Adaptive Immunity: Specific Defenses of the Host

1. 17 Adaptive Immunity: Specific Defenses of the Host

2. SLOs Differentiate between innate and adaptive immunity, and humoral and cellular immunity. Define antigen, epitope, and hapten. Explain the function of antibodies and describe their structural and chemical characteristics. Name one function for each of the five classes of antibodies. Compare and contrast T-dependent antigens and T-independent antigens. Differentiate between plasma cell and memory cell. Describe clonal selection. Describe how a human can produce different antibodies. Describe four outcomes of an antigen-antibody reaction. Differentiate between helper T and cytotoxic T Define apoptosis. Define antigen-presenting cell. Describe the role of antibodies and natural killer cells in antibody-dependent cell-mediated cytotoxicity. Identify at least one function of each of the following: cytokines, interleukins, interferons. Distinguish a primary from a secondary immune response. Contrast the four types of adaptive immunity.

3. Immune System Overview Innate immunity: An individual’s genetically predetermined resistance to certain diseases. Adaptive immunity: Ability of the body to react to specific microbial infection. Adaptive immunity • is antigen specific, has memory • is made up of two branches • Humoral Immunity (B cell mediated) • Cellular Immunity (T cell mediated) • collaborates with innate immunity • hasability to ignore healthy “self” molecules (tolerance)

4. Vocabulary • Antigen (Ag): A substance that causes the body to produce specific antibodies or sensitized T cells. • Antibody (Ab): Proteins made in response to an Ag; can combine with that Ag. • Serology: The study of reactions between antibodies and antigens. • Antiserum: A generic term for serum because it contains Ab. • Globulins: Serum proteins • Immunoglobulins (= Gamma () globulins): Serum antibodies • Complement:

5. Serum Proteins Fig 17.18

6. Antibodies recognize and react with antigenic determinants or epitopes on an antigen The Nature of Antigens Antigens and antigenic Determinants Fig 17.1

7. Haptens Fig 17.2 Definition: Small separable part of an antigen that reacts specifically with an antibody but is incapable of stimulating antibody production except in combination with a carrier protein molecule

8. The Nature of Antibodies Immunoglobulin Structure: 4 polypeptide chains (2 heavy and 2 light) • Variable regions • Constant regions Fig 17.3 Fig 17.3

9. IgGantibodies • Monomer • 80% of serum antibodies • Activate complement • In blood, lymph, and intestine • Cross placenta • Enhance phagocytosis; neutralize toxins and viruses; protects fetus and newborn • Half-life = 23 days

10. IgMAntibodies • Pentamer • 5-10% of serum antibodies • Fix complement • In blood, lymph, and on B cells • Agglutinates microbes; first Ab produced in response to infection • Half-life = 5 days

11. IgA Antibodies • Dimer • 10-15% of serum antibodies • In secretions • Mucosal protection • Half-life = 6 days

12. Monomer 0.002% of serum antibodies On mast cells, basophils, and in blood Allergic reactions; lysis of parasitic worms Half-life = 2 days Monomer 0.2% of serum antibodies In blood, lymph, and on B cells On B cells, initiate immune response Half-life = 3 days IgE Antibodies IgD Antibodies

13. B cells and Humoral Immunity Effective against free antigen (toxins, bacterial surface structures, viruses in between cells) B cell receptors (mostly IgM and IgD) Activated B-cells go through clonal expansion leading to • Plasma cells (effector cell for antibody production) and • Memory cells

14. Clonal Selection Fig 17.5 ANIMATION Humoral Immunity: Clonal Selection and Expansion

15. Response to T – dependent antigens B cells require help of T cells for most protein antigens (T-dependent ag) B cells internalize antigen and present it to T-helper cell in combination with MHC class II molecules If T cell recognizes antigen it activates B cell  clonal expansion  plasma cells and memory cells Review Fig 17.4

16. Antigen Presentation by B-cell Compare to Fig. 17.4

17. Response to T – Independent Antigens No T-helper cells involved Polysaccharides (bacterial capsules) and LPS Weak response with no memory cells Young children react poorly Fig 17.6

