Immune System Part 2

1. Immune System Part 2 http://www.electroresponse.com

2. Much of the text material is from, “Principles of Anatomy and Physiology, 12th edition” by Gerald J. Tortora and Bryan Derrickson (2009). I don’t claim authorship. Other sources are noted when they are used.

3. Due to the complexity of the conceptual material and how it is presented, all visual references are to the detailed illustrations in the textbook. Visuals are not included in these lecture notes.

4. Outline • Adaptive immunity • Cell-mediated immunity • Antibody-mediated immunity • Self-recognition and self-tolerance • Aging

5. Adaptive Immunity

6. Adaptive Immunity • Adaptive immunity involves the ability of the body to defend against various agents including bacteria, toxins, viruses, and foreign tissues in organ transplants. • It is also called specific immunity since its responses are specific to a pathogen. • Substances recognized as foreign and trigger immune responses are known as antigens. Pathogen = any disease-producing agent, especially a virus or bacterium or other microorganism. (http://wordnetweb.princeton.edu) Foreign = introduced from an outside source. Chapter 22, page 846

7. Adaptive Immunity versus Innate Immunity • Adaptive immunity can be distinguished from innate immunity by two properties: • Specificity for particular foreign antigens involving distinguishing ‘self’ from ‘non-self.’ • Memory for most previously-encountered antigens so that subse-quent encounters with the same antigen lead to a rapid and effect-tive response. Self = originating in the body. Non-self = not originating in the body. Chapter 22, page 846

8. Immune System and Immunology • The immune system consists of cells and tissues that produce immune responses. • Immunology is the branch of science that focuses on the responses of the body when challenged by pathogens. Chapter 22, page 846

9. B Cells and T Cells • B cells and T cells—both lymphocytes—mediate adaptive immunity. • Both types of cells develop in the primary lymphatic organs—red bone marrow and thymus—from pluripotent stem cells that originated in red bone marrow. • B cells complete their development in red bone marrow in a process that continues throughout the lifetime. Figure 19.3 Figure 22.11 Chapter 22, page 847

10. T Cells • Most T cells develop prior to puberty, although they continue to mature and exit the thymus throughout a lifetime. • T cells develop from pre-T cells that migrated from red bone marrow to the thymus. Figure 22.11 Chapter 22, page 847

11. Sites of Maturation • B cells and T cells are named based on the body tissues where they mature. • B cells mature in an organ in birds, known as the bursa of Fabricius, where they were first identified. • In humans, B cells mature in the bursa equivalent, which is red bone marrow. • T cells mature in the thymus. Figure 22.11 Chapter 22, page 847

12. Immunocompetence • B cells and T cells develop immunocompetence before exiting their sites of maturation. • Immunocompetence is the capability for adaptive immune responses. • The responses involve synthesizing distinctive proteins for insertion in the plasma membranes of B cells and T cells. • The proteins function as antigen receptors that recognize specific anti-gens. Figure 22.11 Chapter 22, page 848

13. Mature T Cells • Two types of mature T cells exit the thymus—helper T cells and cyto-toxic T cells. • Helper T cells are also known as CD4 T cells since their plasma mem-branes have a protein known as CD4 in addition to antigen receptors. • Cytotoxic T cells are also known as CD8 T cells because their plasma membranes have a protein called CD8 in addition to antigen receptors. • Both types of mature T cells have different functions in an immune re-sponse, as will be covered in these notes. Figure 22.11 Chapter 22, page 848

14. Types of Adaptive Immunity • The two types of adaptive immunity are cell-mediated immunity and antibody-mediated immunity. • Both types of adaptive immune responses are triggered by antigens (Ag). • In cell-mediated immunity, cytoxic T cells directly attack invading anti-gens. Chapter 22, page 848

15. Types of Adaptive Immunity (continued) • In antibody-mediated immunity, B cells are transformed into plasma cells, which synthesize and secrete proteins known as antibodies (Ab) or immunoglobulins. • An antibody binds to and inactivates a specific antigen in the immune response. • Helper T cells assist cell-mediated immunity and antibody-mediated immunity. Chapter 22, page 848

