sequence variability
the N-terminal of the antibody is characterised by _______________ in both heavy and light chains
variable regions
the BCR and antibodies are a key part of the adaptive immune response. They interact and recognise antigens through their _____________.
constant regions
antibodies interact with effector cells through their _______________
gene segments
specificity is generated through recombination of ______________ to generate clonally unique molecules
Ch1; Ch2; & Ch3
the constant portion of the heavy chain is further divided into 3 structurally discrete regions (domains): ________________ stabilised by intra-chain disulphide bonds
variable domains
the site to which the antibody binds antigen are located in the ____________
Ch1 & Ch2
the hinge region is a segment of heavy chain between the _________ and ________ domains
independently
flexibility in the hinge region permits the 2 antigen binding sites to operate _____________
carbohydrate moieties
____________________ are attached to the Ch2 domains on the heavy chain
beta barrel
each immunoglobulin domain is composed of a ____________ 2� structure containing a single disulphide bond enclosing a loop of 60-70 amino acids
VL/ VH and CL/CH
both the heavy and light chain the region's of each antibody have constant and variable regions ____________ & ____________
heterodimers
antibodies are ______________ composed of 4 peptide chains; 2 identical light chains and 2 identical heavy chains
disulphide linkage
each light chain is attached to a heavy chain by a ___________, Ionic Salt linkages and hydrogen bonds as well as hydrophobic interactions. similar ______________ and non-covalent forces that link the 2 heavy and light chain combinations together forming
complimentary determining regions (CDRs)
many of the differences among the antibodies falls in areas of the variable regions called ____________________ and is these _________________ on both the heavy and light chains that constitute the antigen binding site of the Ab
glycosylation
the carbohydrate binding site is located in the Ch2 domain; _______________ of the antibody may make it more soluble
Lambda & Kappa
there are 2 light chain types __________ & ___________:
Lambda
60% of light chains are ______ and 40% of light chains are Kappa in humans. A normal antibody molecule will contain only one form, either ________ or Kappa never both
isotypes
there are 5 different constant heavy chain ______, ? ? ? ? and ?
:IgA
isotype ? belongs to
:IgG
isotype ? belongs to
:IgD
isotype ? belongs to
:IgM
isotype ? belongs to
immunoglobulins
circulating antibodies are called
:IgE
isotype ? belongs to
IgD (?)
all in the Ig isotypes apart from ____ are by functional , e.g., they bind antigen and exhibit more than 1 effector function
3-D conformation
antigen binding sites are specific for the _____________ the target -the antigenic determinants or epitope
affinity
Antibody _________ is a measure of the strength of the interaction between the and antibody combining site and its epitope
avidity
the ___________ the functional combining strength of an antibody with its antigen, which is related to both the affinity of the reaction between the epitopes and the valencies of the antibody and antigen. Depends on the number of binding sites and its abi
constant regions
each antibody isotype or subclass mediates a distinct set of effector functions isotypes are determined by the ___________________ of the heavy chains,
genetic variation
isotypes refer to ______________ within a family of proteins or peptides such that every member of the species of each isotype of the family represented in its genome
predominant
IgG is the __________ class of Ab in normal human serum.
IgG1?, IgG2?, IgG3? and IgG4 ?
IgG has four subclasses: _____________ encoded for by different genes
monomeric 4
the structure of IgG comprises a ______________ chain molecule
70-75%
IgG accounts for ________ of the total serum immunoglobulin pool
switching
IgG is produced after isotype ________ in B cells, and is associated with the acquisition of memory cells
IgG4?
all isotypes of IgG , except ______ activates the complement
IgG (?) all isotypes
neonatal immunity: transfer of maternal antibody across the placenta and can play an important role in protecting the fetus ( innate immunity)
FAB and Fc
IgG has a unique hinge region that contributes to the relative mobility is of the IgG _______________ and _____________ moieties with indie intact molecule
Fc:
fragment crystalline: the portion of an antibody that is responsible for binding to antibody receptors on cells and the C1q components of compliment
FAB - fragment antigen binding,
_____: the region to which antigens can bind, and is composed of one constant and one variable domain of each of the heavy and the light chain
Fc receptors:
surface molecules on a variety of cells that bind to specific regions on the antibody. They are antibody class specific and isotype selective.
