1. Chapter 8 Biology 25: Human Biology Prof. Gonsalves Los Angeles City College Loosely Based on Mader’s Human Biology,7 th edition

3. Introduction Resistance: Ability to ward off disease.  Nonspecific Resistance: Defenses that protect against all pathogens.  Specific Resistance: Protection against specific pathogens. Susceptibility: Vulnerability or lack of resistance.

4. Protection Against Invading Pathogens 1. First Line of Defense: Non-specific natural barriers which restrict entry of pathogen. Examples: Skin and mucous membranes. 2. Second Line of Defense: Non-specific defenses that provide rapid local response to pathogen after it has entered body. Examples: Fever, phagocytes (macrophages and neutrophils), inflammation, and interferon. 3. Third line of defense: Antigen-specific immune responses, specifically target and attack invaders that get past first two lines of defense. Examples: Antibodies and lymphocytes.

5. Defenses Against Infection

6. First Line of Defense: Skin is an Effective Barrier Against Infection by Most Pathogens

7. Second Line of Defense: Interferon is Nonspecific Inhibitor of Viral Infection

8. Inflammation is a Nonspecific Defense 1. Damaged cells release chemical signals: Histamine and other molecules. 2. Local response to chemical signals:  Increase in local blood flow and vascular permeability  Redness  Heat  Swelling  Pain 3. Phagocytic white blood cells come into area: Engulf bacteria, dead cell parts, and other microbes. 3. Phagocytic white blood cells come into area: Engulf bacteria, dead cell parts, and other microbes. 4. Tissue heals

9. Nonspecific Immunity Distinguish between the kinds of carbohydrates that are produced by mammalian cells and those produced by bacteria. Distinguish between the kinds of carbohydrates that are produced by mammalian cells and those produced by bacteria. Bacterial carbohydrates flag the cell for phagocytic attack. Bacterial carbohydrates flag the cell for phagocytic attack. 3 major groups of phagocytic cells: 3 major groups of phagocytic cells:  Neutrophils: 1 st to arrive at infection.  Mononuclear phagocyte system:  Macrophages and monocytes.  Organ-specific phagocytes.

10. Inflammatory Response: Nonspecific Defenses

12. Phagocytosis Neutrophils and monocytes are able to squeeze through tiny gaps between adjacent endothelial cells. Neutrophils and monocytes are able to squeeze through tiny gaps between adjacent endothelial cells.

13. Phagocytosis Phagocytes engulf particles similar to amoeba. Phagocytes engulf particles similar to amoeba.  Particle becomes surrounded by pseudopods.  Forms vacuole.  Vacuole fuses with lysosomes which digest the particle.  Lysosomes can be released into the infected area.

14. Phagocytes Intracellular killing of microbes Regulate inflammation Extracellular killing Activation of clotting or anti-clotting Hormonal regulation Chemical secretion

15. Fever Cell wall of gram – bacteria contains endotoxin. Cell wall of gram – bacteria contains endotoxin. Endotoxin stimulate release of cytokines: Endotoxin stimulate release of cytokines:  Interleukin-1, interleukin-6 and tumor necrosis factor:  Produce fever, increase sleepiness, and decrease plasma iron. May be a component of nonspecific defense system. May be a component of nonspecific defense system.

16. Nonspecific Immunity Endogenous pyrogens: Endogenous pyrogens: Cell wall of gram – bacteria contains endotoxin. Cell wall of gram – bacteria contains endotoxin. Endotoxin stimulates monocytes and macrophages to release cytokines: Endotoxin stimulates monocytes and macrophages to release cytokines:  Interleukin-1, interleukin-2, TNF.  Increased activity of neutrophils.  Increased production of interferon.  Produce fever, increase sleepiness, and decrease plasma iron.

17. Nonspecific Immunity Interferons (cytokines) Interferons (cytokines)  Nonspecific, short-acting resistance to viruses.  Act as messengers that protect other cells in the vicinity from viral infection.   inhibit viral replication, increases NK cells, induces MHC-I antigens.   inhibit viral replication, increases NK cells, induces MHC-I antigens.   activates macrophages, induces MHC-II antigens.

18. Third Line of Defense: The Immune Response Immunity: “Free from burden”. Ability of an organism to recognize and defend itself against specific pathogens or antigens. Immune Response: Involves production of antibodies and generation of specialized lymphocytes against specific antigens. Antigen: Molecules from a pathogen or foreign organism that provoke a specific immune response.

19. Antigens Molecules that stimulate the production of antibodies. Molecules that stimulate the production of antibodies. Combine specifically with antibodies produced. Combine specifically with antibodies produced. Foreign to blood and other body fluids. Foreign to blood and other body fluids. Immune system can distinguish “self” molecules from nonself antigens. Immune system can distinguish “self” molecules from nonself antigens. Large, complex molecules can have different antigenic determinant sites. Large, complex molecules can have different antigenic determinant sites.

