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Chapter 24: The Immune System

Chapter 24: The Immune System. NEW AIM: How does the body defend itself against MO’s?. Nonspecific (innate). vs. Specific (adaptive/acquired) Immunity. Chapter 24: The Immune System. NEW AIM: How does the body defend itself against MO’s?.

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Chapter 24: The Immune System

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  1. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? Nonspecific (innate) vs. Specific (adaptive/acquired) Immunity

  2. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific (innate) vs. Specific (adaptive) Immunity A. Nonspecific immunity i. 1st line of defense ii. Does not distinguish one pathogen from another iii. Components 1. skin - dead, stratified epithelium blocks MO’s - acids secreted from skin glands - Lysozyme * Enzyme that breaks down bacterial cell wall * Found in sweat, saliva, tears

  3. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific (innate) vs. Specific (adaptive) Immunity A. Nonspecific immunity i. 1st line of defense ii. Does not distinguish one pathogen from another iii. Components 1. skin - desquamation of skin * Your skin is stratified epithelium (many layers). Only the bottom layers are alive and doing mitosis. The top (outer) layers are constantly falling off along with anything attached to it like bacteria or viruses.

  4. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity i. 1st line of defense ii. Does not distinguish one pathogen from another iii. Components 2. Beating cilia/mucus of respiratory system 3. Stomach acid 4. Hairs of nostrils

  5. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity i. 1st line of defense ii. Does not distinguish one pathogen from another iii. Components 5. Nonspecific defense cells - cells that confront microbes that get past skin, digestive and resp. surfaces a. Monocytes (become macrophages = big eaters) and neutrophils • Collectively called phagocytes • (cyte = cell; phago = phagocytosis) – cells that phagocytose b. Natural killer cells (do not confuse with killer T-cells) * Attack viral infected body cells

  6. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 6. Proteins - interferons The infected cell is done for and will become a viral producing factory. However, it will secrete a protein called interferon, which will warn neighboring cells that a virus is in town. Fig. 24.1

  7. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 6. Proteins - complement proteins Complement proteins are always in your blood in an inactive form. They are activated by antibodies bound to a foreign cell (cancer cell, bacterium, etc...). When activated, they make a hole in the membrane causing the cell to lyse – nutrients, organelles, etc... diffuse out. Fig. 24.11

  8. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 7. Inflammatory response (local) - triggered by ANY tissue damage Fig. 24.2

  9. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components histamine 7. Inflammatory response (local) Results in: 1. Rubor (redness) - due to vasodilation 2. Edema (swelling) – enhanced leakiness of blood vessesl 3. calor (warmth) – both due to enhances leakiness of blood vessels Fig. 24.2

  10. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 7. Inflammatory response (local) - triggered by ANY tissue damage - Rubor, edema, calor - Coagulation cascade seals off area so bacteria can’t get into the blood… - Pus The dead warriors (white blood cells and bacteria) after the battle… A pimple is a bacterial infection of a skin pore, pus is what is left after the battle.

  11. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 8. Inflammatory response (systemic – entire system) a. MO’s in blood and/or b. toxins from bacteria in blood (recall exo- and endotoxins – ch27) c. Body’s Response - increase WBC count - increase body temp. = fever (this is a normal response) - triggered by toxins or chemicals released by WBC’s - Higher temps stimulates phagocytes, gives your WBC’s and advantage while at the same time inhibits bacterial growth

  12. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 8. Inflammatory response (systemic – entire system) d. Septic shock (when the systemic response goes bad) Septic shock is caused by cytokines (cell signaling molecules secreted by one cell to talk to another – like hormones, but not secreted into blood) and by the toxins produced by some bacteria. These substances cause the blood vessels to widen (vasodilate), which results in a drop in blood pressure. Consequently, blood flow to vital organs—particularly the kidneys and brain—is reduced. This reduction in blood flow occurs despite the body's attempts to compensate by increasing both the heart rate and the volume of blood pumped. Eventually, the toxins and the increased work of pumping weaken the heart, resulting in a decreased output of blood and even poorer blood flow to vital organs. The walls of the blood vessels may leak, allowing fluid to escape from the bloodstream into tissues and causing swelling. Leakage and swelling can develop in the lungs, causing difficulty breathing (respiratory distress).

