Frederick A.

Bettelheim
William H. Brown
Mary K. Campbell
Shawn O. Farrell
www.cengage.com/chemistry/bettelheim

Chapter 31
Immunochemistry

William H. Brown • Beloit College

The Immune System
Figure 31.1 Overview of the immune system; its
components and their interactions.

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Innate Immunity
Innate Immunity: The natural, nonspecific resistance of
the body to foreign invaders. The first line of defense.
• Has two forms: external (skin, mucus, tears) and
internal (dendritic cells, macrophages, and natural
killer (NK) cells.
• Is nonspecific and without memory.
• When NK cells encounter cancerous cells, viral
infected cells, or other suspicious cells, they attach
themselves to these cells.
• Macrophages: Engulf and digest bacteria and reduce
inflammation.
• The capillaries dilate to allow greater flow of blood to
the site of an injury, enabling agents of the internal
innate immunity system to congregate there.
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Adaptive Immunity
• Also called acquired immunity.
• Key features are specificity and memory.
• The key components are T cells and B cells.
• Uses antibodies and cell receptors specifically
designed for each type of invader.
• The invader may be bacteria, viruses, molds, or pollen
grains.
• In a second encounter with the same invader, the
response is more rapid, more vigorous, and more
prolonged.
• The system is flexible; it is capable of making millions
of potential defenders.

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Components
• Antigen: A substance foreign to the body that triggers
an immune response.
• Two types of white blood cells, called lymphocytes,
fight against invaders: T cells and B cells.
• T cells kill invaders by contact.
• B cells synthesize antibodies, which are soluble
immunoglobulins that immobilize antigens.
• The basic molecules of the immune system belong to
the immunoglobulin superfamily.
• The immunoglobulin superfamily:
• Glycoproteins that are composed of constant and
variable protein segments having significant
homologies to suggest that they evolved from a
common ancestry.
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Immunoglobulin Superfamily
• The constant region has the same amino acid
sequence in each of the same class of molecules.
• The variable region is antigen specific.
The three representatives of the Ig superfamily:
• Antibodies, which are soluble immunoglobins secreted
by the plasma cells.
• T cell receptors (TcR), which recognize and bind
antigens presented to them.
• Major histocompability complex (MCH), reside within
cells. They interact with an antigen, and bring a
characteristic portion of it to the surface of the cell.
Such a surface presentation then marks the diseased
cell for destruction.

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Speed of the Immune Response
• The process of making the right immunoglobin is
relatively slow, often taking weeks and months.
• The immune system is complex; it involves molecular
signals and an interplay among various cells.
• Its major elements are:
1. Cells of the immune system.
2. Antigens and their perception by the immune
system.
3. Antibodies (immunoglobulin molecules) designed to
immobilize antigens.
4. Receptor molecules on the surface of cells that
recognize antigens.
5. Cytokines that control these interactions.

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Organs and Cells
• Fig 31.3 Exchange of compounds among three body
fluids: blood, interstitial fluid, and lymph.

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Lymphoid Organs
Lymphoid organs:
• The lymphatic capillary vessels drain the fluids that
bath the cells of the body.
• The fluid in these vessels is called lymph.
• Lymphatic vessels circulate throughout the body and
enter lymphatic organs such as the thymus, spleen,
tonsils, and lymph nodes.
• Lymphocytes: specialized white blood cells that are
primarily responsible for the functioning of the immune
system.
• T cells are lymphocytes that originate in bone marrow
but mature in the thymus gland.

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Lymphoid Organs
• B cells are lymphocytes that originate and mature in
the bone marrow.
• Both T and B cells are found mostly in the lymph, but
small numbers are also found in the blood.
• Their entry into the blood is aided by signaling
molecules called cytokines.

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The Immune System
• Table 31.1 Interactions among the different cells of the
immune system.
Infection
Interferon

NO synthetase

Macrophage
Nonspecific engulfs bacterium
or virus , digesting it

Antigens (digested)
presented on the
surface of macrophage

Helper T cell B cell

Specific Killer T cell Memory cell Plasma cell

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Internal Innate Immunity
Cells of the internal innate immunity:
• The two important cells are macrophages and natural
killer cells.
Macrophages
• They are nonspecific and attack virtually anything that
is not recognized as part of the body.
• They engulf nonself, destroy it, and display a small
portion of it on their surface.
Natural killer (NK) cells
• Target abnormal cells.
• Once in contact, they release proteins called
performins that perforate target cell membranes
creating pores.

