1. Adaptive (Acquired) Immunity (3rd line of defense)
Chapter 7

2. Adaptive/Acquired Immunity
Antigens – Anything that cases a biological immune response by this system of cells
Specificity – Some antibodies are quite specific to an antigen others are general to a “type” or “form”
Memory – b-memory cells are formed and remain to combat future exposures quickly (Active vs Passive immunity
Antibodies – the proteins formed by b-cells that combat antigens whether chemical or biological
Lymphocytes – cells involved in this response

3. Adaptive Immunity Clonal diversity
Production of T (Killer cell mediated response) and B lymphocytes (humoral/antibody response)
Antigen recognition – zone of attachment
Lymphocyte specificity – Classes of Immunoglobulins
Clonal selection – CD cluster recognition table 7-2
Antigen processing – Recognition and binding depend on size of molecule/cell/tissue/organism and class
Cellular interaction

4. 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 antibodies or T lymphocytes are transferred from a donor to a recipient

5. Recognition and Response
Required for a successful immune response
Clusters of differentiation (CD)
Originally used to describe proteins found on the surface of lymphocytes
Now it is a labeling system used to identify a family of proteins on many cells

6. Antigens Immunogens vs. antigens Antigenic determinant (epitope)
Self-antigen
Tolerance
Central and peripheral tolerance
Molecular size
Haptens
Allergens

7. Antigen Presentation Antigen-presenting cells (APCs)
Major histocompatibility complex (MHC)
Glycoproteins on the surface of all human cells (except RBCs)
Also referred to as human leukocyte antigens (HLAs)
MHC class I molecules
A, B, and C
MHC class II molecules
DR, DP, and DQ
MHC class III molecules

8. Antigen Presentation

9. Transplantation
Cells in transplanted tissue from one individual will have a different set of MHC surface antigens than those of the recipient
Therefore, a recipient can mount an immune response against the foreign MHC molecules
Haplotype
Combination of A, B, C, DR, DQ, and DP alleles

10. Transplantation

11. CD1 Antigen-presenting molecules
Found on antigen-presenting and thymus cells
Present lipid antigens

12. Antigen Recognition
Antigen is directly recognized by circulating antibody, antigen receptors on B cells (BCR), and T lymphocytes (TCR)

13. Antibodies Also called immunoglobulins Produced by plasma cells
Classes of antibody
IgG, IgA, IgM, IgE, and IgD
Characterized by antigenic, structural, and functional differences

14. Antibodies

15. Antibodies

16. Immunoglobulin G (IgG)
Most abundant class (80%-85%)
Transported across the placenta
Four classes
IgG1, IgG2, IgG3, and IgG4

17. Immunoglobulin A (IgA)
Two classes
IgA1 molecules are found predominantly in the blood
IgA2 molecules are found predominantly in normal body secretions
IgAs found in body secretions are dimers anchored by a J chain and a “secretory” piece
Secretory piece may function to protect IgAs against enzyme degradation

18. Immunoglobulin M (IgM)
Largest of the immunoglobulins
Pentamer stabilized by a J chain
First antibody produced during the primary response to an antigen
Synthesized during fetal life

19. Immunoglobulin D (IgD)
Limited information on IgD function
Low concentration in the blood
Located primarily on the surface of developing B lymphocytes
Function as one type of B cell antigen receptor

20. Immunoglobulin E (IgE)
Least concentrated of the immunoglobulin classes in the circulation
Mediator of many common allergic responses
Defender against parasites

21. Antibody Structure Antigen-binding fragment (Fab)
Recognition sites (receptors) for antigenic determinants
Crystalline fragment (Fc)
Responsible for biological function
Polypeptide chains (4)
Light chains (2) and heavy chains (2)

22. Antibody Structure Hinge region Constant and variable regions
Complementary determining regions (CDRs)
Framework regions (FRs)

23. Antigen Binding
Amino acid sequences of the variable regions of the heavy and light chains
Framework regions control antibody folding
Lock and key
Noncovalent chemical interactions
Antibody valence
IgG, IgD, and IgE—2
IgA—4
IgM—theoretically 10, likely 5

24. B Cell Receptor Complex
Located on surface of B cells
Consists of:
Antigen-recognition molecules
Monomer IgM and IgD
Accessory intracellular-signaling molecules
Ig-alpha and Ig-beta heterodimers

25. T Cell Receptor Complex
Antibody-like transmembrane protein (TCR)
Accessory proteins for intracellular signaling
Referred to as CD3

26. Generation of Clonal Diversity
All necessary receptor specificities are produced
Takes place in the primary (central) lymphoid organs
Results in immature but immunocompetent T and B cells
Primarily occurs in the fetus

