The Adaptive Immune System

Transcription

1 Chapter 17 Functional Anatomy of Prokaryotic and Eukaryotic Cells Lectures prepared by Christine L. Case The Adaptive Immune System Learning Objectives 17-1 Differentiate innate from adaptive immunity Differentiate humoral from cellular immunity.

2 Immunity Innate immunity: defenses against any pathogen Adaptive immunity: induced resistance to a specific pathogen ANIMATION Host Defenses: The Big Picture Historical Development Pasteur observed immunity in chickens injected with weakened pathogens Von Behring received the Nobel prize for development of antitoxin Ehrlich s work led to the identification of antibodies in serum

3 Dual Nature of Adaptive Immunity T and B cells develop from stem cells in red bone marrow Figure 17.8 Differentiation of T cells and B cells. Dual Nature of Adaptive Immunity Humoral immunity Due to antibodies B cells mature in the bone marrow Chickens: bursa of Fabricius Cellular immunity Due to T cells T cells mature in the thymus ANIMATION Humoral Immunity: Overview

4 Antigens and Antibodies Learning Objectives 17-3 Define antigen, epitope, and hapten Explain the function of antibodies, and describe their structural and chemical characteristics Name one function for each of the five classes of antibodies. The Nature of Antigens Antigen (Ag): a substance that causes the body to produce specific antibodies or sensitized T cells Antibodies (Ab) interact with epitopes, or antigenic determinants Hapten: antigen is combined with carrier molecules

5 Antigens Figure 17.1 Epitopes (antigenic determinants). Haptens Figure 17.2 Haptens.

6 The Nature of Antibodies Globular proteins called immunoglobulins The number of antigen-binding sites determines valence Antibodies Antigenbinding site Heavy chain Light chain Fc (stem) region Hinge region Antibody molecule Epitope (antigenic determinant) Antigen Antigenbinding site Enlarged antigen-binding site bound to an epitope Figure 17.3ab The structure of a typical antibody molecule.

7 Antibodies Antibodies Antibody molecules shown by atomic force microscopy (see page 64) Figure 17.3c The structure of a typical antibody molecule. IgG Antibodies Monomer 80% of serum antibodies Fix complement In blood, lymph, and intestine Cross placenta Enhance phagocytosis; neutralize toxins and viruses; protect fetus and newborn Half-life = 23 days

8 IgM Antibodies Pentamer 5 10% of serum antibodies Fix complement In blood, in lymph, and on B cells Agglutinate microbes; first Ab produced in response to infection Half-life = 5 days IgA Antibodies Dimer 10 15% of serum antibodies In secretions Mucosal protection Half-life = 6 days

9 IgD Antibodies Monomer 0.2% of serum antibodies In blood, in lymph, and on B cells On B cells, initiate immune response Half-life = 3 days IgE Antibodies Monomer 0.002% of serum antibodies On mast cells, on basophils, and in blood Allergic reactions; lysis of parasitic worms Half-life = 2 days

10 B Cells and Humoral Immunity Learning Objectives 17-6 Compare and contrast T-dependent and T-independent antigens Differentiate plasma cell from memory cell Describe clonal selection Describe how a human can produce different antibodies Describe four outcomes of an antigen antibody reaction.

11 Activation of B Cells Major histocompatibility complex (MHC) expressed on mammalian cells T-dependent antigens Ag presented with (self) MHC to T H cell T H cell produces cytokines that activate the B cell T-independent antigens Stimulate the B cell to make Abs ANIMATION Antigen Processing and Presentation: Overview Activation of B Cells Figure 17.6 T-independent antigens.

