Functional organization of the Immune System
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Functional organization of the Immune System Presentation Transcript

  • 1. Presented by Dr. B. Victor, St. Xavier’s College, Palayamkottai-627002,India. Functional Organization of the Immune System: 2.Immunoreactive Cells
  • 2. Leucocytes are the effectors of the immune system.
      • There are five types:
    • Neutrophils
    • Eosinophils
    • Basophils
    • Monocytes
    • Lymphocytes - Two Types:
    • • B-cell lymphocytes
    • • T-cell lymphocytes
  • 3. Blood cell categories Formed elements of the blood Nucleated cells Non-nucleated cells Leucocytes Erythrocytes Thromphocytes Polymorphonuclear cells Eosinophils Neutrophils Basophils Monocytes Lymphocytes Natural killer cells
  • 4. There are two main lineages that derived from the hemopoietic stem cell:
    • 1. the lymphoid lineage
    • T lymphocytes (T cells) B lymphocytes (B cells) Natural killer cells (NK cells)
    • 2. the myeloid lineage
    • Monocytes, macrophages Langerhans cells, dendritic cells Megakaryocytes Granulocytes (eosinophils, neutrophils, basophils)
  • 5. Sub-categories of Leucocytes Leucocytes Granulocytes (Polymorphonuclear cells) Agranulocytes (Mononuclear cells) Eosinophils Neutrophils Basophils Monocytes Lymphocytes Natural killer cells
  • 6. The agranulocytes :
    • They have a clear cytoplasm.
    • Also known as mononuclear leukocytes. These are the
    • Monocytes (4%)
    • Lymphocytes (24%).
    • The tissue macrophages, which are active phagocytes, are probably derived from the monocytes, and have become resident in connective tissue
  • 7. The granulocytes:
    • They contain abundant granules in their cytoplasm. They are also known as polymorphonuclear leukocytes. (PMNs) , because of their lobed nuclei.
    • Granulocytes are identified as different types, based on their staining characteristics with certain dyes.
    • Neutrophils (72% of white cells),
    • Eosinophils (1.5%),
    • Basophils (0.5%).
  • 8. Kinds of Granulocytes
    • Neutrophils
      • Phagocytic as well as granulocytic, neutrophils use granulocytic chemicals to destroy microorganisms which they ingest.
    • Eosinophils
      • Eosinophils release granulocytic chemicals into surrounding tissues, to destroy nearby infectious agents.
    • Basophils
      • Like eosinophils, basophils release granulocytic chemicals, to destroy nearby microorganisms and stimulate the inflammatory response.
  • 9. Granulocytes & Agranulocytes Basophil Eosinophil Neutrophil Lymphocyte Monocyte
  • 10. Role of Granulocytes
    • These cells are predominantly important in the removal of bacteria and parasites from the body.
    • They engulf these foreign bodies and degrade them using their powerful enzymes.
  • 11. N eutrophil
    • multi-lobed nucleus.
    • 50-70% of circulating WBC (higher numbers suggestive of bacterial infection).
    • The fine granules stain poorly with acidic and basic dyes neutrophil.
    • Primary granules electron dense - contain bactericidal enzymes
      • Lysozyme, myeloperoxidase; neutral proteases (i.e. elastase); and acid hydrolases (B-glucoronidase
      • Secondary granules – smaller, not electron dense.
      • lysozyme, collagenase and lactoferrin and cathepsin B).
  • 12. Neutrophil
    • Neutrophils are highly mobile phagocytes.
    • That travel around in the blood & engulf and destroy unwanted material.
  • 13. Role of N eutrophils
    • Phagocytosis and killing of ingested microorganisms.
    • The phagosome fuses with granules to destroy internalized bacteria, o xygen dependent respiratory burst.
    • DO NOT function as APCs.
    • Neutrophils are the 1st cells to arrive. A number of substances produced during an inflammatory response recruit neutrophils to a site of inflammation.
  • 14. Basophil
    • ( represent <1% of circulating WBC)
    • Lobed nucleus--more variable, large coarse granules stain blue with basic dye methylene blue .
    • They play a major role in the allergic response when they release their granules (containing histamine, serotonin, heparin, prostaglandin, etc into the bloodstream following exposure to specific allergens).
