7 immunity


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7 immunity

  2. 2. THE NATURE OF DISEASE • • • • • • Pathogenic Organisms Genetic Disorders Toxic Chemicals Other Environmental Factors Physical Damage to Organs Nutritional Disorders 2
  3. 3. TYPES OF PATHOGENIC ORGANISMS • • • • • • Viruses Bacteria Protozoan Fungi Animal Parasites 3
  4. 4. MECHANISMS OF DISEASE BY PATHOGENS • Utilization of host nutritional resources • Physical damage to host tissues • Production of toxic substances • Chromosomal and gene damage • Body cells behave abnormally 4
  5. 5. VIRUSES envelope capsid nucleic acid 5
  6. 6. BACTERIA cell wall plasma membrane cytoplasm circular DNA 6
  7. 7. Defense Mechanisms 1. External defense 2. Internal Defense 3. Immune Defense 7
  8. 8. 1st Line of Defense • Skin acts as barrier to microbes and viruses - sweat has a low pH • Mucus traps foreign particles • Tears - Lysozyme has antimicrobial action • Gastric stomach acid 8
  9. 9. BODY COVERINGS: THE SKIN epidermis sebaceous glands sweat gland 9
  10. 10. BODY COVERINGS: MUCOUS MEMBRANES mucus cilia columnar epithelium 10
  11. 11. 2nd Line of Defense • Phagocytic cells (WBCs) - N L M E B - Natural Killer (NK) Cells: attack virus infected cells • Inflammatory Response • Antimicrobial proteins - Lysozyme - Interferon - Antibodies 11
  12. 12. NONSPECIFIC PHAGOCYTOSIS Neutrophils Monocytes Eosinophils 12
  13. 13. Mechanism of Phagocytosis MECHANISM OF PHAGOCYTOSIS 13 Macrophage
  14. 14. Lymphatic System 14
  15. 15. Inflammatory Response Histamine & prostaglandins released Capillaries dilate Clotting begins Chemotactic factors attract phagocytic cells Phagocytes consume 15 pathogens & cell debris
  16. 16. 3RD LINE OF DEFENCE Immunity:  It is the ability of body to resist almost all type of foreign organism (bacteria, virus, fungi) or toxins that tend to damage the tissue and organs 16
  17. 17. CHARACTERISTICS OF IMMUNITY • Recognition of self versus non-self • Response is specific • Retains a “memory” allowing an accelerated second response • Can respond to many different materials • Involves lymphocytes and antibodies 17
  18. 18. Type: 1.Innate immunity 2.Acquired / Adaptive immunity 18
  19. 19. Innate immunity: Immunity that develops from general processes rather than from process directed at specific disease organism is called innate immunity. It include 1.Phagocytosis of bacteria and other invaders by WBC and cells of tissue macrophage system 2.Destruction by acid secretion of stomach and digestive enzyme of organisms swallowed into the stomach 3.Resistance of the skin to invasion by organisms 4.Presence of certain chemical compounds in blood that attach to foreign organism or toxins and destroy them some of these compounds are a.Lysozyme: Causes bacteria to dissolute b.Basic polypeptide: Which react with certain type of gram positive bacteria and inactivate them c.Complement complex: These have various functions d.Natural killer lymphocytes: These can recognize and destroy foreign cells, tumor cell, and even some infected cells. 19
  20. 20. Acquired immunity: Immunity that develops against individual invading agents such as bacteria, virus, toxins and even foreign tissue from other animal Acquired immunity is caused by a special immune system that forms antibodies and activated lymphocytes that attack and destroy the specific organisms or toxins Types of acquire immunity: Two basic but closely allied types of acquired immunity occur in body 1.Humoral immunity or B-cell immunity 2.Cell-mediated immunity or T-cell immunity Humoral immunity: In this body develops antibodies, which are globulin molecules in blood that are capable of attacking the invading agents. B-lymphocyte produces the antibodies. Cell-mediated immunity: In this immunity is achieved through the formation of large number of activated lymphocytes that are specifically designed to destroy the foreign agent. Activated lymphocytes are T lymphocyte 20
  21. 21. TYPES OF IMMUNITY • Active Immunity - Naturally-Acquired Active Immunity - Artificially-Acquired Active Immunity • Passive Immunity - Naturally-Acquired Passive Immunity - Artificially-Acquired Passive Immunity 21
  23. 23. ACTIVE IMMUNITY The production of antibodies against a specific disease by the immune system.  Naturally acquired through disease  Artificially acquired through vaccination   Vaccines include inactivated toxins, killed microbes, parts of microbes, and viable but weakened microbes.  Active immunity is usually permanent 23
