Functional organization of the Immune System


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Functional organization of the Immune System

  1. 1. Presented by Dr.B.Victor St.Xavier's College, Palayamkottai-627002,India. Functional organization of the immune system : 1. Immunogenic Organs
  2. 2. Presentation outline <ul><li>Critical functions of immune system </li></ul><ul><li>Dual nature </li></ul><ul><li>Characteristics </li></ul><ul><li>Functions </li></ul><ul><li>Features </li></ul><ul><li>Mechanisms of immune response </li></ul><ul><li>Types of immune systems </li></ul>
  3. 3. The immune system is crucial to human survival. <ul><li>The immune system consists of a complex network of organs, cells, and molecules which work together to defend the body from disease causing organisms (bacteria, viruses, fungi, and parasites). </li></ul><ul><li>The purpose of the immune system is to maintain homeostasis, which includes protecting the body from pathogens and toxins that could disrupt the homeostasis. </li></ul>
  4. 4. The Body’s Defenses: The Immune System <ul><li>Vertebrate Immune Mechanisms </li></ul><ul><li>Innate Immunity </li></ul><ul><li>Acquired Immunity </li></ul><ul><li>Cell-Mediated Response </li></ul><ul><li>Humoral Response </li></ul><ul><li>Lymphatic Tissues </li></ul>
  5. 5. Multilayered and dual nature of the Immune System <ul><li>The architecture of the immune system is multi-layered, with defenses on several levels. </li></ul><ul><li>Several barriers (external to internal /simple to complex) provided at many levels of infection. </li></ul><ul><li>The immune system has a series of dual natures: </li></ul><ul><li>Self/ non-self recognition </li></ul><ul><li>Natural / adaptive </li></ul><ul><li>Cell mediated / humoral </li></ul><ul><li>Passive / active </li></ul><ul><li>Primary / secondary </li></ul><ul><li>Both systems consist of a multitude of cells and molecules that interact in a complex manner to detect and eliminate pathogens. </li></ul>
  6. 6. Characteristics of the immune response <ul><li>Specificity: the ability to distinguish between antigens </li></ul><ul><li>Adaptiveness : the ability to respond to previously unseen molecules. </li></ul><ul><li>Recognition of self and non-self : the ability to recognize and respond to molecules that are foreign or ‘non-self ‘and the molecules that are ‘self’. </li></ul><ul><li>Memory: the ability to recall previous contact with a foreign molecule and respond to it in a learned manner. </li></ul>
  7. 7. Functions of immune system <ul><li>The immune system like any organization, has members that perform different functions to accomplish a common goal. </li></ul><ul><li>Provides defenses against pathogens </li></ul><ul><li>Removes dead or worn out cells like RBCs </li></ul><ul><li>Identifies and destroys abnormal cancer cells </li></ul><ul><li>Protects from autoimmune diseases </li></ul><ul><li>Rejects tissues cells of foreign antigens . </li></ul>
  8. 8. Main features of Immune system : <ul><li>Pattern recognition </li></ul><ul><li> (anomaly detection, noise tolerance), </li></ul><ul><li>distributed, No central point of control </li></ul><ul><li>diversity, </li></ul><ul><li>learning, </li></ul><ul><li>memory, </li></ul><ul><li>redundancy, </li></ul><ul><li>robustness, </li></ul><ul><li>feature extraction, </li></ul><ul><li>multilayered, and </li></ul><ul><li>adaptive. </li></ul>
  9. 9. Mechanism of immune response <ul><li>The immune system specifically recognizes and selectively eliminates pathogens. </li></ul><ul><li>There are two critical steps in the immune response: </li></ul><ul><ul><li>Detection events </li></ul></ul><ul><ul><li>Elimination events </li></ul></ul><ul><li>The detection and elimination of pathogens depend upon the chemical bonding between receptors on the surface of an immune cell and epitopes found on the surface of a pathogen. </li></ul><ul><li>The complementary receptor – epitope binding ( monospecificity) activates a complex system of signalling that mediates the immune response. </li></ul>