  13. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 9. Lymphatic system a. Involved in both nonspecific and specific immunity b. Lymph vessels, lymph nodes, tonsils and adenoids, appendix, spleen, bone marrow, thymus c. Lymph - fluid carried by vessels - similar to IF, less O2 and nutrients

  14. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 9. Lymphatic system d. functions i. return IF to circ. system - vessels resemble veins - valves, skeletal muscles propel lymph - vessels are dead-ended ii. fight infection - in lymph nodes and other lymph organs - lymph nodes - packed with macrophages and lymphocytes - lymphocytes involved in specific immunity

  15. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity 9. Lymphatic system 9. Lymphatic system Fig. 24.3

  16. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity A. Nonspecific immunity iii. Components 9. Lymphatic system Fig. 24.3

  17. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity Fig. 24.3 A. Nonspecific immunity iii. Components 9. Lymphatic system -Spleen - destruction of old RBC’s - rich in B and T cells for fighting infection - “large lymph node” for blood - filters pathogens out of blood

  18. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity Fig. 24.3 A. Nonspecific immunity iii. Components 9. Lymphatic system - Appendix - Thought to be vestigial - Possibly a shrunken cecum since we no longer rely on hard to digest plant material - New studies suggest it harbors and protects bacteria helpful to the colon. - If an infection occurs in the colon, the bacteria living there will be destroyed. Those in the appendix can repopulate the colon. - Contain WBC’s and may be important in fighting infection

  19. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity Fig. 24.3 A. Nonspecific immunity iii. Components 9. Lymphatic system - Appendcitis - Infection of the appendix - Caused by an obstruction of the opening to the appendix - Fills with mucus and swells - Blood flow disrupted, cells begin to die (necrosis = dying cells), walls begin to breakdown and if it breaks, bacteria will enter your body cavity. Appendectomy – removal of the appendix Infected appendix

  20. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity Fig. 24.3 A. Nonspecific immunity iii. Components 9. Lymphatic system - Tonsils and Adenoids - Trap bacteria/viruses as they enter through nose and mouth

  21. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) i. More effective than nonspecific ii. Used when nonspec. fails or in combination iii. antigen a. Foreign molecule that elicits immune response b. Surface molecule of virus, bacteria, mold spores, cancer cells, pollen, transplant, etc… Why must it be a surface molecule? The same reason that when a person is wanted by the FBI they show a picture of their face and not of their heart. The surface of the cells is the part that other cells and antibodies will “see”.

  22. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) iv. Lymphocytes (B and T cells) a. Spend time in lymph tissue b. Produce the specific immune response c. Originate in bone marrow - 2 fates 1. Mature in bone marrow = B-cell 2. Leave bone marrow and circulate to thymus, mature there and become a T-cell

  23. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity Fig. 24.5 B. Specific immunity (The Immune System) iv. Lymphocytes (B and T cells) 1. B cells elicit humoral immunity Humoral implies humors or “fluids”. This response will involve antibodies (proteins), which will be dissolved in the fluids of the body – secretions like saliva and breast milk, the blood plasma, interstitial fluid, lymph fluid, etc… - to recognize foreign substances (antigens) 2. T cells elicit Cell-Mediated immunity In this case cells will be directly involved in recognizing foreign substances (antigens)

  24. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity a. B-cells make and secrete antibodies (a protein) into blood b. We have millions of B-cells and each one produces a different antibody, which will bind to a different antigen (one B-cell, one antigen). (Epitope) Fig. 24.6 Antibody structure (quarternary structure)

  25. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity a. B-cells make and secrete antibodies (a protein) into blood b. We have million of B-cells and each one produces a different antibody, which will bind to a different antigen (one B-cell, one antigen). The antigenic determinant (epitope) is the specific part of the antigen that the antibody binds to via hydrogen/ionic/hydrophobic interactions. Fig. 24.6

  26. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity How can there be millions of B-cells each expressing a unique antibody if we only have 30,000 or so genes?? Wouldn’t we need 1,000,000’s of genes, one for each antibody? Fig. 24.6

  27. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity How can there be millions of B-cells each expressing a unique antibody if we only have 30,000 or so genes?? Wouldn’t we need 1,000,000’s of genes, one for each antibody? Fig. 24.6

  28. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity How can there be millions of B-cells each expressing a unique antibody if we only have 30,000 or so genes?? Wouldn’t we need 1,000,000’s of genes, one for each antibody? Fig. 24.6

