5.2 Complementary Interactions between Proteins and Ligands: The Immune
System and Immunoglobulins
SUMMARY 5.2 Complementary Interactions between Proteins and Ligands: The
Immune System and Immunoglobulins
■ The immune response is mediated by interactions among an array of specialized
leukocytes and their associated proteins. T lymphocytes produce T-cell receptors. B
lymphocytes produce immunoglobulins. In a process called clonal selection, helper T cells
induce the proliferation of B cells and cytotoxic T cells that produce immunoglobulins or
proliferation of T-cell receptors that bind to a specific antigen.
■ Humans have five classes of immunoglobulins, each with different biological functions.
The most abundant class is IgG, a Y-shaped protein with two heavy and two light chains. The
domains near the upper ends of the Y are hypervariable within the broad population of IgGs
and form two antigen- binding sites.
■ A given immunoglobulin generally binds to only a part, called the epitope, of a large
antigen. Binding often involves a conformational change in the IgG, an induced fit to the
antigen.
■ The exquisite binding specificity of immunoglobulins is exploited in analytical techniques
such as ELISA and immunoblotting.
We have seen how the conformations of oxygen-binding proteins affect and are affected by
the binding of small ligands (O2 or CO) to the heme group.
However, most protein-ligand interactions do not involve a prosthetic group. Instead, the
binding site for a ligand is more often like the hemoglobin binding site for BPG—a cleft in the
protein lined with amino acid residues, arranged to make the binding interaction highly
specific. Effective discrimination between ligands is the norm at binding sites, even when
the ligands have only minor structural differences.
All vertebrates have an immune system capable of distinguishing molecular “self” from
“nonself” and then destroying what is identified as nonself. In this way, the immune system
eliminates viruses, bacteria, and other pathogens and molecules that may pose a threat to
the organism. On a physiological level, the immune response is an intricate and
coordinated set of interactions among many classes of proteins, molecules, and cell types.
At the level of individual proteins, the immune response demonstrates how an acutely
sensitive and specific biochemical system is built upon the reversible binding of ligands to
proteins.
The Immune Response Includes a Specialized Array of Cells and Proteins
Immunity is brought about by a variety of leukocytes (white blood cells), including
macrophages and lymphocytes, all of which develop from undifferentiated stem cells in
, the bone marrow. Leukocytes can leave the bloodstream and patrol the tissues, each cell
producing one or more proteins capable of recognizing and binding to molecules that might
signal an infection.
The immune response consists of two complementary systems, the humoral and cellular
immune systems. The humoral immune system (Latin humor, “fluid”) is directed at
bacterial infections and extracellular viruses (those found in the body fluids), but can also
respond to individual foreign proteins. The cellular immune system destroys host cells
infected by viruses and also destroys some parasites and foreign tissues.
At the heart of the humoral immune response are soluble proteins called antibodies or
immunoglobulins, often abbreviated Ig. Immunoglobulins bind bacteria, viruses, or large
molecules identified as foreign and target them for destruction. Making up 20% of blood
protein, the immunoglobulins are produced by B lymphocytes, or B cells, so named
because they complete their development in the bone marrow.
The agents at the heart of the cellular immune response are a class of T lymphocytes, or T
cells (so called because the latter stages of their development occur in the thymus), known
as cytotoxic T cells (TC cells, also called killer T cells). Recognition of infected cells or
parasites involves proteins called T-cell receptors on the surface of TC cells. Receptors are
proteins, usually found on the outer surface of cells and extending through the plasma
membrane, that recognize and bind extracellular ligands, thus triggering changes inside the
cell.
In addition to cytotoxic T cells, there are helper T cells (TH cells), whose function it is to
produce soluble signaling proteins called cytokines, which include the interleukins. T H cells
interact with macrophages. The TH cells participate only indirectly in the destruction of
infected cells and pathogens, stimulating the selective proliferation of those T C and B cells
that can bind to a particular antigen. This process, called clonal selection, increases the
number of immune system cells that can respond to a particular pathogen. The importance
of TH cells is dramatically illustrated by the epidemic produced by HIV (human
immunodeficiency virus), the virus that causes AIDS (acquired immune deficiency
syndrome). TH cells are the primary targets of HIV infection; elimination of these cells
progressively incapacitates the entire immune system. Table 5-2 summarizes the functions
of some leukocytes of the immune system.
Each recognition protein of the immune system, either a T-cell receptor or an antibody
produced by a B cell, specifically binds some particular chemical structure, distinguishing it
8
from virtually all others. Humans are capable of producing more than 10 different
antibodies with distinct binding specificities. Given this extraordinary diversity, any chemical
structure on the surface of a virus or invading cell will most likely be recognized and bound
by one or more antibodies. Antibody diversity is derived from random
reassembly of a set of immunoglobulin gene segments through genetic recombination
mechanisms that are discussed in Chapter 25 (see Fig. 25-43).
