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Adaptive Immune Response. Chapter 16. What am I?. Strategy of Adaptive Immune Response. First response to particular antigen called primary response May take a week or more to develop Immune system remembers pathogen on subsequent exposure Termed secondary response

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strategy of adaptive immune response
Strategy of Adaptive Immune Response
  • First response to particular antigen called primary response
    • May take a week or more to develop
  • Immune system remembers pathogen on subsequent exposure
    • Termed secondary response
  • Adaptive immunity divided into
    • Humoral immunity
      • Eliminates extracellular pathogens
    • Cellular immunity
      • Eliminates intracellular pathogens
strategy of adaptive immune response1
Strategy of Adaptive Immune Response
  • Overview of humoral immunity
    • Mediated by B lymphocytes
      • a.k.a B cells
    • Develops in bone marrow
    • B cells may be triggered to proliferate into plasma cells
      • Plasma cells produce antibodies
        • Antibodies produce when antigen bonds B cell receptor
    • Some B cells produce memory cells
strategy of adaptive immune response3
Strategy of Adaptive Immune Response
  • Overview of cellular immunity
    • Mediated by T lymphocytes
      • a.k.a T cells
    • Matures in thymus
    • Divided into 2 subsets
      • Cytotoxic T cells
      • Helper T cells
        • T cell receptors help with antigen recognition
anatomy of the lymphoid system
Anatomy of the Lymphoid System
  • Lymphoid system collection of tissues and organs designed to bring B and T cells in contact with antigens
    • In order for body to mount appropriate response, immune cells must encounter antigen
  • Lymphoid system includes
    • Lymphatic vessels
    • Secondary lymphoid organs
    • Primary lymphoid organs
anatomy of the lymphoid system2
Anatomy of the Lymphoid System
  • Lymphatic vessels
    • Carry lymph to body tissues
      • Lymph formed as result of body’s circulatory system
    • Lymph travels through vessels to lymph nodes
      • Material such as protein is removed
        • Fluid portion empties back into blood stream
anatomy of the lymphoid system3
Anatomy of the Lymphoid System
  • Secondary lymphoid organs
    • Sites where lymphocytes gather to encounter antigens; organs include
      • Lymph nodes
      • Spleen
      • Tonsils
      • Adenoids
      • Appendix
    • Organs situated strategically
      • Allows for initiation of immune response from nearly any place in body
anatomy of the lymphoid system4
Anatomy of the Lymphoid System
  • Primary lymphoid organs
    • Bone marrow and thymus are primary lymphoid organs
      • Location where stem cells destined to become B and T cells mature
        • B cells mature in bone marrow
        • T cells mature in thymus
      • Once mature, cells leave primary lymphoid organs and migrate to secondary lymphoid organs
nature of antigens
Nature of Antigens
  • Coined from compounds that elicit antibody production
    • Antibody generator
  • Includes an enormous variety of materials
  • Today, term used to describe any compound that elicits an immune response
    • Antigen that causes immune response termed immunogen
  • Proteins and polysaccharides induce string response
    • Lipids and nucleic acids often do not
  • Recognition of antigen directed at antigenic determinant or epitope
nature of antibodies
Nature of Antibodies
  • Structure of the Antibody (Ab)
    • Basic Y-shaped structure
    • Made of four chains of amino acids held together by disulfide bonds
      • Two chains are heavy
      • Two chains are light
    • Each heavy and light chain has a constant region
      • The constant region is known as Fc region
    • Each heavy and light chain has a variable region
      • Variable region is unique to each Ab
      • This region binds to a specific Antigen and is known as “Fab” region
nature of antibodies1
Nature of Antibodies
  • Protective outcomes of antibody-antigen binding
    • Neutralization
      • Prevents toxin from interacting with cell
    • Immobilization and prevention of adherence
      • Antibody bonding to cellular structures to interfere with function
    • Agglutination and precipitation
      • Clumping of bacterial cells by specific antibody
        • Bacteria more easily phagocytized
nature of antibodies2
Nature of Antibodies
  • Protective outcomes of antibody-antigen binding
    • Opsinization
      • Coating of bacteria with antibody to enhance phagocytosis
    • Complement activation
      • Antibody bonding triggers classical pathway
    • Antibody-dependent cellular cytotoxicity
      • Multiple antibodies bind a cell which becomes target for certain cells
nature of antibodies3
Nature of Antibodies
  • Five classes of Ab
    • IgM
      • First Ab to respond to infection
      • 5 – 13% of Ab in circulation
      • Structure: pentamer
        • Five monomer units joined together at the constant region
      • Found on the surface of B lymphocytes as a monomer
      • Only Ab that can be formed by the fetus
nature of antibodies4
Nature of Antibodies
  • Five classes of Ab
    • IgG
      • Dominant Ab in circulation
        • 80 – 85% Ab in circulation
      • Structure = monomer
      • Only Ab that can cross the placenta
      • The antibody of memory!!!!!