  10. 10. Mechanism of immune response <ul><li>Immune recognition phase is critical in the normal functioning of the system. </li></ul><ul><li>This is accomplished by three sets of antigen binding molecules : </li></ul><ul><li>T- cell antigen receptors (TCR) </li></ul><ul><li>Class I and class II molecules of the MHC </li></ul><ul><li>B-cell antigen receptor (BCR, immunoglobulin). </li></ul><ul><li>The effector phase is mediated by a variety of cells and soluble factors. </li></ul>
  11. 11. Immune System <ul><li>Two types of immune system </li></ul><ul><li>􀁺 Innate immune system </li></ul><ul><li>􀁺 Adaptive immune system </li></ul>
  12. 12. Main Types of Immunity in Man Immunity Innate immunity Adaptive immunity Natural Artificial Passive (maternal) Active (Infection) Passive (Serotherapy) Active (Vaccination)
  13. 13. Innate Immunity <ul><li>responds immediately </li></ul><ul><li>protects the body from all foreign substances </li></ul><ul><li>functions on two levels </li></ul><ul><li>first line of defense – prevents entry of pathogens </li></ul><ul><li>mechanical barriers </li></ul><ul><li>skin, mucosa, and secretions </li></ul><ul><li>second line of defense – inhibits spread of pathogen </li></ul><ul><li>antimicrobial proteins </li></ul><ul><li>phagocytes and other cells </li></ul><ul><li>inflammation </li></ul>
  14. 14. Three Lines of Defense <ul><li>1st Line – barriers at portals of entry </li></ul><ul><li> primarily inborn and nonspecific </li></ul><ul><li>2nd Line – protective cells and chemicals </li></ul><ul><li> come into play when barriers are breached </li></ul><ul><li> primarily inborn and nonspecific </li></ul><ul><li>3rd Line – antibodies and cytotoxic cells </li></ul><ul><li> provides long-term immunity after encounters </li></ul><ul><li> primarily acquired and specific </li></ul>
  15. 15. Lines of defense <ul><li>1 st lines of defense are the physical barriers which include the skin, urine, tears, ciliary elevator, mucosal membrane, etc. </li></ul><ul><li>2 nd lines of defense are the macrophage system, complement, fever, interferon and inflammation. </li></ul><ul><li>3 rd lines of defense a re the specific system also known as acquired or adaptive immunity. The specific system consists of B cells (humoral), and T cells (cell-mediated). </li></ul>
  16. 16. Physical and Chemical Defenses
  17. 17. First line of defense-1 <ul><li>The first line of defense are barrier tissues such as the skin that stop the entry of pathogens into our bodies. </li></ul><ul><li>If these barrier layers are penetrated, cells like macrophages and neutrophils engulf foreign organisms and kill them without the need for antibodies </li></ul>
  18. 18. First Line of Defense-2 <ul><li>Skin provides an almost impenetrable biological barrier. </li></ul><ul><li>Lysozyme is an enzyme found in tears and saliva that can break down foreign agents . </li></ul><ul><li>The clotting of blood near open wounds prevents an open space for antigens. </li></ul><ul><li>Mucus and cilia found in the nose and throat can catch foreign agents then sweep them outside via coughing, sneezing and vomiting. </li></ul><ul><li>The cell wall of plants consists of fibrous proteins which provide a barrier to potential parasites (antigens). </li></ul>
  19. 19. A second line of defense-1 <ul><li>A second line of defense is the specific or adaptive immune system which may take days to respond to a primary invasion </li></ul><ul><li>The production of antibodies and cell-mediated responses may occur in which specific cells recognize foreign pathogens and destroy them. </li></ul><ul><li>The response is often more rapid because of the activation of memory B and T cells . </li></ul><ul><li>cells of the immune system interact with one another by a variety of signal molecules . </li></ul><ul><li>These signals may be proteins such as lymphokines, cytokines and chemokines which stimulate cells of the immune system.  </li></ul>