  24. 24.  A vaccinated person has a secondary response based on memory cells when encountering the specific pathogen.  Routine immunization against infectious diseases such as measles and whooping cough, and has led to the eradication of smallpox, a viral disease.  Unfortunately, not all infectious agents are easily managed by vaccination.  HIV vaccine in the works 24
  25. 25. PASSIVE IMMUNITY Passive Immunity- Protection against disease through antibodies produced by another human being or animal. Effective, but temporary Ex. Maternal antibodies Colostrum. 25
  26. 26.  Passive immunity can be transferred artificially by injecting antibodies from an animal that is already immune to a disease into another animal.  Rabies treatment: injection with antibodies against rabies virus that are both passive immunizations (the immediate fight) and active immunizations (longer term defense). 26
  27. 27. IMMUNE SYSTEM RESPONSE TO ANTIGENS Humoral Immunity • Involves antibodies (secreted from B cells) dissolved in the blood plasma. • Demonstrated as a immune response using only the blood serum. • Defense against bacteria, bacterial toxins, & viruses. 27
  28. 28. IMMUNE SYSTEM RESPONSE TO ANTIGENS Cell-Mediated Immunity • Involves the activities of specific white blood cells (T cells). • Defense against cancer cells, virusinfected cells, fungi, animal parasites, & foreign cells from transplants. 28
  29. 29. Lymphocyte Formation 29
  30. 30. B CELLS • Mature in bone marrow • Involved in humoral immunity • Once activated by antigen, proliferate into two clones of cells: plasma cells that secrete antibodies and memory cells that may be converted into plasma cells at a later time 30
  31. 31. B CELLS antibodies 31
  32. 32. B CELLS B Cells 32
  35. 35. CLONAL SELECTION plasma cells memory cells antibodies 35
  36. 36.  Antibodies constitute a group of globular serum proteins called immunoglobins (Igs).  A typical antibody molecule has two identical antigen-binding sites specific for the epitope that provokes its production. 36
  37. 37. ANTIBODY MOLECULE antigen binding sites antigen light chains heavy chains 37
  38. 38. MECHANISMS ON ANTIBODY ACTION • • • • • • Precipitation of soluble antigens Agglutination of foreign cells Neutralization Enhanced phagocytosis Complement activation leading to cell lysis Stimulates inflammation 38
  39. 39. Direct actions of antibodies on invading agents: Antibodies can inactivate the invading agent in one of several ways 1.Agglutination: In which multiple large particles with antigen on their surfaces, such as bacteria or red cells, are bound together into a clump 2.Precipitation: In which the molecular complex of soluble antigen (such as tetanus toxin) and antibody becomes so large that it is rendered and precipitates 3.Neutralization: In which antibodies cover the toxic sites of antigenic agent 4.Lysis: In which some potent antibodies are occasionally capable of directly attacking membrane of cellular agents and thereby causing rupture of cell •These direct actions of antibodies attacking the antigenic invades probably, under normal conditions, are not strong enough to play a major role in protecting the body against the invaders. Most of protection comes through the amplifying effects of complement system. 39
  40. 40.  The binding of antibodies to antigens to form antigen-antibody complexes is the basis of several antigen disposal mechanisms. 40
  41. 41. The classical complimentary pathway, resulting in lysis of a target cell 41
  42. 42. Complement system: Complement system consists of 20 heat liable plasma proteins that are functionally inactive i.e. the components of complement system circulate in blood in an inactive form •These plasma proteins are enzyme in its inactive form •There are 20 plasma protein, out of which the principal actors in this system are 11 proteins designated as C1 to C9, B and D •Synthesis of complement proteins occurs mostly in the liver and some by macrophages •Complement system plays a role in host defense and inflammatory process •The complement protein (enzyme) are usually inactive but can be activated in two pathways 1.Classical pathway 2.Alternate pathway 42
  43. 43. Classical pathway: The classical pathway is activated by antigen-antibody reaction When antibody binds with an antigen ↓ Specific reactive site on constant portion of antibody become uncovered or activated ↓ This activated specific reactive site binds directly with C1 molecule of complement system, setting into motion and cascade of sequential reaction 43
  44. 44. Note: Cleaved fragments are designated with small letter (e.g. C3a, C3b) A horizontal bar over numberal component (e.g. C1) indicates that it has acquired enzymatic activity A horizontal bar over numberal of complex (e.g. C9b67) indicates an activated state 44
