ANTIGEN AND ANTIBODY

Antibodies

 Circulating proteins that are produced in vertebrates in responses to exposures to foreign

structures
 Mediators of humoral immunity again all classes of microbes

Antigens

 The substances that stimulated production of or were recognized by antibodies

Antigen and T cell antigen receptors  two classes of molecules used bye the adaptive immune system
to specifically recognize and respond to antigens. (Table)

Major histocompatibility complex (MHC) molecules

 Bind peptide antigens

 Specificity is very different and function is to display the peptides to T cells, not respond to the
antigens,

Antibodies

 First type of antigen binding molecule to be discovered

 Recognize the widest range of antigenic structures
 Have the greatest ability to discriminate between different antigens
 Bind antigens with the greatest strength

Antibodies are synthesized only by cells of B lymphocyte lineage and exist in two forms:

1. Membrane-bound antibodies on the surface of B lymphocytes  as antigen receptors

- Recognition of antigen by membrane-bound AB on naïve B cells activates these lymphocytes
and initiates a humoral immune response
- Activated B cells differentiate into plasma cells that secrete AB of the same specificity as the
antigen receptor.
- Secreted form AB are present in the plasma, in mucosal secretion, and in the intersitial fluid
of tissues.
2. Secreted antibodies  to protect against microbes
- In the effector phase of humoral immunity,  neutralize microbial toxins, prevent the entry
ad spread of pathogen, and trigger several effector mechanisms that eliminates microbes

The elimination of antigens often requires interaction of antibodies with other components of the
immune system: molecules (complement proteins) and cells (phagocytes and mast cell).
Antibodies remain in the residual fluid  serum

Serum lacks of coagulation factors (which are consumed during clot formation) but contains all the other
proteins found in plasma

Any serum sample that contains detectable antibody molecules that bind to a particular antigen 
antiserum

The study of antibodies and their reactions with antigens  serology

The concentration of antibody molecules in serum specific for a particular antigen is often estimated by
determining how many serial dilutions of the serum can be made before binding to the antigen can no
longer be detected  titer

The more dilutions that are required, the higher the titer of the antibody molecules specific for a
particular antigen

A healthy 70k-kg adult human produces about 2 to 3 g of antibodies every day. Almost two-thirds of this
is a type of antibody called IgA, most of which is produced by activated B cells and plasma cells in the
gastrointestinal tract

ANTIBODY STRUCTURE

Plasma or serum proteins can be physically separated based on solubility characteristics into albumins
and globulins, and may be more precisely separated, based on differences in charge, using a technique
called electrophoresis.

In electrophoretic separations of serum or plasma most antibodies are found in the third fastest
migrating group of globulins  gamma globulins (for the third letter of the Greek alphabet)

Another common name for antibody is immunoglobulin (Ig)  referring to the immunity-conferring
portion of the globulin fraction of serum plasma. The terms immunoglobulin anti anti-body are used
interchangeably.

All antibody molecules share the same basic structural characteristics but display remarkable variability
in the regions that bind antigens.

This variability of the antigen-binding regions accounts for the capacity of different antibodies to bind a
tremendous number of structurally diverse antigens.

In every individual, there are millions of different clones of B cells, each producing antibody molecules
with identical antigen-binding sites but which differ from the antigen-binding sites of anti-bodies
produced by other clones

The effector functions and common physicochemical properties of antibodies are associated with the
non-antigen-binding portions, which exhibit relatively few variations among different antibodies

An antibody molecule has a symmetric core structure composed of two identical light chains and two
identical heavy chains. (Figure 5.1)
Both the light chains and heavy chains contain a series of repeating homologous structural unit, each
about 110 amino acids residues in length, that fold independently in a globular motif  Ig domain 
contains two layers of β-pleated sheet, each layer composed of three to five strands of antiparallel
polypeptide chain (Figure 5.2)  two layers are held together by a disulfide bridge, and adjacent strands
of each β-sheet are connected by short loops. It is the amino acids in some of these loops that are the
most variable and critical for antigen recognition

AB heavy chains and light chains both consist of amino-terminal variable (V) regions that participate in
antigen recognition and carboxy-terminal constant (C) regions

C regions  help mediate some of the protective or effector functions of antibodies

Heavy chains:

V regions is composed one Ig domain

C region is composed of three or four Ig domains

Light chains :

Composed of one V region Ig domain and one C region Ig domain

V (variable) regions  so named because their amino acid sequences vary among antibodies made by
different B cell clones

V region of one heave chain (VH) and V region of one light chain (VL) form an antigen-binding site

Because the core structural unit of each antibody molecule contains two heavy chains and two light
chains  two antigen-binding sites

C-region Ig domains:
- separated from antigen-binding sites and do not participate in antigen recognition
- interact with other molecules and cell of the immune system
- help mediate most of the biologic functions of antibodies
- sometimes called “effector” functions
- C regions of light chains do not participate in effector functions and are not dirtectly
attached to cell membranes.

Heavy chains exist in two forms that differ at their carboxy-terminal ends:

- one form of the heave chain anchors membrane-bound antibodies in plasma membranes of
B lymphocytes
- other forms is found in secreted antibodies.
Heavy and light chains

-  covalently linked by disulfide bonds formed between cysteine residues in the carboxy
terminus of the light chain and the CH1 domain
- noncovalent interactions between the VL and VH domains and between CL and CH1
domains may also contributes to the association of heavy and light chains
- The two heavy chains of each antibody molecule are also covalently linked by disulfide
bonds.
- There are different kinds of antibodies, called classes or isotype, which heavy chain
structures

The antigen-binding portion of an antibody molecule is the Fab (fragment, antigen binding) region
- Consist of the complete light chain (VL and CL) associated with a VH-CH1 fragment of the
heavy chain
- These fragments retain the ability to bind antigen because each contains paired VL and VH
domains
The C-terminal end that is involved in effector functions is the Fc (fragment, crystallizable) region
- Containing the heavy chain CH2 and CH3 domains
- This piece of IgG has a propensity to self-associated and to crystallize into a lattice)

Ig superfamily
All molecules (many other proteins in the immune system, as well as numerous proteins with no known
immunologic function) that contain domains with an Ig fold structure  two adjacent β-pleated sheets
held together by a disulfide bridge.

Ig domains are classified as V-like or C-like in the basis of closest homology to either Ig V or Ig C domains.
V domains:
- formed from a longer polypeptide than C domains
- contain two extra β strands within the β sheet sandwich

example of Ig superfamily members of relevance in the immune system are depicted in Figure 5.4