Adaptive Immunity Chapter 7 1 Adaptive Immunity o

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Adaptive Immunity Chapter 7 1

Adaptive Immunity Chapter 7 1

Adaptive Immunity o o o Antigens Specificity Memory Antibodies Lymphocytes 2 Mosby items and

Adaptive Immunity o o o Antigens Specificity Memory Antibodies Lymphocytes 2 Mosby items and derived items © 2006 by Mosby, Inc.

Adaptive Immunity o Clonal diversity n n n o Production of T and B

Adaptive Immunity o Clonal diversity n n n o Production of T and B lymphocytes Antigen recognition Lymphocyte specificity Clonal selection n n Antigen processing Cellular interaction 3 Mosby items and derived items © 2006 by Mosby, Inc.

Humoral and Cell-Mediated Immunity o o The cellular and humoral responses are not independent

Humoral and Cell-Mediated Immunity o o The cellular and humoral responses are not independent Humoral immunity n n o “Fluid” immunity Circulating antibody Cell-mediated immunity n T cell differentiation 4 Mosby items and derived items © 2006 by Mosby, Inc.

Active vs. Passive Immunity o Active immunity n o Antibodies or T cells produced

Active vs. Passive Immunity o Active immunity n o Antibodies or T cells produced after either a natural exposure to an antigen or after immunization Passive immunity n Preformed antibodies or T lymphocytes are transferred from a donor to a recipient 5 Mosby items and derived items © 2006 by Mosby, Inc.

Recognition and Response o o Required for a successful immune response Clusters of differentiation

Recognition and Response o o Required for a successful immune response Clusters of differentiation (CD) n n 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 Mosby items and derived items © 2006 by Mosby, Inc.

Antigens o o Immunogens vs. antigens Antigenic determinant (epitope) Self-antigen Tolerance n o Molecular

Antigens o o Immunogens vs. antigens Antigenic determinant (epitope) Self-antigen Tolerance n o Molecular size n o Central and peripheral tolerance Haptens Allergens 7 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Presentation o o Antigen-presenting cells (APCs) Major histocompatibility complex (MHC) n n n

Antigen Presentation o o Antigen-presenting cells (APCs) Major histocompatibility complex (MHC) n n n Glycoproteins on the surface of all human cells (except RBCs) Also referred to as human leukocyte antigens (HLAs) MHC class I molecules o n MHC class II molecules o n A, B, and C DR, DP, and DQ MHC class III molecules 8 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Presentation 9 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Presentation 9 Mosby items and derived items © 2006 by Mosby, Inc.

Transplantation o o o Cells in transplanted tissue from one individual will have a

Transplantation o o o 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 n Combination of A, B, C, DR, DQ, and DP alleles 10 Mosby items and derived items © 2006 by Mosby, Inc.

Transplantation 11 Mosby items and derived items © 2006 by Mosby, Inc.

Transplantation 11 Mosby items and derived items © 2006 by Mosby, Inc.

CD 1 o o o Antigen-presenting molecules Found on antigen-presenting and thymus cells Present

CD 1 o o o Antigen-presenting molecules Found on antigen-presenting and thymus cells Present lipid antigens 12 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Recognition o Antigen is directly recognized by circulating antibody, antigen receptors on B

Antigen Recognition o Antigen is directly recognized by circulating antibody, antigen receptors on B cells (BCR), and T lymphocytes (TCR) 13 Mosby items and derived items © 2006 by Mosby, Inc.

Antibodies o o o Also called immunoglobulins Produced by plasma cells Classes of antibody

Antibodies o o o Also called immunoglobulins Produced by plasma cells Classes of antibody n Ig. G, Ig. A, Ig. M, Ig. E, and Ig. D o Characterized by antigenic, structural, and functional differences 14 Mosby items and derived items © 2006 by Mosby, Inc.

Antibodies 15 Mosby items and derived items © 2006 by Mosby, Inc.

Antibodies 15 Mosby items and derived items © 2006 by Mosby, Inc.

Antibodies 16 Mosby items and derived items © 2006 by Mosby, Inc.

Antibodies 16 Mosby items and derived items © 2006 by Mosby, Inc.

Immunoglobulin G (Ig. G) o o o Most abundant class (80%-85%) Transported across the

Immunoglobulin G (Ig. G) o o o Most abundant class (80%-85%) Transported across the placenta Four classes n Ig. G 1, Ig. G 2, Ig. G 3, and Ig. G 4 17 Mosby items and derived items © 2006 by Mosby, Inc.

Immunoglobulin A (Ig. A) o Two classes n n o Ig. A 1 molecules

Immunoglobulin A (Ig. A) o Two classes n n o Ig. A 1 molecules are found predominantly in the blood Ig. A 2 molecules are found predominantly in normal body secretions Ig. As found in body secretions are dimers anchored by a J chain and a “secretory” piece n Secretory piece may function to protect Ig. As against enzyme degradation 18 Mosby items and derived items © 2006 by Mosby, Inc.

