Presentation on theme: "Bacterial infection and immunity Xiao-Kui Guo PhD."— Presentation transcript:
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 Mucous membrane 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 Immuno cells 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 keeping 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 Immuno cells Immuno cells Long term usage of antibiotics Immuno-compromise Causing diseases Dysbacteriosis Relocated by force 免疫功能低下 定位转移 菌群失调
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 Amount of invasive bacteria Pathway of invasive bacteria
The virulence of bacteria consists following parts The virulence of the bacteria Adherence Factor Invasive of host cells and tissues Toxins Endotoxin Exotoxin Enzymes Antiphagocytic Factors Bacterial biofilms invasiveness
Adherence factor The mechanism of the adherence between bacteria and tissue consists of two parts as following: Surface hydrophobicity and net surface The combination between de ligands and receptors
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 adhesion
The mechanism of adhesion adhesin EPITHELIUMreceptorBACTERIUM fibronectin lipoteichoic acid F-protein mannose Type 1 galactose – glycolipids – glycoproteins P E. coli fimbriae
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 influenzae, 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 phagocytosis Protein A Fc receptor BACTERIUM PHAGOCYTE rr r peptidoglycan Complement fibrinogen M protein immunoglobulin M protein inhibits phagocytosis
Toxins Exotoxin Endotoxin Secreted by the living bacteria Released only when the bacteria die
Exotoxins 外毒素 ① excreted by living cells ② produced by both gram-positive and gram-negative bacteria, mainly gram- positive bacteria. ③ proteins, often enzymes ④ heat-unstable 热不稳定, toxicity often destroyed at 60°C, for 1-2hr.
Exotoxins ⑤ Strong antigenicity 抗原性 stimulate formation of antitoxin 抗 毒素 ; converted to toxiod 类毒素 Toxoids are used to immunize. ⑥ highly toxic ⑦ High 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 activity. The B subunits are nontoxic.
Endotoxins 内毒素 ① part of the cell wall of Gram-negative bacteria. Released on bacteria death 细菌 死亡后释放 ② Found only in Gram-negative bacteria. ③ Lipopolysaccharides complexes.
Endotoxins 内毒素 ④ Relatively stable ⑤ Weakly immunogenic. Not converted to toxoids. ⑥ Moderately toxic ⑦ specific 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 virulence immunity Disease = Balance between infection and immunity
The element of the human defense Human defense Innate immunity Acquired immunity Physiology barriers Normal flora Phagocytosis Humoral immunity Cell-mediated immunity Chemical barriers
The physiology barriers Skin Mucous Of the respiratory tract Oral MucousMucous of stomachIntestinal 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
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 ( granulocytes ) Phagocytic monocytes ( macrophages )
The mechanism of reticuloendothelial system Blood stream Lymphoid fluid Lymphoid fluid returns to blood LiverSpleenBone marrow Lymphoid nods Bacteria 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 by bacteria Antibody can promote phagocytosis Antibody can activate the classic pathway of the complement 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
Section D The initiation and courses of infection
Source of infection Exogenous infection: patient, carrier, diseased animal or animal carrier. Endogenous condition: most are normal flora, cause infection under abnormal condition. Respiratory Gastroenteric Genitourinary tract Closely contact Insect bitting Blood transfusion Wound Routes of infection
A. Inapparent infection Inapparent infections are termed subclinical, and the individual is sometimes referred to as a carrier. B. Apparent infection ( 显性感染 ) The hosts have evident clinic symptoms. If bacteria spread to whole body, the following clinic situations may occur: 1. Toxemia ( 毒血症 ) Bacteria multiply at invading location and do not enter blood stream, but 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 internal organs. C. Carrier A person or animal with asymptomatic infection that can be transmitted to another susceptible person or animal.