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Introduction to Immunology

Introduction to Immunology. Martin Liška. The immune system and its importance for homeostasis of organism.

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Introduction to Immunology

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  1. Introduction to Immunology Martin Liška

  2. The immune system and its importance for homeostasis of organism • The immune system = a system of non-specific and specific mechanisms protecting the organism from damage caused by infectious factors of environment and providing surveillance of own structures (elimination of damaged and death cells) • The aim is maintenance of homeostasis and integrity of macroorganism

  3. Mechanisms of immune system and their cooperation 1/ Innate (non-specific) immune system • innate, not developed after the exposition to infection • uniform response, prompt, no immunological memory • mechanical barriers (mucosa, skin) • phagocytic cells (microphages, macrophages) • acute phase proteins (CRP) • complement system

  4. Mechanisms of immune system and their cooperation 2/ Adaptive (specific) immune system • adaptability, developed after the exposition to infection • the immune response is not inherited, immunological response • B and T cells, immunoglobulins

  5. The components of immune system 1/ Cells a/ innate immune system • neutrophils, eosinophils, basophils • macrophages • nature killer cells (NK cells) b/ adaptive immune system - lymphocytes

  6. The components of immune system 2/ Organs • liver, skin etc. • primary lymphoid organs – bone marrow, thymus - secondary lymphoid organs - spleen, lymph nodes, mucus associated lymphoid tissue (MALT)

  7. The components of immune system 3/ Substances • The complement system • Cytokines – molecules which ensure the communication between the components of immune system (e.g.IFN, IL, growth factors) • Acute phase proteins (CRP, MBL) • Hormones (immunostimulatory/immunesuppressive effects) • Immunoglobulins

  8. The immune system of mucosa and skin 1/ Mucosa • intact surface, clearance of surface (microcillia, saliva, tears, urine) • lysozyme • IgA • lymphoid tissue of mucosa (MALT) • macrophages (dendritic cells)

  9. The immune system of mucosa and skin 2/ Skin • intact surface • lipid barrier (eczema) • immunocytes of the skin (e.g.Langerhans cells)

  10. Non-specific immune mechanisms 1/ Barriers • see above (skin, mucosa) • secretions (fatty acids, HCl, lysozyme) 2/ Various physiological mechanisms • body temperature • hormones

  11. Non-specific immune mechanisms 3/ Phagocytosis • the process by which particular substances or cells are ingested and destroyed by specialized cells • neutrophils, macrophages (monocytes, tissue macrophages)

  12. Neutrophils • The most abundant population of leucocytes (cca 70%) • Granulocytes • They stain a neutral pink when stained by H&E • Nucleus divided into 2-5 lobes, cytoplasm with granules • Neutrophils participate in defense against extracellular pathogens

  13. Neutrophils • The average half-life in circulation is about 12 hours • Upon activation, they marginate (position adjacent to the endothelium) → rolling (selectins) → adhesion to endothelium (integrins) → diapedesis (integrins) →chemotaxis (movement toward sites of inflammation by cytoplasmic streaming in response to chemotaxins (IL-8, IFN-g, C5a) → binding to microbe

  14. Neutrophils - phagocytosis • Interaction with some surface molecules of microbes (PAMPs, lectin interactions, binding of TLR to some surface molecules of microorganisms) • Opsonisation (= enhancement of binding of phagocytes to microbes) – Ig, complement system components, CRP, MBL

  15. Neutrophils - phagocytosis • Surrounding of microorganism → forming of vacuole (phagosome) → fusion with the lysosome→phagolysosome • Phagosome formation depends on contractile proteins action

  16. Neutrophils – intracellular destruction of microbes 1/ Oxygen independent systems • substances that are contained in granules • myeloperoxidase, lysozyme, alkaline phosphatase, lactoferrin → hydrolysis microbe’s cell wall components • defensins → forming of channels in microbial cell membrane

  17. Neutrophils – intracellular destruction of microbes 2/ Oxygen-dependent systems • Respiratory burst • NADPH oxidase system→ production of reactive oxygen agents (hydrogen peroxide, superoxide anion, singlet oxygen, hydroxyl radicals) • Disorder of this system in CGD

  18. Neutrophils – intracellular destruction of microbes 2/ Oxygen-dependent systems • Myeloperoxidase, in the presence of toxic oxygen metabolites, catalyzes peroxidation of surface molecules on microorganisms

  19. Macrophages • Intracellular destruction of microorganisms mainly by NO synthase (system stimulated by the action of IFN-g or TNF) • Production of numerous substances: lysozyme, some components of the complement system, oxygen metabolites (H2O2, NO), cell function regulators (IL-1, IFN-a), arachidonic acid metabolites, endogenous pyrogens

  20. Natural killer cells • Granular lymphocytes, different from T- and B-lymphocytes • Cytotoxicity to tumor cells and virally infected autologous cells (perforins) • Play a role in defense against some bacterial, fungal and helminthic diseases • Participate in reactions of antibody-dependent cell- mediated cytotoxicity (ADCC) • They are not subject to MHC restriction (= NK-cells do not need to recognize MHC molecules in the target cells)

  21. Natural killer cells • They kill target cells by perforins (formation of channels, abnormal ion flux, depolarization, essential metabolite leakage, cell destruction) • NK cells are protected against perforins by specialized cell membrane protein (protectin)

  22. Interferons • Proteins that induce antiviral activity in cells • We can distinguish two types: a/type I: IFN-a (macrophages and other cells) IFN-b (fibroblasts) b/ type II: IFN-g (T-lymphocytes)

  23. Function of interferons • Stimulation of cell production of antiviral proteins (protein kinase, oligonucleotide polymerase – interference with the translation of viral mRNA) • Enhancement of T-cell activity • Activation of macrophages • Enhancement of NK cells cytotoxic action

  24. Adaptive immune mechanisms 1/ Humoral • generation of antibodies (Ig) – B cells (plasma cells) • in majority of antigens, the cooperation with T helper cells is necessary 2/ Cell-mediated • generation of antigen-specific T cells (helper, cytotoxic) • antigen presentation is necessary

  25. Adaptive immune mechanisms • Antibodies→ neutralization and opsonization (specific „adapter“) of microbes, complement system activation • T cells→ cytotoxic effects to microbes, helpfor B cells, macrophages activation, cytokines

  26. Innate/adaptive immune mechanisms • Innate (non-specific) immune system: prompt reaction x less effective, less directed • Adaptive (specific) immune system: slower development of reaction x more effective, more directed, immunological memory • Both systems cooperate (complement system is activated by IC, cytokines recruit other cells to the site of reaction, antigen presentation)

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