structure and function of antibodies
what is the difference between Fab and Fc regions of an antibody?
Fab: antigen binding site containing CDR Fc: effector part, that will activate complement, etc.
what two antibodies are produced in the greatest quantity?
IgA and IgG are the most synthed antibodies
what is the composition of IgA, what two forms is it found in, and what are its actions?
IgA is composed of 2 α heavy chains (3 Ig domains) AND either 2 κ OR 2 λ light chains 1. secretory: found in external secretions, consists of dimer or tetramer connected by a J chain, and contains a polypeptide chain called a SECRETORY COMPONENT actions: 1. predominant Ig in BREAST MILK, saliva, tears, and mucus
what is the primary antibody found in breast milk?
IgA is the primary antibody found in breast milk
what is the composition of IgD, and what are its actions?
IgD is composed of 2 δ heavy chains (3 Ig domains) AND either 2 κ OR 2 λ light chains membrane bound monomer action: none known
what is the composition of IgE, and what are its actions?
IgE is composed of 2 ε heavy chains (4 Ig domains) AND either 2 κ OR 2 λ light chains monomer actions: 1. mediates immediate hypersensitivity rxns a. responsible for HAY FEVER, ASTHMA, HIVES, and ANAPHYLACTIC SHOCK
what antibody is involved in immediate hypersensitivity rxns (ie anaphylaxis, hay fever, asthma)?
IgE is the antibody that is involved in immediate hypersensitivity reactions
which 2 antibodies are able to activate the classic complement pathway?
IgG and IgM are able to activate the classic complement pathway 1. antibody binds IgG or Igm 2. causes conformational change allowing for C1 to bind 2. C1 binds antibody-IgG/IgM, allowing for cleavage and activation
what is the composition of IgG, and what are its actions?
IgG is composed of 2 γ heavy chains (3 Ig domains) AND either 2 κ OR 2 λ light chains 4 sublasses based off of the γ chain sequences actions: 1. opsonization of antigens 2. activate classical complement pathway 3. ADCC 4. placental immunity
which antibody crosses past the placenta to give immunity to neonates?
IgG is passed from mother to child through the placenta
what antibody is able to opsonize microbes, activate the classical complement pathway, and mediate antibody-dependent cell mediated cytotoxicity (ADCC)?
IgG is the antibody that is able to opsonize microbes, activate the classical complement pathway, and mediate antibody-dependent cell mediated cytotoxicity (ADCC) most abundant antibody in the body
what is the single most abundant class of antibody?
IgG is the single most abundant antibody in serum 80%
what is different in the IgM and IgE C region vs IgA, IgG, and IgD?
IgM and IgE contain 4 Ig domains, while IgA, IgG, and IgD contain 3 Ig domains
what is the composition of IgM, and what are its actions?
IgM is composed of 2 µ heavy chains (4 Ig domains) AND either 2 κ OR 2 λ light chains 1. monomer when membrane bound 2. pentamer when secreted by plasma cells, joined by a J chain actions: 1. FIRST Ig PRODUCED in a primary immune response to an antigen 2. activate complement 3. 10 antigen binding sites
what is the first antibody produced in a primary immune response to an antigen?
IgM is the first antibody produced in a primary immune response to an antigen
how are antibodies divided into classes and subclasses?
classes are formed by the differences in structure of the Cheavy regions, named for the type of heavy chain α, γ, δ, ε, µ α and γ are further divided into subclasses IgA1, IgA2 IgG1, IgG2, IgG3, IgG4
where are the majority of differences among antibodies found?
differences are found in 3 10 AA long regions of the Vheavy and Vligh chains called the HYPERVARIABLE SEGEMENTS or COMPLEMENTARY-DETERMINING REGIONS form the antigen binding surface
what are the two types of light chains in an antibody?
each antibody contains 2 identical light chains, either 2 κ or 2 λ chains 60κ:40λ → ratio used to dx B cell tumors
expression of what 2 antibodies in the membrane of a B cell is the mark of a mature B cell?
