM

fibronectinfibronectin

lipoteichoiclipoteichoic acidacidF-proteinF-protein

mannosemannose

Type 1Type 1

galactosegalactose – glycolipidsglycolipids – glycoproteinsglycoproteins

PP

E. coliE. coli fimbriaefimbriae

Invasive of the host cell and tissue

Invasive is the term commonly used to describe the entry of bacteria into host cells.

Being eaten sometimes is the intrigue of certain kind of bacteria

to enter the host cells and the solid who safeguards the human

body sometimes become the traitor who screens the enemy!

Antiphagocytic Factor

Antiphagocytic substance:Polysaccharide capsules: S. pneumoniae, Haemophilus influe

nzae, Treponema pallidum ; B. anthracis and Klebsiella pneumoniae.

M protein and fimbriae: Group A streptococci Surface slime : Pseudomonas aeruginosa O polysaccharide: LPS of E. coli K antigen: E. coli or the analogous Vi antigen: Salmonella typhi

Protein A: Staphylococcus aureus.

Mechanism of antiphagocytic factors

Protein A inhibits phagocytosisProtein A inhibits phagocytosis

Protein AProtein A

Fc receptorFc receptor

BACTERIUM BACTERIUM

PHAGOCYTEPHAGOCYTE

rrr

peptidoglycanpeptidoglycan

ComplementComplement fibrinogenfibrinogen

M proteinM protein

immunoglobulinimmunoglobulin

M protein inhibits phagocytosisM protein inhibits phagocytosis

Toxins

Toxins

Exotoxin

Endotoxin

Secreted by the living bacteria

Released only when the bacteria die

Exotoxins外毒素 ①excreted by living cells

②produced by both gram-positive and gr

am-negative bacteria, mainly gram-positiv

e bacteria.

③proteins, often enzymes

④heat-unstable 热不稳定 , toxicity often d

estroyed at 60°C, for 1-2hr.

Exotoxins

⑤Strong antigenicity 抗原性 stimulate formation of antitoxin抗毒素 ;

converted to toxiod类毒素 Toxoids are used to immunize. ⑥highly toxic ⑦High selection for tissues

neurotoxin神经毒素： . cytotoxin 细胞毒素 : enterotoxin肠毒素 Cytolytic toxins 溶细胞毒素

⑧ A-B toxins The A subunit provides the toxic a

ctivity. The B subunits are nontoxic.

Endotoxins内毒素

①part of the cell wall of Gram-negative bacteria. Released on bacteria death 细菌死亡后释放

②Found only in Gram-negative bacteria. ③Lipopolysaccharides complexes.

Endotoxins内毒素

④Relatively stable

⑤Weakly immunogenic. Not converted to

toxoids.

⑥Moderately toxic

⑦specific receptors not found on cells

The pathophysiologic effect of endotoxins

Fever

Leukopenia

hypotension and shock

disseminated intravascular coagulation

(DIC)

Section C

Host defense against bacteria infection

infection immunity

Bolus of infection x virulenceimmunity

Disease =

Balance between infection and immunity

The element of the human defense

Humandefense

Innate immunity

Acquiredimmunity

Physiology barriers

Normal flora

Phagocytosis

Humoral immunity

Cell-mediated immunity

Chemical barriers

The physiology barriers

Skin

MucousOf the respiratory tract Oral Mucous Mucous of stomach Intestinal Mucous

Bacteria The skin acts as a physiology and the sweat and sebaceous

secretions also contain antimicrobial substances

Swept out by ciliated cells Saliva contains

numerous hydrolytic enzyme

Caught by IgA

Killed by low pH

Resisted by normal flora

Blood-brain barrier Placental barrier

The chemical barrier

The low pH in skin Complement Antibactrial peptide C-reaction protein Cytokines

Reticuloendothelial system

Reticuloenothelial system like a series of military base of phagocytes which situated all over the human body.

It acts as a filtering system of human’s blood stream and lymphoid fluid.

The soliders of reticuloendothelial system

Polymorphonuclear leukocytes ( granuloc

ytes )

Phagocytic monocytes

( macrophages )

The mechanism of reticuloendothelial system

Blood stream

Lym

phoi

d flu

id

Lymphoid fluid returns to blood

LiverSpleen Bone marrow

Lymphoid nodsBacteria which entered human’s circulation system

Devoured by the phagocytes in blood.

Humoral Immunity The mechanism of antibody-Mediated immunity

Antibody can neutralize the toxicity.Antibody can inhibit essential nutrition assimilated b

y bacteriaAntibody can promote phagocytosisAntibody can activate the classic pathway of the co

mplement cascade.Antibody can recognize the foreign antigens on host

cell and find out the potential infection

Cell-mediated immunity

Cell-mediated immunity is mostly expressed as a response to obligate or facultative intracellular pathogens.

Antigen-MHC class I complex

Antigen-MHC class II complex

CD4+

T-cell

CD8+

T-cell

Trigger the cell-mediated immunity

response

Innate Immunity Adaptive Immunity

No Immunologic

memory

Antigen independent

No time lag

Not antigen specific

Antigen dependent

A lag period

Antigen specific

Development

of memory

Characteristics of Innate and Adaptive Immunity

Immunity of Infection

Immunity of extracellular bacterial infection: antibodies (IgG, IgM, SIgA); phagocytes (neutrophils); complement; humoral immunity mainly.

Immunity of intracellular bacterial infection: cell-mediated immunity (delayed-type hypersensitivity, DTH response (DTH) involving TH1and macrophages) mainly.

Section D

The initiation and courses of infection

Source of infection Exogenous infection: patient, carrier, diseased a

nimal or animal carrier. Endogenous condition: most are normal flora, ca

use infection under abnormal condition.

Respiratory Gastroenteric Genitourinary tract Closely contact Insect bitting Blood transfusion Wound

Routes of infectionRoutes of infection

A. Inapparent infection Inapparent infections are termed subclinical, and the individual is som

etimes referred to as a carrier.B. Apparent infection (显性感染 ) The hosts have evident clinic symptoms. If bacteria spread to whole b

ody, the following clinic situations may occur:1. Toxemia (毒血症 ) Bacteria multiply at invading location and do not enter blood stream, b

ut the exotoxins enter blood and cause corresponding toxic symptoms.

2. Endotoxemia (内毒素血症 ) Gram-negative bacteria multiply at location or in blood stream, release

a lot of amount endotoxin released from bacterial cell rupture.3. Bacteremia (菌血症 ) After entering blood, bacteria circulate but not multiply in the blood.4. Septicemia(败血症 ) Bacteria circulate and multiply in the blood, in which bacteria produce

toxic products and cause high swinging type of fever and other toxic symptoms.

5. Pyemia (脓毒血症 ) Pyemia bacteria produce septicemia with multiple abscesses in interna

l organs.C. Carrier A person or animal with asymptomatic infection that can be

transmitted to another susceptible person or animal.

The End

Thanks