Adaptive Immune Response

1. Adaptive Immune Response Chapter 16

2. What am I?

3. Strategy of Adaptive Immune Response • First response to particular antigen called primary response • May take a week or more to develop • Immune system remembers pathogen on subsequent exposure • Termed secondary response • Adaptive immunity divided into • Humoral immunity • Eliminates extracellular pathogens • Cellular immunity • Eliminates intracellular pathogens

4. Strategy of Adaptive Immune Response • Overview of humoral immunity • Mediated by B lymphocytes • a.k.a B cells • Develops in bone marrow • B cells may be triggered to proliferate into plasma cells • Plasma cells produce antibodies • Antibodies produce when antigen bonds B cell receptor • Some B cells produce memory cells

5. Strategy of Adaptive Immune Response

6. Strategy of Adaptive Immune Response • Overview of cellular immunity • Mediated by T lymphocytes • a.k.a T cells • Matures in thymus • Divided into 2 subsets • Cytotoxic T cells • Helper T cells • T cell receptors help with antigen recognition

7. Anatomy of the Lymphoid System • Lymphoid system collection of tissues and organs designed to bring B and T cells in contact with antigens • In order for body to mount appropriate response, immune cells must encounter antigen • Lymphoid system includes • Lymphatic vessels • Secondary lymphoid organs • Primary lymphoid organs

8. Anatomy of the Lymphoid System

9. Anatomy of the Lymphoid System • Lymphatic vessels • Carry lymph to body tissues • Lymph formed as result of body’s circulatory system • Lymph travels through vessels to lymph nodes • Material such as protein is removed • Fluid portion empties back into blood stream

10. Anatomy of the Lymphoid System • Secondary lymphoid organs • Sites where lymphocytes gather to encounter antigens; organs include • Lymph nodes • Spleen • Tonsils • Adenoids • Appendix • Organs situated strategically • Allows for initiation of immune response from nearly any place in body

11. Anatomy of the Lymphoid System • Primary lymphoid organs • Bone marrow and thymus are primary lymphoid organs • Location where stem cells destined to become B and T cells mature • B cells mature in bone marrow • T cells mature in thymus • Once mature, cells leave primary lymphoid organs and migrate to secondary lymphoid organs

12. Nature of Antigens • Coined from compounds that elicit antibody production • Antibody generator • Includes an enormous variety of materials • Today, term used to describe any compound that elicits an immune response • Antigen that causes immune response termed immunogen • Proteins and polysaccharides induce string response • Lipids and nucleic acids often do not • Recognition of antigen directed at antigenic determinant or epitope

13. Nature of Antibodies • Structure of the Antibody (Ab) • Basic Y-shaped structure • Made of four chains of amino acids held together by disulfide bonds • Two chains are heavy • Two chains are light • Each heavy and light chain has a constant region • The constant region is known as Fc region • Each heavy and light chain has a variable region • Variable region is unique to each Ab • This region binds to a specific Antigen and is known as “Fab” region

14. Nature of Antibodies • Protective outcomes of antibody-antigen binding • Neutralization • Prevents toxin from interacting with cell • Immobilization and prevention of adherence • Antibody bonding to cellular structures to interfere with function • Agglutination and precipitation • Clumping of bacterial cells by specific antibody • Bacteria more easily phagocytized

15. Nature of Antibodies • Protective outcomes of antibody-antigen binding • Opsinization • Coating of bacteria with antibody to enhance phagocytosis • Complement activation • Antibody bonding triggers classical pathway • Antibody-dependent cellular cytotoxicity • Multiple antibodies bind a cell which becomes target for certain cells

16. Nature of Antibodies • Five classes of Ab • IgM • First Ab to respond to infection • 5 – 13% of Ab in circulation • Structure: pentamer • Five monomer units joined together at the constant region • Found on the surface of B lymphocytes as a monomer • Only Ab that can be formed by the fetus

17. Nature of Antibodies • Five classes of Ab • IgG • Dominant Ab in circulation • 80 – 85% Ab in circulation • Structure = monomer • Only Ab that can cross the placenta • The antibody of memory!!!!! • IgA • Found in secretions • 10 - 13 % of Ab in circulation • Structure • Monomer in serum • Dimer in secretions • Breast milk, mucus, tears and saliva

18. Nature of Antibodies • Five classes of Ab • IgD • <1% of total Ab in circulation • Structure = monomer • Maturation of antibody response • IgE • Barely detectable in circulation • Structure = monomer • Active in allergic reaction

19. Clonal Selection of Lymphocytes • When antigen introduces into body, only appropriate antibody bonds • Initiates multiplication of specific antigen • Process called clonal selection • Repeated cycles of cell division generates population of copied antibodies • Termed clonal expansion • Without sustained stimulation, cells undergo apoptosis

20. Clonal Selection of Lymphocytes • Lymphocyte characteristics include • Immature • Antigen specific receptors not fully developed • Naive • Have antigen receptor but have not encountered antigen • Activated • Able to proliferate • Have bound antigen • Effectors • Descendents of activated lymphocytes • Able to produce specific cytokines • Plasma cells, T helper and cytotoxic T cells effector cells • Memory lymphocytes • Long-lived descendents of activated lymphocytes • Memory cells responsible for seed and effectiveness of secondary response • Remembers antigen on subsequent exposure