    • IgA
      • Found in secretions
      • 10 - 13 % of Ab in circulation
      • Structure
        • Monomer in serum
        • Dimer in secretions
          • Breast milk, mucus, tears and saliva
nature of antibodies5
Nature of Antibodies
  • Five classes of Ab
    • IgD
      • <1% of total Ab in circulation
      • Structure = monomer
      • Maturation of antibody response
    • IgE
      • Barely detectable in circulation
      • Structure = monomer
      • Active in allergic reaction
clonal selection of lymphocytes
Clonal Selection of Lymphocytes
  • When antigen introduces into body, only appropriate antibody bonds
    • Initiates multiplication of specific antigen
      • Process called clonal selection
      • Repeated cycles of cell division generates population of copied antibodies
        • Termed clonal expansion
  • Without sustained stimulation, cells undergo apoptosis
clonal selection of lymphocytes1
Clonal Selection of Lymphocytes
  • Lymphocyte characteristics include
    • Immature
      • Antigen specific receptors not fully developed
    • Naive
      • Have antigen receptor but have not encountered antigen
    • Activated
      • Able to proliferate
      • Have bound antigen
    • Effectors
      • Descendents of activated lymphocytes
      • Able to produce specific cytokines
      • Plasma cells, T helper and cytotoxic T cells effector cells
    • Memory lymphocytes
      • Long-lived descendents of activated lymphocytes
      • Memory cells responsible for seed and effectiveness of secondary response
        • Remembers antigen on subsequent exposure
b lymphocyte and antibody response
B Lymphocyte and Antibody Response
  • Antigen binds to B cell receptor
    • Poises B cell to respond
      • In many cases B cell needs conformation from helper T cells
  • Ag enters the body and is phagocytized and processed by macrophages
    • These macrophages destroy Ag and present a portion on the surface of the macrophage next to self Ag
      • Macrophages are called antigen-presenting cells (APC)
  • Processed Ag combines with specific TH with the appropriate receptor
  • APC releases substances to activate TH cell
  • TH cell activates B cells to divide and differentiate
    • Produce plasma cells and memory B cells
b lymphocyte and antibody response2
B Lymphocyte and Antibody Response
  • Characteristic of primary response
    • Lag period of 10 to 12 days occurs before antibody detection in blood
      • Activated B cells proliferate and differentiate into increasing numbers of plasma cells as long as antigen is present
    • Net result is slow steady increase in antibody titer
b lymphocyte and antibody response3
B Lymphocyte and Antibody Response
  • Over time, some B cells undergo changes enhancing immune response including
      • Affinity maturation
      • Class switching
      • Formation of memory cell
  • Affinity maturation
    • Form of natural selection
      • Occurs among proliferating B cells
    • Fine tunes quality of response with respect to specificity
      • B cell receptors more and more specific to antigen
        • Antibody bonds antigen more tightly
b lymphocyte and antibody response4
B Lymphocyte and Antibody Response
  • Class switching
    • B cells initially programmed to differentiate into plasma cells
      • Plasma cells secrete IgM antibodies
    • Helper T cells produce cytokines
      • Some B cells switch programming
        • Differentiate to plasma cells that secrete other classes of antibodies
          • Commonly IgG
b lymphocyte and antibody response5
B Lymphocyte and Antibody Response
  • Formation of memory
    • B cells that have undergone class switching
      • Produce IgG antibody
        • IgG is antibody of memory
      • IgG antibody can circulate in body for years allowing protection against specific antigens
b lymphocyte and antibody response6
B Lymphocyte and Antibody Response
  • Characteristics of secondary response
    • Memory cells responsible for swift effective reaction of secondary response
      • Often eliminate invaders before noticeable harm is done
    • Vaccine exploits phenomenon of immunologic memory
    • Some memory B cells will differentiate into plasma cells
      • Results in rapid production of antibodies
b lymphocyte and antibody response7
B Lymphocyte and Antibody Response
  • T-independent antigens
    • Can stimulate antibody response
