Immune system

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Immune System: Review of Anatomy and Physiology, Natural immunity, Acquired immunity

Immune System: Review of Anatomy and Physiology, Natural immunity, Acquired immunity

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  • 1. ANATOMY AND PHYSIOLOGYIMMUNITYMaria Carmela L. Domocmat, RN, MSNInstructorSchool of NursingNorthern Luzon Adventist College
  • 2.  To protect the body against pathogens, the immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals.  first line of defense – any barrier that blocks invasion at the portal of entry – nonspecific  second line of defense – protective cells and fluids; inflammation and phagocytosis – nonspecific  third line of defense – acquired with exposure to foreign substance; produces protective antibodies and creates memory cells – specific 2
  • 3. Nonspecific and Specific responses of the Immune System
  • 4. Physical or Anatomical Barriers
  • 5. Skin and mucous membranes of respiratory, urogenital, eyes and digestive tracts  outermost layer of skin is composed of epithelial cells compacted, cemented together and impregnated with keratin; few pathogens can penetrate if intact  flushing effect of sweat glands  damaged cells are rapidly replaced  mucous coat impedes attachment and entry of bacteria  blinking and tear production  stomach acid  nasal hair traps larger particles 5
  • 6.  Sebaceous secretions Lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears High lactic acid and electrolyte concentration in sweat Skin’s acidic pH Hydrochloric acid in stomach Digestive juices and bile of intestines Semen contains antimicrobial chemical. Vagina has acidic pH. 6
  • 7. 7
  • 8.  Some hosts are genetically immune to the diseases of other hosts. Some pathogens have great specificity. Some genetic differences exist in susceptibility. 8
  • 9.  The study of the body’s second and third lines of defense is called immunology. Functions of a healthy immune system: 1. Constant surveillance of the body 2. Recognition of foreign material 3. Destruction of entities deemed to be foreign 9
  • 10. 10
  • 11.  Large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue Four major subdivisions of immune system are: 1. Reticuloendothelial system (RES) 2. Extracellular fluid (ECF) 3. Bloodstream 4. Lymphatic system 11
  • 12. 12
  • 13.  Network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs Inhabited by phagocytic cells – mononuclear phagocyte system – macrophages ready to attack and ingest microbes that passed the first line of defense 13
  • 14.  Whole blood consists of plasma and blood cells – red blood cells and white blood cells.  Serum is the liquid portion of the blood after a clot has formed-minus clotting factors. Plasma – 92% water, metabolic proteins, globulins, clotting factors, hormones and all other chemicals and gases to support normal physiological functions 14
  • 15.  Neutrophils- 55-90% - lobed nuclei with lavender granules; phagocytes Eosinophils – 1-3% - orange granules and bilobed nucleus; destroy eucaryotic pathogens Basophils, mast cells – 0.5% - constricted nuclei, dark blue granules; release potent chemical mediators Lymphocytes – 20-35% - large nucleus B (humoral immunity) and T cells (cell-mediated immunity) involved in the specific immune response Monocytes, macrophages – 3-7%- large nucleus; phagocytic 15
  • 16. 1. Provides an auxiliary route for return of extracellular fluid to the circulatory system2. Acts as a drain-off system for the inflammatory response3. Renders surveillance, recognition, and protection against foreign material 18
  • 17. 19
  • 18.  Lymph is a plasma-like liquid carried by lymphatic circulation Formed when blood components move out of blood vessels into extracellular spaces Made up of water, dissolved salts, 2-5% proteins Transports white blood cells, fats, cellular debris and infectious agents 20
  • 19.  Lymphatic capillaries permeate all parts of the body except the CNS. Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles Functions to return lymph to circulation; flow is one-direction-toward the heart- eventually returning to blood stream 21
  • 20.  Classified as primary and secondary Primary lymphoid organs – sites of lymphocytic origin and maturation – thymus and bone marrow Secondary lymphoid organs and tissues – circulatory-based locations such as spleen and lymph nodes; collections of cells distributed throughout body tissues – skin and mucous membranes – SALT, GALT, MALT 22
  • 21. 23
  • 22.  Thymus – high rate of growth and activity until puberty, then begins to shrink; site of T- cell maturation Lymph nodes - small, encapsulated, bean- shaped organs stationed along lymphatic channels and large blood vessels of the thoracic and abdominal cavities Spleen – structurally similar to lymph node; filters circulating blood to remove worn out RBCs and pathogens 24
  • 23. Nonspecific response
  • 24. • Inflammation• Fever• Phagocytosis, NK cells, Interferon• Complement 26
  • 25. Classic signs and symptoms characterized by: Redness – increased circulation and vasodilation in injured tissue in response to chemical mediators and cytokines Warmth – heat given off by the increased blood flow Swelling – increased fluid escaping into the tissue as blood vessels dilate-edema; WBC’s, microbes, debris and fluid collect to form pus; helping prevent spread of infection Pain – stimulation of nerve endings Possible loss of function 27
  • 26.  pain (dolor) heat (calor) redness (rubor) swelling (tumor) loss of function (functio laesa).
