2. Essentials of Human Anatomy & Physiology Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Seventh Edition Elaine N. Marieb Chapter 12- ppt 2 3rd line of defense AKA Immunity Pgs 389-390

3. 3rd Line of Defense- T and B lymphocytes Slide 12.17a Review: Antigen (Ag)- any substance that causes immune response (3rd line / “specific” defense) Pathogens - viruses, bacteria, fungi, protein-hapten combo (allergen-pollen) are Ag’s AMI (Humoral) – Antibody Mediated Immune Response carried out primarily by B Cells (and their antibodies) to attack extracellular pathogens (ex. bateria, fungi, viruses) CMI – Cell Mediated Immune Response carried out primarily by T Cells (and their helpers) to attack intracellular pathogens (ex. cancer, transplanted tissue)

4. Activation of Lymphocytes Slide 12.30 Figure 12.9 NOTE: Both T and B Cells (Lymphocytes) are made in Bone Marrow! 1. B Cells - stay in bone marrow to become “immunocompetent” T Cells - go to Thymus to become “immunocompetent” 2. Immunocompetent (but still Naïve) B & T Cells Travel to Lymph Nodes & other Lymphoid Tissues to face their “Antigen Challenge” in which they become Mature (Activated) 3. Mature B and T cells recirculate through blood & lymph ready to help you!

5. Antibody Mediated Immune Response (AMI) – aka “Humoral” Slide 12.17a AMI (“humoral”) 1. Extracellular Antigen (Ag) (ex. bacteria, extracellular viruses) is detected and MHC1 is presented by antigen presenting cell This leads to… 2. B lymphocytes (B cells) and their antibodies (Ab’s) attack the extracellular Antigens (Ags) by producing: 1.Plasma Cells 2.Antibodies 3.Complement

6. Cell Mediated Immune Response (CMI) Slide 12.17a CMI (cell mediated) 1. Phagocytosis of antigen (by macrophage) 2. Macrophage presents MHC2 Which lead to… 3. Helper T Cells (type of T cell) to trigger Cytotoxic T Cells to release their chemicals to attack intracellular Ag’s (ex. cancer, viral infected cells & transplanted tissue): Those Chemicals Include: Lymphokines Lymphotoxins Interferon

7. FYI ONLY Slide 12.30 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Remember…..If 1st line of defense fails, it leads to 2nd line, if 2nd line fails, it leads to 3rd line In lymph nodes are T and B lymphocytes (cortex) and macrophages and other phagocytes (medulla) Lymph nodes filter lymph and the macrophages/“phagocytes” are called antigen presenting cells (APC). Phagocytosis (2nd line of defense) activates T and B cells (3rd line) which function in the cortex of lymph nodes

8. Antigen Determines Pathway!! Intracellular = CMI or Extracellular = AMI Slide 12.43 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.15 IL-1 IL-2 CMI AMI

9. Macrophages (APC) DIRECT AMI or CMI: IL-1 (Interleukin 1) - secreted by macrophages and Helper T cells to stimulate B cells (AMI) Antibody Mediated Immunity (Plasma Cells, Antibodies, complement, B memory Cells) T Helper cells - circulate and recruit other cells to fight invaders; called the “directors” IL-2 (Interleukin 2) - released by Helper T cells which stimulate cytotoxic T cells Cytotoxic T cells - (CMI) Carry out Cell Mediated Immunity by making chemicals (below) when activated (Interferon, Lymphokines, Lymphotoxins, T memory cells )

10. Warm-Up (like a pyrogen ) On the chart, put the following descriptors into the correct category (either AMI or CMI or BOTH): B Cell Directed APC presents MHC2 Intracellular antigens T Cell Directed Helper T Cells involved APC presents MHC1 Extracellular antigens Uses Cytotoxic T Cells Stimulated by IL-1 APC involved CMI AMI Both

11. Primary (first encounter) Vs Secondary Exposure (memory) Slide 12.17a (MHC2) ( w/ IL-2)

12. Summary of Possible Immune Responses Slide 12.45 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.16 IL-1 extracellularintracellular CMI AMI IL-2Growth factor w/ MHC 2w/ MHC 1 **complement lymphotoxin **interferon lymphokines T s cell inhibits Antigen (2nd exposure)

13. CMI Immune Response Slide 12.17a macrophage Cytotoxic T Cells Interferon, lymphotoxins, lymphokines produced (MHC2)

14. Summary of CMI Slide 12.45 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.16 Il-1 extracellularintracellular CMI AMI Il-2Growth factor w/ MHC 2w/ MHC 1 **complement lymphotoxin **interferon lymphokines T s cell inhibits Antigen (2nd exposure) 1. Antigen encounter 2. Macrophage presents MHC 2 to Helper T cells which secrete IL-2 3. IL-2 stimulates Cytotoxic T cells (killer T cells) 4. Cytotoxic T cells Produce/stimulates lymphokines, lymphotoxins and interferons (Some cytotoxic T cells also produce T memory cells

15. Interferons, Lymphokines & Lymphotoxins Lymphokines Stimulate additional Cytoxic T cells Attract other WBC (produce more IL1 & IL2 Enhance macrophages Lymphotoxins Protein produced by T-cells and induces phagocytic cells to bind to invaders Interferons Made by infected cells as a “warning”! Prevents viruses from infecting new healthy cells!