  20. 20. Second Line of Defense-2 <ul><li>Second lines of defense deal with antigens that have bypassed the first lines of defense. </li></ul><ul><li>Interferons are a family of proteins that are released by a cell that is under attack by an antigen. </li></ul><ul><li>One method of attacking antigens is by phagocytosis , where the contents of the antigen are broken down by molecules called phagocytes. </li></ul>
  21. 21. Adaptive immunity <ul><li>The second level of defence increases in strength and effectiveness with each encounter. The foreign agent is recognised in a specific manner and the immune system acquires memory towards it. </li></ul><ul><li>The first encounter with an antigen is known as the primary response . Re-encounter with the same antigen causes a secondary response that is more rapid and powerful </li></ul>
  22. 22. Adaptive immunity <ul><li>As response produce antibodies to specific infections </li></ul><ul><li>Some features </li></ul><ul><li>– Memory </li></ul><ul><li>Each successive encounter with the same pathogen improve the response </li></ul><ul><li>– Clonal selection </li></ul><ul><li>Select the best and matured immune cells to defend the organism against infections </li></ul>
  23. 25. <ul><li>Whenever T cells and B cells are activated, some become &quot;memory&quot; cells . The next time that an individual encounters that same antigen, the immune system is primed to destroy it quickly. This is active immunity . </li></ul><ul><li>Long-term active immunity can be naturally acquired by infection or artificially acquired by vaccines </li></ul><ul><li>Short-term passive immunity can be transferred artificially from one individual to another via antibody-rich serum; </li></ul>Active and Passive Immunity
  24. 27. Active and Passive Acquired Immunity <ul><li>Active immunity </li></ul><ul><ul><li>Conferred by recovery from infectious disease </li></ul></ul><ul><ul><li>Depends on persons own immune system. </li></ul></ul><ul><ul><li>May be acquired artificially with vaccines . </li></ul></ul><ul><li>Passive immunity </li></ul><ul><ul><li>transferred from person to person through transfer of antibodies. </li></ul></ul><ul><ul><li>Natural instances include antibodies passing across placenta from mother to fetus (provides temporary protection) or through the milk. </li></ul></ul><ul><ul><li>Transferred artificially. E.g. antibody injections for rabies, anti rhesus factor, snake venom, botulinun toxin. </li></ul></ul>
  25. 28. <ul><li>Lymphatic vessels are responsible for flow of lymph within the lymphoid system </li></ul><ul><li>Plasma constantly leaks out of capillaries to deliver oxygen and nutrients to cells of the surrounding tissue. Once in the tissue, the plasma is now called tissue fluid . </li></ul><ul><li>While most of this tissue fluid re-enters capillaries and is returned directly to the bloodstream, some fluid enters lymph vessels as lymph . </li></ul><ul><li>LYMPH- flows from the intercellular tissue spaces into lymphatic capillaries and then into a series of larger collecting vessels called lymphatic vessels . Lymphatic vessels converge into the thoracic duct , which returns the fluid to the circulatory system by dumping into the left subclavian vein. </li></ul>Lymphatic vessels
  26. 29. Overview of blood and lymph system and how leukocytes travel from one system to another Thoracic duct Site of exchange between the blood and lymph systems Lymph carrying antibodies and immune cells collect in thoracic duct where the lymph empties back into the blood circulatory system
  27. 30. Immune cells travel back and forth from the blood and lymph circulatory systems and interact with extra-vascular tissues in the process-- extravasation muscle
  28. 31. Lymphatic vessels.