12 Activation of B Cells Extracellular antigens Ag fragment MHC class II with Ag fragment MHC class II with Ag fragment displayed on surface Antibodies B cell B cell B cell Immunoglobulin receptors coating B cell surface T H cell Cytokines Plasma cell Immunoglobulin receptors on B cell surface recognize and attach to antigen, which is then internalized and processed. Within the B cell a fragment of the antigen combines with MHC class II. MHC class II antigenfragment complex is displayed on B cell surface. Receptor on the T helper cell (T H ) recognizes complex of MHC class II and antigen fragment and is activated producing cytokines, which activate the B cell. The T H cell has been previously activated by an antigen displayed on a dendritic cell (see Figure 17.10). B cell is activated by cytokines and begins clonal expansion. Some of the progeny become antibody-producing plasma cells. Figure 17.4 Activation of B cells to produce antibodies. Clonal Selection ANIMATION Humoral Immunity: Clonal Selection and Expansion

13 Activation of B Cells B cells differentiate into: Antibody-producing plasma cells Memory cells Clonal deletion eliminates harmful B cells Antigen Antibody Binding Agglutination Opsonization Activation of complement Antibody-dependent cell-mediated cytotoxicity Neutralization ANIMATION Humoral Immunity: Antibody Function

14 The Results of Ag-Ab Binding Figure 17.7 The results of antigen antibody binding. T Cells and Cellular Immunity Learning Objectives Describe at least one function of each of the following: M cells, T H cells, T C cells, T reg cells, CTLs, NK cells Differentiate T helper, T cytotoxic, and T regulatory cells Differentiate T H 1, T H 2, and T H 17 cells Define apoptosis.

15 T Cells and Cellular Immunity T cells mature in the thymus Thymic selection eliminates many immature T cells T cells respond to Ag by T-cell receptors (TCRs) T cells require antigen-presenting cells (APCs) Pathogens entering the gastrointestinal or respiratory tracts pass through M (microfold) cells over Peyer s patches, which contain APCs M Cells on Peyer s Patch Figure 17.9 M cells.

16 M Cells ANIMATION Cell-Mediated Immunity: Overview Figure 17.9 M cells. T Helper Cells CD4 + or T H cells TCRs recognize Ags and MHC II on APC TLRs are a costimulatory signal on APC and T H T H cells produce cytokines and differentiate into: T H 1cells T H 2 cells T H 17 cells Memory cells

17 T Helper Cells T H 1 produce IFN-γ, which activates cells related to cell-mediated immunity, macrophages, and Abs T H 2 activate eosinophils and B cells to produce IgE T H 17 stimulate the innate immune system TF stimulate B cells to produce plasma cells and are involved in class switching ANIMATION Antigen Processing and Presentation: Steps Antibodies Recruits neutrophils; provides protection against extracellular bacteria and fungi B cell T H cell T H 1 cells T H 2 cells T H 17 cells Cell-mediated immunity; control of intracellular pathogens, delayed hypersensitivity reactions (page 535); stimulates macrophages. T H 17 cells IL-17 IFN-γ T H 1 cells Fungi IL-4 T H 2 cells Extracellular bacteria Neutrophil Macrophage Intracellular bacteria and protozoa Mast cell Basophil Eosinophil Important in allergic responses, especially by production of IgE Stimulates activity of eosinophils to control extracellular parasites such as helminths (see ADCC, page 495). Helminth Figure Lineage of effector T helper cell classes and pathogens targeted.

18 Activation of CD4 + T Helper Cells Figure Activation of CD4 + T helper cells. ANIMATION Cell-Mediated Immunity: Helper T Cells T Cytotoxic Cells CD8 + or T C cells Target cells are self-cells carrying endogenous antigens Activated into cytotoxic T lymphocytes (CTLs) CTLs recognize Ag + MHC I Induce apoptosis in target cell CTL releases perforin and granzymes ANIMATION Cell-Mediated Immunity: Cytotoxic T Cells

19 T Cytotoxic Cells Figure Killing of virus-infected target cell by cytotoxic T lymphocyte. Apoptosis Figure Apoptosis.

20 T Regulatory Cells T reg cells CD4 and CD25 on surface Suppress T cells against self T Cells and Cellular Immunity Learning Objectives Define antigen-presenting cell Describe the function of natural killer cells Describe the role of antibodies and natural killer cells in antibody-dependent cell-mediated cytotoxicity Identify at least one function of each of the following: cytokines, interleukins, chemokines, interferons, TNF, and hematopoietic cytokines.