  • 27. Insert figure 14.13 Events in inflammation 29
  • 28.  Diapedesis – migration of cells out of blood vessels into the tissues Chemotaxis – migration in response to specific chemicals at the site of injury or infection 30
  • 29. 31
  • 30. Inflammation http://images.google.com/imgres?imgurl=http://www.vacadsci.org/jsr/imuneR.jpg&imgrefurl=http://www.vacadsci.org/jsr/tlist2.htm&h=663&w=1009&sz=460&tbnid=w5XN6XPgUBEJ:&tbnh= 97&tbnw=149&hl=en&start=9&prev=/images%3Fq%3Dimmune%2Bresponse%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DG
  • 31.  Initiated by circulating pyrogens which reset the hypothalamus to increase body temperature; signals muscles to increase heat production and vasoconstriction  exogenous pyrogens – products of infectious agents  endogenous pyrogens – liberated by monocytes, neutrophils, and macrophages during phagcytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF) Benefits of fever:  inhibits multiplication of temperature-sensitive microorganisms  impedes nutrition of bacteria by reducing the available iron  increases metabolism and stimulates immune reactions and protective physiological processes 34
  • 32. 3 main types of phagocytes: 1. Neutrophils – general-purpose; react early to bacteria and other foreign materials, and to damaged tissue 2. Eosinophils – attracted to sites of parasitic infections and antigen-antibody reactions 35
  • 33.  3. Monocytes  called wandering cells until they enter a tissue where they become fixed and turn into macrophages  Macrophages  scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes ▪ destroy old, damaged and dead cells in the body ▪ macrophages are found in the liver, spleen, lungs, lymph nodes, skin and intestine
  • 34. Macrophages in action Copyright © 2006 Dr. Salme Taagepera, All rights reserved.