    • Basophils bear Fc receptors for IgE  
    • When an individual is exposed to an allergen, allergen specific IgE is produced. This IgE binds to the surface of basophils
  • 15. Basophil
    • Basophils release histamine and heparin.
    • Important in allergic responses.
  • 16. Eosinophil
    • (represent 1-3% of circulating WBCs)
    • Possess a bi-lobed nucleus and a heavily granulated cytoplasm.
    • Granules stain orange/red with the acidic dye Eosin Y.
    • Somewhat phagocytic but DO NOT act as APCs.
    • The major role of the eosinophil is believed to be against parasites, particularly parasitic worms.
  • 17. Eosinophil
    • Eosinophils secrete chemicals that fight parasites (worms).
  • 18. Immunocytic system Immunocytic system Cell mediated immunity Humoural Immunity Production of Lymphokines Production of Antibodies T-Lymphocytes B-Lymphocytes (Plasma cells)
  • 19. Lymphopoiesis
    • The process of lymphopoiesis (lymphocyte origination and differentiation into functional effector cells) begins in the yolk sac and continues later in life in the thymus gland, liver, spleen, and finally the bone marrow.
  • 20. Origin of cells of the immune system 
  • 21. Lymphocytes
    • Lymphocytes are the main actors of the immunocytic system.
    • responsible for the specific immune response.
    • Represent 20-40% of circulating WBC in blood extravasate and enter the tissues – return 99% of cells in lymph
    • small 6µm, contain a single nucleus, little visible cytoplasm around their nucleus.
    • T lymphocytes and B lymphocytes and natural killer cells.
  • 22. Lymphocytes Lymphocytes T-Lymphocytes B-Lymphocytes T-helper cells T-suppressor cells T-cytotoxic cells T-delayed hypersensitivity cells Plasma cells B-memory cells
  • 23. T and B-Lymphocytes
    • T and B lymphocytes are small, motile, nonphagocytic cells which cannot be distinguished from each other morphologically.
    • Once stimulated with antigen enlarges 15µm into a blast cell. Lymphoblasts further differentiate into effector cells or memory cells.  [Plasma cells, T-helper cells, T-cytotoxic cells].
    • The memory cells are long-lived cells that reside in the Go phase of the cell cycle until activated by a secondary encounter with antigen.
    • Different lineages or different maturational stages of lymphocytes can be distinguished by their expression of membrane CD molecules ( Cluster of Differentiation (CD)
  • 24. T and B lymphocytes
    • T cells are chiefly responsible for Cell mediated immunity
    • B cells are primarily responsible for Humoral mediated immunity (relating to antibodies).
    • T cells are named such because these lymphocytes mature in the thymus;
    • B cells, named for the Bursa of fabricius in which they mature in bird species, are thought to mature in the bone marrow in humans.
    • In the presence of an antigen, B cells can become much more metabolically active and differentiate into plasma cells, which secrete large quantities of antibodies.
  • 25.  
  • 26. T Lymphocytes (T-cells ) attack the invaders directly
    • T cells are antigen specific. They acquire receptors for this specificity in the thymus .
    • Some of them (CD4+) secrete lymphokines which act on other cells involved in the immune response.
    • Others (CD8+, cytotoxic) are able to cause lysis of infected cells.
  • 27.  
  • 28. Human T-lymphocyte (SEM x12,080).
  • 29. T Lymphocytes (T Cells)
    • Helper T cells
      • Helper T cells are responsible for activating and orchestrating the response against an invading organism.
    • Cytotoxic (or Killer) T Cells
      • Killer T cells are responsible for destruction of virus-infected or malignant (cancerous) body cells.
    • Suppressor T Cells
      • Suppressor T cells are responsible for turning off the immune response after an infection has been cleared.
  • 30. T Lymphocytes
  • 31. Role of T-lymphocytes
    • T- helper cells interact with B- lymphocytes and help them to divide, differentiate and antibodies.
    • T- helper cells interact with mononuclear phagocytes and help them destroy pathogens.
    • T- cytotoxic cells are responsible for the destruction of host cells infected with viruses or other intracellular pathogens.
  • 32. B lymphocytes
      • B lymphocytes are responsible for producing antibodies, specialized proteins which react against foreign invaders.
  • 33. B cells mature into plasma cells that produce antibodies.
  • 34. B cells perform antibody mediated immunity.