20. Lymphatic and Immune System Components: Lymph, lymphatic vessels, bone marrow, thymus, spleen, and lymph nodes. Functions:  Defends against infection: bacteria, fungi, viruses, etc.  Destruction of cancer and foreign cells.  Synthesis of antibodies and other immune molecules.  Synthesis of white blood cells. Homeostatic Role:  Returns fluid and proteins that have leaked from blood capillaries into tissues.  Up to 4 liters of fluid every day.  Fluid returned near heart/venae cavae.

21. Lymphatic System

25. The Immune Response Destroys Specific Invaders Antigen: Molecule that elicits an immune response. “Antibody generating”.  Microbial antigens: Viral capsid, bacterial call wall, etc.  Nonmicrobial antigens: Pollen, latex, food, etc. Antibody: Protein found in blood plasma that attaches to antigen and helps counteract its effects. Vaccination or Immunization: Process in which harmless forms of antigen or pathogen are introduced into body to provoke an immune response.

26. Lymphocytes Derived from stem cells in the bone marrow. Derived from stem cells in the bone marrow. Stem cells produce the specialized blood cells. Stem cells produce the specialized blood cells. Replace themselves by cell division so the stem cell population is not depleted. Replace themselves by cell division so the stem cell population is not depleted. Lymphocytes seed the thymus, spleen, and lymph nodes. Lymphocytes seed the thymus, spleen, and lymph nodes.

27. Lymphocytes Lymphocytes that seed the thymus become T lymphocytes (T cells). Lymphocytes that seed the thymus become T lymphocytes (T cells). Have surface characteristics and immunological function that differ from other lymphocytes. Have surface characteristics and immunological function that differ from other lymphocytes. Do not secrete antibodies. Do not secrete antibodies. Must come in close or direct contact to destroy them. Must come in close or direct contact to destroy them. T cells are 65 – 85% of the lymphocytes in blood and most in the germinal centers of lymph nodes and spleen. T cells are 65 – 85% of the lymphocytes in blood and most in the germinal centers of lymph nodes and spleen.

28. Lymphocytes Most of the lymphocytes that are not T cells are B lymphocytes (B cells). Most of the lymphocytes that are not T cells are B lymphocytes (B cells). Processed in the bone marrow. Processed in the bone marrow. Function in specific immunity. Function in specific immunity. B cells combat bacterial infections as well as some viral infections by secreting antibodies into the blood and lymph. B cells combat bacterial infections as well as some viral infections by secreting antibodies into the blood and lymph. Provide humoral immunity (blood and lymph are body fluids (humors). Provide humoral immunity (blood and lymph are body fluids (humors).

29. Lymphocytes Mount a Dual Immune Defense 1. Cell Mediated Immunity u Immunity that requires cell to cell contact. u Carried out by T cells:  Develop in the thymus.  Only recognize antigen associated with self-protein.  T cytotoxic cells: Important in defense against:  Cancer cells  Self cells infected with fungi, viruses, protozoans, and bacteria.  T helper cells: Play a central role in immunity. Act indirectly by controlling the immune functions of other cells:  Increased antibody production by B cells.  Increased phagocytosis by macrophages.  Increased killing of foreign and cancer cells.

31. Development of T and B Lymphocytes

32. T helper cells play a central role in immunity

33. Lymphokines Interleukin-1: Interleukin-1:  Secreted by macrophages and other cells.  Activates T cells. Interleukin-2: Interleukin-2:  Released by helper T cells.  Activates killer T cells. Interleukin-3: Interleukin-3:  Serves as a growth factor.  Activates killer T cells. Interleukin-4: Interleukin-4: Secreted by T cells. Secreted by T cells.  Required for proliferation and clone development of B cells.

34. Lymphocytes Mount a Dual Immune Defense 2. Humoral (Antibody Mediated) Immunity Antibodies are found in our body fluids: Antibodies are found in our body fluids:  Blood  Lymph  Interstitial fluid Antibodies are produced by B cells. Antibodies are produced by B cells.  B cells develop in bone marrow. Antibodies are specific molecules that circulate through out our body and attach to foreign antigens, marking them for destruction. Antibodies are specific molecules that circulate through out our body and attach to foreign antigens, marking them for destruction. Foreign antigen does not have to be associated with a self antigen to be recognized. Foreign antigen does not have to be associated with a self antigen to be recognized. Antibodies can be passed from one individual to another: Antibodies can be passed from one individual to another:  Mother-child: Mother’s antibodies cross placenta. Also found in breast milk.  Serum: Snake bite antivenom.

