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Immune system - introduction

Immune system - introduction. Radek Spisek Institute of Immunology, 2nd Medical School, Charles University. Edward JENNER 1749-1823. Eradication of variola (smallpox). ‘Know Th e Enemy’. The immune system exists to prevent and combat infection

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Immune system - introduction

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  1. Immune system - introduction Radek Spisek Institute of Immunology, 2nd Medical School, Charles University

  2. Edward JENNER 1749-1823

  3. Eradication of variola (smallpox)

  4. ‘Know The Enemy’ • The immune system exists to prevent and combat infection • Everything else is secondary to this primary objective • Autoimmunity • Allergy • Tumour immunology • Transplantation

  5. Viruses Bacteria HIV E coli Influenza Parasites Mycobacteria M TB Fungi Schistosomiasis The Enemy Fungi Candida

  6. Antigens • exo - antigens: microbes, foreign substances (alo, xeno-grafts, vaccines, sera, drugs – haptens • auto-antigens: self tissue • Chemical structure: proteins, glykoproteins, mucoproteins, polysacharides, lipids, glykolipids, fosfolipids • Membrane receptors, enzymes, nuclear structures, secerned products (bacterial toxines)

  7. Components of the immune system

  8. Hematopoetic system

  9. Hematopoetic stem cell- CD34 SCT- stem cell transplantation

  10. The Defence Innate Defence • Non Specific barriers • Anatomical/Physiological • Acute phase reactants and Inflammation • Complement/Interferons/CRP • Innate cells • PMN/Macrophages/NK cells • Adaptive immunity • B cells – Antibody • T cells – Orchestration, Cytokines, Lytic granules Adaptive Defence

  11. Innate Immunity Characteristics: Universal Rapid Lacks memory Non specific but ... Acquired Immunity Characteristics: Not universal ‘Slow’ to develop Possesses memory Specific but…. ‘Plays to the tune of the Innate immune system’ Why Differentiate between the Innate and Acquired Immunity ?

  12. Innate Immunity • Mechanical barriers • Inhibit attachment and penetration of microorganisms • Intact skin • Mucus • Cilia • Saliva,tears, urine for expelling microbes • Coughing, sneezing and shedding! • Chemical barriers • HCL • Lysozyme • pH

  13. Innate Immunity • Inflammation • Proteolytic cascades • Phagocytosis • Cytokines • Natural Killer cells

  14. 2.ANTIGEN NONSPECIFICMECHANISMS; PHAGOCYTES, GRANULOCYTES

  15. PHAGOCYTOSIS

  16. ESSENTIAL LINK BETWEEN THE INNATE AND ADAPTIVE SYSTEMS:DENDRITIC CELLS

  17. DENDRITIC CELLS MUST BE PRE-STIMULATED BYDANGER SIGNALS TO BE ABLE TO ACTIVATE T LYMPHOCYTES

  18. DANGER SIGNALS:- EXOGENOUS (PAMPs) - ENDOGENOUS (e.g. STRESSPROTEINS RELEASED FROM NECROTIC CELLS)

  19. TOLL-LIKE RECEPTORS

  20. Adaptive Immunity Effector cells APCs

  21. Lymphoid Tissues Primary (Central) Lymphoid organs Secondary (Peripheral) Lymphoid organs Thymus Bone Marrow Spleen Lymph nodes MALT GALT

  22. THYMUS • T cell selection takes place in the thymus • Requirement for antigen presentation to T cells • Positive/negative selection • Emergence of self tolerant CD4 T cells and CD8 T cells

  23. Lymph Node • The lymph node is the meeting point of recirculating T cells B cells and APC with foreign antigen • B cell development continues in the LN through the process of CLONAL SELECTION • SHM and CSR are important changes that occur here • Plasma cells (Ig producing factories) return to the BM

  24. The soldiers and artillery of the Adaptive defense CD4 T cells

  25. The soldiers and artillery of the Adaptive defense CD8 • CD8 T cells are the CTLs • Exocytosis of granules or a FAS/FASL sytem operates to mediate apoptotic cell death in the target cell • Targeted to MHC class I presented viral peptides

  26. The soldiers and artillery of the Adaptive defense B cells • Antibodies specific for a pathogen can engage multiple effector responses • The Fc region determines the effector response that is used • The Fab region provides the specificity

  27. Immunoglobulin structure

  28. CytotoxicTcellsHelper Th1 Helper Th2

  29. SELF-TOLERANCE

  30. BIG PROBLEM:HOW TO MAINTAIN SELF-TOLERANCE AND PREVENT AUTOIMMUNITY?

  31. IMMUNOLOGICAL HIT(WITH EMBARRASSING HISTORY…)REGULATORY (= SUPPRESSOR) T LYMPHOCYTES (Treg, Ts, Th3, Tr1…)

  32. REGULATORY T LYMPHOCYTES ARISE IN:- THYMUS (SUPPRESS AUTOIMMUNITY)- PERIPHERY (THESE DOWN-REGULATE EXCESSIVE IMMUNE RESPONSES

  33. Immune reaction

  34. Disorders of immunity • immune deficiencies • allergy • autoimmunity • tumors

  35. Imunodeficiencies • Decreased resistance to infections • Primary (inherited)- genetic disorders • aquired – malnutrition • - infection (HIV, mumps..) - metabolic diseases - drugs, iatrogenic - stress

  36. Allergy Inhalation allergy – hay fever, asthma atopic ekzema food allergy drug allergy

  37. alergen IgE Fc-  receptor Imunopatologická reakce I.typu - časná přecitlivělost fosfolipáza A2 kyselina arachidonová cyklooxygenáza lipoxygenáza degranulace histamin prostaglandiny leukotrieny žírná buňka tromboxany

  38. Autoimmune diseases systemic- lupus erytematodes revmatoid artritis Sjogren syndrom vasculitis Organ specific - endocrinopathies (thyreoiditis, type I. diabetes, multiple sclerosis)

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