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

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

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

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

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

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

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

Antigen Presentation

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

Transplantation

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

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

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

Antibodies

Antibodies

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

Antigen Processing and Presentation

Antigen Processing and Presentation

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

Antigen Processing and Presentation

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

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

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

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

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

B Cell Clonal Selection

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

T Cell Activation

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

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

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

Secretory (Mucosal) Immune System

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

IgE Function

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

Cell-Killing Mechanisms

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

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

Fetal and Neonatal Immunity

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