  29. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity How can there be millions of B-cells each expressing a unique antibody if we only have 30,000 or so genes?? Wouldn’t we need 1,000,000’s of genes, one for each antibody? 1. V(D)J recombination There are many genes coding for each segment (V, D or J) of the variable region. The genes will undergo recombination in a given B-cell and a unique combination of VDJ will result in both chains (light chain doesn’t have a D segment). Fig. 24.6

  30. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity How can there be millions of B-cells each expressing a unique antibody if we only have 30,000 or so genes?? Wouldn’t we need 1,000,000’s of genes, one for each antibody? 2. Somatic hypermutation When a B-cell is activated it begins to rapidly divide. The VDJ regions have an abnormally high rate of mutation (1 nucleotide change per variable gene [VDL] per division) during S-phase resulting in a slight variations in all daughter cells – genetic diversity followed by natural selection!! Fig. 24.6

  31. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) Another name for an antibody is an immunoglobulin or Ig for short. There are five major types of antibodies (IgG, IgM, IgA, IgD and IgE – or G-MADE), each has a slightly different function in the body. For example: IgG - found in the blood and interstitial fluid and can cross the placenta giving immunity to the fetus IgA - found in external secretions like saliva and breast milk.

  32. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) The five antibody (immunoglobulin) types of mammals…

  33. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity a. B-cells make and secrete antibodies (a protein) into blood b. We have million of B-cells and each one produces a different antibody, which will bind to a different antigen (one B-cell, one antigen). c. B-cells display the antibody they make (~100,000 of them) on their surface as an antigen receptor and wait in the lymph system and spleen for an antigen that will bind the antibody it makes… Fig. 24.5

  34. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) - OVERVIEW Memory T-cells are also made form T-cells activated by Helper T-cells. For a future encounter with the same antigen carrying pathogen.

  35. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) d. Clonal selection v. Humoral immunity - If the antigen does come along one day, it will bind to the B-cell’s antibody and activate the B-cell. - The single activated B-cell will undergo mitosis resulting in the formation of plasma cells (antibody secreting cells) and memory B cells… (Activation actually requires a second signal by a helper T-cell that we will discuss shortly) - Why are plasma cells shown with a lot of ER? They are secreting incredible amounts of protein (antibodies) and the ER/Golgi are required to do this – recall endomembrane system. Now what do these antibodies do? Fig. 24.9

  36. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity Antibodies bind to antigens (surface molecules), flagging them for phagocytosis by phagocytes or activating complement. Know all the terms like neutralization, agglutination, precipitation… What about those memory B-cells? Fig. 24.11 http://catalog.nucleusinc.com/generateexhibit.php?ID=15529&ExhibitKeywordsRaw=&TL=1&A=2

  37. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s?

  38. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity 1. Memory B-cells are soldiers that will wait in reserve for the return of the same antigen. 2.These cells with memory T-cells are what gives you immunity. STORY: You are infected with the virus Varicellazoster, which causes chicken pox. A B-cell will recognize the virus somewhere in your spleen or lymph nodes and be activated with the help of a helper-T cell (discussed shortly). The B-cell will undergo mitosis forming plasma and memory B-cells, which all make the same antibody (it is mitosis so they are all ALMOST genetically identical clones). Plasma cells will make and secrete antibodies to fight the current virus, while many, many memory B-cells will sit in lymph nodes and the spleen for the rest of your life possibly, with the same antibody on their surface awaiting the return of the virus/antigen. Initially there was only a handful of B-cells activated, the second response will activate 10,000’s!! Fig. 24.9

  39. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) v. Humoral immunity Why not make Memory B-cells for all 100+ million antibodies? A. You do not have enough room in your lymph and spleen and B. You would spend a huge amount of ATP to do this. You would need to eat incredible amounts of food to maintain such a system. Fig. 24.9

  40. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity a. B-cells fight the battle outside our cells, but what about when the pathogen has gotten in like a virus that has turned your cell into a virus producing factory? - T-cells fight this one b. We have million of T-cells in our lymph nodes and spleen and each one produces a slightly different antigen receptor called a T-cell receptor (this is the “antibody” of the T-cell although it well never secrete it).

