antibodies and antigens Flashcards
antibodies were orginally identified in the serum and termed _______ which is often used interchangeably with Abs
immunoglobulins
most Abs are found in the third slowest migrating group of globulins, named _____ globulins for the third letter of the greek alphabet
gamma
effector properties of Abs
- FcR (Fc receptor) - opsonization and phagocytosis of microbes
- activation of classical complement pathway
- toxin neutralization
- direct antibacterial activity - formation of three dimensional lattices (agglutination of bacteria) and wait for phagocytes to come and eliminate
- potential to modulate an immune response by immunization with AG-Ab complexes
- reduce damage to hose from inflammatory response
- organized T-cell (used to control acute T-cell mediated transplant rejection)
Abs have a basic unit of 4 polypeptide chains (2 light chains and 3 heavy chains) - bound together by covalent _______ _______ as well as by noncovalent interactions
disulfide bridges
both heavy and light chains are divided into _____ and _____ regions
variable (V)
constant (C)
the variable (V) region contains the ______ site and the constant (C) region determines the _____ properties of the Abs
Ag-binding
biological
Abs can be proteolytically cleaved to yield two ____ fragments and an ____ fragment that are responsible for effector functions
Fab (Fragment Ag-Binding)
Fc (Fragment Crystallized)
IgG is cleaved by what enzymes
papain and pepsin
papain digestion allows separation of ___ monovalent (having only 1 site of attachment) Fab fragments and complement and Fc receptors-binding the Fc fragment
2
pepsin digestion generates a single ______ Ag-binding fragment (F(ab’)2
bivalent (having two sites of attachment)
there are 5 different types of H-chains which determine the class of Ab
mu - IgM
delta - IgD
gamma - IgG
epsilon - IgE
alpha - IgA
there are 2 different types of light chains
kappa
lambda
(each with MW of 23kDa)
both heavy and light chains have intrachain disulfide bridges every 90 amino acid residues which create ______ ______ ; these Ig domains are referred to as ____ , ____, ____, and ____
polypeptide loops
Vh, Vl, Ch1, Ch2
a large group of cell surface and soluble proteins that are involved in the recognition, binding, or adhesion processes of cells belongs to the immunoglobulin superfamily they include:
T cell receptors
MHC molecules
CD4 coreceptor of T cells
CD28 (costimulatory receptor on T cells)
adhesion molecule ICAM-1
is IgG secreted or membrane-bound?
secreted
is IgM secreted or membrane-bound?
membrane-bound
secreted IgG:
the Ag-binding sites formed by juxtaposition of ___ and ___ domains
the heavy chain Constant regions end in ____ pieces
the locations of complement and Fc receptor - binding sites within the heavy chain constant regions are ____
VL and VH
tail
approximations
membrane- bound IgM:
has an additional ___ domain
CH4 domain has C-terminal transmembrane and ____ portions that anchor the molecule in the plasma membrane
CH4
cytoplasmic
hinge allows flexibility and abilty for Ab to bind to widely spaced cell surface determinants and closely spaced cell surface determinants; the hinge is located between what 2 domains?
CH1 and CH2
what Ags are recognized by Abs
conformational determinant
linear determinant
neoantigenic determinant (created by proteolysis)
different Abs vary in their _____ to the same Ag determinant
affinity
the higher the ____ constant (Ka) the less likely the Ab is to dissociate from the Ag
binding
Abs formed in the primary response soon after the injection of an Ag generally have ____ affinity (IgM)
lower
Abs produced by a memory response have ____ affinity than Ka in a primary response (IgG)
higher
the Ab affinity is critical when the Ag is a ___ or ___ and msut be neutralized rapidly at low titers of toxin or pathogen
toxin
virus
valence of an Ab is the ____ number of antigenic determinants with which it can react with Ag
maximum
molecule of IgG contains 2 Fab regions and it can bind 2 molecules of Ag or 2 identical epitopes on a single pathogen, and thus has a valence of ___
2
the valence is important for binding affinity, as having 2 or more binding sites for an Ag can dramatically increase the ____ of binding of the Ab to Ags
tightness
avidity gives a measure of the overall strength of an Ab-Ab complex. avidity depends on:
1.
2.
