-antibody is secreted form of B cell receptor
-recognition of antigen mediated by 2 antigen binding sites of variable region
-constant region of heavy chain determines antibody’s biological role in immune response
-all immunoglobulin molecules consist of 4 polypeptide chains
2 identical H chains
2 identical L chains
-some antibodies exist as dimers or pentamers of immunoglobulin molecules
-kappa (κ) chain
-lambda (λ) chain
-gamma (γ) chain
-mu (μ) chain
-delta (δ) chain
-epsilon (ε) chain
-alpha (α) chain
-type of H chain defines immunoglobulin class or isotype
immunoglobulin may have κ chain or λ chain L chain, but never both
-N-terminal portions of both H and L chains are different for different antibodies → variable (V) regions
-within variable regions of immunoglobulins → 3 short stretches of amino acids that vary most from one antibody to another
hypervariable (HV) regions
-H, L chain V regions (HVH and HVL) contribute significantly to antigen-binding site are part of antibody that contacts the antigen
-rest of H and L chains are constant (C) region
-each H chain (μ, δ, γ ε, α) has a different amino acid sequence in its C region
determines function of antibody
-different isotypes of antibodies have different roles in immune system
-C regions of L chains have different amino acid sequences
but doesn’t influence function of antibodies
-difference in amino acid sequence of C regions of heavy chains. between species is significant
can cause a clinical setting when human patient needs to be transfused with antibody from non-human species
-single antibody molecule has
2 identical H chains
2 identical L chains
→ antibodies are bivalent
single antibody molecule has 2 antigen-binding sites
-antigen-binding site is a 3D pocket
side chains of amino acids make up H & L chain hypervariable regions determine shape of antigen-binding site
shape of antigen-binding site determines specificity of antibody
-single antibody molecule binds to only small portion of antigen molecule (epitope/antigen determinant)
epitope has 3D structure
antigen-binding site of antibody has shape that is complementary to epitope
epitope on antigen fits in antibody’s antigen-binding site like key and lock
-different antibodies have antigen-binding sites with different shapes
bind epitopes with different 3D structures
-single antigen can have many epitopes
there can be many copies of same epitope, different epitopes or both
-epitopes on surface of antigen are accessible to antibody
many antibodies with different specificities can bind to their particular epitope on one antigen particle
possible for 2 different antigens to have an epitope in common
-antibody binds to epitopes with a complementary shape
close contact between surface of epitope and surface of antigen-binding site is required for strong binding
-poor fit suggests there is weak binding or no binding
-close contact allows formation of H bonds, ionic and hydrophobic interactions between epitope and antigen-binding site
-single antibody will bind only one or a few similarly shaped epitopes
-IgM, IgA, IgG are main types of secreted antibodies
-made by activated B cells
-IgD not secreted
only found on cell surface of naive B cells
-antibodies of different isotypes can recognize same antigen because they have same V region
-secreted IgM is a pentameter consisting of 5 IgM monomers that are joined to each other by disulfide bonds
2 IgM monomers are connected by a polypeptide (J/Joining chain)
-low binding affinity
-pentameric IgM has high avidity (total binding strength)
10 binding sites instead of 2
-more binding sites = greater binding strength
-amino acid sequence in μ chain constant region binds efficiently to complement proteins
bacteria coated with IgM killed when complement is activated
-able to neutralize pathogen
-found in blood
-incapacitate pathogens by neutralizing them
-kills bacteria in 2 ways
complement proteins kill bacteria coated with IgA
amino acid sequence in γ chain constant region binds effectively to complement proteins
phagocytes ingest bacteria coated with IgG antibodies more readily than bacteria without IgG
amino acid sequence in γ chain constant region facilities binding of IgG to specific receptors on phagocytic cells
-IgG antibodies from mother can cross placenta to protect fetus
-in serum — monomer
-in bodily secretions — dimer
-J chain joins 2 monomer IgA units
-dimeric IgA in bodily secretions associated with another polypeptide (secretory chain)
secretory chain help IgA cross layers of epithelial cells and get to appropriate body sites
-IgA is main immunoglobulin class in bodily secretions
bind to and neutralize pathogens
prevents attachment of pathogens to host surfaces
-secreted into serum
almost all binds immediately to mast cells and basophils
-not available in serum to neutralize pathogens
-amino acid sequence in ε chain constant region binds to receptor on these cells
IgE is the only antibody class that can bind to this receptor (FCεRI)
-responsible for triggering allergic reactions
-when IgE on mast cell or basophil binds an antigen
cell degranulates and releases large amounts of histamine
-main class of immunoglobulin induced in response to infection by parasites such as intestinal worms
worms are too big to be killed via phagocytosis
mast cell degranulation results in diarrhea and vomiting to expel the worms
-B cell uses a different CH region
class and function of Ig is different
antigen specificity remains the same
-first antibodies produced in immune response always IgM
activated T helper cells may induce some B cells to switch to a different class (isotype) of Ig by providing specific cytokines
-class switching is an important method of tailoring adaptive response to best match antibody to pathogen
-immunoglobulin class switching involves cutting out DNA
B cells may undergo class switching on more than one occasion
mechanism of switching is uni-directional
B cell can’t be switched back to original Ig type after splicing because DNA is lost
-some B cells that undergo immunoglobulin class switching may differentiate into long plasma cells and secrete the new class of Ig
other cells may become long-lived memory B cells
-antibodies protect against pathogens
prevent viruses and toxins from binding to cell surfaces and entering cells (neutralization)
coat virus and bacteria, improve efficiency of phagocytosis by neutrophils & macrophages (opsonization)
allow more types of bacteria to be killed by complement proteins (complement activation)
-alternate pathway can activate complement after complement C3b binds to surface of pathogen
complement proteins are regarded as part of innate response → they still work with IgM and IgG antibodies generated during adaptive immune response
-after IgM and IgG has bound to surface of pathogen
early complement proteins are recruited
formation of C3 convertase
C3c cleaves C3 to C3a and C3b
binding of C3b to pathogen surface recruits additional proteins to form C5 convertase which cleaves to C5a and C5b
C5 is also deposited on pathogen surface and initiates assembly of late proteins to form membrane attack complex (MAC)