  • 35. General activities of phagocytes:1. To survey tissue compartments and discover microbes, particulate matter and dead or injured cells2. To ingest and eliminate these materials3. To extract immunogenic information from foreign matter 38
  • 36. 39
  • 37.  Small protein produced by certain white blood cells and tissue cells  alpha interferon- lymphocytes and macrophages  beta interferon – fibroblasts and epithelial cells  gamma interferon – T cells Produced in response to viruses, RNA, immune products, and various antigens Bind to cell surfaces and induce expression of antiviral proteins Inhibit expression of cancer genes 40
  • 38. 41
  • 39.  Consists of 26 blood proteins that work in concert to destroy bacteria and viruses there are only a handful of proteins in the complement system, and they are floating freely in your blood. manufactured in the liver. activated by and work with (complement) the antibodies, hence the name. they cause lysing (bursting) of cells and signal to phagocytes that a cell needs to be removed 42
  • 40. 43
  • 41. 45
  • 42. Specific defense
  • 43. Third line of defense – acquired Production of specific antibodies by dual system of B and T lymphocytes in response to an encounter with a foreign molecule, called an antigen Two features that characterize specific immunity:  specificity – antibodies produced, function only against the antigen that they were produced in response to  memory – lymphocytes are programmed to “recall” their first encounter with an antigen and respond rapidly to subsequent encounters 47
  • 44. Nonspecific and Specific responses of the Immune System T cells B cellshttp://images.google.com/imgres?imgurl=http://www.vacadsci.org/jsr/imuneR.jpg&imgrefurl=http://www.vacadsci.org/jsr/tlist2.htm&h=663&w=1009&sz=460&tbnid=w5XN6XPgUBEJ:&tbnh=97&tbnw=149&hl=en&start=9&prev=/images%3Fq%3Dimmune%2Bresponse%26svnum%3D10%26hl%3Den%26lr%3D%26sa%3DG
  • 45.  Made up of two cellular systems (lymphocytes) 1. humoral or circulating antiBody system - B cells 2. cell mediaTed immunity - T cells
  • 46. B cells make antibodies T cells mount direct attack on foreign/infected cellhttp://www.people.virginia.edu/~rjh9u/gif/irsum.gif
  • 47.  Aka: humoral immunity Involves antigen-antibody interactions to neutralize, eliminate, or destroy foreign proteins. Purpose:  Main function of B-cells: to become sensitized to a specific protein (antigens) and to produce antibodies directed specifically against that protein
  • 48.  B-cells Macrophages T-lymphocytes All these work with B-cells to start and complete antigen-antibody interactions Therefore: for optimal AMI, the entire immune system must function adequately
  • 49.  Start in bone marrow Released in the blood Then migrate into secondary lymphoid tissues where maturation is completed  Spleen  Parts of lymph nodes  Tonsils  Peyer’s patches of GIT
  • 50. Two main functions:1) Return tissue fluid to circulation2) Fights infection - both specific and non-specific resistance.Lymph- fluid carried by lymphatic vessels
  • 51. - fluid enters lymphatic system by diffusing into dead-end lymphatic capillaries- infection-fighting activities occur in the lymph nodes
  • 52.  Lymphocytes (25-35% of WBCs)  T-cells: 70% of lymphocytes ▪ Cell mediated immunity  B-cells: 20-25% of lymphocytes ▪ Humoral immunity
  • 53.  Body learns to make enough of any specific antibody to provide long-lasting immunity against specific organisms or toxins 7 Steps needed to make a specific antibody against an antigen
  • 54. 1. Exposure (invasion)2. Antigen recognition3. Lymphocyte sensitization4. Antibody production and release5. Antigen-antibody binding6. Antibody-binding actions7. Sustained immunity: Memory
  • 55.  B cell activation occurs in response to exposure to a specific foreign antigen Invasion must occur in large #s that some may evade detection by other lines of defense
  • 56.  Helper T cells secrete a chemical called interleukins  Interleukin 6 – induces maturation of B cells and proliferation of T cells
  • 57. 1. Exposure (invasion)2. Antigen recognition3. Lymphocyte sensitization4. Antibody production and release5. Antigen-antibody binding6. Antibody-binding actions7. Sustained immunity: Memory
  • 58.  “virgin” or “naïve” unsensitized B-cells must recognize the antigen as non-self Need help of macrophages and helper/inducer T-cells
  • 59. 1. Exposure (invasion)2. Antigen recognition3. Lymphocyte sensitization4. Antibody production and release5. Antigen-antibody binding6. Antibody-binding actions7. Sustained immunity: Memory
  • 60.  Virgin B-cell can be sensitized only once Therefore each B-cell can be sensitized to only one type of antigen Immediately after it is sensitized –it divides and form two types of B-lymphocytes
  • 61.  B cells divide: 1. Plasma cells = synthesize and secrete large numbers of antibodies with the same antigen target ▪ Can make as much as as 300 molecules of antibody /sec 2. Memory B cells = remain in reserve for future attacks by the same antigen
  • 62.  When an antibody binds to the outer coat of a virus particle or the cell wall of a bacterium it can stop their movement through cell walls. Or a large number of antibodies can bind to an invader and signal to the complement system that the invader needs to be removed.
