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Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 15 Lecture Outline.

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Presentation on theme: "Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 15 Lecture Outline."— Presentation transcript:

1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 15 Lecture Outline

2 T Cells 15-43

3 Killer or Cytotoxic T Cells  Carry CD8 cell surface marker  Destroy body cells that possess foreign antigens  Usually from a pathogen, but can be from malignancy or self cells never seen by immune system  Kill by cell-mediated destruction  That is, must be in contact with victim cell  Kill by secreting perforins which create a pore in victim's membrane and cause lysis  Also secrete granzymes which cause destruction of victim's DNA 15-44

4 Helper and Suppressor T Cells  Helper T-cells carry CD4 surface marker  Indirectly participate by enhancing responses of both killer T-cells and B- cells  Regulatory T-cells decrease responses of killer T-cells and B cells  Carry CD25 surface marker (and CD4)  Help protect against autoimmune responses 15-45

5 Lymphokines  Are cytokines secreted by lymphocytes  Usually called interleukin-1, 2, 3... or IL- 1, IL-2... 15-46

6 T Cell Receptor Proteins  Only protein antigens are recognized by most T cells  T cell receptors cannot bind to free antigens  T cells respond to foreign antigens when they are presented on surface of antigen-presenting cells  Chief antigen presenting cells are macrophages and dendritic cells 15-47

7  Originate in marrow, then migrate to most tissues  Prominent where pathogens might enter body  Engulf protein antigens, partially digest them, and display polypeptide fragments on surface for T cells to "see" Dendritic Cells 15-48

8 Dendritic Cells continued  Fragments are associated on surface with histocompatibility antigens which are necessary to activate T-cells  To increase chance of interacting with correct T-cells, dendritic cells migrate to secondary lymphoid organs  Where secrete chemokines to attract T-cells 15-49

9 Histocompatibility Antigens 15-50

10 Histocompatibility Antigens  Are on surface of all body's cells except mature RBCs  Also called human leukocyte antigens (HLAs)  Are coded for by group of 4 genes on chromosome 6 called the major histocompatibility complex (MHC)  The 4 genes have multiple alleles creating many possible MHC types 15-51

11  MHC genes produce 2 types of cell surface molecules: class-1 and class-2  Class-1s are made by all cells except RBCs  Class-2s are made only by antigen-presenting cells and B-cells  These present class-2s, together with foreign antigens, to helper T-cells  This is the only way to activate helper T-cells so they can promote B-cell activity MHC 15-52

12  In order for killer and helper T-cells to function they require co-presentation of antigen with a specific MHC marker  Killer T-cells are activated to kill victim cell only by co- presentation of antigen and class-1 marker  Helper T-cells require antigen and class-2 marker MHC continued 15-53

13  Co-presentation requirement comes from presence of different coreceptors on killer and helper T cells  Killer T coreceptor CD8 interacts only with class-1s  Helper T coreceptor CD4 interacts only with class-2s MHC continued 15-54

14 Interactions Between Antigen Presenting Cells and Lymphocytes 15-55

15 T Cell Response to a Virus  When virus infects body it is phagocytized by macrophage or dendritic cell  Its partially-digested polypeptide fragments are antigens that are displayed on surface  Form a complex with class-2 MHC molecules that macrophages present to helper T-cells  Helper T-cells bind and are activated  Can now promote B-cell activity 15-56

16 15-57 The interaction of an antigen-presenting cell (a macrophage in this example), T- cells, and B-cells: Contact between a macrophage and a T-cell requires helper T-cell interact with antigen and Class 2-MHC molecule. The helper T-cell is now activated and able to interact with B-cell

17  When macrophages and T cells form a complex, macros secrete IL-1 and Tumor Necrosis Factor (which is good at killing cancer cells)  IL-1 stimulates cell division and proliferation of helper T-cells  Activated helpers secrete M-CSF and gamma- interferon and IL-2  Promotes activity of macrophages  Activated helpers activate B cells Macrophage-T cell Interaction 15-58

18 Killer T cell Activity  Killer Ts destroy infected cells if class-1 markers are present 15-59

19 Helper T cell-B cell Interactions  Activated helper Ts promote humoral response of B cells by binding to their surface antigens and MHC class 2s  This stimulates proliferation of Bs, their conversion to plasma cells, and their secretion of antibodies 15-60

20 Destruction of T cells  Activated Ts must be destroyed after infection is over  Occurs because Ts produce a surface receptor called FAS  FAS production increases during infection  After a few days, Ts begin to produce FAS ligand  Binding of FAS to FAS ligand triggers apoptosis (cell suicide) 15-61

21 Active Immunity 15-62

22 Primary and Secondary Responses  On 1st exposure to pathogen, there is latency of 5-10 days before specific antibodies are made (= primary response)  Antibody levels plateau after few days and decline after a few weeks  Subsequent exposure to same antigen causes secondary response  Antibody production is much more rapid and sustained 15-63

