 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

 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

 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

 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

 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

 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

 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

 Coined from compounds that elicit antibody production › Anti body gen erator  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

 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

 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

 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

 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

 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  % of Ab in circulation  Structure  Monomer in serum  Dimer in secretions  Breast milk, mucus, tears and saliva

 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

 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

 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

 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 T H with the appropriate receptor  APC releases substances to activate T H cell  T H cell activates B cells to divide and differentiate › Produce plasma cells and memory B cells

 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

 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

 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

 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

 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

 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

 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

 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

 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

 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

 Functions of T H (CD4) cells › Orchestrate immune response  Recognize antigen presented by MHC class II molecules  MHC class II molecules found only on APC  If T H cell recognizes antigen, cytokines are delivered  Cytokines activate APC to destroy antigen

 Role of T H cells in B cell activation › If T H cell encounters B cell bearing peptide: MHC calls II complex  T H 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

 Role of T H cells in macrophage activation › Macrophages routinely engulf invading microbes resistant to lysosomal killing › T H cells recognize macrophage with engulfed microbes resistant to killing › T H cells activate macrophages by delivering cytokines that induce more potent destructive mechanisms

 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

 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