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Host defences

Host defences. Resistance to and recovery from bacterial infections. Barriers to infection and innate host defences. And. Phagocytic cells polymorphonuclear phagocytes (PMNs, neutrophils) macrophages and monocytes Complement system lyse and bacteria opsonise bacteria

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Host defences

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  1. Host defences Resistance to and recovery from bacterial infections

  2. Barriers to infection and innate host defences And Phagocytic cells polymorphonuclear phagocytes (PMNs, neutrophils) macrophages and monocytes Complement system lyse and bacteria opsonise bacteria Iron binding proteins Starve microbes for iron

  3. Phagocytes Polymorphonuclear leucocytes – neutrophils Macrophages

  4. Neutrophil phagocytosing bacteria

  5. Only found in inflamed tissues Single mature form Rapidly form pus Short lived Die after phagocytosis Found in healthy tissues Variety of mature forms Slowly form granuloma – with T-cell help Long lived Survive after phagocytosis Neutrophils V Macrophages Neutrophils Macrophages

  6. Phagosome Lysosome Phagolysosome H+ Phagocytosis and bacterial destruction Phagocytosis Oxidative burst

  7. Activated macrophages • Enhanced antibacterial activity • Enhanced respiratory burst • Production of nitric oxide • Enhanced phagolysosome fusion • Enhanced secretion of pro-inflammatory cytokines

  8. How do host cells recognise foreign invaders? • Recognise conserved molecules present on many pathogens • Recognise essential component • little opportunity to vary • Bacterial molecules that have these characteristics • Lipid A (LPS), G –ve bacteria • Peptidoglycan, mainly G +ve bacteria • Bacterial DNA, all bacteria • Bacterial lipoproteins, all bacteria

  9. TLR-2 TLR-4 TLR-5 TLR-9 Pattern-recognition receptors Toll-like receptors (TLRs) Peptidoglycan, Lipoproteins LPS, lipid A Flagellin Bacterial DNA

  10. Cytokine production by macrophages and their effects LPS, peptidoglycan etc Inflammation IL-1, IL-6, TNF TH2 T cell development IL-1 Fever IL-1, IL-6 TH1 T cell development IL-12 Enhanced IFN production by TH1 T cells IL-18 Acute phase response IL-1, IL-6, TNF Activation of M TNF IL-12 (via NK cells producing IFN) B cell development IL-6 Attract Neutrophils, monocytes & T cells IL-8, CCL2, CCL3, CCL4, CCL5.

  11. Figure 2-45 Inflammatory response

  12. Adaptive immune response • Function of the adaptive immune response • Amplify, focus and augment the activity of components of the innate immune system • Complement • Phagocytes • Memory of contact with pathogen • rapid, amplified response on subsequent contact

  13. Antigen processing and presentation Dendritic cells (DC), macrophages, B cells Secretion of cytokines Macrophages, DC, NK cells, others MHC class I - CD8+ T cells MHC class II - CD4+ T cells Activation, proliferation and differentiation of Lymphocytes T helper cells (CD4+) Cytotoxic T cells (CD8+) B cells, Plasma cells Provide help for B cells, Macrophage activation, Cytotoxic T cells Lysis of infected cells Produce antibodies Induction of the acquired immune response Encounter of leucocytes with bacteria or their products

  14. Roles of effector T helper cells TH1 T cell TH2 T cell IFN TNF TNF others IL-4 IL-5 IL-6 IL-10 IL13 others Attraction and activation of macrophages Proliferation and secretion of antibody by B cells

  15. Effector T cells

  16. Function of antibodies in bacterial infections Antibody mediated immunity Inhibit nutrient uptake Anti-transporter Anti-capsules Anti-LPS Anti-surface antigen Opsonisation Anti-adhesins, anti-invasins Anti-toxins Inhibit adhesion and invasion Neutralisation of toxins

  17. Immunoglobulin A • Major Ig at mucosal surfaces • IgA plasma cells –Lamina Propria • IgA good: • Neutralisation • Anti-adhesion • Agglutination • IgA poor: • C’ activation • Phagocytosis • Poor inflammation

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