Mechanisms Of Defense Immune System.ppt


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Mechanisms Of Defense Immune System.ppt

  1. 1. By Dr. Shamanthakamani Narendran Immune System
  2. 2. <ul><li>An immune system is a collection of mechanisms within an organism that protects against disease by identifying and killing pathogens and tumor cells. </li></ul><ul><li>It detects a wide variety of agents, from viruses to parasitic worms. </li></ul><ul><li>Detection is complicated as pathogens adapt and evolve new ways to successfully infect the host organism. </li></ul><ul><li>The adaptation process creates immunological memories </li></ul>
  3. 3. <ul><li>Acquired immune deficiency syndrome (AIDS) that is caused by the retrovirus HIV. </li></ul><ul><li>Autoimmune diseases result from a hyperactive immune system attacking normal tissues – Rheumatoid arthritis, diabetes mellitus type 1 and lupus erythematosus. </li></ul><ul><li>Antigens (non-self molecules) elicit an immune response </li></ul>
  4. 4. LAYERED DEFENSE Components of the immune system Found only in jawed vertebrates Found in nearly all forms of life Exposure leads to immunological memory No immunological memory Cell-mediated and humoral components Cell-mediated and humoral components Lag time between exposure and maximal response Exposure leads to immediate maximal response Pathogen and antigen specific response Response is non-specific Adaptive immune system Innate immune system
  5. 5. COMPLEMENT SYSTEM <ul><li>Biochemical cascade attacks the surfaces of foreign cells. </li></ul><ul><li>Contains over 20 different proteins and is named for its ability to “complement” the killing of pathogens by antibodies. </li></ul><ul><li>Complement is the major humoral component </li></ul>
  6. 6. LYMPHOCYTES <ul><li>Lymphocytes – Cells of the adaptive immune system are special types of leukocytes. </li></ul><ul><li>B cells and T cells – major types of lymphocytes derived from hematopoietic stem cells in the bone marrow. </li></ul><ul><li>B cells involved in the humoral immune response. </li></ul><ul><li>T cells involved in cell-mediated immune response. </li></ul><ul><li>Two major subtypes of T cells: the killer T cell and the helper T cell. </li></ul>
  7. 7. <ul><li>Killer T cells only recognize antigens coupled to Class I MHC molecules. </li></ul><ul><li>Helper T cells only recognize antigens coupled to Class II MHC molecules. </li></ul><ul><li>B cell antigen-specific receptor is an antibody molecule on the B cell surface, recognizes whole pathogens without any need for antigen processing. </li></ul><ul><li>Each lineage of B cell expresses a different antibody, so the complete set of B cell antigen receptors represent all the antibodies that the body can manufacture. </li></ul>
  8. 8. KILLER T CELLS <ul><li>Directly attack other cells carrying foreign or abnormal antigens on their surfaces. </li></ul><ul><li>Sub-group of T cells that kill cells infected with viruses and other pathogens </li></ul><ul><li>As with B cells, each type of T cell recognises a different antigen. </li></ul>
  9. 9. HELPER T CELLS <ul><li>Regulate both the innate and adaptive immune responses and help determine which types of immune responses the body will make to a particular pathogen. </li></ul><ul><li>These cells have no cytotoxic activity and do not kill infected cells or clear pathogens directly. </li></ul><ul><li>Control the immune response by directing other cells to perform these tasks. </li></ul>
  10. 10. B LYMPHOCYTES & ANTIBODIES <ul><li>Identifies pathogens when antibodies on its surface bind to a specific foreign antigen. </li></ul>HYPERSENSITIVITY <ul><li>Is an immune response that damages the body's own tissues. </li></ul>
  11. 11. IMMUNODEFICIENCIES <ul><li>Occur when one or more of the components of the immune system are inactive. </li></ul><ul><li>Obesity, alcoholism, and drug use are common causes of poor immune function. </li></ul><ul><li>However, malnutrition is the most common cause of immunodeficiency in developing countries. </li></ul>