16. AMI Immune Response PREVIEW Slide 12.32 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings

17. Summary of AMI Slide 12.45 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.16 Il-1 extracellularintracellular CMI AMI Il-2Growth factor w/ MHC 2w/ MHC 1 **complement lymphotoxin **interferon lymphokines T s cell inhibits Antigen (2nd exposure) 1.Antigen encounter 2.APC secretes IL1 or presents MHC 1 3. Stimulates B cells to differentiate into Plasma cells (which produces antibodies) which activate: Phagocytosis Complement Lysis chemotaxis Note: Some B cells also differentiate into memory B cells

18. AMI: Antibody Mediated or Humoral Immunity (in Detail) Extracellular Ag is detected by an APC (macrophage or Helper T cell) B cells are activated B cells differentiate into Memory B Cells or Plasma cells Plasma Cells- synthesize Antibodies (Ig) Antibodies - agglutinate (sticks to) with the antigen & activates: » Phagocytosis »Complement (inflammatory response and opsonization) »Lysis »Chemotaxis (& its resulting inflammation)

19. Activation of Complement Slide 12.41 Figure 12.14 Made in 3rd line Acts in 2nd line inflammation

20. Antibodies or Immunoglobulins: (Ab or Ig’s) Slide 12.37 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Antibodies (Ab’s) are proteins secreted by plasma cells (made from B Cells)  Circulates in blood plasma  Ab’s bind to a specific antigen (Ag)

21. Antibody (Ig) Structure Slide 12.38a Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.13b 4 polypeptide chains (attached by disulfide bonds): 2 heavy 2 light Variable region specific for Ag Constant region determines type of Ig

22. 5 Types of Antibody (Ig) Classes Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings M.A.D.G.E. IgM IgA IgD IgG IgE

23. Types of Ig’s Slide 12.39 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Five major Ig classes:  IgM – fixes complement  IgA – in mucus membranes and their secretions, ex. milk, saliva, tears, etc. Agglutination agent; pentamer Monomer and dimer; prevents pathogen from entering body

24. Types of Ig’s Slide 12.39 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Five major Ig classes  IgD – on B cells, activates other B cells  IgG – crosses the placenta during pregnancy, fix complement. Most abundant  IgE – leads to allergies monomers Binds to mast cells & basophils & triggers the release of histamines and other chemicals that mediate inflammation In skin, mucosae of resp tract, intestines, and tonsils

25. Monoclonal Antibodies Slide 12.36 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings  Isolate one single B cell line that produces one kind of Ab  Clone the Ab in a lab  Examples of uses:  Pregnancy tests  Treatment for hepatitis, cancer, rabies

26. Primary and Secondary Responses and Memory Cells Slide 12.33 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.11 Memory cells Primary response (1st exposure) causes illness AND memory cells made Secondary response is quicker for future exposures because memory cells are made during the primary response Primary response (1st exposure) causes illness AND memory cells made Secondary response is quicker for future exposures because memory cells are made during the primary response Gradual rise & rapid decline Rapid rise & remains high for some time

27. Vaccines Slide 12.33 Vaccination is a preventative shot that contains weakened or dead viruses that cause a primary response WITHOUT illness and memory cells are made protect against future exposures for secondary response Active Artificially Acquired Immunity

28. Antibiotics Slide 12.33 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Medicine given to kill bacterial infection, cannot be used for viral infections Must take it for full 7-10 days otherwise, bacterial infection can come back and/or can cause antibiotic resistance in bacteria Medicine given to kill bacterial infection, cannot be used for viral infections Must take it for full 7-10 days otherwise, bacterial infection can come back and/or can cause antibiotic resistance in bacteria

29. Antibiotic resistance Slide 12.33 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings

30. Why we get sick…why the symptoms Slide 12.34 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings The Ag’s attack and kill our cells We attack the Ag’s with our immune responses ex fever, inflammation, etc

31. Antiserum Slide 12.34 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Animal’s Ab’s produced against an Ag that can be given to a human to protect it against same Ag

32. Types of Immunity Slide 12.34 Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings Figure 12.12 ( antiserum ) animal’s Ab’s Active – body makes memory as a result of an antigen challenge! Passive - B Cells are not challenged so no immunological memory…but you are “cured” for the time being Active – body makes memory as a result of an antigen challenge! Passive - B Cells are not challenged so no immunological memory…but you are “cured” for the time being