23 Clonal Selection Theory  Is mechanism by which secondary immune responses are produced  Each B cell produces only 1 kind of antibody and related antigen receptor (on its surface)  Exposure to its antigen stimulates a B cell to divide until a large population of genetically identical cells (clones) is produced  Some of these become plasma cells and secrete antibodies  Some become memory cells that can be stimulated to produce antibodies in the secondary response 15-64

24 15-65 The clonal selection theory as applied to B- lymphocytes

25 15-66

26 Germinal Centers  Develop in lymph nodes and spleen from a cloned and activated B-cell  Which proliferate and undergo hypermutation  Generating and secreting diverse antibodies for the secondary immune response 15-67

27 Active Immunity  Development of a secondary response provides active immunity  Immunizations induce primary responses by inoculating people with pathogens whose virulence has been attenuated or destroyed (vaccinations)  Cause development of B-cell clones that can provide secondary response 15-68

28 Immunological Tolerance  Ability to produce antibodies against non-self antigens while tolerating self-antigens (immunological competence) occurs during 1 st month of life  Tolerance requires continuous exposure to an antigen  Some self-antigens, such as lens protein in eye, are normally hidden from blood  Exposure to such self-antigens results in production of autoantibodies  Killer T-cells that attack self-antigens are called autoreactive T-cells 15-69

29 Immunological Tolerance continued  2 possible mechanisms for tolerance:  Clonal deletion : tolerance occurs because T cells that recognize self-antigens are destroyed  Clonal anergy: lymphocytes directed against self- antigens are present throughout life but don't attack self-antigens  Central tolerance: mechanisms that occur in thymus or bone marrow (T-cells by apoptosis; B- cells by clonal deletion and anergy  Peripheral tolerance: involves complex mech. that produce anergy 15-70

30 Passive Immunity 15-71

31 Passive Immunity  Is immune protection produced by transfer of antibodies to a recipient from a donor  Donor was actively immunized  Person who receives these ready-made antibodies is passively immunized  Used to treat snakebite, rabies, tetanus, hepatitis 15-72

32 Passive Immunity continued  Occurs naturally before and after birth  Some antibodies from mother pass placenta to fetus during pregnancy and provide passive immunity  During 1st 2-3 days of nursing, mother produces colostrum which is rich in her antibodies and gives her immunity to infant  Immunological competence (ability to mount a specific immune response) does not develop until 1 month after birth 15-73

33 15-74

34 Monoclonal Antibodies  In a variation of passive immunity, animals (mice, sheep, rabbits) are injected with antigens and used to obtain monoclonal antibodies which are prod. by an isolated pure clone of cells  A single B-cell is fused with a cancerous myeloma cell to form a hybrid cell capable of dividing indefinitely  Result is a clone of cells that secretes monoclonal antibodies specific for single antigenic determ. site  Use for diagnosis, lab tests, and medical treatment of some cancers 15-75

35 15-76 The Production of Monoclonal Antibodies

36 Immune System and Cancer 15-77

37 Tumor Immunology  Believed that tumor cells arise often but are normally recognized and killed by immune system  When cancer develops, the immunological surveillance system of T-cells and natural killer cells has failed  Tumor biology is similar to and interrelated with functions of immune system  Most tumors are clones of single cells whose mitosis is not controlled by normal inhibitory mechanisms 15-78

38 Tumor Immunology continued  Tumor cells dedifferentiate (become less specialized like cells of an embryo)  As dedifferentiate, produce surface antigens that are normally recognized by immunological surveillance and destroyed  Because were absent at the time immunological competence was established  Body treats these antigens as foreign  Presence of these antigens provides basis of laboratory diagnostic tests for some cancers 15-79

39 Natural Killer (NK) Cells  Are lymphocytes related to T-cells  Provide first line of cell-mediated defense  Considered to be part of the innate immune system  Possess an array of surface receptors that allow them to fight viruses, bacteria, parasites and malignant cells  NK cells destroy tumors in a non-specific fashion; backed up by specific response of killer T-cells  NKs are stimulated by interferon from T-cells  NKs attack cells that lack class-1 MHC antigens  Kill with perforins and granzymes 15-80

40 Immunotherapy for Cancer  Monoclonal antibodies have been used  About 20-25% of breast cancer patients have HERZ receptors on plasma membrane of tumor cells  Monoclonal antibodies for these receptors is commercially available as Hereceptin, which blocks these receptors.  Human interferons obtained from genetically engineered bacteria are now available  Have been used for treatment of some types of lymphomas, renal carcinoma, and melanoma 15-81

41 Effects of Aging and Stress  Little is known about why susceptibility to cancer is so variable  Cancer risk increases with age  One factor may be that aging lymphocytes accumulate genetic errors that decrease effectiveness  Thymus function declines with age  Tumors grow faster in stressed animals  Stress hormones (corticosteroids) cause decreased immune function 15-82

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