A specialized lexicon is used to describe the unique interactions between antibodies or T-cell
receptors and the molecules they bind. Any molecule or pathogen capable of eliciting an
immune response is called an antigen. An antigen may be a virus, a bacterial cell wall, or
an individual protein or other macromolecule. A complex antigen may be bound by several
System and Immunoglobulins
SUMMARY 5.2 Complementary Interactions between Proteins and Ligands: The
Immune System and Immunoglobulins
■ The immune response is mediated by interactions among an array of specialized
leukocytes and their associated proteins. T lymphocytes produce T-cell receptors. B
lymphocytes produce immunoglobulins. In a process called clonal selection, helper T cells
induce the proliferation of B cells and cytotoxic T cells that produce immunoglobulins or
proliferation of T-cell receptors that bind to a specific antigen.
■ Humans have five classes of immunoglobulins, each with different biological functions.
The most abundant class is IgG, a Y-shaped protein with two heavy and two light chains. The
domains near the upper ends of the Y are hypervariable within the broad population of IgGs
and form two antigen- binding sites.
■ A given immunoglobulin generally binds to only a part, called the epitope, of a large
antigen. Binding often involves a conformational change in the IgG, an induced fit to the
antigen.
■ The exquisite binding specificity of immunoglobulins is exploited in analytical techniques
such as ELISA and immunoblotting.
We have seen how the conformations of oxygen-binding proteins affect and are affected by
the binding of small ligands (O2 or CO) to the heme group.
However, most protein-ligand interactions do not involve a prosthetic group. Instead, the
binding site for a ligand is more often like the hemoglobin binding site for BPG—a cleft in the
protein lined with amino acid residues, arranged to make the binding interaction highly
specific. Effective discrimination between ligands is the norm at binding sites, even when
the ligands have only minor structural differences.
All vertebrates have an immune system capable of distinguishing molecular “self” from
“nonself” and then destroying what is identified as nonself. In this way, the immune system
eliminates viruses, bacteria, and other pathogens and molecules that may pose a threat to
the organism. On a physiological level, the immune response is an intricate and
coordinated set of interactions among many classes of proteins, molecules, and cell types.
At the level of individual proteins, the immune response demonstrates how an acutely
sensitive and specific biochemical system is built upon the reversible binding of ligands to
proteins.
The Immune Response Includes a Specialized Array of Cells and Proteins
Immunity is brought about by a variety of leukocytes (white blood cells), including
macrophages and lymphocytes, all of which develop from undifferentiated stem cells in
, the bone marrow. Leukocytes can leave the bloodstream and patrol the tissues, each cell
producing one or more proteins capable of recognizing and binding to molecules that might
signal an infection.
The immune response consists of two complementary systems, the humoral and cellular
immune systems. The humoral immune system (Latin humor, “fluid”) is directed at
bacterial infections and extracellular viruses (those found in the body fluids), but can also
respond to individual foreign proteins. The cellular immune system destroys host cells
infected by viruses and also destroys some parasites and foreign tissues.
At the heart of the humoral immune response are soluble proteins called antibodies or
immunoglobulins, often abbreviated Ig. Immunoglobulins bind bacteria, viruses, or large
molecules identified as foreign and target them for destruction. Making up 20% of blood
protein, the immunoglobulins are produced by B lymphocytes, or B cells, so named
because they complete their development in the bone marrow.
The agents at the heart of the cellular immune response are a class of T lymphocytes, or T
cells (so called because the latter stages of their development occur in the thymus), known
as cytotoxic T cells (TC cells, also called killer T cells). Recognition of infected cells or
parasites involves proteins called T-cell receptors on the surface of TC cells. Receptors are
proteins, usually found on the outer surface of cells and extending through the plasma
membrane, that recognize and bind extracellular ligands, thus triggering changes inside the
cell.
In addition to cytotoxic T cells, there are helper T cells (TH cells), whose function it is to
produce soluble signaling proteins called cytokines, which include the interleukins. T H cells
interact with macrophages. The TH cells participate only indirectly in the destruction of
infected cells and pathogens, stimulating the selective proliferation of those T C and B cells
that can bind to a particular antigen. This process, called clonal selection, increases the
number of immune system cells that can respond to a particular pathogen. The importance
of TH cells is dramatically illustrated by the epidemic produced by HIV (human
immunodeficiency virus), the virus that causes AIDS (acquired immune deficiency
syndrome). TH cells are the primary targets of HIV infection; elimination of these cells
progressively incapacitates the entire immune system. Table 5-2 summarizes the functions
of some leukocytes of the immune system.
Each recognition protein of the immune system, either a T-cell receptor or an antibody
produced by a B cell, specifically binds some particular chemical structure, distinguishing it
8
from virtually all others. Humans are capable of producing more than 10 different
antibodies with distinct binding specificities. Given this extraordinary diversity, any chemical
structure on the surface of a virus or invading cell will most likely be recognized and bound
by one or more antibodies. Antibody diversity is derived from random
reassembly of a set of immunoglobulin gene segments through genetic recombination
mechanisms that are discussed in Chapter 25 (see Fig. 25-43).
A specialized lexicon is used to describe the unique interactions between antibodies or T-cell
receptors and the molecules they bind. Any molecule or pathogen capable of eliciting an
immune response is called an antigen. An antigen may be a virus, a bacterial cell wall, or
an individual protein or other macromolecule. A complex antigen may be bound by several