    • B lymphocytes have receptors on its surface to recognize one unique antigen.
    • Antigens stimulate B cells to convert into plasma cells that produce antibodies (specific to that antigen).
    • A plasma cell produces antibody molecules that can combine with a specific kind of antigen (like a lock & key).
    • All antibodies eventually enter the blood or lymph.
    • B-cells specialize in fighting bacterial invaders.
  • 35. Plasma Cells
    • 1. B- cells on stimulation, grow, proliferate and differentiate into plasma cells.
    • 2. Plasma cells have a nucleus with chromatin arranged in a wheel-spoke pattern and an abundant, basophilic cytoplasm.
    • 3. Their extensive granular endoplasmic reticulum produces immunoglobulins.
    • 4. After completing secretion, most plasma cells die; however, some may survive for months or even years and serve as memory cells .
  • 36. Plasma Cell
  • 37. Antibodies (Immunoglubulins)
    • Proteins produced by B cells to interact with and incapacitate and/or eliminate specific foreign invaders
      • Antibodies can work in one of several ways :
        • Antitoxin Effect- Binding of antibody to a bacterial toxin can inactivate the toxin directly.
        • Opsonization - Microbes coated with antibody are a more attractive target for phagocytic cells such as macrophages
        • Complement Activation- Binding of antibody to an invading microbe can activate the complement cascade resulting in destruction of the microbe
        • Virus Neutralization- Binding of antibody to a virus can block the virus from entering body cells.
        • Antibody-Dependent Cell-Mediated Cytotoxicity- Binding of antibody to cells makes cells susceptible to destruction by cytotoxic (killer) immune cells.
  • 38. Natural Killer Cells
    • Natural killer cells (lymphocyte-like cells) attack & destroy virus-infected cells and cancer cells on first exposure to them.
    • – They lyse (rupture) cell membranes upon first exposure to these cells.
    • – NK cells provide an immediate, nonspecific defense.
    • They act to slow the spread of viruses & cancer cells until the more specific adaptive immune cells can be mobilized.
  • 39. Natural Killer Cells
  • 40. Natural killer cell, Killer cell and cytotoxic T lymphocytes
  • 41. B cell-T cell interaction
  • 42. B cell-T cell interaction
  • 43. B cell receptor (BCR) and T cell receptor (TCR
    • Each B cell and T cell is specific for a particular antigen. This means that each is able to bind to a particular molecular structure.
    • The specificity of binding resides in a receptor for antigen:
    • the B cell receptor (BCR)
    • the T cell receptor (TCR).
  • 44. Both BCRs and TCRs share these properties
    • They are integral membrane proteins.
    • They are present in thousands of identical copies exposed at the cell surface.
    • They are made before the cell ever encounters an antigen.
    • They are encoded by genes assembled by the recombination of segments of DNA.
    • They have a unique binding site.
    • This site binds to a portion of the antigen called an antigenic determinant or epitope.
    • The binding depends on complementarity of the surface of the receptor and the surface of the epitope.
    • The binding occurs by non- covalent forces (again, like an enzyme binding to its substrate).
  • 45. BCRs and TCRs differ in:
    • their structure;
    • the genes that encode them;
    • the type of epitope to which they bind.
  • 46. Antigen receptors expressed as transmembrane molecules on B and T lymphocytes
  • 47. Other cells of the immune system
    • Natural Killer Cells
    • Natural killer cells are responsible for non-specific destruction of virus-infected or malignant body cells.
    • Monocytes
    • Monocytes are large white blood cells which circulate in the blood, then migrate into tissues to mature into macrophages.
    • Macrophages
    • Macrophages are phagocytic cells responsible for engulfing and digesting foreign invaders. 
    • Examples of tissue-specific macrophages include:
      • Alveolar Macrophages (in the lungs)
      • Mesangial Macrophages (in the kidneys )
      • Microglial Cells (in the brain)
      • Kupffer Cells (in the liver)
  • 48. Monocytes
    • Monocytes are produced by the bone marrow from haematopoietic stem cells precursors.
    • They circulate in the blood stream for about one to three days and then typically move into tissues throughout the body.
    • In the tissues monocytes mature into different types of macrophages at different anatomical locations.
  • 49. Monocyte
    • Monocytes can perform phagocytosis using intermediary ( opsonising ) proteins such as antibodies or complement that coat the pathogen.