  12. 12. HISTORY OF IMMUNOLOGY <ul><li>Paul Ehrlich: Immunology is a science that examines the structure and function of the immune system. </li></ul><ul><li>It originates from medicine and early studies on the causes of immunity to disease. </li></ul><ul><li>The earliest known mention of immunity was during the plague of Athens in 430 BC. </li></ul><ul><li>Thucydides noted that people who had recovered from a previous bout of the disease could nurse the sick without contracting the illness a second time. </li></ul>
  13. 13. <ul><li>This observation of acquired immunity was later exploited by Louis Pasteur in his development of vaccination and his proposed germ theory of disease. </li></ul><ul><li>Pasteur's theory was in direct opposition to contemporary theories of disease, such as the miasma theory. </li></ul><ul><li>It was not until Robert Koch's 1891 proofs, for which he was awarded a Nobel Prize in 1905, that microorganisms were confirmed as the cause of infectious disease. </li></ul>
  14. 14. <ul><li>Viruses were confirmed as human pathogens in 1901, with the discovery of the yellow fever virus by Walter Reed. </li></ul><ul><li>Immunology made a great advance towards the end of the 19th century, through rapid developments, in the study of humoral immunity and cellular immunity. </li></ul>
  15. 15. <ul><li>Particularly important was the work of Paul Ehrlich, who proposed the side-chain theory to explain the specificity of the antigen-antibody reaction; his contributions to the understanding of humoral immunity were recognized by the award of a Nobel Prize in 1908, which was jointly awarded to the founder of cellular immunology, Elie Metchnikoff. </li></ul>
  16. 16. THE MECHANISMS OF DEFENSE <ul><li>All living beings have evolved methods by which they can protect themselves against microorganisms in their environment. </li></ul><ul><li>Some operate on the body surface and the mucous membranes, while others come into play when the deeper tissues are in danger. </li></ul>
  17. 17. <ul><li>Surface defenses </li></ul><ul><li>Skin – so long as it is intact – acts as a mechanical barrier, preventing organisms reaching the tissue beneath. </li></ul><ul><li>Mucous membranes – like skin, mucous membranes also act as a mechanical barrier, protecting the deeper tissues. Some of the secretions (saliva, nasal mucus, and tears) contain enzymes (lysozyme) which can rapidly kill an invading organism. </li></ul>
  18. 18. <ul><li>Inner defenses </li></ul><ul><li>In case organisms do pass through the surface defenses, and reach the tissues underneath, there are still other powerful defense mechanisms. </li></ul><ul><li>Immunity </li></ul><ul><li>Defined as the ability of the body to recognize, destroy, and eliminate material foreign to itself . </li></ul><ul><li>This response to an invader occurs as two phases, a primary and the secondary response. </li></ul><ul><li>The primary response is the way the body’s defense (immune) system behaves when it encounters an intruder for the first time . </li></ul>
  19. 19. <ul><li>After a gap of about 3-10 days, specific cells are activated. </li></ul><ul><li>Depending on the type of intruder the cells either produce substances to destroy it, or rush to the defense themselves. </li></ul><ul><li>If the alien organism is present in small amounts, the response does not last more than a week. </li></ul><ul><li>Large amounts of the intruder result in production of ‘defense weapons’ called ‘antibodies,’ which remain in the bloodstream for several weeks. </li></ul>
  20. 20. <ul><li>It is now known that both the lymphocytes which go to the defense themselves (T lymphocytes) and those which produce antibodies (B lymphocytes) are able to ‘remember’ an invader, sometimes for a number of years after the first contact. </li></ul><ul><li>These memory cells thus recognize the invader when it enters the body the next time. </li></ul><ul><li>This secondary immune response takes place more rapidly than the primary response. </li></ul><ul><li>The system is already prepared, thus producing a more extensive response, as well. </li></ul>
