2. Chapter 6

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

7. Adaptive Immunity  Antigens – “foreign or non self” (Ag= foreign proteins) ◦ 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 ONE specific Ag

9.  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.  “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.  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.  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.  “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 – 1 st 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 * 10 8 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 10 8 antigens  B lymphocytes – bone marrow “hormones” – to secondary lymphoid organs*  T lymphocytes – thymus “hormones” to second lymphoid organs*  *lymph nodes & spleen

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.  “ 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 reacts with 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

33. Classes of Immunoglobul ins  IgG ◦ Most abundant (80 to 85%) ◦ Transported across the placenta ◦ Four classes  IgA ◦ Two classes  IgA 1 – blood  IgA 2 – 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