  29. 32. The organs of the immune system 
  30. 33. Kinds of lymphoid Organs <ul><ul><li>Primary/central lymphoid organs </li></ul></ul><ul><ul><li>bone marrow, </li></ul></ul><ul><ul><li>thymus </li></ul></ul><ul><ul><li>Secondary /peripheral lymphoid tissue </li></ul></ul><ul><ul><li>lymph nodes, </li></ul></ul><ul><ul><li>spleen, </li></ul></ul><ul><ul><li>mucosa-associated lymphoid tissue </li></ul></ul>
  31. 34. Kinds of Lymphoid Organs The Lymphoid Organs Primary or Central organs Secondary or Peripheral organs 1.Bone marrow 2.Thymus gland 3.Bursa of fabricius 1.Lymp nodes 2.Spleen 3.Diffuse lymphoid tissues
  32. 35. <ul><li>The bone marrow and the thymus constitute the primary lymphoid organs . </li></ul><ul><li>Both B-lymphocytes and T-lymphocytes are produced from stem cells in the bone marrow. B-lymphocytes mature in the bone marrow while T-lymphocytes migrate to the thymus and mature there . </li></ul><ul><li>After maturation, both B-lymphocytes and T-lymphocytes circulate through and accumulate in secondary lymphoid organs . </li></ul>Primary lymphoid organs
  33. 36. <ul><li>The secondary lymphoid organs include lymph nodes and the spleen, as well as lymphoid tissues. </li></ul><ul><li>The lymphoid tissues include the tonsils, the appendix, the Peyer's patches in the lining of the small intestines ( gut-associated lymphoid tissue or GALT ), </li></ul><ul><li>The lymphoid tissue found beneath the mucous membranes of the bronchi ( bronchial-associated lymphoid tissue or BALT ), </li></ul><ul><li>The lymphatic tissue found in the mucous membranes ( mucosa-associated lymphoid tissue or MALT ) </li></ul><ul><li>The lymphatic tissue found beneath the skin ( skin-associated lymphoid tissue or SALT ). </li></ul>Secondary lymphoid organs
  34. 37. Primary and Secondary Lymphoid organs
  35. 38. Primary/central lymphoid organs <ul><li>BONE MARROW is a central organ where all the immune cells are born and only B cells mature (process termed as B lymphopoiesis). </li></ul><ul><li>THYMUS is the other central organ in which T cells mature ( T lymphopoiesis ). </li></ul>
  36. 39. The bone marrow <ul><li>Bone marrow is a spongy tissue found within bones. </li></ul><ul><li>All blood cells are produced within the bone marrow. </li></ul><ul><li>The bone marrow of an adult produce about three million red blood cells and 120,000 white blood cells every second. </li></ul><ul><li>All these cells originate from a small population of stem cells, which may be as few as one in a million of the bone marrow cells. </li></ul>
  37. 41. Thymus <ul><li>The thymus is an organ located in the upper chest. </li></ul><ul><li>Immature lymphocytes leave the bone marrow and find their way to the thymus where they are “educated” to become mature T-lymphocytes. </li></ul>
  38. 42. Thymus <ul><li>Flat, bilobed organ situated above the heart and below the thyroid gland. </li></ul><ul><li>Each lobe is surrounded by a capsule and is divided into lobules. </li></ul><ul><li>The lobules are separated from each other by strands of connective tissue called trabeculae. </li></ul><ul><li>Each lobule is organized into two compartments: the cortex (outer compartment) the medulla (inner compartment). </li></ul><ul><li>Cortex and Medulla are both crisscrossed by a network of stromal cells composed of: </li></ul><ul><li>loosely packed thymic epithelial cells </li></ul><ul><li>interdigitating dendritic cells </li></ul><ul><li>macrophages </li></ul>
  39. 43. Thymus <ul><li>In the cortex, the network is densely packed with thymocytes.  Cells are less dense in medulla . </li></ul><ul><li>In medulla, the epithelial cells are more visible and HASSAL's Corpuscles are present (Function Unknown). </li></ul><ul><li>The thymus is at its l argest relative size at birth and its l argest actual size is at puberty . </li></ul><ul><li>After puberty the thymus begins to shrink. In elderly individuals it is usually less than 3 grams in weight. </li></ul><ul><li>There is relationship between aging and a decline in immune responsiveness. </li></ul><ul><li>Stress can also result in shrinkage of the thymus. </li></ul>
  40. 44. Thymus <ul><li>Precursor T cells enter thymus from the blood ( there are no afferent lymphatic vessels ] and mature into functional T lymphocytes. </li></ul><ul><li>However, the vast majority of these cells are destined to die due to (APOPTOSIS) - programmed cell death. </li></ul><ul><li>The T cells (thymocytes) go through a selection process in the thymus based upon the TcR that they possess. </li></ul>