  • 63. 1. Exposure (invasion)2. Antigen recognition3. Lymphocyte sensitization4. Antibody production and release5. Antigen-antibody binding6. Antibody-binding actions7. Sustained immunity: Memory
  • 64.  Antibody molecules are released in blood and other body fluids as free antibody Each remain in the blood for 3 to 30 days Note: circulating antibodies can be transferred from one person to another to provide the receiving person with immediate immunity of short duration
  • 65. 1. Exposure (invasion)2. Antigen recognition3. Lymphocyte sensitization4. Antibody production and release5. Antigen-antibody binding6. Antibody-binding actions7. Sustained immunity: Memory
  • 66.  When a pathogen enters the body it stimulates specific lymphocytes to make antibodies These antibodies are proteins of a very specific shape and they will attach to the specific antigens on the surface of the pathogen Binding of the antibody to the pathogen targets the pathogen for destruction by macrophages
  • 67. http://www.biology.arizona.edu/immunology/ tutorials/antibody/graphics/antibody.gif http://www.blc.arizona.edu/courses/181summer/graphics/gr aphics%20lect16/Life7e-Fig-18-10- 2%20structure%20of%20antibody%20p2.jpgAntibodies are protein complexes made of 2 heavy chain and 2 light chain peptides •Constant region (shown dark blue and dark red) = same in all antibodies •Variable region (shown light blue and light red)= unique in each antibody
  • 68. http://www.accessexcellence.org/RC/VL/GG/images/Fig_5.03b.jpg
  • 69. Type Number of Site of action Functions ag binding sitesIgG 2 •Blood •Increase •Tissue fluid macrophage activity •CAN CROSS •Antitoxins PLACENTA •AgglutinationIgM 10 •Blood Agglutination •Tissue fluidIgA 2 or 4 •Secretions (saliva, •Stop bacteria tears, small intestine, adhering to host vaginal, prostate, cells nasal, breast milk) •Prevents bacteria forming colonies on mucous membranesIgE 2 Tissues •Activate mast cells  HISTAMINE •Worm response
  • 70. IgG (75% of Total Immunoglobulin)• Appears in serum and tissues (interstitial fluid)• Assumes a major role in bloodborne and tissue infections• Activates the complement system• Enhances phagocytosis• Crosses the placentaIgA (15% of Total Immunoglobulin)• Appears in body fluids (blood, saliva, tears, breast milk, andpulmonary, gastrointestinal, prostatic, and vaginal secretions)• Protects against respiratory, gastrointestinal, and genitourinaryinfections• Prevents absorption of antigens from food• Passes to neonate in breast milk for protection
  • 71. IgM (10% of Total Immunoglobulin)• Appears mostly in intravascular serum• Appears as the first immunoglobulin produced in responseto bacterial and viral infections• Activates the complement systemIgD (0.2% of Total Immunoglobulin)• Appears in small amounts in serum• Possibly influences B-lymphocyte differentiation, but roleis unclearIgE (0.004% of Total Immunoglobulin)• Appears in serum• Takes part in allergic and some hypersensitivity reactions• Combats parasitic infections
  • 72.  IgD IgG IgA IgM IgE
  • 73.  Actual binding of antibody to antigen is usually not lethal to the antigen Instead it starts other actions that neutralize, eliminate, or destroy antigen
  • 74. 1. Exposure (invasion)2. Antigen recognition3. Lymphocyte sensitization4. Antibody production and release5. Antigen-antibody binding6. Antibody-binding actions7. Sustained immunity: Memory
  • 75.  Agglutination Lysis Complement fixation Precipitation Inactivation-neutralization
  • 76. 1. Exposure (invasion)2. Antigen recognition3. Lymphocyte sensitization4. Antibody production and release5. Antigen-antibody binding6. Antibody-binding actions7. Sustained immunity: Memory
  • 77. The first exposure to a pathogen gives only a slow and small immune responseLevels of antibodies in the blood build up slowly when you are first exposed toa particular pathogen. •It takes over 5 days for the antibodies to reach a level that will fight off the infection. •During this time, you will feel the symptoms of the infection and damage will be caused to your body tissues. •In serious diseases, this can be fatal.