21 Antigen-Presenting Cells Digest antigen Ag fragments on APC surface with MHC B cells Dendritic cells Activated macrophages ANIMATION Antigen Processing and Presentation: MHC Figure A dendritic cell.

22 Activated macrophages Resting (inactive) macrophage Figure Activated macrophages. Natural Killer (NK) Cells Granular leukocytes destroy cells that don t express MHC I Kill virus-infected and tumor cells Attack parasites

23 ADCC Antibody-dependent cell-mediated cytotoxicity

24 ADCC Figure Antibody-dependent cell-mediated cytotoxicity (ADCC). Cytokines Chemical messengers Overproduction leads to cytokine storm

25 Cells Communicate via Cytokines Cytokine Interleukin-1 (IL-1) Representative Activity Stimulates T H cells in presence of antigens; attracts phagocytes Interleukin-2 (IL-2) Interleukin-12 (IL-12) Proliferation of antigen-stimulated CD4 + T helper cells, proliferation and differentiation of B cells; activation of CD8 + T cells and NK cells Inhibits humoral immunity; activates T H 1 cellular immunity Cells Communicate via Cytokines Cytokine Chemokines Representative Activity Induce the migration of leukocytes TNF-α Hematopoietic cytokines IFN-α and IFN-β IFN-γ Promotes inflammation Influence differentiation of blood stem cells Response to viral infection; interfere with protein synthesis Stimulates macrophage activity

26 T Cells and Cellular Immunity Learning Objectives Distinguish a primary from a secondary immune response Contrast the four types of adaptive immunity. Immunological Memory Antibody titer is the amount of Ab in serum Primary response occurs after initial contact with Ag Secondary (memory or anamnestic) response occurs after second exposure ANIMATION Humoral Immunity: Primary Immune Response ANIMATION Humoral Immunity: Secondary Immune Response

27 Immune Responses to an Antigen Figure The primary and secondary immune responses to an antigen. Types of Adaptive Immunity Naturally acquired active immunity Resulting from infection Naturally acquired passive immunity Transplacental or via colostrum Artificially acquired active immunity Injection of Ag (vaccination) Artificially acquired passive immunity Injection of Ab

28 Figure Terminology of Adaptive Immunity Serology: the study of reactions between antibodies and antigens Antiserum: the generic term for serum because it contains Ab Globulins: serum proteins Immunoglobulins: antibodies Gamma (γ) globulin: serum fraction containing Ab

29 Serum Proteins Figure The separation of serum proteins by gel electrophoresis. Figure The dual nature of the adaptive immune system. Humoral (antibody-mediated) immune system Control of freely circulating pathogens Check Your Understanding Extracellular antigens Cellular (cell-mediated) immune system Control of intracellular pathogens Intracellular antigens are expressed on the surface of an APC, a cell infected by a virus, a bacterium, or a parasite. A B cell binds to the antigen for which it is specific. A T-dependent B cell requires cooperation with a T helper (T H ) cell. B cell Cytokines activate T helper (T H ) cell. Cytokines T cell Cytokines activate macrophage. Cytokines A T cell binds to MHC antigen complexes on the surface of the infected cell, activating the T cell (with its cytokine receptors). The B cell, often with stimulation by cytokines from a T H cell, differentiates into a plasma cell. Some B cells become memory cells. Cytokines from the T H cell transform B cells into antibody-producing plasma cells. T H cell Activation of macrophage (enhanced phagocytic activity). Plasma cell Plasma cells proliferate and produce antibodies against the antigen. Memory cell Some T and B cells differentiate into memory cells that respond rapidly to any secondary encounter with an antigen. Cytotoxic T lymphocyte The CD8 + T cell becomes a cytotoxic T lymphocyte (CTL) able to induce apoptosis of the target cell. Lysed target cell