Immunoglobulin M (Ig. M) o o Largest of the immunoglobulins Pentamer stabilized by a

Immunoglobulin M (Ig. M) o o 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 Mosby items and derived items © 2006 by Mosby, Inc.

Immunoglobulin D (Ig. D) o o Limited information on Ig. D function Low concentration

Immunoglobulin D (Ig. D) o o Limited information on Ig. D 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 Mosby items and derived items © 2006 by Mosby, Inc.

Immunoglobulin E (Ig. E) o o o Least concentrated of the immunoglobulin classes in

Immunoglobulin E (Ig. E) o o o Least concentrated of the immunoglobulin classes in the circulation Mediator of many common allergic responses Defender against parasites 21 Mosby items and derived items © 2006 by Mosby, Inc.

Antibody Structure o Antigen-binding fragment (Fab) n o Crystalline fragment (Fc) n o Recognition

Antibody Structure o Antigen-binding fragment (Fab) n o Crystalline fragment (Fc) n o Recognition sites (receptors) for antigenic determinants Responsible for biological function Polypeptide chains (4) n Light chains (2) and heavy chains (2) 22 Mosby items and derived items © 2006 by Mosby, Inc.

Antibody Structure o o Hinge region Constant and variable regions n n Complementary determining

Antibody Structure o o Hinge region Constant and variable regions n n Complementary determining regions (CDRs) Framework regions (FRs) 23 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Binding o o o Amino acid sequences of the variable regions of the

Antigen Binding o o o Amino acid sequences of the variable regions of the heavy and light chains Framework regions control antibody folding Lock and key n o Noncovalent chemical interactions Antibody valence n n n Ig. G, Ig. D, and Ig. E— 2 Ig. A— 4 Ig. M—theoretically 10, likely 5 24 Mosby items and derived items © 2006 by Mosby, Inc.

B Cell Receptor Complex o o Located on surface of B cells Consists of:

B Cell Receptor Complex o o Located on surface of B cells Consists of: n Antigen-recognition molecules o n Monomer Ig. M and Ig. D Accessory intracellular-signaling molecules o Ig-alpha and Ig-beta heterodimers 25 Mosby items and derived items © 2006 by Mosby, Inc.

T Cell Receptor Complex o o Antibody-like transmembrane protein (TCR) Accessory proteins for intracellular

T Cell Receptor Complex o o Antibody-like transmembrane protein (TCR) Accessory proteins for intracellular signaling n Referred to as CD 3 26 Mosby items and derived items © 2006 by Mosby, Inc.

Generation of Clonal Diversity o o All necessary receptor specificities are produced Takes place

Generation of Clonal Diversity o o 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 Mosby items and derived items © 2006 by Mosby, Inc.

Clonal Selection o o Immunocompetent T and B cells migrate from the primary lymphoid

Clonal Selection o o 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 n Plasma cells that produce antibody, effector cells that help Th, Tc, or Treg, and memory B and T cells 28 Mosby items and derived items © 2006 by Mosby, Inc.

T Cell Maturation o o o The thymus is the central lymphoid organ of

T Cell Maturation o o o The thymus is the central lymphoid organ of T cell development T cells move from the thymic cortex to the medulla Changes n o 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 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Processing and Presentation o Antigens require processing and presentation by antigen-presenting cells (APCs)

Antigen Processing and Presentation o Antigens require processing and presentation by antigen-presenting cells (APCs) n o 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 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Processing and Presentation 31 Mosby items and derived items © 2006 by Mosby,

Antigen Processing and Presentation 31 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Processing and Presentation 32 Mosby items and derived items © 2006 by Mosby,

Antigen Processing and Presentation 32 Mosby items and derived items © 2006 by Mosby, Inc.

Helper T Lymphocytes o o o “Help” the antigen-driven maturation of B and T

Helper T Lymphocytes o o o “Help” the antigen-driven maturation of B and T cells Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes Steps n n n Th interacts through antigen-specific and antigenindependent mechanisms Undergoes differentiation Mature Th interacts with plasma or T-effector cells 33 Mosby items and derived items © 2006 by Mosby, Inc.

Antigen Processing and Presentation 34 Mosby items and derived items © 2006 by Mosby,

Antigen Processing and Presentation 34 Mosby items and derived items © 2006 by Mosby, Inc.

Helper T Lymphocytes o Subsets n n n Th 1 cells provide help in

Helper T Lymphocytes o Subsets n n n Th 1 cells provide help in developing cellmediated immunity Th 2 cells provide help in developing humoral immunity Differences based on cytokine production 35 Mosby items and derived items © 2006 by Mosby, Inc.

B Cell Activation o o o When an immunocompetent B cell encounters an antigen

B Cell Activation o o o 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 n Single class or subclass of antibody 36 Mosby items and derived items © 2006 by Mosby, Inc.

Primary and Secondary Responses o Primary response n n Initial exposure Latent period or

Primary and Secondary Responses o Primary response n n Initial exposure Latent period or lag phase o n n B cell differentiation is occurring After 5 to 7 days, an Ig. M antibody for a specific antigen is detected An Ig. G response equal or slightly less follows the Ig. M response 37 Mosby items and derived items © 2006 by Mosby, Inc.