21. B Lymphocyte and Antibody Response • Antigen binds to B cell receptor • Poises B cell to respond • In many cases B cell needs conformation from helper T cells • Ag enters the body and is phagocytized and processed by macrophages • These macrophages destroy Ag and present a portion on the surface of the macrophage next to self Ag • Macrophages are called antigen-presenting cells (APC) • Processed Ag combines with specific TH with the appropriate receptor • APC releases substances to activate TH cell • TH cell activates B cells to divide and differentiate • Produce plasma cells and memory B cells

22. B Lymphocyte and Antibody Response

23. B Lymphocyte and Antibody Response • Characteristic of primary response • Lag period of 10 to 12 days occurs before antibody detection in blood • Activated B cells proliferate and differentiate into increasing numbers of plasma cells as long as antigen is present • Net result is slow steady increase in antibody titer

24. B Lymphocyte and Antibody Response • Over time, some B cells undergo changes enhancing immune response including • Affinity maturation • Class switching • Formation of memory cell • Affinity maturation • Form of natural selection • Occurs among proliferating B cells • Fine tunes quality of response with respect to specificity • B cell receptors more and more specific to antigen • Antibody bonds antigen more tightly

25. B Lymphocyte and Antibody Response • Class switching • B cells initially programmed to differentiate into plasma cells • Plasma cells secrete IgM antibodies • Helper T cells produce cytokines • Some B cells switch programming • Differentiate to plasma cells that secrete other classes of antibodies • Commonly IgG

26. B Lymphocyte and Antibody Response • Formation of memory • B cells that have undergone class switching • Produce IgG antibody • IgG is antibody of memory • IgG antibody can circulate in body for years allowing protection against specific antigens

27. B Lymphocyte and Antibody Response • Characteristics of secondary response • Memory cells responsible for swift effective reaction of secondary response • Often eliminate invaders before noticeable harm is done • Vaccine exploits phenomenon of immunologic memory • Some memory B cells will differentiate into plasma cells • Results in rapid production of antibodies

28. B Lymphocyte and Antibody Response • T-independent antigens • Can stimulate antibody response • Activate B cells without helper T cells • Few antigens are T-independent • B cell receptors bind antigen simultaneously • Leads to B cell activation • Some polysaccharides and lipopolysaccharides act as T-independent antigens

29. T LymphocytesAntigen Recognition and Response • General characteristics of T cells • Have multiple copies of T cell receptors • Receptors have variable sites of antigen bonding • Role of T cells different from B cells • T cells never produce antibodies • T cells armed with effectors that interact directly with antigen • T cell receptor does not react with free antigen • Antigen must be present by APC

30. T LymphocytesAntigen Recognition and Response • General Characteristics • During antigen presentation, antigen cradled in grove of major histocompatability complex molecule (MHC molecule) • Two types MHC • MHC class I • Bind endogenous antigen • MHC class II • Bind exogenous antigen

31. T LymphocytesAntigen Recognition and Response • General characteristics • Two major function T cell populations • Cytotoxic T cells • Proliferate and differentiate to destroy infected or cancerous “self” cells • Have CD8 marker • Recognize MHC class I • Helper T cells • Multiply and develop into cells that activate B cells and macrophages • Stimulate other T cells; orchestrate immune response • Have CD4 marker • Recognize antigen display by MHC class II

32. T LymphocytesAntigen Recognition and Response • Functions of Tc (CD8) cells • Induce apoptosis in “self” cells • Cells infected with virus or intracellular microbe • Destroys cancerous “self” cells • Nucleated cells degrade portion of proteins • Load peptides into groove of MHC class I molecule • MHC class I molecule recognized by circulating Tc cell • Cell destroyed by lethal effector function of Tc cell • Tc cells releases pre-formed cytokines to destroy cell

33. T LymphocytesAntigen Recognition and Response • Functions of TH (CD4) cells • Orchestrate immune response • Recognize antigen presented by MHC class II molecules • MHC class II molecules found only on APC • If TH cell recognizes antigen, cytokines are delivered • Cytokines activate APC to destroy antigen

34. T LymphocytesAntigen Recognition and Response • Role of TH cells in B cell activation • If TH cell encounters B cell bearing peptide: MHC calls II complex • TH cell responds by producing cytokines • B cell is activated in response to cytokine stimulation • B cell proliferates and undergoes class switching • Also drives formation of B memory cells

35. T LymphocytesAntigen Recognition and Response • Role of TH cells in macrophage activation • Macrophages routinely engulf invading microbes resistant to lysosomal killing • TH cells recognize macrophage with engulfed microbes resistant to killing • TH cells activate macrophages by delivering cytokines that induce more potent destructive mechanisms

36. Natural Killer Cells • Natural killer cells descend from lymphoid stem cells • They lack antigen specificity • No antigen receptors • Recognize antigens by means of Fc portion of IgG antibodies • Allow NK cells to attach to antibody-coated cells • Actions augment adaptive immune response • Important in process of antibody dependent cellular toxicity • Enable killing of host cells with foreign protein in membrane • Natural killer cells recognize destroyed host cells with no MHC class I surface molecules • Important in viral infection

37. Lymphocyte Development • During lymphocyte development, B and T cells acquire ability to recognize distinct epitopes • Once committed to specific antigen, cells “checked out” to ensure proper function • B cells undergo developmental stages in bone marrow • T cells go through process in thymus

38. Summary of Adaptive Immune Response