16. Cell-Mediated Immunity • Cell-mediated immunity—which involves directly attacking cells— is most effective in response to: • Intracellular pathogens, including viruses, bacteria, and fungi • Some cancer cells • Foreign tissue transplants Intracellular = within a cell. Chapter 22, page 848

17. Antibody-Mediated Immunity • Antibody-mediated immunity is involved primarily in response to extra-cellular pathogens. • The pathogens include viruses, bacteria, and fungi in the body fluids found outside of cells. • Antibody-mediated immunity is also known as humoral immunity since antibodies bind to antigens in humors (fluids), including the blood and lymph. Extracellular = outside of a cell. Chapter 22, page 848

18. Antigenic Responses • Usually, when an antigen first enters the body, only a small group of lymphocytes exists that has the correct antigen receptors to respond to the antigen. • These lymphocytes include helper T cells, cytotoxic T cells, and B cells. • An antigen triggers either cell-mediated or antibody-mediated immunity depending on the site of the antigen (i.e., intracellular or extracellular). Chapter 22, page 848

19. Antigenic Responses (continued) • An antigen inside body cells trigger an cell-mediated immune response by cytotoxic T cells. • An antigen in extracellular fluids trigger an antibody-mediated response by B cells. • Both immune responses work together in eliminating an antigen from the body. Chapter 22, page 848

20. Clonal Selection • An antigen usually initially outnumbers helper T cells, cytotoxic T cells, and B cells that have the correct antigen receptors. • These lymphocytes undergoes a process called clonal selection when they encounter the antigen. • Clonal selection is the process in which a lymphocyte proliferates and differentiates in response to a specific antigen. • Clonal selection produces a population of identical cells, known as a clone, that can recognize the same antigen as the original lymphocytes. Figure 22.11 Chapter 22, page 848

21. Clonal Selection (continued) • Once clonal selection occurs, thousands of lymphocytes can respond to the antigen. • Clonal selection of lymphocytes occurs in secondary lymphatic organs and tissues including the spleen, lymph nodes, and lymphatic nodules. • Swollen tonsils or lymph nodes in the neck during an illness are often the result of clonal selection of lymphocytes involved in the immune re-sponse. Chapter 22, page 848

22. Effector Cells • A lymphocyte that undergoes clonal selection will produce effector cells and memory cells. • The many thousands of effector cells in the clone carry-out immune responses that result in the destruction or inactivation of the antigen. • Effector cells include helper T cells, active cytotoxic T cells, and B cells, all of which are part of their respective clones. • Most effector cells die after an immune response ends since their work is done. Chapter 22, page 848

23. Memory Cells • Memory cells do not actively participate in an initial immune response to an antigen. • If the same antigen is encountered again in the future, thousands of memory cells of a clone can initiate a more rapid response than during the first encounter. • Memory cells respond to subsequent appearances of the antigen by proliferating and differentiating into effector cells and more memory cells. • This response to the antigen is usually rapid and vigorous so that the antigen is destroyed before any signs or symptoms of the disease are apparent. Chapter 22, page 848

24. Memory Cells (continued) • Memory cells include memory helper T cells and memory cytotoxic T cells that are part of a T cell clone, and memory B cells that are part of a B cell clone. • Memory T cells can persist for decades following an initial immune re-sponse. Chapter 22, page 848

25. Immunogenicity • Two functional characteristics of antigens are their immunogenicity and reactivity. • Immunogenicity is the ability to trigger an immune response by stim-ulating the production of specific antibodies or proliferation of specific T cells. • The term antigen is derived from its function as an antibody generator. Chapter 22, page 849

26. Reactivity • Reactivity is the ability of an antigen to react or respond specifically to the antibody or cells it provoked. • Immunologists define antigens as substances that have reactivity, and complete antigens as substances that have both immunogenicity and reactivity. • In common practice, including in these notes, the term ‘antigen’ is used to imply both aspects. Chapter 22, page 849

27. Antigenic Substances • Entire microbes or individual parts of microbes serve as antigens. • Bacterial structures—including flagella, capsules and cell walls—can be antigenic. • Toxins released by bacterial (bacterial toxins) are also antigenic. • Non-microbial antigens include chemical components of pollen, egg white, incompatible blood cells, and transplanted organs and tissues. Chapter 22, page 849