A, D, E, G, & M
antibody classes: _______________
rapidly produced
IgG is the most abundant but not ____________ has a short 30 day half life
IgG (image)
IgA (image)
10-15%
IgA contributes ________ of antibody in serum
IgA -
the predominant class of antibody in external secretions such as breast milk, saliva, tears and mucosa of the bronchial, GU and GI tracts
dimer
IgA is secreted as a _______ structure
J-chain
IgA has a _____________ polypeptide and a polypeptide called the secretory component. The ___________ polypeptide holds the dimer structure of the IgA together
degredative enzymes
IgA is resistant to __________ found in secretions of the eyes and gut
C-terminals
IgA monomer units are linked by disulphide linkages at the ____________ to form the dimer structure
opsonise
IgA ________ antigen for phagocytosis
Basolateral
IgA receptors are expressed on the _________ surface of most mucosal epithelial cells
IgA1 and IgA2
IgA has two subclasses: ______________
cross-link
secretory IgA serves important effector functions at mucous membrane sites (main pathogen entry sites) , where it can ____________ large antigens with multiple epitopes
mucosal cells
binding of secretory IgA to bacterial and viral surface antigens prevents the attachment of pathogens to the __________ thus preventing infection
cilliated
IgA-antigen complexes are easily entrapped in mucus and eliminated by the _____________ respiratory cells or peristalsic movement of the GI tract.
antibody-dependent cell mediated cytotoxicity (ADCC)
effector functions of IgG include: opsonization of antigens for phagocytosis by macrophage and neutrophils/ activation of the classical pathway of compliment/ neonatal immunity/ neutralisation of microbes and toxins/ feedback inhibition of B cell activati
ADCC
a cytotoxic reaction in which Fc receptor bearing killer cells recognise target cells via specific antibodies. NK cells are activated to discharge their granules which contain proteins to kill the opsonised targets
Ch2 & Ch3 CDR
the Fc receptor/ region and complement binding sites found on the ____________ domains
IgM and IgD
the antigen receptors of naive B lymphocytes, which are mature B cells that have not encountered antigen, are membrane-bound _____ and ______
isotype switching or heavy chain class switching
some of the progeny of IgM- and IgD- expressing cells may secrete IgM, and other progeny of the same B cells may produce antibodies of other heavy chain class. This change in Ig isotype production is called _______________
reversible, noncovalent
antibodies bind to antigens by ________________ interactions, including hydrogen bonds and charge interactions.
4 antigen binding sites
secreted IgA is a dimer , and therefore has _____________________
2 antigen binding site
each IgD, IgE and IgG have ____________________
10 antigen binding sites
IgM is a pentameric structure and therefore has ___________________
cross-reaction
antibodies produced against one antigen may bind to other, structurally similar, antigens. Such binding to similar epitopes is called a __________________
mucosal immunity
IgA is responsible for __________________: secretion of IgA into lumens of gastrointestinal and respiratory tracts, neutralisation of microbes and toxins
defence against helminths
IgE is responsible for __________________ and mast cell degranulation (immediate hypersensitivity reactions)
peripheral site
antibodies enter the bloodstream, from where they may reach any ___________ of infection
bone marrow
antibody production begins within the 1st week after infection of vaccination. Some of the plasma cells migrate to the ______________ living in this issue continuing to secrete small amount of antibodies for months or years. If the same microbe again trie
FAB (fragment antigen binding)
antibodies to use their antigen binding ____________ region to bind and block harmful effects of microbes and toxins
Fc regions
antibodies use their _______________ to activate diverse effector mechanisms to eliminate microbes and toxins
FcRn
neonatal _____ is expressed in placenta, in endothelium and a few other cell types. In the endothelium, it plays a special role in protecting IgG antibodies from intracellular catabolism. _______ protects IgG from lysosomal degradation by binding to it in
Fc?RI
the _________ receptor expressed by neutrophil and macrophage, induces the phagocytosis of microbes that have been opsonised by IgG1 or IgG3 molecules. The antibody Fc regions bind with high affinity to the _______ expressed by the phagocytes activating p
monomer
in human serum IgA occurs as a _________, but it secreted at a dimer
secretory chain
IgA has a _____________ which is acquired on transport across mucosal epithelial cells during secretion into mucus
memory cells
IgG is produced after isotype switching in B cells and is associated with the acquisition of ________________.
