Basic Immunology

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  • 1. Basic Immunology Dr Russell Watkins
  • 2.  
  • 3.  
  • 4.  
  • 5. INTRODUCTION
    • Immunology is the study of host defence mechanisms.
    • Immunity is the ability of the host to protect itself against foreign organisms.
    • The immune system comprises the tissues, cells & molecules which mount the immune response .
  • 6. Coagulation Cascade Fibrinolytic Cascade Kinin Cascade Thrombin Plasmin Kallikrein Plasma Fibrinogen Complement Cascade MAC Bradykinin Fibrin XIIa PCV Cellular mediators
  • 7. Immunology
    • Natural (‘innate’) immune system
      • Skin, tears, saliva, mucus, acids
      • Property of all living creatures
    • Adaptive (‘acquired’) immune system
      • Specialist cells, cytokines, antibodies
      • Specific and has ‘memory’
      • Specialised mucosal lymphoid tissue
  • 8.  
  • 9.  
  • 10.  
  • 11. INTRODUCTION
    • Immunogenicity is the capacity to induce an immune response by foreign, complex, high molecular weight compounds
    • Antigenicity is the ability to bind to Ig or immune cells; an immune response need not result
    • Haptens
  • 12. INTRODUCTION
    • Epitopes
      • aka antigenic determinants
    • Immunological cross-reactivity
      • the sharing of epitopes by different substances
      • toxoids & immunisation
  • 13. THE INNATE IMMUNE SYSTEM
      • Synonyms are the natural or native immune system
      • Rapidly mobilised first line of defence
      • Not dependent on prior exposure to a foreign invader
      • Non-specific
      • May not be sufficient to prevent foreign material persisting in the host
  • 14. THE INNATE IMMUNE SYSTEM
    • Innate immunity comprises:
      • physicochemical barriers
      • molecules normally present in body fluids e.g. lysozyme, complement, antiproteases
      • phagocytic & cytotoxic cells such as neutrophils, macrophages, natural killer cells
  • 15.  
  • 16. THE INNATE IMMUNE SYSTEM
    • The “Respiratory Burst”
      • aka the “oxidative burst”
      • membrane-bound NADPH system produces
        • superoxide radicals
        • hyperchlorous acid
        • H 2 O 2
        • chloramines
  • 17. THE INNATE IMMUNE SYSTEM
    • A reliable means of protecting the host in the first instance against many extracellular organisms
    • It is a property of every living organism
    • Unable to deal with all intracellular organisms (e.g protozoa, viruses & certain bacteria are not killed)
  • 18. THE ACQUIRED IMMUNE SYSTEM
    • Specific & has immunologic memory
    • Dedicated immune cells - the lymphoid cells (lymphocytes)
    • Molecules that specifically counteract antigens (antibodies or immunoglobulins)
    • Specific immune systems associated with barrier surfaces e.g. MALT, GALT
    • Lymphocyte secreted cytokines
  • 19. T-LYMPHOCYTES
    • Cell-mediated immunity especially intracellular organisms, protozoa & fungi
    • Graft rejection
    • Immune surveillance of neoplasia
    • 70-80% of total lymphocytes
    • Long-lived memory cells
    • Activity is by cytokine production
  • 20. T-LYMPHOCYTES
    • T h - CD4+: Respond to antigen in association with MHC Class II
    • T c - CD8+: Respond to antigen presented via MHC Class I
    • Antigen MUST be peptide
    • T dth
    • T s
  • 21. T-LYMPHOCYTES
    • CD4+ cells recognize antigens that have been taken up by antigen presenting cells which present antigen fragments on the cell surface
    • CD8+ cells recognise cells infected with virus, which they then kill
  • 22. T-LYMPHOCYTES
    • CD4 (T h ) cells interact directly with other cells by releasing cytokines to control development of the immune response
    • Two types of T h cell
      • T h -1 cells activate macrophages to destroy material phagocytosed
      • T h -2 cells help B-cells make antibody
  • 23. B-LYMPHOCYTES
    • Specialised for the production of immunoglobulins after differentiation into plasma cells
    • Controls pyogenic bacteria
    • Prevents blood-borne infections
    • Neutralise toxins
    • 12% of total lymphocytes
  • 24. B-LYMPHOCYTES
    • Can respond to peptide, carbohydrate & glycolipids
    • Usually require T-cell help to respond to antigen (interleukins) but can also recognise antigen directly through surface Ig
    • B cells mature & proliferate in lymph nodes
  • 25. B-LYMPHOCYTES
    • B-cells process & present antigen via surface MHC class II
    • Responses are antigen-specific but effects are not specific - mainly via complement
  • 26. IMMUNOGLOBULINS
    • The 5 classes of Ig are:
      • IgM
      • IgA
      • IgD
      • IgG
      • IgE
  • 27. IMMUNOGLOBULINS
    • 4-chain structure
      • 2 light chains
      • 2 heavy chains
    • Chains linked by disulphide bonds
    • Chains are coiled into “domains”
      • 110 amino acids
      • stabilised by intrachain disulphide bond
  • 28.  