  41. 45. Process of thymic education <ul><li>The complete process of thymic education is a two-step process in which Thymic cortical epithelial cells function as the effector cells in a process known as POSITIVE SELECTION . </li></ul><ul><li>In positive selection, T cells which bear a TcR which can bind SELF-MHC are selected to survive and proliferate. Cells which are not positively selected are triggered to undergo APOPTOSIS . </li></ul><ul><li>Positively selected thymocytes must go through a second phase of selection known as NEGATIVE SELECTION . </li></ul><ul><li>Functionally, during negative selection any T cell that is presented antigen + MHC within the thymus is triggered to undergo APOPTOSIS. </li></ul><ul><li>Most importantly: thymic macrophages and dendritic cells serve as APCs in the process of negative selection </li></ul>
  42. 46. Thymic hormones <ul><li>Stromal cells secrete soluble factors which are important in T cell maturation. </li></ul><ul><li>Some examples include : alpha- 1- thymosin beta - 4- thymosin thymopoietin thymulin </li></ul>
  43. 47. Lymph nodes <ul><li>Small, bean-shaped lymph nodes are laced along the lymphatic vessels, with clusters in the neck, armpits, abdomen, and groin. </li></ul><ul><li>Each lymph node contains specialized compartments where immune cells congregate, and where they can encounter antigens. </li></ul><ul><li>Immune cells and foreign particles enter the lymph nodes via incoming lymphatic vessels. All lymphocytes exit lymph nodes through outgoing lymphatic vessels. </li></ul>
  44. 48. Lymph Node
  45. 50. The regions of Lymph node <ul><li>3 regions to the lymph node: </li></ul><ul><li>Cortex (outermost layer- contains mostly B lymphocytes , plus both follicular dendritic cells and macrophages all arranged in clusters called primary follicles ) . </li></ul><ul><li>Following antigenic stimulation the primary follicles become secondary follicles consisting of concentric rings of densely packed lymphocytes and central lymphocytes, macrophages, and dendritic cells. </li></ul><ul><li>The GCs (germinal centers) contain large proliferating B lymphocytes and plasma cells interspersed with macrophages and dendritic cells.  </li></ul>
  46. 51. The regions of Lymph node <ul><li>The GC is a site of intense B-Cell activation and differentiation into plasma cells and memory cells. </li></ul><ul><li>Paracortex - (layer just beneath the cortex) This region is sometimes called the T dependent region of the lymph node. It is an area populated with T lymphocytes and also interdigitating dendritic cells. It is an important site for T cell activation by these APCs. </li></ul><ul><li>Medulla - inner most region, more sparsely populated by cells. Many of the cells are plasma cells, activated Th and Tc are also present. In addition, there is a high concentration of immunoglobulin in this region due to the large population of plasma cells. </li></ul>
  47. 52. Swelling of lymph nodes <ul><li>This huge increase in the number of lymphocytes is due to: </li></ul><ul><li>proliferation of lymphocytes within the lymph node </li></ul><ul><li>influx of lymphocytes from the circulatory system </li></ul><ul><li>-Clearly, the concentration of lymphocytes in the lymph nodes can increase greatly following antigenic stimulation accounting for &quot;swelling of lymph nodes &quot;. </li></ul>
  48. 53. The spleen <ul><li>The spleen is the largest of the lymphoid organs. </li></ul><ul><li>The spleen is a flattened organ at the upper left of the abdomen. </li></ul><ul><li>Like the lymph nodes, the spleen contains specialized compartments where immune cells gather and work, and serves as a meeting ground where immune defenses confront antigens. </li></ul>
  49. 54. Spleen
  50. 55. Spleen
  51. 56. Spleen <ul><li>The spleen is adapted to filter the blood, it responds therefore to systemic infections . </li></ul><ul><li>It is surrounded by a capsule, which sends trabeculae into the interior to form a compartmentalized structure. There are two types of compartments [ Red Pulp and White Pulp ]. </li></ul>