    • They bind to the microbe directly via pattern-recognition receptors that recognize pathogens.
    • Monocytes are also capable of killing infected host cells via antibody, termed antibody-mediated cellular cytotoxicity.
  • 50. Dendritic Cells
    • originate in the bone marrow
    • function as antigen presenting cells (APC).
    • found in the structural compartment of the lymphoid organs
    • found in the bloodstream and other tissues of the body
    • capture antigen or bring it to the lymphoid organs where an immune response is initiated.
  • 51. Dendritic Cells
    • Stationed in skin
    • Particularly susceptible to infection by viruses
    • Present internally-produced antigens on MHC I
  • 52. Antigen Presenting cell (APC)
  • 53. Phagocytes and Their Relatives
  • 54.  
  • 55. Monocytes and Macrophages
    • represent 5-8% of WBCs
    • monocytes enter the tissues through the process of extravastion.
    • Changes which occur during this transition: Cells enlarge [5-10x] intracellular organelles increase in number and complexity cells acquire increased phagocytic ability increased secretion of many soluble factors
    • Macrophages play the following important roles: 1) phagocytosis 2) antimicrobial activity 3) secretion of soluble factors
    • Macrophages are activated by a variety of stimuli in the course of an immune response. - One of the earliest activating signals comes from chemokines. - Phagocyotosis itself is an important activating stimulus. - Macrophages are further activated by cytokines secreted by T helper cells [IFN-gamma] - and by mediators of the inflammatory response - and by various microbial products (such as LPS)
  • 56. Macrophages
    • These cells are derived from the bone marrow and have a variety of functions in the immune response:
    • phagocytosis
    • secretion of cytokines
    • The cells performing these various functions have differing microscopic appearances but they are grouped together as the mononuclear phagocytic system.
  • 57. Phagocytes
    • Phagocytes are large white cells that can swallow and digest microbes and other foreign particles. Monocytes are phagocytes that circulate in the blood.
    • When monocytes migrate into tissues, they develop into macrophages .
    • Specialized types of macrophages can be found in many organs, including lungs, kidneys, brain, and liver.
  • 58.  
  • 59. Macrophages play many roles.
    • As scavengers, they rid the body of worn-out cells and other debris. –
    • They display bits of foreign antigen in a way that draws the attention of matching lymphocytes.
    • They churn out an amazing variety of powerful chemical signals, known as monokines , which are vital to the immune responses.
  • 60. Macrophage attacking E.coli (SEM x8,800 ).
  • 61. Normal anti-bacterial action 1. PHAGOCYTIC CELL ENGAGES MICROBE 2. PHAGOCYTOSIS OF THE MICROBE 3. DESTRUCTION OF THE MICROBE
  • 62. Mast cell
    • A mast cell (or mastocyte ) is a resident cell of connective tissue that contains many granules rich in histamine and heparin.
    • Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing and defense against pathogens.
  • 63. Mast cell
    • The mast cell is a twin of the basophil, except that it is not a blood cell.
    • it is found in the lungs, skin, tongue, and linings of the nose and intestinal tract, where it is responsible for the symptoms of allergy.
  • 64. Mast cells
    • Mast cells are released from the bone marrow as undifferentiated precursor cells and do not differentiate until they enter the tissues (skin, connective tissue, mucosal epithelium, etc.)
    • Morphology and function similar to circulating basophils - but clearly derived from a distinct cell lineage.
    • Mast cells bear Fc receptors for IgE ( FcRs) and contain large numbers of cytoplasmic granules which also play a very important role in the allergic response.
    • They produce a variety of cytokines
    • TNF is produced and stored within the cytoplasm of the mast cell, and it can be released quickly following mast cell activation.
  • 65. About the presenter
    • Dr.B.Victor is a highly experienced postgraduate biology teacher, recently retired from the reputed educational institution St. Xavier’ s College, Palayamkottai, India-627001.Presently HOD of Biotech at Annai Velankanni college, Tholayavattam. K .K Dist
    • He was the dean of sciences and assistant controller of examinations of St. Xavier’s college.
    • He has more than 32 years of teaching and research experience and has guided more than 12 Ph. D scholars.
    • He has taught Immunology and biochemistry to graduate and post graduate students.
    • Send your comments to : bonfiliusvictor@gmail.com
  • 66. Thank you