  41. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity c. STORY Fig. 24.13 1. It all starts when some kind microorganism (microbe) gets engulfed by a macrophage (a mature monocyte) of the innate immune system. The macrophage needs to warn the specific immune system as to what is going on!! (MHC-II) The phagocytosed microbe will be in a vesicle which will fuse with a lysosome thereby partially digesting the microbe. 2 and 3. The pieces of the microbe will then bind to MHC-II receptors of the macrophage and be displayed on the surface – the macrophage is now called an Antigen Presenting Cell (APC).

  42. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity c. STORY Fig. 24.13 4. You have millions of Helper T-cells, each one making a slightly different T-cell receptor (analogous to B-cells each making a different antibody receptor). A helper T-Cell (the same ones that HIV infects), with a matching T-cell receptor to the displayed antigen will bind to the antigen/MHC-II receptor of the APC. (MHC-II) (MHC-II)

  43. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity Interleukin-1 (IL-1) Interleukin-2 (IL-2) c. STORY 5. The APC will secrete interleukin-1, a cytokine (a protein that acts as a signal to instruct cells what to do), which will bind to interleukin receptors on the Helper T-Cell. Interleukin: Inter – between; leukos - white A signal between white blood cells. 5 The combination of IL-1 and the MHC-II complex activates the Helper T-Cell, and the specific immune system has been notified! Time to find out what the Helper T-Cell does… Fig. 24.13

  44. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity Interleukin-1 (IL-1) Interleukin-2 (IL-2) c. STORY 6. The helper T-cell will secrete interleukin-2, also a cytokine, which will bind to receptors on the T-cell itself, cytotoxic (toxic to cells) T-cells, and B-cells, both of which that have been partially activated by the SAME antigen (remember earlier that I said a B-cell would not fully activate with a helper-T cell) 6 5 IL-2 stimulates the same Helper T-cell that secreted it to undergo mitosis… IL-2 will activate the B and cytotoxic T cells, which have been partially activated already by the SAME antigen – antigen binds to antibodies on B-cell surface or MHC-II on Cyto T-cell surface. Cytotoxic T-Cell is also called a Killer T-Cell Fig. 24.13

  45. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity Interleukin-1 (IL-1) Interleukin-2 (IL-2) Fig. 24.13

  46. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity Interleukin-1 (IL-1) Interleukin-2 (IL-2) c. STORY **All of these lymphatic cells (B and T cells) need two signals to be active: 1. The antigen • An APC displays the antigen bounds to MHC-II (the antigen/MHC-II complex), which will bind to the T-celI receptor of a Helper T-cell • Binds directly to T-cell receptor of a Cytotoxic T-cell that recognizes that antigen. 6 5 - Binds directly to an antibody on the surface of a B-cell. Fig. 24.13

  47. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity Interleukin-1 (IL-1) Interleukin-2 (IL-2) c. STORY **All of these lymphatic cells (B and T cells) need two signals to be active: 1. The antigen What if the T-cell or B-cell does not have an T-cell receptor or antibody, respectively, that can bind to the antigen? 6 5 Nothing, that cell will not be selected. Fig. 24.13

  48. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity Interleukin-1 (IL-1) Interleukin-2 (IL-2) c. STORY **All of these lymphatic cells (B and T cells) need two signals to be active: 2. Interleukins 6 IL-1 from the APC will activate the partially activated Helper T-cell. 5 IL-2 from the Helper T-cell will activate the already partially activated Cytotoxic T-cells and B-cells as well as itself Now what will the activated Cytotoxic T-cells do? Fig. 24.13

  49. Chapter 24: The Immune System AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) vi. Cell-mediated immunity c. STORY The cytotoxic T-cells will now bind to infected cells displaying the SAME antigen on MHC-I (MHC-ONE) receptors. APC’s display antigen using MHC-II, while infected cells use MHC-I. Cytotoxic T-cells secrete the protein perforin onto any cell with the proper MHC-I/antigen complex. Perforin puts holes in the cell membrane causing the cell to lyse... Fig. 24.13

  50. Chapter 24: The Immune System NEW AIM: How does the body defend itself against MO’s? I. Nonspecific vs. Specific Immunity B. Specific immunity (The Immune System) - OVERVIEW Memory T-cells are also made from T-cells activated by Helper T-cells. For a future encounter with the same antigen carrying pathogen.

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