expression of IgD and IgM in the membrane of a B cell is the mark of a mature B cell
expression/secretion of what antibody is the mark of an immature B cell?
expression/secretion of IgM is the mark of an immature B cell
what antibodies are monomeric, and what antibodies are multimeric?
monomeric: a. secreted IgG and IgE b. all membrane bound antibodies multimeric: a. secreted IgM (pentamer) b. secreted IgA (dimer)
what fragments remain when IgG is cleaved with papain? when cleaved with pepsin?
papain: 2 Fab (Vl & Vh), and Fc pepsin: F(ab')₂ + peptide fragments of Fc
which antibody has the ability to bind up to 10 antigens?
secreted IgM is found as a pentamer, and it is able to bind 10 antigens at once (2 binding sites per IgM antibody)
in which complementary-determining region does the most extensive contact occur between antigen and antibody?
the CDR3 portion of the antibody forms the most extensive connection with the antigen
what is formed by the 12 complementary-determining (hypervariability) regions in an antibody?
the antigen binding site of antibody is formed from the 12 complementary-determining regions these are 10 AA long regions found on the Vlight and V heavy chains
what is the difference between a membrane and a soluble form of an antibody?
the difference between the two is in the tail of the antibody membrane form: hydrophobic tail that is embedded in the membrane secreted form: hydrophillic tail
how are antibodies synthesized?
1. Ig H and L chain mRNA translated in polyribosomes on the RER 2. assembly of H and L chains, disfulide bond formation, and glycosylation occurs in the RER 3. golgi packs into secretory vesicles 4. expressed in PM 5. maturation of B cells in bone marrow changes Ig gene expression, leading to dif antibodies being synthed a. IgM in the membrane is mark of immature B cell b. IgM and IgD in the membrane is mark of mature B cell
what are effects that are triggered by antibodies to remove antigens?
1. activated compliment (IgG, IgM) 2. neutralization of microbes or toxins (IgG) 3. opsonization of microbe (IgG) 4. antibody-dependent cell mediated cytotoxicity (ADCC) leading to cell lysis (IgG)
what 3 molecules are able to recognize and bind antigens?
1. antibodies (synthed by B cells) 2. MHC (class 1 → intracellular and 2 → extracellular) 3. TCR (bind antigens-MHC presented to T cells by APCs)
what are the effector function of antibodies?
1. antigen-IgG/IgM can activate the classic complement pathway via binding of C1 a. inflammation 2. neutralization of microbes or toxins 3. opsonization of microbe (IgG) a. via Fc receptor 4. antibody-dependent cell mediated cytotoxicity (ADCC) leading to cell lysis (IgG) 5. prevent binding of toxins/microbes to cells
in what 2 forms can antibodies be found?
1. membrane bound: IgD and IgM on naive B cells a. every B cell will express a membrane bound antibody 2. secreted: circulating antibodies secreted by antigen-activated B-cells (all, but most common is IgG) b. secretion/expression of IgM is the mark of an immature B cell
what are some general features of antibodies?
1. same basic structure 2. variability in region that bind antigens (Vheavy and Vlight) 3. core of 2 identical light chains and 2 identical heavy chains 4. Ig domain composed of repeating 110 AA stretch in both light and heavy chains 5. amino terminal variable region and carboxy terminal constant region a. C region of heavy binds effector cells 6. disulfide bonds between cysteine residues link chains, w/ further noncovalent rxns between Vl and Vh, and Ch and Cl
what are antibodies, and what do they recognize?
antibodies are circulating proteins produced in response to antigens antibodies recognize antigens
if run out via electrophoresis, what group (in terms of speed) are antibodies found in?
antibodies are found in the third fastest group that run through gel gives them their name (gamma globulins, γ is the third letter in the greek alphabet)
what receptors do antibodies bind on effector cells?
antibodies bind effector cells on the Fc receptor effector cells include phagocytes, NK cells, and mast cells