Adaptive Immunity

2. Adaptive Immunity Chapter 6

3. Adaptive Immunity “third line of defense” • Develops more slowly • Specific • Memory

6. Men in Black: T & B Cells

7. Adaptive Immunity • Antigens– “foreign or non self” (Ag= foreignproteins) • Viruses, bacteria, cancer, fungi or parasites • Noninfectious – pollens, foods, bee venoms • Drugs, vaccines, transfusions and transplants

8. Adaptive Immunity • Principal cells: Lymphocytes • Accessory cells: APC & dendritic cells • Effector cells • B cells → antibodies to blood → Ag • T cells → attack Ag directly • Functionally • Regulatory • Effector • Specific • Each cell recognizes only ONEspecific Ag

9. Lymphocytes • 25-35% of blood leukocytes • 99% reside in the lymph glands • 60-70% of blood lymphocytes are T-cells and 10-20% are B-cells • Foreign protein recognition:”surface receptor proteins-unique” • B-cells: membrane bound immunoglobulin • T-cells: self-recognition protein(major histocompatibility complex)

10. Major Histocompatibility Complex Molecules:all cells* • “self from non self” • Chromosome # 6 • Two Classes Class I *: endogenous pathogens -viruses & cancer • Cytotoxic T cells… “must destroy me” • Class II : extracellular pathogens - bacteria & toxins • Phagocytic cells: macrophages, dendritic cells, B lymphocytes : Ag binds with MHC II Helper T cell (CD4+) • Human Leukocyte Antigens:WBCs • Multiple allelles: A (120 genes) & B (250 genes) • Halotype: inherited unit • * all nucleated cells… not on RBCs

12. Major Histocompatibility Complex Molecules • Class I… “all nucleated cells” (endogenous antigens)* Function:present processed antigen to cytotoxic CD8+ T cells or NK cells “constant screening” * Seen as abnormal…autoimmune disease

13. Major Histocompatibility Complex Molecule • Class II …APC (dendritic, B cells, macrophage) (exogenous antigens) Function: presents processed antigen fragment to CD4+ T cells effective interaction among immune cells* *Figure:6-1

14. Cluster of Differentiation • “Additional membrane bound proteins” • Uses • Aid the function of the immune cells • Define the functionally distinct subset of cells • CD4+ helper T cells – binding receptor: from APCs • CD8+ cytotoxic T cells- binding receptor: from all nucleated cells

15. Adaptive Immunity • Clonal diversity– 1st phase – fetus • Recognition of millions* of foreign Ag • Large population of T & B cells • Develop in primary lymphoid organ (thymus, bone marrow) • Migrate to secondary lymphoid organs *108 or 100 million foreign antigens(proteins)

16. Generation of Clonal Diversity “primary lymphoid organ – fetus” Lymphoid stem cell B and T cells recognize more than 108 antigens B lymphocytes – bone marrow “hormones” – to secondary lymphoid organs* T lymphocytes – thymus “hormones” to second lymphoid organs* *lymph nodes & spleen

21. Macrophages attacking Pathogen

22. Macrophage engulfing bacteria to present to B Cells

23. Secretory (Mucosal) Immune System • Lymphoid tissue that protects the external surface of the body • Ab present in tears, sweat, saliva, mucus and breast milk. • IgA dominant immunoglobulin • Prevent attachment and invasion of pathogens

25. Adaptive Immunity “two arms” • Humoral –B cells • Antibodies – bacteria, viruses, and toxins • Cell mediated– T cells • Subpopulations • React directly with Ag on cell surfaces – NK(see next slide) • Stimulate other leukocytes (cell to cell or cytokines) T • Cytotoxic cells – viruses infected cells and cancer

26. Natural Killer Cells • “lymphocytes” :functionally & phenotypically distinct from T cells, B cells, and monocyte-macrophages • Automatically kill foreign cells: programmed • No activation as with cytotoxic T cells • Inhibition with contact of normal host MHC molecules

27. Antigens “molecule that reactswith antibodies or receptors on B and T cells” • Immunogens-antibodies • Epitope – antigenic determinant (recognized) • Paratope – Ag binding site (antibody or lymphocyte)

29. Antigens • Self-antigen – every cell*, genetically determined (MHC), HLAs+ *glycoproteins – not RBC + human leukocyte antigens • Tolerance

30. Humoral* Immune Response • Antibodies • Immunoglobulins • Plasma cells • Classes • IgG, IgA, IgM, IgE and IgD *fluid

31. Plasma Cell producing Antibodies

33. Classes of Immunoglobulins • IgG • Most abundant (80 to 85%) • Transported across the placenta • Four classes • IgA • Two classes • IgA1 – blood • IgA2 – body secretions

34. Classes of Immunoglobulins • IgM • Largest • First Ab produced during 1° response to an Ag • Synthesized during fetal life • IgD • Low concentration • Ag receptor on surface of early B cells • IgE • Allergic responses • Parasite infections

35. Functions of Antibodies • Direct effects • Neutralization • Agglutination • Precipitation • Indirect effects • Opsonization • Complement

38. B Cell Antigen Receptor • Surface of B cell • Consists • Antigen – recognition molecule : IgM,IgG monomer • Intracellular signaling molecules

39. Cell Mediated Immune Response • Mature T cells • 1.Cytotoxic (Tc) – attack and destroy directly • 2.Regulatory helper T (Th) – controls • Cell mediated • Humoral mediate • Suppressors (Ts) • 3.Memory cells “viruses, tumors, pathogens resistant to neutrophils and macrophages”

40. T Cell Recognition of a Target Cell • T cell receptor complex • Antibody-like transmembrane protein • Accessory proteins for intracellular signaling • Antigen presentation molecules • By antigen presenting cells • Major histocompatibility complex (dendritic cells*, macrophages,B-lymphocytes) • *Nobel Prize Medicine & Physiology 2011: Beutler, Hoffman & Steinman

41. Functions of T-lymphocyte • “Killing abnormal cell” • Cytotoxic T lymphocytes (viruses, tumors) • Attach to target cell : MHC-I molecules • Appropriate CD molecules • Activate macrophages • Cytokines – chronic inflammation • Regulate immune response • T-helper (Th) cell – humoral & cellular • T-suppressor cells – affects immune response

42. Primary and Secondary Immune Responses • Primary • Initial exposure • Latent period (B cell differentiation) • After 5 - 7 days – IgM antibodies detected • An IgG response follows

43. Primary and Secondary Immune Responses • Secondary • More rapid • Large amounts of Ab are produced • Rapid response - 2° to memory cells • IgM – similar to 1° response, IgG – greater number Figure 6-15 Page 161 • “MEMORY”

44. Active vs. Passive Immunity • Active Immunity • Antibodies or T cells produced after either a natural exposure to an antigen or after immunization • Passive Immunity • Preformed Ab or T lymphocytes are transferred from a donor to a recipient. • Example: IgG for hepatitis A exposure : tetanus toxoid

45. Figure 2-7: Secondary response begins more rapidly after exposure to antigen, produces more antibodies, and lasts for a longer time than initial exposure.