Primary and Secondary Responses o Secondary response n n More rapid Larger amounts of

Primary and Secondary Responses o Secondary response n n More rapid Larger amounts of antibody are produced Rapidity is due to the presence of memory cells that do not have to differentiate Ig. M is produced in similar quantities to the primary response, but Ig. G is produced in considerably greater numbers 38 Mosby items and derived items © 2006 by Mosby, Inc.

Class Switch o o Immunocompetent B cells use Ig. M and Ig. D as

Class Switch o o Immunocompetent B cells use Ig. M and Ig. D as receptors During clonal selection, B cells have the option of changing the class of the antibody n n One of four Ig. Gs, one of two Ig. As, Ig. E, or an Ig. M in a pentamer form DNA rearrangement 39 Mosby items and derived items © 2006 by Mosby, Inc.

B Cell Clonal Selection 40 Mosby items and derived items © 2006 by Mosby,

B Cell Clonal Selection 40 Mosby items and derived items © 2006 by Mosby, Inc.

T Cell Activation o o Binding antigen to specific T cell receptors Allows: n

T Cell Activation o o Binding antigen to specific T cell receptors Allows: n n o T regulatory cells (Treg) n o Direct killing of foreign or abnormal cells Assistance or activation of other cells Regulate the immune response to avoid attacking “self” Memory T cells 41 Mosby items and derived items © 2006 by Mosby, Inc.

T Cell Activation 42 Mosby items and derived items © 2006 by Mosby, Inc.

T Cell Activation 42 Mosby items and derived items © 2006 by Mosby, Inc.

Superantigens (SAGs) o o o Bind the variable portion of the TCR and the

Superantigens (SAGs) o o o 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 n Causes fever, low blood pressure, fever, and potentially shock 43 Mosby items and derived items © 2006 by Mosby, Inc.

Antibody Function o Direct n n n o Indirect n o Neutralization Agglutination Precipitation

Antibody Function o Direct n n n o Indirect n o Neutralization Agglutination Precipitation Opsonization Degree of antibody protection is assessed by an antibody titer 44 Mosby items and derived items © 2006 by Mosby, Inc.

Secretory (Mucosal) Immune System o o o Lymphoid tissues that protect the external surfaces

Secretory (Mucosal) Immune System o o o Lymphoid tissues that protect the external surfaces of the body Antibodies present in tears, sweat, saliva, mucus, and breast milk Ig. A is the dominant immunoglobulin n Small numbers of Ig. G and Ig. M are present 45 Mosby items and derived items © 2006 by Mosby, Inc.

Secretory (Mucosal) Immune System 46 Mosby items and derived items © 2006 by Mosby,

Secretory (Mucosal) Immune System 46 Mosby items and derived items © 2006 by Mosby, Inc.

Ig. E Function o Provides protection from large parasites n o Initiates an inflammatory

Ig. E Function o Provides protection from large parasites n o Initiates an inflammatory reaction to attract eosinophils When produced against innocuous environmental antigens, they are a common cause of allergies n Fc portions of Ig. Es are bound to mast cells 47 Mosby items and derived items © 2006 by Mosby, Inc.

Ig. E Function 48 Mosby items and derived items © 2006 by Mosby, Inc.

Ig. E Function 48 Mosby items and derived items © 2006 by Mosby, Inc.

Cell-Killing Mechanisms o Cytotoxic T lymphocytes n n Destroy cancer cells or cells infected

Cell-Killing Mechanisms o Cytotoxic T lymphocytes n n Destroy cancer cells or cells infected with virus Perforin, granzymes, or direct receptor interactions 49 Mosby items and derived items © 2006 by Mosby, Inc.

Cell-Killing Mechanisms 50 Mosby items and derived items © 2006 by Mosby, Inc.

Cell-Killing Mechanisms 50 Mosby items and derived items © 2006 by Mosby, Inc.

Other Cells o Natural killer (NK) cells n o Complement Tc cell mechanisms Regulatory

Other Cells o Natural killer (NK) cells n o Complement Tc cell mechanisms Regulatory T cells (Treg) n n Provide peripheral tolerance Affect recognition of antigen and suppress proliferative steps of antigen recognition 51 Mosby items and derived items © 2006 by Mosby, Inc.

Fetal and Neonatal Immunity o Antibody function is deficient n o Capable of primary

Fetal and Neonatal Immunity o Antibody function is deficient n o Capable of primary Ig. M response; unable to produce an Ig. G challenge Immunity provided by maternal antibody n n Trophoblastic cells transport maternal Ig. G across the placenta Newborn Ig. G levels are near adult levels 52 Mosby items and derived items © 2006 by Mosby, Inc.

Fetal and Neonatal Immunity 53 Mosby items and derived items © 2006 by Mosby,

Fetal and Neonatal Immunity 53 Mosby items and derived items © 2006 by Mosby, Inc.

Aging and Immune Function o Decreased T cell activity n o o Thymic size

Aging and Immune Function o Decreased T cell activity n o o 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 54 Mosby items and derived items © 2006 by Mosby, Inc.