18. Antibody Diversity 1015 different B-cell receptors How many genes in human genome? Mechanism of antibody diversity: somatic recombination(during embryonic development) Primarily through Gene rearrangement (mix and match) Susumu Tonegawa Nobel Prize 1987

19. Antigen—Antibody Binding and its Results • Affinity: Strength of bond between Ag and Ag. • Specificity: Ab recognizes a specific epitope. Antibody function: • agglutinate and precipitate • opsonize • neutralize (immobilize and prevent adherence) • activate complement • Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) via NK cells and eosinophils Protective outcome  disposal of antigen (based on antigen-antibody binding)

20. The Results of Ag-Ab Binding Fig 17.7

22. T Cells and Cellular Immunity Compare to Fig 17.10 T cells have TCR on surface. TCR does not recognize free antigen. Ag must be presented in association with MHC on an antigen-presenting cell (APC). Antigens are processed by APC and positioned on the surface of the APC.

23. APCs • Digest antigen • Ag fragments on APC surface with MHC-II • B cells • Dendritic Cells • Macrophages • Activated macrophages: Macrophages stimulated by ingesting Ag or by cytokines. ANIMATION Cell-Mediated Immunity: Helper T Cells

24. Classes of T cells Helper T Cells (CD4, TH) • are activated by antigen presented by MHC class II. After binding to Ag presented by APC, CD4 cells secrete cytokines activating other T cells and B cells • TH1 cells activate cells involved in cellular immunity • TH2 stimulate production of eosinophils, IgM, and IgE ( associated with allergic reactions and parasitic infections) Cytotoxic T cells (CD8, TC, CTL) • activated by endogenous antigens and MHC class I • When activated transform into CTLs and memory cells • CTLs lyse target cell or induce apoptosis

25. Antigen Recognition by T Cells MHC Class I on all nucleated cells MHC Class II on surface of APCs (Macrophages, B-cells, dendritic cells)

26. Mechanism of Action of CTL Destruction of cells displaying MHC-I-Ag complexes Perforinmolecules create protein channels in target cell membrane Granzymesenter and trigger apoptosisin target cell Similar but different from MAC !! Compare to Fig. 17.11

27. Natural Killer (NK) Cells Granular leukocytes. Not immunologically specific. Lyse virus-infected and tumor cells. Kill target cell in absence of MHC-I (early stages of virus infection and tumor cells) Similar mechanism to CTLs In Antibody-Dependent Cell Mediated Cytotoxicity (ADCC) NK cells and macrophages lyse antibody-coated cells (protozoans and helminths) Fig 17.15

28. Immunological Memory • Amount of antibody in serum is called the antibody titer. • 1 response: Response of the body to the first contact with an antigen. Mostly IgM • 2 response: any subsequent contact with the same antigen. Rapidly very high antibody titer. Mostly IgG Fig 17.16

29. Self Tolerance: Negative Selection Goal: eliminate B and T cells, recognizing “self” molecules Clonal deletion of B cells taking place in bone marrow  apoptosis Negative selectionof T cells in thymus Failure results in auto-antibodies and autoimmune disease

30. Types of Specific Immunity Active immunity Protection via introduction of antigen into responsive host, e.g.: • Naturally acquired via infection or • Artificially acquired via vaccination

31. Passive Immunity Protection via transfer of antibodies or immune cells into a non-immune host, e.g.: • Naturally acquired: Fetus receives mothers antibodies via placenta • Artificially acquired via vaccination injection of immune serum after exposure(snake bite, Rh+ child with Rh- mother etc.)

32. Compare to Fig 17.17

33. Cellular Immunity Review T-cells specific surface receptors (TCRs) TCR cannot bind free ag. Ag must be presented by APCs Activated T-cells go through clonal expansion effector and memory T cells. CTLs directly kill virus infected and tumor cells T-helper cells help the humoral and cellular immunity The End