Host defence - PowerPoint PPT Presentation

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Host defence

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  1. Host defence

  2. Who is the Host ?

  3. Who are we defending against in ICU ? • Bacteria • Fungi • Viruses • Parasites • Protozoa • Auto-immunity ? • Malignancy ?

  4. What is the structure of our defence system ? • Innate system ( “old school”Castle with infantry defending ) • - Castle : skin and mucous membrane • -infantry ( phagocytes ) • Adaptive system (“modern “ intelligence gathering , IT and guided missiles and smart bombs)

  5. Major components of the innate system

  6. Where does the enemy attack us ? External epithelia: External surface Wounds & abrasions Insect bites Mucosal surfaces: Airway Gastrointestinal tract Reproductive tract (Fig. 2.2)

  7. In what compartment of the body is the enemy found ?

  8. The general response to infection

  9. Stages of infection

  10. MALT ( behind the walls stands a force) • Mucosa associated lymphoid tissue • 80% of all immune cells • 3 functions : • Protect mucous membranes • Prevent uptake of foreign antigens from food • Prevent pathological responses if foreign antigens cross the mucous membrane

  11. Where does the defence start ?Castle walls

  12. If a pathogen breaches the epithelium ?Enemy over the wall • then the innate immune response begins. • The cells of the immune system determine “self” from “non-self” by recognizing molecules on the microbe surface. • Macrophages and dendritic cells are immune cells (phagocytes) that reside within the tissue. Neutrophils are phagocytes that reside in the blood but can extravagate into tissue during inflammation. • There are circulating proteins, called complement, that either kill microbes or mark them for effective phagocytization.

  13. The compliment system Complement is a system of plasma proteins that interacts with pathogens to mark them for destruction. 1. Alternative pathway : pathogen surfaces 2. Mannan binding-lectin pathway : lectin binding to pathogen surfaces 3. Classical pathway : Ag:Ab complexes Functions: phagocytosis inflammation lysis

  14. How do the phagocytes recognise the enemy ? • Through pattern recognition ( genetically programmed ) • PAMPS • Toll like receptors

  15. What do the macrophages do : release IL-1B •  • Activates vascular endothelium • Activates lymphocytes • Local tissue destruction • Increases access of effector cells •  • Fever, • production of IL-6

  16. Macrophage secret TNF-alpha •  • Activates vascular endothelium • Increases vascular permeability •  • Increased entry of IgG, complement, and cells to tissues • Increased fluid drainage to lymph nodes •  • Fever • Mobilization of metabolites • Shock

  17. Macrophage secret IL-8 •  • Lymphocyte activation • Increased antibody production •  • Fever • Induces acute-phase protein production

  18. Macrophages secret IL-12 •  • Activates NK cells • Induces the differentiation of CD4 T cells into TH1 cells

  19. Expression of selectins and ICAM

  20. Acute phase response

  21. Acute phase response • Hypothalamusincreased body temperature • Fat, muscleprotein & energy mobilization to allow increased body temperature  • decreased viral & bacterial replication & • increased antigen processing & specific immune response

  22. Interferons

  23. NK-Cell

  24. NK recognise virus infected cells

  25. Adaptive immunity ( once bitten twice shy) Antigen specific response to antigen / pathogen Key feature if this system is that subsequent exposure to the initial antigen leads to more rapid and vigorous response ( Immunological memory) T and B lymphocytes drive this response from common stem cell

  26. T and B cell response • T-cell : cellular immunity through differentiation in TH-1 ( cellular )and TH-2 pathways ( humoral) • B-cell clonal response initially producing IgM and then IgG to infections : Memory cells produced that react much faster to future threats from the same pathogen.

  27. Innate vs Adaptive immunity

  28. Thymus • Positive and negative selection of t-cells • CD-4 , CD-8 and T-killer cells emerge • Thymus continues to work in adult life especially when t-cell pool is damages as in AIDS and cancer chemotherapy

  29. Investigating Immunity • 4 Major components : • Humoral immunity • Cell mediated immunity : lymphocytes • Phagocyts and polymorphnuclear cells • Complement

  30. If we’re so good how does the enemy kill us ?