27. Clonal Selection
Immunocompetent T and B cells migrate from the primary lymphoid organs to the secondary lymphoid organs to await antigen
Primarily after birth
Clonal selection is initiated by antigen
Final products
Plasma cells that produce antibody, effector cells that help Th, Tc, or Treg, and memory B and T cells

28. T Cell Maturation
The thymus is the central lymphoid organ of T cell development
T cells move from the thymic cortex to the medulla
Changes
Development of the T cell receptors and expression of surface molecules
T cells are released into the blood and take up residence in the secondary lymph organs

29. Antigen Processing and Presentation
Antigens require processing and presentation by antigen-presenting cells (APCs)
Dendritic cells, macrophages, and B lymphocytes
For processing and presentation to occur, the antigen must be of the appropriate type, the lymphocytes must be prepared to recognize the presented antigen, and the antigen must be presented appropriately

30. Antigen Processing and Presentation

31. Antigen Processing and Presentation

32. Helper T Lymphocytes
“Help” the antigen-driven maturation of B and T cells
Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes
Steps
Th interacts through antigen-specific and antigen-independent mechanisms
Undergoes differentiation
Mature Th interacts with plasma or T-effector cells

33. Antigen Processing and Presentation

34. Helper T Lymphocytes Subsets
Th1 cells provide help in developing cell-mediated immunity
Th2 cells provide help in developing humoral immunity
Differences based on cytokine production

35. B Cell Activation
When an immunocompetent B cell encounters an antigen for the first time, B cells with specific BCRs are stimulated to differentiate and proliferate
A differentiated B cell becomes a plasma cell
A plasma cell is a factory for antibody production
Single class or subclass of antibody

36. Primary and Secondary Responses
Primary response
Initial exposure
Latent period or lag phase
B cell differentiation is occurring
After 5 to 7 days, an IgM antibody for a specific antigen is detected
An IgG response equal or slightly less follows the IgM response

37. Primary and Secondary Responses
More rapid
Larger amounts of antibody are produced
Rapidity is due to the presence of memory cells that do not have to differentiate
IgM is produced in similar quantities to the primary response, but IgG is produced in considerably greater numbers

38. Class Switch Immunocompetent B cells use IgM and IgD as receptors
During clonal selection, B cells have the option of changing the class of the antibody
One of four IgGs, one of two IgAs, IgE, or an IgM in a pentamer form
DNA rearrangement

39. B Cell Clonal Selection

40. T Cell Activation Binding antigen to specific T cell receptors Allows:
Direct killing of foreign or abnormal cells
Assistance or activation of other cells
T regulatory cells (Treg)
Regulate the immune response to avoid attacking “self”
Memory T cells

41. T Cell Activation

42. Superantigens (SAGs)
Bind the variable portion of the TCR and the MHC class II molecules outside of their antigen-presentation sites
Activates a large population of T lymphocytes regardless of antigen specificity
SAGs induce an excessive production of cytokines
Causes fever, low blood pressure, fever, and potentially shock

43. Antibody Function Direct Indirect
Neutralization
Agglutination
Precipitation
Indirect
Opsonization
Degree of antibody protection is assessed by an antibody titer

44. Secretory (Mucosal) Immune System
Lymphoid tissues that protect the external surfaces of the body
Antibodies present in tears, sweat, saliva, mucus, and breast milk
IgA is the dominant immunoglobulin
Small numbers of IgG and IgM are present

45. Secretory (Mucosal) Immune System

46. IgE Function Provides protection from large parasites
Initiates an inflammatory reaction to attract eosinophils
When produced against innocuous environmental antigens, they are a common cause of allergies
Fc portions of IgEs are bound to mast cells

47. IgE Function

48. Cell-Killing Mechanisms
Cytotoxic T lymphocytes
Destroy cancer cells or cells infected with virus
Perforin, granzymes, or direct receptor interactions

49. Cell-Killing Mechanisms

50. Other Cells Natural killer (NK) cells Regulatory T cells (Treg)
Complement Tc cell mechanisms
Regulatory T cells (Treg)
Provide peripheral tolerance
Affect recognition of antigen and suppress proliferative steps of antigen recognition

51. Fetal and Neonatal Immunity
Antibody function is deficient
Capable of primary IgM response; unable to produce an IgG challenge
Immunity provided by maternal antibody
Trophoblastic cells transport maternal IgG across the placenta
Newborn IgG levels are near adult levels

52. Fetal and Neonatal Immunity

53. Aging and Immune Function
Decreased T cell activity
Thymic size is 15% of its maximum size
Decreased production of specific antibodies
Increase in circulating antigen-antibody complexes
Increase in circulating autoantibodies
Decrease in circulating memory B cells