hinge region
the 4 subclasses of IgG are very similar, most variation is in the ______________. IgG3 in particular, has an elongated ______________ allowing better biological activity
half life
the high abundance of IgG is due to its much greater _________ of 30 days , as opposed to less than 6 days for other antibodies
<1%
IgD makes up ____ of serum antibody, as it is susceptible to spontaneous proteolysis due to extended hinge region
IgD (image)
oligosaccharides
the heavy chains of IgD have 3 N- linked ___________
IgD ? -
may play a role in signalling when the young B cells in the spleen already to be activated
proline
the ?, ? and ? Hinge regions contain an extended peptide sequence rich in _________ residues and is flexible, giving IgA, IgD and IgG segmental flexibility. As a result, the 2 FAB arms it can assume various angles to each other when antigens bound
macrophage and neutrophils.
FC receptors, which can bind to the constant region of immunoglobulin molecules are present on the surface of ___________and______________. The binding of Fc molecules to antibody complexed with the same target antigen leads to endocytosis of the antigen-
mast cells, eosinophils and basophils
a unique function of IgE is the activation of __________,__________and____________
IgE -
binds to allergens triggering histamine release from mast cells and basophils, to mediate immediate hypersensitivity reactions
IgE (image)
conformation determinant
Ab-Ag recognition: _____________ complex 3-D structure of proteinepitope on adjacent ?-helices in close proximity is lost by denaturing. Antibody can not recognise denatured/linear epitope.
linear determinant
Ab-Ag recognition: _______________ 2 scenarios: the determinants are inaccessible until they have been the denatured, 1: Ig binds to determinant in the nature protein only ; or 2: Ig binds to determinant in both native and denatured protein
scarce
IgE is ________ in serum, as it is absorbed to mast cells and basophils by Fc?RI
neoanligenic determinants
Ab-Ag recognition: ________________ the determinant is absent . Therefore proteolysis creates new groups of antigen, to allow antigen recognition
5-10%
IgM accounts for _______ this of total antibody in serum
IgM pentamer
IgM :
pentamer with 5 disulphide linkages linking each heavy chain, cross-linked by Ch3 and Ch4 domains. expressed as part of the BCR. The Fc regions are situated in the centre of the pentamer and 10 antigen binding sites on the periphery of the molecule.
J-chain polypeptide
IgM has an additional Fc- linked __________________which is disulphide linked to the C terminal of 2 heavy chains. The IgM ________________ appears to be required for polymerisation of monomers to form the pentamer.
IgM -
is the 1st class of antibody produced in a primary response to an antigen, and is also the 1st antibody produced by the neonate
5 large antigen
IgM has a high valancy and combined up to 10 small hapten molecules or _________________ molecules simultaneously
IgM is
more efficient at binding multiple episodes, and less is required to neutralise a target
Fc Regions
IgM has greater efficiency and activating complement activation requires there to be at least 2 _____________ in close proximity, which is fulfilled by the Pentamer structure
Humoral immunity
IgM eliminates pathogens in the early stages of ______________ before there is sufficient IgG
neutralising
a function of antibodies that inhibits a pathogen from infecting his cell e.g. blocking receptors on a cell of pathogen
IgG and IgM
_____ and ____ can activate the classical complement pathway