  45. 45. Alternate pathway Sometime complement system is activated without the intermediation of an antigen-antibody reaction through alternate pathway The alternate pathway can be triggered by 1.Large polysaccharide molecule in cell surface of some invading microorganism 2.Endotoxins of gram-negative bacteria 3.Teichoic acids of gram-positive bacteria 4.Aggregated IgA 5.Cobra venom •These substances react with complement factors B and D forming an activation products that activates factor C3 setting off the remainder of complement cascade beyond C3 level same as classical pathway. ** MAC= Membrane attack complex 45
  46. 46. 46
  47. 47. Importance of Complement system: Multiple end products are formed and several of these cause important effects that help to prevent damage by the invading organism or toxins. Among these more important effects are the following: 1.Opsonization and phagocytosis: C3b strongly activated phagocytosis by neutrophil and macrophage causing them to engulf the bacteria to which antigen-antibody complexes are attached. This process is called opsonization. •It often enhances the number of bacteria that can be destroyed by many hundred folds. 2. Lysis: Lytic complex (C5b6789) can directly rupture the cell membrane of bacteria and other invading organism 3.Agglutination The complement products also change the surfaces of the invading organism, causing them to adhere to one another, thus promoting agglutination 4. Neutralization of viruses Complement enzyme and other complement products can attack the structure of some viruses and thereby render them nonvirulent 47
  48. 48. 5.Chemotaxis C5a causes chemotaxis of neutrophil and macrophage thus causing migration of large number of phagocytes into the local region of antigenic agent 6.Activation of mast cells and basophils: • Fragment C3a, C4a, and C5a all activate mast cell and basophils causing them to release histamine, heparin, and several other substance into local fluids These substances in turn cause a..Increased local blood flow b.Increased leakage of fluid and plasma protein in tissue c.Cause other local tissue reaction that help to inactivate or immobilse the antigenic agent These factors play major role in inflammation. 7.Inflammatory effects: Several other complement products in addition to inflammatory effect caused by activation of mast cells and basophils contribute to local inflammation These products cause a.Already increased blood flow to increase still further b.More increase in capillary leakage of protein and coagulation of protein in tissue spaces Thus preventing movement of invading organism through the tissue 48
  49. 49. Lymphocyte: Lymphocyte is one of the type of white blood cells •Lymphocyte originate from multipotent hemopoietic stem cells of bone marrow •Lymphoid stem cell in bone marrow mature into B lymphocytes •Lymphoid stem cell which migrate in thymus mature into T lymphocytes •During development each B cell or T cell becomes immunologically committed to a specific epitope of an antigen There is continual recirculation of lymphocytes between the blood and lymphoid tissue B cells have a shorter life span of 5 to 7 days and T cells have a long life span of months or years Classification of lymphocytes: According to size 1.Small lymphocyte 2.Large lymphocyte Immunologically/functionally 1.T lymphocyte 2.B lymphocyte 3. NK cells 49
  50. 50. All lymphocytes originate in the bone marrow, but while T- lymphocyte mature further in thymus, Blymphocyte leave the bone marrow as mature cells. For this reason none marrow and thymus are called central lymphoid organ Lymphocyte migrate from these organs to blood and peripheral lymphoid organs (Spleen, lymph nodes, solitary nodule, tonsil, appendix and Peyer’s patch of ileum) where they proliferate and complete their differentiation 50
  51. 51. B lymphocyte (B cells) •These are responsible for humoral immune response due to synthesis and secretion of antibody •B cells originate from stem cell in bone marrow and differentiate in fetal life in liver then in bone marrow in adult •The letter “B” was derived from the first letter of “Bursa of febricius” in birds where they were first found •When B cells are activated by specific antigen it lead to proliferation and differentiation of B cell into plasma cell •Plasma cells synthesize and secrete antibodies # derive from bone marrow, migrate to non-thymic lymphoid structure where they nest, proliferate when activated and differentiate into antibody secreting plasma cell 51
