1. Adaptive immunity 2440 spring lecture #7 5/27/10

2. Specific Defenses Figure 22–14 Forms of Immunity.

3. Review Innate immunity Membranes, surface barriers inflammation fever neutrophils- macrophages complement NK cells interferons

4. Figure 21.1 Innate defenses Surface barriers Skin Mucous membranes Internal defenses Phagocytes NK cells Inflammation Antimicrobial proteins Fever Humoral immunity B cells Cellular immunity T cells Adaptive defenses

5. Specific Defenses Four Properties of Immunity –Specificity Each T or B cell responds only to a specific antigen and ignores all others –Versatility The body produces many types of lymphocytes: –each fights a different type of antigen –active lymphocyte clones itself to fight specific antigen

6. Specific Defenses Four Properties of Immunity –Memory Some active lymphocytes (memory cells): –stay in circulation –provide immunity against new exposure –Tolerance Immune system ignores “normal” (self) antigens

7. Specific Defenses The Immune Response –Two main divisions Cell-mediated immunity (T cells) Antibody-mediated immunity (B cells)

8. Specific Defenses 22–15 An Overview of the Immune Response.

9. T Cells and Immunity Cell-mediated immunity (T cells) –Cytotoxic T cells (also called T C cells) Attack cells infected by viruses Responsible for cell-mediated immunity –Helper T cells (also called T H cells) Stimulate function of T cells and B cells –Suppressor T cells (also called T S cells) Inhibit function of T cells and B cells

10. T Cells and Immunity MHC Proteins Involved in self/nonself recognition –The membrane glycoproteins that bind to antigens –Genetically coded in chromosome 6 The major histocompatibility complex (MHC) Differs among individuals

11. T Cells and Immunity Antigen Recognition –T cells only recognize antigens that are bound to glycoproteins in plasma membranes Antigens must be presented

12. T Cells and Immunity Antigen-Presenting Cells (APCs) –Responsible for activating T cells against foreign cells and proteins

13. Antigen-Presenting Cells (APCs) Engulf antigens Present fragments of antigens to be recognized by T cells Major types –Dendritic cells in connective tissues and epidermis –Macrophages in connective tissues and lymphoid organs –B cells

14. Macrophages and Dendritic Cells Present antigens and activate T cells –Macrophages mostly remain fixed in the lymphoid organs –Dendritic cells internalize pathogens and enter lymphatics to present the antigens to T cells in lymphoid organs Activated T cells release chemicals that –Prod macrophages to become insatiable phagocytes and to secrete bactericidal chemicals

15. Figure 21.10

16. Self-Antigens: MHC Proteins Protein molecules (self-antigens) on the surface of cells Antigenic to others in transfusions or grafts Example: MHC proteins –Coded for by genes of the major histocompatibility complex (MHC) and are unique to an individual

17. Diversity of antigen receptors –Human immune system able to recognize and bind to at least a billion different epitopes –Result of genetic recombination – shuffling and rearranging of a few hundred versions of several small gene segments Major Histocompatibility Complex Antigens –MHC or human leukocyte antigens (HLA) –Normal function to help T cells recognize foreign or self –Class I MHC (MHC-I) – built into all body cells except RBCs –Class II MHC (MHC-II) – only on antigen presenting cells

18. T Cells and Immunity Class I MHC Proteins –Pick up small peptides in cell and carry them to the surface T cells ignore normal peptides Abnormal peptides or viral proteins activate T cells to destroy cell

19. T Cells and Immunity Class II MHC Proteins –Antigenic fragments From antigenic processing of pathogens Bind to Class II proteins Inserted in plasma membrane to stimulate T cells

20. T Cells and Immunity CD Markers –Also called cluster of differentiation markers In T cell membranes Molecular mechanism of antigen recognition More than 70 types: –designated by an identifying number CD3 Receptor Complex –Found in all T cells

21. T Cells and Immunity CD4 Markers (target for HIV virus) –Found on cytotoxic T cells and suppressor T cells –Respond to antigens on Class I MHC proteins CD8 Markers –Found on helper T cells –Respond to antigens on Class II MHC proteins

22. T Cells and Immunity CD8 or CD4 Markers –Bind to CD3 receptor complex –Prepare cell for activation

23. MHC Proteins Classes of MHC proteins –Class I MHC proteins, found on virtually all body cells –Class II MHC proteins, found on certain cells in the immune response (APCs) MHC proteins display peptides (usually self- antigens) In infected cells, MHC proteins display fragments of foreign antigens, which help mobilize

24. Figure 21.21 Ag-infected body cell engulfed by dendritic cell Becomes Activates Induce co-stimulation Free Ags may directly activate B cell Naïve CD4 T cells Activated to clone and give rise to Naïve CD8 T cells Antigen- activated B cells Activated to clone and give rise to Cytokines stimulate Activated cytotoxic T cells Memory helper T cells Activated helper T cells Memory cytotoxic T cells Together the nonspecific killers and cytotoxic T cells mount a physical attack on the Ag Nonspecific killers (macrophages and NK cells of innate immunity) Circulating lgs along with complement mount a chemical attack on the Ag Antibodies (Igs) Secrete Plasma cells (effector B cells) Memory B cells Clone and give rise to Inhibits Antigen (Ag) intruder Innate defenses Surface barriers Internal defenses Adaptive defenses Triggers Ag-presenting cell (APC) presents self-Ag complex Cell-mediated immunity Humoral immunity