35. Antibodies Antibody proteins are also known as immunoglobulins. Antibody proteins are also known as immunoglobulins. Found in the gamma globulin class of plasma proteins. Found in the gamma globulin class of plasma proteins. Different antibodies have different structure, as the antibodies have specific actions. Different antibodies have different structure, as the antibodies have specific actions.

36. Antibodies ImmunoglobulinFunctions lgGMain form of antibodies in circulation: production increased after immunization; secreted during secondary response lgAMain antibody type in external secretions, such as saliva and mother’s milk lgEResponsible for allergic symptoms in immediate hypersensitivity reactions lgMFunction as antigen receptors on lymphocyte surface prior to immunization; secreted during primary response lgDFunction as antigen receptors on lymphocyte surface prior to immunization; other functions unknown

37. Active Immunity Primary response: Primary response:  First exposure to pathogen, immune response insufficient to combat disease.  Latent period of 5-10 days before measurable amounts of specific antibodies appear in blood.

38. Active Immunity Secondary response: Secondary response: Subsequent exposure to same antigen. Subsequent exposure to same antigen. Antibody production is much more rapid. Antibody production is much more rapid.  Maximum antibody concentration reached in < 2 hrs.  Maintained longer period of time.

39. Clonal Selection Theory B lymphocytes inherit the ability to produce a particular antibody. B lymphocytes inherit the ability to produce a particular antibody. T lymphocytes inherit the ability to respond to particular antigens. T lymphocytes inherit the ability to respond to particular antigens. Inherited specificity reflected in antigen receptor proteins on surface of lymphocytes. Inherited specificity reflected in antigen receptor proteins on surface of lymphocytes.

40. Clonal Selection Theory Exposure stimulates specific lymphocytes to divide many times until a large population of genetically identical cells (clone) is produced. Exposure stimulates specific lymphocytes to divide many times until a large population of genetically identical cells (clone) is produced. Antigens select lymphocytes that are already able to make antibodies. Antigens select lymphocytes that are already able to make antibodies.

43. Antibody Structure 100 million trillion antibody molecules that contain 4 polypeptide chains. 100 million trillion antibody molecules that contain 4 polypeptide chains. F ab regions are variable, provide a specific bonding site for antigen. F ab regions are variable, provide a specific bonding site for antigen. B lymphocytes have antibodies that serve as receptors for antigens B lymphocytes have antibodies that serve as receptors for antigens Provides active immunity. Provides active immunity.

44. Antibodies are Protein Molecules that Recognize Specific Foreign Antigens

46. Antibodies Help Eliminate Foreign Antigens

47. Complement Proteins Nonspecific defense system. Nonspecific defense system. The combination of antibodies with antigens does not cause destruction of the antigens or pathogen. The combination of antibodies with antigens does not cause destruction of the antigens or pathogen. Antibodies serve to identify the targets for immunological attack. Antibodies serve to identify the targets for immunological attack. Identified antibodies activate the complement against specific invaders. Identified antibodies activate the complement against specific invaders.

48. Activated Complement Proteins Direct destruction by MAC Vasodilation Increased capillary permeability Chemotaxis Opsinization

49. There are 11 complement proteins, designated C-1 to C-9. There are 11 complement proteins, designated C-1 to C-9. Complement proteins can be subdivided into 3 components: Complement proteins can be subdivided into 3 components:  C1: recognization.  C4, C2, C3: activation.  C5-C9: attack (complement fixation). Complement Types

50. Complement Fixation Complement proteins attach to the cell membrane and destroy it. Complement proteins attach to the cell membrane and destroy it. Antibodies of IgG and IgM attach to antigens on invading cell membranes, bind to C1 activating the process. Antibodies of IgG and IgM attach to antigens on invading cell membranes, bind to C1 activating the process. Activated C1 hydrolyzes C4 into C4 a and C4 b. Activated C1 hydrolyzes C4 into C4 a and C4 b. C4 b binds to the cell membrane. C4 b binds to the cell membrane. C4 b splits C2 into C2 a and C2 b. C4 b splits C2 into C2 a and C2 b.

51. Complement Fixation C2 a attaches to C4 b and cleaves C3 into C3 a and C3 b. C2 a attaches to C4 b and cleaves C3 into C3 a and C3 b. Fragment C3 b becomes attached to the complex in the cell membrane. Fragment C3 b becomes attached to the complex in the cell membrane. C3 b converts C5 to C5 a and C5 b. C3 b converts C5 to C5 a and C5 b. C5 b and C6 through C9 become fixed to the cell membrane. C5 b and C6 through C9 become fixed to the cell membrane.

52. Complement Fixation Complement proteins C5 to C9 create large pores in membrane, causing osmotic influx of H 2 0. Complement proteins C5 to C9 create large pores in membrane, causing osmotic influx of H 2 0. Complement proteins kill the cell. Complement proteins kill the cell.