28. Immune Response Triggers • Antigens originating in the external environment offer many opportun-ities to trigger an immune response. • Small parts of an antigen molecule, known as epitopes, often serve as the trigger. • An antigen can have many epitopes—each one elicits the production of a specific antibody or activates a specific T cell in the immune system response. Epitope = a unique shape or marker carried on an antigen's surface, which triggers a corresponding antibody response. (http://www.thyroid-info.com) Chapter 22, page 849

29. Routes Into Lymphatic Tissue • Antigens that breach the innate defenses of the body follow one of three paths into lymphatic tissue: • Most antigens entering the blood are trapped in the spleen. • Antigens penetrating the skin enter lymphatic vessels and lodge in lymph nodes. • Antigens penetrating mucous membranes are trapped by mucosa-associated lymphatic tissue (MALT). Chapter 22, page 849

30. Chemical Nature of Antigens • Antigens are generally large, complex molecules—many are proteins. • Lipoproteins, glycoproteins, some polysaccharides, and nucleic acids may also act as antigens. • Large molecules that have simple, repeating units—such as cellulose and plastics—are inert and usually not antigenic. • Plastics are often used for artificial hearts and joints since they are inert and not as subject to rejection by the recipient. Inert = having no biological or catalytic activity. Chapter 22, page 849

31. Haptens • Smaller antigenic molecules that have reactivity but lack immunogen-icity are known as haptens. • A hapten can trigger an immune response if attached to a larger carrier molecule. • The toxin in poison ivy is a hapten, which triggers an immune response once combines with a body protein. Chapter 22, page 849

32. Haptens (continued) • Some drugs, such as penicillin, can combine with certain proteins of the body to form immunogenic complexes (some people are allergic to pen-icillin). • Hapten-stimulated responses can trigger allergic reactions to drugs and substances. Chapter 22, page 849

33. Autoimmune Disorders • Antigens, as discussed so far, are foreign substances that are not part of the body’s tissues. • Sometimes the immune system can fail to distinguish self from non-self (‘friend-or-foe’). • In autoimmune disorders, molecules or cells of the body are attacked by the immune system as if they were foreign invaders. • A brief discussion of autoimmune disorders can be found on pages 867-68 of the textbook. Chapter 22, page 849

34. Diversity of Antigen Receptors • The immune system can recognize and respond to more than a billion different epitopes on antigens. • T cells and B cells are present in the body even before an antigen enters the body. • The ability of these cells to recognize a very large number of epitopes is due to the large and diverse number of antigen receptors on their plasma membranes. • The immune system also recognizes many synthetic molecules that do not exist in nature. Chapter 22, page 849

35. Genetic Recombination • The diversity of antigen receptors results from the rearrangement of a few hundred versions of small gene segments in a process known as genetic recombination. • The gene segments are assembled in various combinations while B cells and T cells differentiate from stem cells in the red bone marrow and thymus. • Each B cell and T cell has a unique set of genetic segments that codes for a unique antigen receptor due to genetic recombination. • The receptors are inserted into the plasma membrane of the B cell or T cell after transcription and translation (from DNA, to messenger RNA, to protein). Chapter 22, page 849

36. Major Histocompatibility Complexes • Major histocompatibility complex (MHC) antigens are ‘self-antigens’ found on the plasma membrane of body cells. • These glycoproteins are also known as human leukocyte antigens (HLA) because they were first identified on the membranes of white blood cells. • MHC antigens are unique to each individual except in monozygotic twins. • Between several thousand and 100,000 MHC molecules characterize the plasma membrane of body cells (except for red blood cells). Monozygotic twins = sometimes called identical twins although this is not a completely accurate characterization. Chapter 22, page 850

37. MHCs (continued) • MHC antigens assist T cells in recognizing that an antigen is not-self— the recognition process is the first step in an adaptive immune response. • MHC antigens are classified as: • Class I (MHC-I) built into the plasma membranes of all body cells except for red blood cells, and • Class II (MHC-II) found on the surfaces of antigen-presenting cells. • MHC antigens are the reason organs and other tissues may be rejected when transplanted from one person to another. Chapter 22, page 850