  • 78. •The first exposure to a pathogen gives only a slow and small immune response.•Repeated exposure to the same pathogen gives a much stronger and quicker memory response.
  • 79.  When your body is first infected with a pathogen, the main task of the immune system is to combat the infection. However, it also produces lymphocytes that remain in your body for many years and remember the pathogen in case it returns. Immune memory  If you get infected a second time, your immune system is already prepared for the pathogen and can quickly make enough antibodies to kill the infection before any symptoms are felt.  Vaccination takes advantage of this feature of the immune system.
  • 80. Once a T cell is activated by the presentation of thecombined MHC/Ag, it will clone (by mitosis) &differentiate into:  cytotoxic T cells  helper T cells  memory T cells  suppressor T cells
  • 81. T-cell receptor structure similar to antibody
  • 82. 1. Cytotoxic T cells  attack foreign cells  seek out the specific pathogen/infected cell that contains the targeted Ag & destroys it by secreting various chemicals Killer cell Target cell
  • 83. 2. Memory T-cells  remain in reserve  When body sees the same antigen again, these cells produce a rapid, specific response  these cells can immediately differentiate into cytotoxic & helper T cells, causing a swift secondary response to the invasion
  • 84. 3. Suppressor T-cells  depress the response of T and B cells  are slow to activate but effectively “put on the brakes” or end the immune response  activated more slowly than the other T cells  inhibit the response of the immune cells to prevent potential “autoimmune” response
  • 85. 4. Helper T cells  orchestrate immune response  necessary for coordination of both specific & non-specific defenses, as well as for stimulating both cell-mediated & antibody-mediated immunity.  In cell-mediated immunity they release chemicals (cytokines) that strengthen the activity of cytotoxic T cells.  In antibody-mediated immunity they release cytokines that stimulate activated B cell division & differentiation into plasma cells
  • 86. Helper T cells release a variety of compounds called cytokines cytokines 1. coordinate both specific and non-specific defenses 2. stimulate production of more t cells 3. stimulate production of antibodies by B cells
  • 87.  T lymphocytes (T cells) – they mature in the thymus and are responsible for cell-mediated immunity a) Helper T cells – direct the rest of the immune system by releasing cytokines b) Cytotoxic T cells – release chemicals that break open and kill invading organisms c) Memory T cells – remain afterwards to help the immune system respond more quickly if the same organism is encountered again d) Suppressor T cells – suppress the immune response so that it does not get out of control and destroy normal cells once the immune response is no longer needed
  • 88. Activated T cells clone & differentiate into: stimulate Direct physical &  Cytotoxic T cells  Helper T cells B cell activation chemical attack  Memory T cells  Suppressor T cells Prevent autoimmune Antigens Remain in response reserve CELL MEDIATED IMMUNITY ANTIGENSbacteria SPECIFIC APC’s phagocytize Ag & activate Tbacteria DEFENSES cells viruses (Immune response)viruses
  • 89.  Immunization raises host resistance, defenses, and immunity
  • 90. Immunity is the resistance to injuries/disease caused by specific pathogensTypes of immunity:http://faculty.ircc.edu/faculty/tfischer/images/types%20of%20immunity.jpg
  • 91. Overview of Immunity
  • 92.  present at birth independent of previous exposure to Ag genetically determined species dependent
  • 93.  arises throughout life by active or passive means
  • 94. Active immunity Lymphocytes are activated by antigens on the surface of pathogens Takes time for enough B and T cells to be produced to mount an effective response.