- affinity of the Ab for a single epitope
2. valence of both the Ab and Ab
low affinity IgM can be extremely effective in neutralizing a microorganism because it has 10x Ag binding ____
domains
Ig vs T Cell Receptor (TCR)
Ag-binding site:
Ig: three CDRs in VH and three CDRs in VL domains
TCR: three CDRs in Valpha and three CDRs in Vbeta domains
Ig vs T Cell Receptor (TCR)
Ag that may be bound
Ig: proteins, lipids, polysaccharides, and small chemicals
TCR: peptide-MHC complexes
Ig vs T Cell Receptor (TCR)
Antigenic determinants recognized
Ig: linear and conformation determinants of various macromolecules and chemicals
TCR: linear determinants; only 2 or 3 aa residues of a peptide bound to an MHC molecules
Ig vs T Cell Receptor (TCR)
affinity of Ag binding
Ig: higher
TCR: lower
Ig vs T Cell Receptor (TCR)
on-rate/off-rate
Ig: rapid on-rate ; variable off-rate
TCR: slow on-rate ; slow off-rate
all 5 classes of Ig originate from B cells that contain what B-cell receptors
IgM or IgD
original B-cell with B-cell receptor –> Ag binds –> affinity maturation (somatic mutations in variable region) –> _____ affinithy
increased
original B-cell with B-cell receptor –> activated and differentiates into plasma cell –> change from membrane bound Ab to secreted form –> change from B-cell receptor function to ____ function
effector
original B-cell with ……
.
what chain of Ab determines class?
heavy chain
what Ig classes have basic 4 chain Ab structure?
IgG
IgD
IgE
what Ig class has dimer Ab structure
IgA
what Ig class has pentamer Ab structure
IgM
B cell proliferation cytokines
activated B cell IgM/IgD –> proliferating B cells
IL-2 IL-4 IL-5
proliferating B cells —> cytokine _____ –> IgG3 (Phagocytosis)
IFN-gamma
proliferating B cells –> cytokine ____ –> IgA (mucosal defenses)
TFG-beta
proliferating B cells –> cytokine ____ –> IgE (allergy) and IgG1 (phagocytosis)
IL-4
proliferating B cells –> cytokine ____ , ____ , ____ –> IgM (complement activation)
IL-2 IL-4 IL-5
IgA is the most common Ab in
mucosal secretions
IgM is mainly found in
the plasma
IgE is absorbed on the surface of
mast cells
IgG penetrates deeper into the
tissue
IgA in serum is mainly _____ but in secretions (tears, saliva, mucus, sweat, gastric fluid) IgA is found as a _____ connected by a joining peptide
monomeric
dimer
IgG functions
neutralization
opsonization
NK cell activation
complement activation
maternal IgG is bound by placental
FcRn which is recycled
placenta performs _____ immunity of fetus
passive
IgD properties
low quantities in circulation
primary function: an Ag receptor on B lymphocytes
when IgM and IgD is expressed on a B cell, they act as receptors for an Ag for which they are specific, the Ag is internalized, processed, and presented to _____ cells
helper T
naive B cells express both ____ and ____ in approx 50/50 proportions
IgM and IgD
what is the first Ab produced by any Ag-activated B cell prior to contact with T helper cells?
IgM
T-cell independent
IgM heavy chain
2 mu heavy chains
functions of IgM
complement activation*
activation of B cells, some neutralization (low affinity)
what is the first Ig presented on developing B cell (BCR- B cell receptor)
IgM
overall avidity of IgM is very ____ , making IgM very effective in removal of the microbe
high
what Ig forms a pentamer in blood (J joining chain)
IgM
IgM is a big molecule and therefore found primarily in the ______ and provides protection from ______ pathogens
bloodstream
bloodborne
what is the most abundant immunoglobulin in the blood
IgG
IgG provides the bulk of immunity to most ______ and ______ pathogens
bloodborne
tissue
IgG has 2 heavy ____ chains with either 2 ____ or 2 ____ light chains
gamma
kappa
lambda
heavy chain of IgA
alpha chains
in addition to heavy and light chains, IgA also contains 2 other polypeptides chains, they are
- secretory component (SC)
2. J-chain (joining chain)
IgA is found in the blood as a _____ and found in mucosa as a _____
monomer
dimer (J-chain)
major function of IgA
neutralization in mucosa
IgA stimulation of secretion:
interactions with Th cells in presence of TGF-beta
IgA secretory component is responsible for
crossing epithelium
what Ig is found in secretions (saliva and breast milk)
IgA
IgA from breast milk provides newborn immunity in transition period between _____ and when the infant produces their own Ig
fetal IgG
IgE is present in the serum at very ____ levels
low
major functions of IgE
acute inflammation
protection from infection by worms and allergic rxns
activation of mast cells
IgE is an important component of immediate hypersensitivity syndromes such as
hay fever and asthma
production of monoclonal Ab
- splenocytes from a mouse that has been immunized with a known Ag are isolated
- myeloma cells have immortalized properties but do not secrete its own Ig
- isolated cells are fused with myeloma cells to form hybrid cells
- only Ab-secreting hybrid cells survive in HAT medium