25. Exogenous and Endogenous Antigens Exogenous antigens – present in fluid outside body cells –Antigen-presenting cells (APCs) include dendritic cells, macrophages and B cells –Ingest antigen, process, place next to MHC-II molecule in plasma membrane, and present to T cells Endogenous antigens – antigens inside body cells –Infected cell displays antigen next to MHC-I

26. Phagocytosis or endocytosis of antigen APCs present exogenous antigens in association with MHC-II molecules Antigen- presenting cell (APC) MHC-II self-antigen Antigen peptide fragments Key: Exogenous antigen 1 Phagocytosis or endocytosis of antigen Digestion of antigen into peptide fragments Phagosome or endosome APCs present exogenous antigens in association with MHC-II molecules Antigen- presenting cell (APC) MHC-II self-antigen Antigen peptide fragments Key: 1 2 Exogenous antigen Phagocytosis or endocytosis of antigen Digestion of antigen into peptide fragments Phagosome or endosome APCs present exogenous antigens in association with MHC-II molecules Antigen- presenting cell (APC) Synthesis of MHC-II molecules MHC-II self-antigen Antigen peptide fragments Key: Endoplasmic reticulum 1 3 2 Exogenous antigen Phagocytosis or endocytosis of antigen Digestion of antigen into peptide fragments Phagosome or endosome APCs present exogenous antigens in association with MHC-II molecules Antigen- presenting cell (APC) Packaging of MHC-II molecules into a vesicle Synthesis of MHC-II molecules MHC-II self-antigen Antigen peptide fragments Key: Endoplasmic reticulum 1 4 3 2 Exogenous antigen Phagocytosis or endocytosis of antigen Digestion of antigen into peptide fragments Phagosome or endosome APCs present exogenous antigens in association with MHC-II molecules Antigen- presenting cell (APC) Vesicles containing antigen peptide fragments and MHC-II molecules fuse Packaging of MHC-II molecules into a vesicle Synthesis of MHC-II molecules MHC-II self-antigen Antigen peptide fragments Key: Endoplasmic reticulum 1 5 4 3 2 Exogenous antigen Phagocytosis or endocytosis of antigen Digestion of antigen into peptide fragments Antigen peptide fragments bind to MHC-II molecules Phagosome or endosome APCs present exogenous antigens in association with MHC-II molecules Antigen- presenting cell (APC) Vesicles containing antigen peptide fragments and MHC-II molecules fuse Packaging of MHC-II molecules into a vesicle Synthesis of MHC-II molecules MHC-II self-antigen Antigen peptide fragments Key: Endoplasmic reticulum 1 5 6 4 3 2 Exogenous antigen Phagocytosis or endocytosis of antigen Digestion of antigen into peptide fragments Antigen peptide fragments bind to MHC-II molecules Phagosome or endosome APCs present exogenous antigens in association with MHC-II molecules Antigen- presenting cell (APC) Vesicles containing antigen peptide fragments and MHC-II molecules fuse Packaging of MHC-II molecules into a vesicle Synthesis of MHC-II molecules MHC-II self-antigen Antigen peptide fragments Key: Endoplasmic reticulum Vesicle undergoes exocytosis and antigen – MHC-II complexes are inserted into plasma membrane 1 5 6 7 4 3 2 Exogenous antigen

27. Activation and clonal selection of a helper T cell

28. Endogenous Antigens

29. T Cells and Immunity Costimulation –For T cell to be activated, it must be costimulated By binding to stimulating cell at second site Which confirms the first signal Without co-stimulation, anergy occurs T cells Become tolerant to that antigen Are unable to divide Do not secrete cytokines

30. Activation and clonal selection of a cytoxic T cell

31. Figure 21.16 Maturation CD4 cell T cell receptor T cell receptor CD4 Helper T cells (or regulatory T cells) Cytotoxic T cells APC (dendritic cell) APC (dendritic cell) Activation Memory cells CD8 cell CD8 Lymphoid tissues and organs Blood plasma Thymus Class I MHC protein Class II MHC protein Effector cells Adaptive defensesCellular immunity Immature lymphocyte Red bone marrow

32. B Cells and Immunity B Cell Division –Activated B cell divides into Plasma cells Memory B cells

33. B Cells and Immunity Plasma Cells –Synthesize and secrete antibodies into interstitial fluid Memory B Cells –Like memory T cells, remain in reserve to respond to next infection

34. Five Classes of Antibodies (Immunoglobulins) 1.IgG: the main class of antibodies found in the blood 2.IgA: occurs in small amounts in blood and in larger amounts in body secretions (tears, milk, saliva and mucus) 3.IgM: a huge antibody made up of five monomer units and is the first to arrive to neutralize antigen 4.IgE: has a special affinity for receptors on the plasma membranes of basophils in blood or mast cells in tissues 5.IgD: found mainly on B-cell membranes and is rarely secreted

35. Immune System Development Four Effects of Aging on the Immune Response –Thymic hormone production is greatly reduced –T cells become less responsive to antigens –Fewer T cells reduces responsiveness of B cells –Immune surveillance against tumor cells declines