54. Active Immunity Primary response: Primary response:  First exposure to pathogen, immune response insufficient to combat disease.  Latent period of 5-10 days before measurable amounts of specific antibodies appear in blood.

55. Active Immunity Secondary response: Secondary response: Subsequent exposure to same antigen. Subsequent exposure to same antigen. Antibody production is much more rapid. Antibody production is much more rapid.  Maximum antibody concentration reached in < 2 hrs.  Maintained longer period of time.

56. Passive Immunity Immune protection produced by the transfer of antibodies to a recipient from a donor. Immune protection produced by the transfer of antibodies to a recipient from a donor. Donor has been actively immunized. Donor has been actively immunized. Occurs naturally in mother to fetus during pregnancy and mother to infant during nursing. Occurs naturally in mother to fetus during pregnancy and mother to infant during nursing.

57. Passive Immunity Immunological competence: Immunological competence:  Ability to mount a specific immune response.  Does not develop until 1 month after birth.  Passive immunity disappears when infant is 1 month old.  Infant did not itself produce lymphocyte clones.

61. Lymphokines Interleukin-1: Interleukin-1:  Secreted by macrophages and other cells.  Activates T cells. Interleukin-2: Interleukin-2:  Released by helper T cells.  Activates killer T cells. Interleukin-3: Interleukin-3:  Serves as a growth factor.  Activates killer T cells. Interleukin-4: Interleukin-4: Secreted by T cells. Secreted by T cells.  Required for proliferation and clone development of B cells.

62. Major Histocompatability Complexes (MHC) All cells except mature RBCs are genetically marked with histocompatability antigens on the membrane surface. All cells except mature RBCs are genetically marked with histocompatability antigens on the membrane surface. Also called human leukocyte antigens (HLAs). Also called human leukocyte antigens (HLAs). The histocompatability antigens are coded for a group of genes called MHC located on chromosome 6. The histocompatability antigens are coded for a group of genes called MHC located on chromosome 6. MHC of genes produces 2 classes of MHC molecules: MHC of genes produces 2 classes of MHC molecules:  Class-1  Class-2

63. Major Histocompatability Complexes MHC-class-1: MHC-class-1:  Produced by all cells but RBCs.  Picks up cytoplasmic peptides and transports to membrane.  Killer T cells (cytotoxic) interact with antigens.  Coreceptor CD8 permits each type of T cell to interact only with a specific class of MHC molecules.

64. Major Histocompatability Complexes MHC-class-2: MHC-class-2:  Produced only on antigen-presenting cells and B cells  Appear only on cell membrane when cell is processing antigens.  Activate T cells.  Helper T cells react with antigens.  Coreceptor CD4 interact with only a specific class of MHC molecule.

65. Monoclonal Antibodies Commercially prepared. Commercially prepared. Exhibit specificity for one antigenic determinant only. Exhibit specificity for one antigenic determinant only. Results in more sophisticated clinical laboratory tests. Results in more sophisticated clinical laboratory tests. May aid in the diagnosis of cancer. May aid in the diagnosis of cancer.

67. Diseases Caused by the Immune System Ability of immune system to tolerate self- antigens while it identifies and attacks foreign antigens that can be deranged. Ability of immune system to tolerate self- antigens while it identifies and attacks foreign antigens that can be deranged. Diseases caused by the immune system can be grouped into 3 categories: Diseases caused by the immune system can be grouped into 3 categories:  Autoimmune disease.  Immune complex diseases.  Allergy or hypersensitivity.

68. Autoimmunity Those produced by failure in the immune system to recognize and tolerate self-antigens. Those produced by failure in the immune system to recognize and tolerate self-antigens. Failure due to: Failure due to:  An antigen that does not normally circulate in the blood may be exposed to the immune system.  Thyroglobulin.  A self-antigen that is otherwise tolerated may be altered by combining with a foreign hapten.  Thrombocytopenia.

69. Autoimmunity Antibodies may be produced that are directed against other antibodies. Antibodies may be produced that are directed against other antibodies.  Rheumatoid arthritis. Antibodies produced against foreign antigens may cross-react with self-antigens. Antibodies produced against foreign antigens may cross-react with self-antigens.  Rheumatic fever. Self-antigens may be presented to the helper T cells together with class-2 MHC molecules. Self-antigens may be presented to the helper T cells together with class-2 MHC molecules.  Type I diabetes.

70. Immediate Hypersensitivity Production of IgE antibodies. Production of IgE antibodies. Do not circulate in the blood. Do not circulate in the blood. Attach to mast cells and basophils. Attach to mast cells and basophils. When exposed again to same allergen, histamine and prostaglandin D are secreted. When exposed again to same allergen, histamine and prostaglandin D are secreted. Produce symptoms. Produce symptoms.