  • 29. IMMUNOGLOBULINS
    • Terminal regions of H & L chains are the variable regions
    • The variable region is the site where Ig combines with antigen
    • This region’s variability is responsible for wide range of antigen specificity
  • 30. IMMUNOGLOBULINS
    • The other domains are the constant regions which are similar within isotypes of Ig
    • Using enzymes, a number of Ig fragments have been identified. Important ones are:
      • F ab
      • F c
  • 31. IMMUNOGLOBULINS
    • F c regions formed from H chains & determine isotype & so biological function
    • Hinge region also has effect on function
    • These functions are distinct from antigen binding
  • 32. IMMUNOGLOBULINS
    • IgG
      • neutralises toxins
      • activates complement
      • opsonisation
      • able to cross placenta (only Ig that can)
  • 33. IMMUNOGLOBULINS
    • IgA
      • monomeric & dimeric forms
      • dimeric = “secretory IgA” - found in secretions
      • important antiviral Ig
  • 34.  
  • 35. IMMUNOGLOBULINS
    • IgM
      • pentameric
      • good agglutinator
      • good at activating complement
  • 36.  
  • 37. IMMUNOGLOBULINS
    • IgD
      • true function unknown
      • appears to be involved in B-cell differentiation
  • 38. IMMUNOGLOBULINS
    • IgE
      • parasitic infections
      • F c portion binds to mast cells
      • triggers mast cell degranulation
  • 39.  
  • 40.  
  • 41. T- & B-LYMPHOCYTES
    • T- & B-cells recognise the antigen, proliferate in response to it, & migrate back to the site of injury
    • There they release cytokines that attract effector cells (cytotoxic T-cells, activated macrophages, committed B-cells)
  • 42.  
  • 43. THE ACQUIRED IMMUNE SYSTEM
    • CD System
      • WBCs are distinguished according to groups of molecules they express on their surfaces - mostly “CD” molecules
      • >130 CD molecules identified
      • may be lineage specific or shared between different cell types
      • may only appear during cell development or only when activated
  • 44.  
  • 45. THE ACQUIRED IMMUNE SYSTEM
    • MHC expression
      • Class I molecules expressed on all nucleated cells
      • Class II molecules expressed on a small group of antigen presenting cells
      • Class II molecules may also be induced to be expressed on other cells during immune reactions by interferon- 
  • 46. THE ACQUIRED IMMUNE SYSTEM
    • Cytokines are short-range, multifunctional, short-acting mediators of cellular activities, especially within the immune system
    • Released primarily by activated T-cells & other immune and non-immune cells.