  52. 52. T lymphocytes (T cells) •T cells are responsible for cell mediated immune response •T cells develop and differentiate within thymus from migrating stem cell and thus called T cells •T cells leave the thymus as mature T lymphocytes and are found in blood, secondary lymphoid organ like lymph node, spleen, tonsil and elsewhere throughout the body Type of T lymphocytes: On basis of functional properties T cells are: 1.Helper T cells 2.Suppressor T cells 3.Cytotoxic T cells T cells originate in bone marrow ↓ Migrate to thymus, where they proliferate and produce cells that colonize ↓ # These call then Migrate to non-thymic lymphoid tissue where they mature # Here in non-thymic lymphoid tissue they also differentiate further into subpopulation T Helper cell, T cytotoxic cell. T Suppressor cell and T memory cell 52
  53. 53. NK cells In addition to B and T lymphocytes , there is a natural killer or NK, lymphocyte, which lacks the marker molecules characteristic of B and T cells Function of NK cells 1. Main function is to kill virus infected cells 2.It is also believed that NK cells kills malignant cells and thus take part in Immunologic defense against cancer cell In peripheral blood T cell are 70 –80% B cell is 10-15% NK cell are 10-15% 53
  54. 54. Memory B-cell/T-cells Responsible for accelerated response to second exposure to same antigen Suppressor T-cells Decrease immune response of T and B-cells. Deficiency may cause autoimmune disease Cytotoxic T-cells (Killer cells or T8 cells) Destroy transplanted and other foreign cell 54
  55. 55. 55
  56. 56. Helper T cells The Helper T cells form about 65% of total lymphocyte count in peripheral blood. They help in function of immune system Function: They serve as major regulator of all immune function by forming a series of protein mediator called lymphokines. These lymphokines act on cells of immune system as well as on bone marrow cell Important lymphokines secreted by helper T cells 1.Interleukin – 2, 3, 4, 5, 6 2.Granulocyte-monocyte colony stimulating factor 3.Interferon So function of T Helper cell (lymphokines) 1.Stimulation of growth an proliferation of cytotoxic T cells and suppressor T cells 2.Stimulation of B cells growth and differentiation to form plasma cell so ultimately help in formation of antibody 3.Activation of macrophage system: They increase efficiency of phagocytosis done by macrophage so that they can attack and destroy greatly increased number of invading organisms. 4.Feedback, stimulatory effect on Helper cells themselves: Some lymphokines produced by Helper T cells can stimulate Helper T cells directly thus act as an amplifier in further enhancing the helper cell response as well as the entire immune response to an invading antigen. 56
  57. 57. Cytotoxic T cells Cytotoxic T cell is a direct attack cell that is capable of killing microorganisms and at times even some of body’s own cells so they are also called killer cells. The receptor proteins on surface of cytotoxic cell cause theses cells to bind tightly to those organisms or cells that contain their binding specific antigen ↓ After binding, cytotoxic T cells secrete hole-forming proteins called Perforins ↓ These Perforins punch large round holes in membrane of attacked cells ↓ ↓ Then fluid rapidly flow into the cell They also release cytotoxic substance directly into the attacked cell From interstitial space ↓ ↓ Kills the cell Cells become swollen ↓ Cells burst ↓ These effect destroys the attacked cell Functions: They directly attack the microorganisms and kill them They also play important role in destroying cancer cells, heart transplant cell, or other types of cells that are 57 foreign to person’s own body.
  58. 58. 58
  59. 59. Suppressor T cells: •They suppress the function of both cytotoxic and helper T cells •Suppressor function done by suppressor T cells regulates the activities of other cells, keeping them from causing excessive immune reactions that might be severely damaging to the body It is also probable that the suppressor T cells play an important role in limiting the ability of immune system to attack a person’s own body tissue 59
  60. 60. 60
  61. 61. Types of T cells On the basis of surface marker on lymphocyte cell surface they are: 1.CD4 lymphocyte: Helper T cells (Th or T H cells) 2.CD8 lymphocyte: Cytotoxic T cell (Tc) Suppressor T cell (Ts) •CD4 cells form about 65% and CD8 cells form about 35% of T cells in peripheral blood •Normal ratio of CD4 to CD8 cells is greater than 1.5 •In AIDS the ratio is lost as CD4 cells are destroyed by HIV and the ratio of CD4:CD8 is less than 1. •In absence of lymphokines from the helper T cells, the remainder of immune system is almost paralyzed •So in AIDS, it is the helper T cells that are inactivated or destroyed by HIV, which leads body almost totally unprotected against infectious disease. 61