  21. 21. <ul><li>This fact is made use of in immunization programmes, in which booster doses of weakened forms of the organism are given at specified intervals. </li></ul><ul><li>In this way, the body is ‘ready’ to deal with large amounts of the organism if they enter on their own. </li></ul>
  22. 22. Host Defenses Complement system Leuco/ Lymph Macro phage
  23. 23. Allergy Autoimmunity Rejection of organ transplant An immune cell undergoing an allergic reaction Protects against infectious agents
  24. 24. <ul><li>The two types of lymphocytes differ in their defense strategy. </li></ul><ul><li>There are the T lymphocytes which undergo further ‘processing’ in the thymus . </li></ul><ul><li>Some T lymphocytes are called ‘effecter’ cells, they directly kill the intruding organism. </li></ul><ul><li>Others are called ‘controller’ cells, as they regulate the activities of the other lymphocytes which are involved in defense responses. </li></ul><ul><li>Examples of ‘effecter’ cells include – Cytotoxic T cells , and Natural killer cells . </li></ul>
  25. 25. <ul><li>The ways in which these cells destroy an alien organism are many – sometimes they may release substances which break up the cell membrane of the organism, leading to death. </li></ul><ul><li>Alternatively, other substances may be released which activate other, migratory cells – macrophages . </li></ul><ul><li>These cells engulf and destroy the organism by phagocytosis . </li></ul><ul><li>The effector T cells defend the body against viruses, they also attack abnormal or cancerous cells. </li></ul>
  26. 26. <ul><li>An example of an unwanted response is fighting the tissues of a transplanted organ. </li></ul><ul><li>This leads to rejection of the transplant. </li></ul><ul><li>Effecter T cells may inactivate and remove an invader the very first time they are exposed to it. </li></ul><ul><li>There are also ‘memory’ cells, which can ‘remember’ an invader and ‘recognize’ it, when it next enters the body. </li></ul><ul><li>This ‘memory’ may last for some years. </li></ul><ul><li>The second response is always more extensive and occurs more quickly than the first response. </li></ul>
  27. 27. <ul><li>Controller T cells include – Helper T cells and Suppressor T cells. </li></ul><ul><li>These controller cells influence the activity of other T cells. </li></ul><ul><li>These controller cells influence the activity of other T cells, as well as the other category of lymphocytes, called B lymphocytes. </li></ul><ul><li>These controls are very necessary. </li></ul><ul><li>It is essential that unwanted organisms should be destroyed and removed without any damage to the body. </li></ul>
  28. 28. Themectomy TT given 1. Thymosin fraction V (Calf thymus) 2. Synthetic polypeptides Thymus
  29. 29. Ontogeny of Immune System Fetus T cells Functions at 7- 1/2 wks Thymus functions at 12 wks B cells Functions at 13 wks IgM First to develop. Rises in intrauterine infection Reaches adult levels by 1 yr IgG Develops at 4 years IgA At adolescence
  30. 30. T cell subpopulation Helper cells (IgA & IgG) Suppressor (Homeostasis) Killer cells (Kills invading organisms) B cell subpopulation IgM, IgG, IgA, IgD, & IgE Hay fever, Asthma, Autoimmune disorder (Hemolytic anemia)
  31. 31. <ul><li>In case these controls do not function properly, serious problems arise. </li></ul><ul><li>One extreme may be immune incompetence , whereas the other extreme is autoimmunity . </li></ul><ul><li>In autoimmune disorders the immune system has started to fight against the body’s tissues. </li></ul>
  32. 32. Eosinophil Neutrophil
  33. 33. <ul><li>The B lymphocytes are the second type of lymphocytes. </li></ul><ul><li>They are also produced in the bone marrow. </li></ul><ul><li>Unlike the T lymphocytes, their subsequent processing occurs in lymphoid tissue other than the thymus. </li></ul><ul><li>In birds this occurs in a structure called the Bursa of Fabricus. </li></ul><ul><li>In man the exact site of processing is not certain – it may occur in lymphoid tissue in the intestine or in the bone marrow. </li></ul><ul><li>When these cells come in contact with an intruder, they get activated and divide to form cells called plasma cells . </li></ul>
