• Each IgG molecule is made up of two identical heavy chains and two identical light chains with carbohydrates
• Variable and Constant regions
• Aminoacid terminal regions of heavy and light chains are variable in seq. from one IgG to another
• Contains a flexible hinge region located between the two arms and stem of Y IgG molecule

• Mature B cell expresses membrane bound immunoglobulin (Ig) of single antigen specificity
• When foreign antigen first binds to immunoglobulin, B cell is stimulated to proliferate
• Progeny differentiate into plasma cells that secrete antibody of the same specificity as the membrane bound immunoglobulin

• Antibodies act to:
• Neutralize microbe or toxin, which inhibits growth, replication/cell contact
• Opsonize microbes: coat microbe by antibody and engulf for destruction OR coat with antibody and complement components for engulfment
• Macrophages and neutrophils will participate in opsonization
• FcR (FcRepsilon) and complement receptors

• Antibodies neutralize to protect from infection
• Bind to viral hemagglutinin preventing virus from binding to the cell and halt infection at 1st step.
• IgA dimers, form at which IgA is made and secreted by mucosal surfaces
• Without vaccination virus can bind by entering cell using endosome and fusion of viral lipid envelop and endosome membrane - release into cytoplasm  

• Abs neutralize to protect from infection/colonization
• Previous infections, host produces neutralizing IgA antibodies - coat bacteria and impair ability to attach to fibronectin in EM - keeps pop. down for no disease
• No previous infection, size of bacterial infection not regulated and under favorable cond. it can expand, causing damage to mucosal surface inducing inflammation - sore throat and adaptive imm. response with neutralizing antibodies

• Ex. snake venom - antivenom
• Protein toxins produced by many bacteria - mod. const. One part of toxin binds to cellular receptor, which allows toxin to be internalized whereupon the 2nd part posions the cell
• High affinity neutralizing IgG antibodies bind to the receptor-binding part of toxin and prevent entry

• Abs act to opsonize -  active receptor mediated event that req. signaling
• Specific IgG coat pathogen surface and tether bacterium to phagocyte by binding Fc receptors. Signals from Fc receptors enhance phagocytosis of bacterium and fusion of lysosome (deg. enzymes) with phagosome - Fc receptors provide myeloid cells, such as phagocytes

Many common diseases are caused by bacterial toxins

Fig. 9.27

• Several examples of exotoxins (secreted) and endotoxins (non-secreted released when bacterium dies)
• Endotoxins include LPS are important for pathogenesis of disease, but int. with host are more complicated that exotoxins and less understood

• Infection in tissue, whole pathogen or antigens found in interstital fluid will drain to lymph nodes through afferent lymph vessels
• This Ag will bind the BCR on B cell if in LN
• Ag will be processed and presented on MHC II for CD4 help
• Most Ab responses need CD4 T cell help - some dont
• Cell cooperation between B & T cells through recognition of same of different parts of same Ag (linked recognition)
• Vaccines - both B and T cell activation

• Ex. Three IgG molecules are shown binding with both arms to antigens that are located at different distances apart on the surfaces of a bacterium

• Ab quality improves over the course of an immune response
• Somatic hypermutation: nucleotide substitution throughout variable regions
• Isotype switching/class switch recombination: changes out the constant region; retains Ag-specificity; improves ability to do effector functions

• Induction of mutations mostly in Ag-binding V region; driven by Ag in proliferating cells
• Enzyme AID (activation induced deaminase) changes cytosines to uracil in DNA
• 1 mutation per V region per cell division - 1 million times greater than normal mutation rates
• Results in Ig with higher affinity for Ag and the cells bearing these receptors compete better for Ag, thus better chance developing into plasma cell
• Over time, repetition of somatic mutation in clonal cells drive affinity maturation of the B cell response

• Change in heavy chain (C) region; does not change Ag-specificity
• More diverisity on effector responses: better opsonization, interaction with particular receptors
• Occurs in proliferating cells, determination of isotype (Ch) to be produced is directed by cytokines
• AID is one enzyme that participates - causes nicks in DNA at switch area upstream of Cu, as well as in switch area upstream of newly targets Ch
  
• Intervening DNA is lost, thus cant go back to producing certain isotypes of Ab

• Hypervariable region in antibody is found in antigen-binding site

• Different classes of Ab/Ig
• Naive B cells have IgM and IgD on their surface
• Initial class of Ab that is secreted after B cell activation is IgM
• IgD never secreted
• IgD (hinge), IgE, and IgG (hinge) monomers in soluble secreted form
• IgA (hinge) forms monomers and dimers
• IgM only forms pentamers

• Monomeric IgM is found on cell surface
• Secreted IgM is good at binding antigen - 10 binding sites
• IgM pentamer held together by a polypeptide called J chain (joining chain)
• Monomers are cross linked by disulfide bonds to each other and to the J chain

• Most Ab secreted as monomeric molecules. 
• IgM secreted as pentamer. 
• IgA can be dimer or monomer
• In mucosal lymphoid tissue IgA is synthesized as a dimer in association with the same J cahin as that found in pentameric IgM
• Dimeric IgA monomers have disulfide bonds to J chain but not each other

1. Pocket
2. Groove
3. Extened surface binding
4. Antigen binding site intrusion of pocket binding (knobs)

• Ag for Ab can be multivalent: can contain more than 1 epitope or more than 1 copy of the same epitope
• All bind to the protein antigen using a single Fab arm or multiple Fab arms depending on either single or multiple epitopes

• Antigen can be linear or conformational/discontinuous
• A linear epitope of a protein antigen is formed from contiguous amino acids
• A discontinuous epitope is formed from amino acids from different parts of the polypeptide that are brought together when the chain folds

• Ab are secreted and can be found circulating in all areas of body. IgE usually doesnt circulate: pre bound on mast cells via FcRepsilon
• Inflammation will act to dilate BV - cause increase of fluid flow and increase antibody conc. in tissue spaces
• Low Half Life (days): IgE(2), IgD(3), IgA1(6), IgA2 (6), IgG3(7)
• High Half Life: IgM(10), IgG2(20), IgG1(21), IgG4(21)