  • 95.  Natural active immunity  naturally acquired active immunity  acquired due to infection  natural exposure results in immune response & development of long term immunity Artificial active immunity  Vaccination  induced (artificial) active immunity – deliberate “artificial” exposure to Ag (i.e. vaccine/immunization)
  • 96.  Passive immunity – development of immunity due to transfer of “pre-made” antibodies  naturally acquired passive immunity – Ab’s transferred from mom  baby across placenta or in breast-milk  induced (artificial) passive immunity – administration of Ab’s to fight disease after exposure to pathogen
  • 97. Passive immunity B and T cells are not activated and plasma cells have not produced antibodies. The antigen doesn’t have to be encountered for the body to make the antibodies. Antibodies appear immediately in blood but protection is only temporary.
  • 98.  Used when a very rapid immune response is needed  e.g. after infection with tetanus. Human antibodies are injected. In the case of tetanus these are antitoxin antibodies.  Antibodies come from blood donors who have recently had the tetanus vaccination. Only provides short term protection as abs destroyed by phagocytes in spleen and liver.
  • 99.  A mother’s antibodies pass across the placenta to the foetus and remain for several months. Colostrum (the first breast milk) contains lots of IgA which remain on surface of the baby’s gut wall and pass into blood
  • 100. A preparation containing antigenicmaterial: Whole live microorganism Dead microorganism Attenuated (harmless) microorganism Toxoid (harmless form of toxin) Preparation of harmless ags
  • 101.  Injection into vein or muscle Oral
  • 102. 117
  • 103. Why aren’t they always effective? Natural infections persist within the body for a long time so the immune system has time to develop an effective response, vaccinations from dead m-os do not do this. Less effective vaccines need booster injections to stimulate secondary responses Some people don’t respond well/at all to vaccinations Defective immune systems Malnutrition particularly protein
  • 104.  Antigenic variation caused by mutation Antigenic drift – small changes (still recognised by memory cells) Antigenic shift – large changes (no longer recognised) No vaccines against protoctists (malaria and sleeping sickness) Many stages to Plamodium life cycle with many antigens so vaccinations would have to be effective against all stages (or be effective just against infective stage but given in very small time period).
  • 105.  Sleeping sickness – Trypanosoma has a thousand different ags and changes them every 4-5 days Antigenic concealment parasites live inside body cells Plasmodium – liver and blood cells Parasitic worms – cover themselves in host proteins HIV – live inside T-helper cells
  • 106. Review of the immune response Non- specific response Specific response NOTE: key role played by Helper T cells!!!http://www.vacadsci.org/jsr/imuneR.jpg
  • 107.  Recommended Adult  Recommended Immunization pediatric immunization Schedule schedule • Contraindications
  • 108.  Who should not get the vaccine or should wait?  1. people who have had a life threatening allergic reaction to gelatin, neomycin, or a previous dose of the vaccine  2. people who are moderately or severely ill should wait  3. pregnant women should wait until after birth, women should not get pregnant for 1 month after getting the vaccine  4. people with HIV/AIDS, immune system problems, taking any drugs that affect the immune system, have cancer, or taking chemotherapy or x-ray therapy for cancer should check with their doctor before receiving the vaccine  5. people who recently had a blood transfusion should check with their doctor
  • 109.  Live-microbial vaccines should not be given simultaneously with blood, plasma, or immune globulin, which can interfere with development of desired antibodies; ideally, such vaccines should be given 2 wk before or 6 to 12 wk after the immune globulins. Immunocompromised patients should not receive live- virus vaccines, which could provoke severe or fatal infections. In patients receiving short-term (ie, < 14 days) immunosuppressive therapy (eg, corticosteroids, antimetabolites, alkylating compounds, radiation), live- virus vaccines should be withheld until after treatment.
  • 110.  Immunity may or may not be life-long with vaccines. To help keep the antibody levels high enough to keep you protected you sometimes need to have “booster shots”.
  • 111.  Nutrition and the immune system  Malnutrition impairs immune function  Fish oil: anti inflam Stress and the immune system  Chronic stress has detrimental effects on immune system Ageing and the immune system Vaccination