  34. 34. Lymphoid Precursor Cells Liver Bone marrow
  35. 35. Differentiation of lymphoid stem cells T cells (associated with thymus) B cells (associated with bone marrow)
  36. 36. Peripheral Lymphoid organs Spleen GI tract tissue
  37. 37. <ul><li>These cells secrete proteins called antibodies or immunoglobulins . </li></ul><ul><li>This defense strategy is used to combat many infections. </li></ul><ul><li>Some B lymphocytes survive for many years and ‘remember’ the intruder, to recognize it later on. </li></ul><ul><li>The antibodies are specific. </li></ul><ul><li>That is they reach with the same organism which provoked their production. </li></ul><ul><li>As a result of this specificity, the protection offered is limited. </li></ul>
  38. 38. <ul><li>Very often, both T and B lymphocyte immune responses are seen . </li></ul><ul><li>This helper T cells are necessary for the B lymphocytes to be active. </li></ul><ul><li>Interferon is another important factor in the body’s defense mechanisms. </li></ul><ul><li>Interferons are small glycoproteins (protein molecules in combination with carbohydrate molecules). </li></ul><ul><li>Various agents such as viruses, bacteria, and certain single cellular organisms trigger the interferon response. </li></ul><ul><li>This mechanism comes into operation before the appearance of specific antibodies. </li></ul>
  39. 39. <ul><li>Circulating substances </li></ul><ul><li>In addition to lymphocytes and interferon, there are circulating substances in the tissue fluids – properdin and complement . </li></ul><ul><li>These substances cause the wall of the microorganism to break up, which eventually leads to death of the organism. </li></ul>
  40. 40. <ul><li>Allergic responses </li></ul><ul><li>Like autoimmune disorders, are conditions in which the property of the immune system as a ‘defense system’ is modified. </li></ul><ul><li>These defenses are activated by substances which are not actually harmful. </li></ul><ul><li>These allergy producing substances are all around us. </li></ul><ul><li>Harmless substances in the air we breathe – dust, pollen; in our food and drink, in the clothes we wear, and the things we touch. </li></ul>
  41. 41. THE ALLERGIC RESPONSE allergen IgE release of histamine ALLERGIC REACTION Mast cell
  42. 42. PSYCHONEUROIMMUNOLOGY (BRAIN + IMMUNE SYSTEM) <ul><li>In recent years there has been a growing awareness that the way we feel can influence out body’s immune mechanisms. </li></ul><ul><li>This suggests that there are connections between the nervous and the immune system. </li></ul><ul><li>This was apparent from an observation that just before an exam a larger number of school children were likely to suffer from (genuine!) sore throats compared to the rest of the year. </li></ul>
  43. 43. <ul><li>Another observation was that just a period of extreme grief (e.g. the death of a close relative) there was a greater incidence of developing one of the most severe diseases – cancer. </li></ul><ul><li>This can also be linked with the immune system – an efficient immune system should be able to detect a cancer cell and eliminate it before it has the chance to spread. </li></ul><ul><li>These observations lead to a great deal of interest and speculations. </li></ul>
  44. 44. PSYCHONEUROIMMUNOLOGY (BRAIN + IMMUNE SYSTEM) killer cells sudden stress increased killer cells reduced killer cells repeated stress
  45. 45. Diseases due to Immunologic deficiency Primary Secondary
  46. 46. AIDS Acquired immunodeficiency syndrome Pathophysiology Clinical diagnosis Treatment Prevention HIV, the virus that causes AIDS, is shown budding out of a human immune cell.
  47. 47. HIV Treating HIV infected woman during pregnancy Natural history of HIV infection Transmission Signs and symptoms of AIDS in new born How does pediatric AIDS differ from adult AIDS Management & Specific retroviral therapies AZT (3’ Azido, 2’ 3’ deoxythymdine) DDI (2’ 3’ Dideoxyinosine) Immunotherapy (Hyposensitization)