  52. 57. Spleen <ul><li>Red Pulp- Network of sinusoids populated with macrophages and numerous erythrocytes. Site where old RBCs are destroyed and removed. </li></ul><ul><li>White Pulp- Surrounds the splenic arteries, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes. </li></ul><ul><li>Clusters of B lymphocytes in the White Pulp form primary follicles occupying a more peripheral position. </li></ul><ul><li>Upon antigenic challenge, these primary follicles develop into characteristic secondary follicles containing germinal centers . </li></ul><ul><li>The spleen is NOT supplied by afferent lymphatics . </li></ul>
  53. 58. Functions of the Spleen <ul><li>The spleen functions both as immune and hematopoietic systems. </li></ul><ul><li>The immune functions include: </li></ul><ul><li>proliferation of lymphocytes </li></ul><ul><li>production of humoral antibodies </li></ul><ul><li>removal of macromolecular antigens from the blood </li></ul><ul><li>The hematopoietic functions include: </li></ul><ul><li>formation of blood cells in fetal life </li></ul><ul><li>removal and destruction of senile, damaged and abnormal RBCs and platelets </li></ul><ul><li>retrieval of the iron from hemoglobin </li></ul><ul><li>storage of blood in some species (not humans) </li></ul>
  54. 59. Lymphoid tissues <ul><li>Clumps of lymphoid tissue are found in many parts of the body, especially in the linings of the digestive tract and the airways and lungs—territories that serve as gateways to the body. These tissues include the tonsils , adenoids , and appendix . </li></ul>
  55. 60. Peyer's patches <ul><li>Peyer's patches are areas of lymphoid tissue located in the wall of the intestine, and in some mammalian species such as sheep, cattle  and rabbits, </li></ul><ul><li>Peyer's patches have a function similar to the bursa of fabricius of birds and bone marrow of other mammals: B cell differentiation and maturation. </li></ul><ul><li>Actually: Two types of Peyer's patches seem to occur: one with primary lymphoid function and another with secondary lymphoid function. </li></ul>
  56. 61. Functions of lymphatic organs <ul><li>Generate immuno-competant lymphocytes. </li></ul><ul><li>Concentrate antigens into lymphoid organs. </li></ul><ul><li>Circulate lymphocytes through lymphoid organs, exposing antigen to a variety of lymphocytes. </li></ul><ul><li>Deliver antibodies and effector T cells to the blood and tissues. </li></ul>
  57. 62. Kinds of Adaptive immunity <ul><li>Adaptive immune responses are actually reactions of the immune system to antigens . </li></ul><ul><li>There are two types of adaptive immune responses: </li></ul><ul><li>Humoral and cell mediated. </li></ul>
  58. 63. Adaptive Humoral immunity <ul><li>During humoral immune responses , proteins called antibodies , destroy antigens, appear in the blood and other body fluids. </li></ul><ul><li>Humoral immune responses resist invaders that act outside of cells, such as bacteria and toxins (poisonous substances produced by living organisms). </li></ul><ul><li>Humoral immune responses can also prevent viruses from entering cells. </li></ul>
  59. 64. Adaptive cellular immunity <ul><li>During cell-mediated immune responses, cells that can destroy other cells that are either infected with, or producing, a specific antigen. </li></ul><ul><li>Cell-mediated immune responses resist invaders that reproduce within the body cells, such as viruses. </li></ul><ul><li>Cell-mediated responses may also destroy cells making mutated (changed) forms of normal molecules, as in some cancers. </li></ul>
  60. 65. Immunity is a coordinated effort by the body. <ul><li>• It was previously believed that the immune system functioned independently in the body. </li></ul><ul><li>It’s now known that there are several links between the immune, nervous and endocrine systems. </li></ul><ul><li>Certain immune responses trigger endocrine &/or nervous activity. </li></ul><ul><li>Lymphocytes & macrophages are responsive to signals from the nervous system and certain endocrine glands. </li></ul><ul><li>Therefore, immunity is the job of the entire body not just one system. </li></ul>
  61. 66. About the presenter <ul><li>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 </li></ul><ul><li>He was the dean of sciences and assistant controller of examinations of St. Xavier’s college. </li></ul><ul><li>He has more than 32 years of teaching and research experience and has guided more than 12 Ph. D scholars. </li></ul><ul><li>He has taught Immunology and biochemistry to graduate and post graduate students. </li></ul><ul><li>Send your comments to : </li></ul>
  62. 67. Thank you