38. Antigen Processing and Presentation • B cells and T cells must recognize the foreign antigen for an adaptive im-mune response to occur. • B cells recognize and bind to antigens in lymph, interstitial fluid, and blood plasma. • T cells recognize fragments of antigenic proteins that are processed and presented. Chapter 22, page 850

39. Antigen Processing and Presentation (continued) • Antigenic proteins are broken-down into peptide fragments that associate with MHC molecules. • The antigen-MHC complex is then inserted into the plasma membrane of a body cell in a process known as antigen presentation. • T cells ignore the antigen-MHC complex when its peptide fragment is from a self-protein. Chapter 22, page 850

40. Antigen Processing and Presentation (continued) • If the peptide fragment is from a foreign protein, T cells recognize the antigen-MHC complex as a foreign intruder, which triggers an immune response. • Antigen processing and presentation is either exogenous or endogenous. Chapter 22, page 850

41. Exogenous Antigens • Exogenous antigens are foreign antigens found outside of body cells (I.e., extracellular). • They include bacteria, bacterial toxins, parasitic worms, dust, pollen, and viruses that have not yet infected body cells. • Antigen-presenting cells (APCs)—dendritic cells, macrophages, and B cells—process and present exogenous antigens. • The steps in the processing and presenting of an exogenous antigen are described on the next two slides. Chapter 22, page 850

42. Exogenous Processing Steps Ingestion of an antigen by an APC via phagocytosis or endocytosis— ingestion can occur almost anywhere in the body. Digestion of the antigen to form peptide fragments—protein-digesting enzymes split the antigen into short peptide fragments within a phago-some or endosome of the APC. Synthesis of MHC-II molecules in the endoplasmic reticulum of the APC. Packaging of the MHC-II molecules into vesicles contained within the APC. Figure 22.13 Chapter 22, page 850

43. Exogenous Processing Steps (continued) Fusion and merging of the vesicles containing peptide fragments and MHC-II molecules. Binding of the peptide fragments with the MHC-II molecules to form anti-gen-MHC-II complexes. Insertion of the antigen-MHC-II complexes into the plasma membrane of the APC via exocytosis. Figure 22.13 Chapter 22, page 850

44. Post-Processing • The APC migrates to lymphatic tissue to present the antigen to T cells. • A small number of T cells with receptors of comparable shape recognize and bind to the antigen fragment-MC II complex to trigger an adaptive immune response. • The presentation of these antigen-MC-II complexes informs the T cells that pathogens are in the body and that defensive actions are needed. Chapter 22, page 850

45. Endogenous Antigens • Foreign antigens found inside body cells are called endogenous antigens. • Endogenous antigens may be viral proteins once a virus has infected a cell and controls its metabolism. • They may also be: • Toxins produced by an intracellular bacterium. • Abnormal proteins synthesized by a cancerous cell. Chapter 22, page 850

46. Endogenous Antigens (continued) • The steps in the processing and presenting of an endogenous antigen by an infected cell are described on the next two slides. • Most body cells can process and present endogenous antigens to trigger immune responses. Chapter 22, page 850

47. Endogenous Processing Steps Digestion of an antigen into peptide fragments—enzymes split the anti-gen into short peptide fragments within the infected cell. Synthesis of MHC-I molecules by endoplasmic reticulum in the infected cell. Binding of the peptide fragments to MHC-I molecules—the fragments enter the endoplasmic reticulum and bind with MHC-I molecules to form antigen-MHC-I complexes. Figure 22.14 Chapter 22, page 850

48. Endogenous Processing Steps (continued) Packaging of the antigen–MHC-I complexes into vesicles by the endo-plasmic reticulum. Insertion of the antigen-MHC-I complexes into the plasma membrane of the infected cells via exocytosis. Figure 22.14 Chapter 22, page 851

49. Cytokines • Cytokines are small protein hormones that can either stimulate or inhibit many cell functions such as those involved in growth and differentiation. • Lymphocytes, antigen-presenting cells, monocytes, hepatocytes, and cells in the kidneys secrete cytokines. • Some cytokines stimulate the proliferation of progenitor cells in red bone marrow, and others regulate the activities of cells in innate defenses or adaptive responses. • Table 22.2 in the textbook summarizes the roles of cytokines in immune responses. Table 22.2 Chapter 22, page 852

50. Cell-Mediated Immunity