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Chapter 4

BIO120H1 Chapter Notes - Chapter 4: Peptidoglycan, Polysaccharide, Flow Cytometry


Department
Biology
Course Code
BIO120H1
Professor
Bebhinn Treanor
Chapter
4

Page:
of 4
Chapter 4
In an adaptive immune response, the body is cleared of extracellular
pathogens and toxins by antibodies (secreted form of B cell antigen
receptor)
o Antibodies are produces by effector B lymphocytes or plasma cells of
the immune system in response to infection
o Circulate as major component of plasma in blood and lymph and
always present at mucosal surface
o Antibodies most often recognize proteins and carbohydrates
o Binding of antibody to bacterium or virus can disable the pathogen
and make it susceptible to destruction by other components of
immune system
o Antibodies are best source of protective immunity and the most
successful vaccines protect through stimulating production of high
quality antibodies
An individual antibody molecule is said to be specific
o Can bind to only one antigen or small number of different antigens
Antibodies are diverse in their antigen binding specificities
o The total number of diff specific antibodies that can be made by an
individual=antibody repertoire can be high as 1018. In practice, the
number of B cell limits actual repertoire to 109.
Antibodies are the secreted form of immunoglobulins
o During its development, individual B cell becomes committed to
producing Ig of a unique antigen specificity; thus mature B cells
collectively produce Ig of many diff specificities
o Before it encounters antigen, mature B cell only expresses Ig in a
membrane bound form that serves as the cells receptors for antigen.
o When antigen binds to this receptor, the B cell is stimulated to
proliferate and to differentiate into plasma cells, which then secrete a
lot of antibodies with same specificity as that of the membrane bound
Ig. (clonal selection)
Agammaglobulinemia-inability to make Ig. Highly susceptible to infection
Function of an antibody in host defense is to recognize and bind to
corresponding antigen and to target the bound antigen to other complements
of the immune system...which then destroy it
One part of the antibody is high variable in that its AA sequence differs from
antibody to antibody. Variable part contains site of antigen binding and
confers specificity on antibody. Constant part of antibody is what interacts
with other immune system components.
Immunoglobulins have 5 classes/isotypes
o IgA , IgD, IgE, IgG, IgM
o Distinguished on the basis of structural differences in the constant
part of the molecule and have different effector function
Antibodies are glycoproteins built from basic unit of 4 polypeptide chains
o 2 heavy chains (H chains) and 2 light chains (L chains) assembled
into Y shape
o Each arm of the Y made up of light chains paired with amino terminal
part of heavy chain, covalently bonded by disulfide bond
o Stem of Y consists of paired carboxy terminal portions of the 2 heavy
chains (linked by disulfide bonds)
Variable region (V region)-amino terminal region of chain, vary in amino
acid sequence
o This variability is reason for diversity of antigen binding specificities
among antibodies, because the paired V regions of heavy and light
chains form antigen binding site-1 at each arm of Y (its identical)
o Remaining parts of light and heavy chain are much more limited in
amino acid sequence btw diff antibodies=constant region (C region)
In IgG, unstructured protion in middle of heavy chain forms flexible hinge
region where molecule cleaved to produce defined antibody fragments
o Fragments provide info about antibody structure and function
o Fragments corresponding to arms are called Fab (fragment antigen
binding) because they bind antigen
o Fragment corresponding to stem is called Fc (Fragment crystallizable)
because it crystallizes
o The stem of a complete antibody molecule known as Fc region or Fc
piece and the arms as Fab
o The hinge of IgG allows the two Fabs to adopt many different
orientations with respect to each other…flexibility allows antigens far
away on surface of pathogens to be bound by both Fab arms
Differences in the heavy chain C regions define main isotypes or classes of Ig
o IgA =
o IgD =
o IgE =e
o IgG =
o IgM =
Light chains have 2 isotypes= kappa () and lambda ()
o No functional difference found btw antibodies carry k light chains and
those carrying light chains
o Each antibody contains either k or , not both
o In humans-2/3 K, 1/3-
Antibodies function in extracellular environments in the presence of
infection, where they can encounter variation in pH, [salt], proteolytic
enzymes, and other destabilizing factors
o Structure of antibody helps them withstand harsh condition
o Heavy and light chains each consist of a series of similar sequence
motifs; single motif=100 AA and folds up into compact and
exceptionally stable protein domain called immunoglobulin domain
V region at amino terminal end of each heavy or light chain is composed of
single variable domain (V domain)
o VH is in heavy chain and Vl is in light chain…combine to form an
antigen binding site
Constant domains (C domains), which make up the C regions have no
sequence diversity
o Constant region of a light chain is made up single C1 domain
o Heavy chain-made up of 3 or 4 C domains depending on isotype
heavy chains of IgG=CH1, CH2, CH3
structure of single Ig domain has 2 beta sheets held together by hydrophobic
force btw their AA side chains. Stabilized by disulfide bonds btw the 2 beta
sheets. Adjacent strands within Beta sheets connected by loops of the
polypeptide chain. Arrangement of beta sheets provide stable framework for
al Ig domains, whereas AA sequence of loops can vary for diff binding
properties on domain
Although immunoglobulin domains first found in antibodies, similar domains
called immunoglobulin like domains bound in many proteins and common
in cell surface and secreted proteins of the immune system
o Immunoglobulin superfamily
V domains-the differences in AA sequence are concentrated within
hypervariable regions (HV), which are flanked by much less variable
framework regions
3 hypervariable regions found in each V domain
o when mapped onto the folded structure of V domain, the
hypervariable regions locate to 3 of the loops that are exposed at the
end of the domain farthest from the constant region
o framework region corresponds to the Beta strands and remaining
loops
pairing of a heavy and light chain in an antibody molecule brings together the
hypervariable loops from each V domain to create a composite hypervariable
surface, which forms the antigen-binding site at the tip of each Fab arm
the differences in the loops btw different antibodies create both the
specificity of antigen-binding sites and their diversity
The hypervariable loops are also called complementarity determining
regions (CDR) because they provide a binding surface that’s complementary
to that of antigen
The antibodies that are most effective against infection are usually those that
bind to the exposed and accessible molecules making up the surface of a
pathogen
Part of antigen which antibody binds is called antigenic determinant or
epitope
o Usually carbohydrate or protein because surface molecules of
pathogens are commonly glycoproteins, polysaccharides, glycolipids,
and peptidoglycans
o Complex macromolecules like these will contain several different
epitopes, each of which can be bound by diff antibody