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

Secreted Antibodies

-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)

Secreted IgM

-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

Secreted IgG

-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

Secreted IgA

-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 IgE

-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

Immunoglobulin Class Switching

-B cell uses a different C_H 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

Functions of Secreted Antibodies

-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)

Complement Activation by Antibodies

-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)

Knowt