  • 47. THE ACQUIRED IMMUNE SYSTEM
    • There are 4 major classes of cytokines
      • interleukins (IL-1 to IL-12)
      • interferons (IF-  , IF-  & IF-  )
      • colony stimulating factors (CSFs)
      • tumour necrosis factors (TNF-  & TNF-  )
  • 48. NATURAL KILLER CELLS
    • Natural Killer (NK) cells:
      • classed as part of the lymphoid system but have no differentiating surface markers
      • they are particularly effective against virus-infected & tumour cells
      • also called large granular lymphocytes
  • 49. ANTIGEN PRESENTING CELLS
    • Examples of APCs are:
      • macrophages
      • B-cells
      • dendritic cells
    • Macrophages & B-cells recognise antigen through the Ig molecule
    • Dendritic cells process & present antigen to naïve T-cells via MHC Class II
  • 50. THE ACQUIRED IMMUNE SYSTEM
    • Macrophages
      • long-lived
      • widespread distribution
      • they express receptors for Ig & activated complement components which they use to take up immune complexes
  • 51. ANTIGEN PRESENTING CELLS
    • Antigen Presenting Cells (APCs):
      • normally, initiation of the acquired immune response does not take place at the site of injury or penetration of foreign organisms
      • antigen is taken up by APCs at the site of inflammation & transported to regional lymph nodes &/or spleen where it is presented to T- & B-cells
  • 52.  
  • 53. THE ACQUIRED IMMUNE SYSTEM
    • Macrophages & B-cells are involved in the perpetuation of the immune response
    • Dendritic cells are implicated in the initiation of the immune response
  • 54. THE ACQUIRED IMMUNE SYSTEM
      • Antigen specificity is the single most important aspect of the acquired immune system (mediated by lymphocytes)
      • Each clone of a lymphoid cell responds only to a single antigen
      • T-cells deal with surface bound antigen (usually cell associated)
      • B-cells deal with soluble (extracellular) antigen
  • 55. THE ACQUIRED IMMUNE SYSTEM
    • Specific immunity is termed humoral when antibodies are involved in removing the antigen
    • It is termed cell-mediated when T-cells & macrophages are involved
  • 56.  
  • 57. THE ACQUIRED IMMUNE SYSTEM
      • Immunity after infection is termed active immunity (because the host has responded actively to the stimulus)
      • Immunity may be transferred passively by antibodies or cells (breast milk, vaccination)
      • Vaccination may be passive (using Ig) or active (using antigen or attenuated organism)
  • 58. THE ACQUIRED IMMUNE SYSTEM
    • The development of acquired immunity begins with a primary immune response :
      • an afferent phase involving APCs
      • T-cell transformation from a resting to an active state
      • an effector phase - induction of other cells (B-cells & macrophages) by active T-cells
  • 59. THE ACQUIRED IMMUNE SYSTEM
      • The primary immune response is accompanied by the appearance of antigen-specific T-cells & Ig-secreting B-cells
      • The secondary immune response :
        • on second (& subsequent) exposure to the same antigen, antigen-specific memory T- & B-cells are recruited much sooner & more efficiently
        • Ig levels are consequently much higher
  • 60.  
  • 61. INNATE & ACQUIRED IMMUNITY
      • Extracellular foreign antigen is normally cleared by the innate immune system, with some assistance from B-cell activity
      • Intracellular foreign antigen is handled by the acquired immune system in which self & foreign antigen are jointly recognised
      • All cellular defence mechanisms involve interactions of cell surface molecules (receptors) with complementary molecules (ligands)
  • 62. COMPLEMENT
    • The complement system
        • comprises at least 9 plasma proteins & some regulatory factors, that mediate several functions of the inflammatory process
        • synthesised by macrophages or hepatocytes
        • usually circulate as inactive proenzymes
        • heat labile (c.f. Ig is heat stable)
  • 63. COMPLEMENT
    • Complement pathways
      • Cascade of sequential activation converts each proenzyme into its active state & amplifies the response.
      • Two main pathways:
        • “ Classical” pathway - bound IgG, IgM
        • “ Alternative” pathway - certain antigens (LPS, endotoxin, IC)
  • 64. COMPLEMENT
    • Functions
      • opsonisation, chemotaxis, immune adherence (MAC)
      • acceleration of acute inflammation
      • immune cytolysis
      • virus neutralisation
  • 65.