      • Activate B cells without helper T cells
      • Few antigens are T-independent
    • B cell receptors bind antigen simultaneously
      • Leads to B cell activation
    • Some polysaccharides and lipopolysaccharides act as T-independent antigens
t lymphocytes antigen recognition and response
T LymphocytesAntigen Recognition and Response
  • General characteristics of T cells
    • Have multiple copies of T cell receptors
      • Receptors have variable sites of antigen bonding
    • Role of T cells different from B cells
      • T cells never produce antibodies
      • T cells armed with effectors that interact directly with antigen
        • T cell receptor does not react with free antigen
          • Antigen must be present by APC
t lymphocytes antigen recognition and response1
T LymphocytesAntigen Recognition and Response
  • General Characteristics
    • During antigen presentation, antigen cradled in grove of major histocompatability complex molecule (MHC molecule)
      • Two types MHC
        • MHC class I
          • Bind endogenous antigen
        • MHC class II
          • Bind exogenous antigen
t lymphocytes antigen recognition and response2
T LymphocytesAntigen Recognition and Response
  • General characteristics
    • Two major function T cell populations
      • Cytotoxic T cells
        • Proliferate and differentiate to destroy infected or cancerous “self” cells
        • Have CD8 marker
        • Recognize MHC class I
      • Helper T cells
        • Multiply and develop into cells that activate B cells and macrophages
        • Stimulate other T cells; orchestrate immune response
        • Have CD4 marker
        • Recognize antigen display by MHC class II
t lymphocytes antigen recognition and response3
T LymphocytesAntigen Recognition and Response
  • Functions of Tc (CD8) cells
    • Induce apoptosis in “self” cells
      • Cells infected with virus or intracellular microbe
      • Destroys cancerous “self” cells
    • Nucleated cells degrade portion of proteins
      • Load peptides into groove of MHC class I molecule
      • MHC class I molecule recognized by circulating Tc cell
        • Cell destroyed by lethal effector function of Tc cell
      • Tc cells releases pre-formed cytokines to destroy cell
t lymphocytes antigen recognition and response4
T LymphocytesAntigen Recognition and Response
  • Functions of TH (CD4) cells
    • Orchestrate immune response
      • Recognize antigen presented by MHC class II molecules
        • MHC class II molecules found only on APC
      • If TH cell recognizes antigen, cytokines are delivered
        • Cytokines activate APC to destroy antigen
t lymphocytes antigen recognition and response5
T LymphocytesAntigen Recognition and Response
  • Role of TH cells in B cell activation
    • If TH cell encounters B cell bearing peptide: MHC calls II complex
      • TH cell responds by producing cytokines
    • B cell is activated in response to cytokine stimulation
      • B cell proliferates and undergoes class switching
      • Also drives formation of B memory cells
t lymphocytes antigen recognition and response6
T LymphocytesAntigen Recognition and Response
  • Role of TH cells in macrophage activation
    • Macrophages routinely engulf invading microbes resistant to lysosomal killing
    • TH cells recognize macrophage with engulfed microbes resistant to killing
    • TH cells activate macrophages by delivering cytokines that induce more potent destructive mechanisms
natural killer cells
Natural Killer Cells
  • Natural killer cells descend from lymphoid stem cells
    • They lack antigen specificity
      • No antigen receptors
      • Recognize antigens by means of Fc portion of IgG antibodies
        • Allow NK cells to attach to antibody-coated cells
  • Actions augment adaptive immune response
    • Important in process of antibody dependent cellular toxicity
      • Enable killing of host cells with foreign protein in membrane
  • Natural killer cells recognize destroyed host cells with no MHC class I surface molecules
    • Important in viral infection
lymphocyte development
Lymphocyte Development
  • During lymphocyte development, B and T cells acquire ability to recognize distinct epitopes
    • Once committed to specific antigen, cells “checked out” to ensure proper function
    • B cells undergo developmental stages in bone marrow
    • T cells go through process in thymus