Bacterial infection and immunity

1. Bacterial infection and immunity Xiao-Kui Guo PhD

2. Content: • Normal microbial flora and opportunistic bacteria • Bacteria pathogenesis • Host defense against bacteria infection • The initiation and courses of infection

3. The battle between body and bacteria Hostile agents Skin The normal microbial flora Mucous membrane Body defense PMN B cell Macrophage T cell Immuno-cells and antibody

4. Section A Normal microbial flora and opportunistic bacteria

5. 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

6. The contribution of the normal flora We want to live here! No, it is so crowded here and the environment is in great harmony, you have no permission to live here! Stimulating the immuno-cells constantly and keeping them awaken. Immuno cells Producing the essential nutrient for human body

7. Intestinal mucous Bladder mucous Opportunistic bacteria • Sometimes, the normal flora will rebel the host if they are not properly treated Relocated by force 定位转移 Immuno-compromise Causing diseases Immuno cells Immuno cells 免疫功能低下 Dysbacteriosis Long term usage of antibiotics Long term usage of antibiotics 菌群失调

8. Section BBacteria pathogenesis

9. Pathogenesis • Virulence • Amount of invasive bacteria • Pathway of invasive bacteria • 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.

10. The virulence of bacteria consists following parts Adherence Factor invasiveness Invasive of host cells and tissues Enzymes The virulence of the bacteria Bacterial biofilms Antiphagocytic Factors Exotoxin Toxins Endotoxin

11. 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

12. Surface hydrophobicity and net surface The hydrophobicity power is much powerful than the electrostatic force and causes the adhesion DNA - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - It exists repulsive electrostatic forces, but it’s very slight The bacteria and host cells have net negative surface.

13. Type 1 receptor BACTERIUM adhesin mannose P EPITHELIUM • galactose • glycolipids • glycoproteins The mechanism of adhesion lipoteichoicacid F-protein E. colifimbriae fibronectin

14. 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!

15. Antiphagocytic Factor • Antiphagocytic substance: • Polysaccharide capsules:S. pneumoniae, Haemophilus influenzae, Treponema pallidum; B. anthracisand 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.

16. r r r PHAGOCYTE Fc receptor Protein A BACTERIUM Mechanism of antiphagocytic factors Protein A inhibits phagocytosis immunoglobulin M protein inhibits phagocytosis Complement fibrinogen M protein peptidoglycan

17. Toxins Exotoxin Secreted by the living bacteria Toxins Endotoxin Released only when the bacteria die

18. Exotoxins外毒素 • ①excreted by living cells • ②produced by both gram-positive and gram-negative bacteria, mainly gram-positive bacteria. • ③proteins, often enzymes • ④heat-unstable热不稳定, toxicity often destroyed at 60°C, for 1-2hr.

19. 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 activity. The B subunits are nontoxic.

20. Endotoxins内毒素 • ①part of the cell wallof Gram-negative bacteria. Released on bacteria death细菌死亡后释放 • ②Found onlyin Gram-negative bacteria. • ③Lipopolysaccharidescomplexes.

21. Endotoxins内毒素 • ④Relativelystable • ⑤Weakly immunogenic. Not converted to toxoids. • ⑥Moderately toxic • ⑦specific receptors not found on cells

22. The pathophysiologic effect of endotoxins • Fever • Leukopenia • hypotension and shock • disseminated intravascular coagulation (DIC)

23. Section CHost defense against bacteria infection

24. infection immunity Disease = Bolus of infection x virulence immunity Balance between infection and immunity

25. The element of the human defense Physiology barriers Innate immunity Chemical barriers Phagocytosis Human defense Normal flora Humoral immunity Acquired immunity Cell-mediated immunity

26. The physiology barriers Bacteria The skin acts as a physiology and the sweat and sebaceous secretions also contain antimicrobial substances Skin Mucous Of the respiratory tract Oral Mucous Mucous of stomach Intestinal Mucous Swept out by ciliated cells Killed by low pH Resisted by normal flora Saliva contains numerous hydrolytic enzyme Caught by IgA

27. Blood-brain barrier • Placental barrier

28. The chemical barrier • The low pH in skin • Complement • Antibactrial peptide • C-reaction protein • Cytokines

29. 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.

30. The soliders of reticuloendothelial system Polymorphonuclear leukocytes ( granulocytes ) Phagocytic monocytes ( macrophages )

31. The mechanism of reticuloendothelial system Bacteria which entered human’s circulation system Lymphoid nods Lymphoid fluid Lymphoid fluid returns to blood Blood stream Spleen Liver Bone marrow Devoured by the phagocytes in blood.

32. 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

33. Cell-mediated immunity • Cell-mediated immunity is mostly expressed as a response to obligate or facultative intracellular pathogens. CD8+ T-cell Antigen-MHC class I complex Trigger the cell-mediated immunity response CD4+ T-cell Antigen-MHC class II complex

34. No Immunologic memory Innate Immunity Adaptive Immunity Characteristicsof Innate and Adaptive Immunity Antigen independent Antigen dependent No time lag A lag period Not antigen specific Antigen specific • Development of memory

35. 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.

36. Section DThe initiation and courses of infection

37. 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

38. 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.

39. The End Thanks