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Cells of Adaptive Immunity
The two types of cells are T and B cells.
• T cells interact with the antigen presented by the
macrophage and produce other T cells that are now
highly specific to the antigen.
• When these T cells differentiate, they become killer T
cells.
• Killer T cells act through perforin.
• Other T cells become memory cells.
• B cells are produced by plasma cells.
• Most plasma cells reside in lymph nodes.

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Antigens and MHC
Antigen: Any foreign substance that elicits an immune
response.
• They are also called immunogens.
• Three features characterize an antigen:
1. Foreignness.
2. A molecular weight greater than 6000.
3. Sufficient complexity to elicit a response.
• The smallest unit of an antigen capable of binding an
antibody is called the epitope.
• To elicit a response, the antigen or epitope must be
brought to the surface of the infected cell.

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Antigens and MHC
Figure 31.7 Differential processing of antigens in the MHC
class II pathway (left) or MHC class I pathway (right).

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Immunoglobulins
Table 31.2 Immunoglobulin Classes

Carbohydrate Serum
Molecular Content Concentration
Class Weight (%) (mg/100 mL)
IgA 200,00 - 700,00 7 - 12 90 - 420
IgD 160,000 <1 1 - 40
IgE 190,000 10 - 12 0.01 - 0.1
IgG 150,000 2-3 600 - 1800
IgM 950,000 10 - 12 50 - 90

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Immunoglobulins
Figure 31.8(a) Schematic diagram of an IgG-type antibody
consisting of two light chains connected by a disulfide
bond. The amino terminal end of each chain has the
variable portion.

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Immunoglobulins
Figure 31.8(b) A model showing
how an antibody bonds to an
antigen.

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Antibody-Antigen Binding
An antibody binding to the epitope of an antigen.

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B Cells and Antibodies
Figure 31.11 B cells have antibodies in their surfaces,
which allow them to bind to antigens. The B cells with
antibodies for the antigens present grow and develop into
plasma cells. When B cells develop into plasma cells, they
release circulating antibodies into the bloodstream.

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B Cells and Antibodies

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Antigen-antibody Reaction
Figure 31.10 An antigen-antibody reaction forms a
precipitate. The aggregation thus formed precipitates and
is attacked by phagocytes and the complement system.

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Diversification of Igs
Figure 31.12 Diversification of immunoglobulins by V(J)D
recombination.

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Diversification of Igs
Figure 31.12 Diversification of Igs by V(J)D recombination
cont’d

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Monoclonal Antibodies
• When an antigen is injected into an organism, it may be
1 to 2 weeks before an antibody appears in the serum.
• The antigen may have many epitopes, and the antisera
contains a mixture of immunoglobins with varying
epitope specificities.
• Even antibodies to a single epitope usually have a
variety of specificities.
• Monoclonal antibodies, in contrast, are the product of
cells cloned from a single B cell and have a single
specificity.

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Monoclonal Antibodies
• Figure 31.13 A procedure for producing monoclonal
antibodies against a protein antigen X.

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T Cells and Their Receptors
T Cell Receptors:
• Each different T cell carries on its surface a unique T
cell receptor (TcR) that is specific for one antigen only.
• TcR is a glycoprotein made of two different subunits
cross-linked by disulfide bonds.
• Like immunoglobulins, TcRs also have constant (C)
and variable (V) regions.
• The antigen binds to the variable region.
• TcRs can interact with an antigen only when the
epitope of an antigen is presented by a MHC.

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TcR Complex
Figure 31.14
Schematic
structure of a
TcR complex.

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TcR Complex
• TcR alone, however, is not sufficient for antigen
binding.
• Also needed are proteins called cluster determinants
(CD) that act as coreceptors and/or signal transducers
• CD3 is a signal transducer.
• Upon antigen binding, CD3 becomes phosphorylated
which sets up a signaling cascade inside the cell.
• CD4 and CD8 act as adhesion molecules as well as
signal transducers.
• A unique feature of CD4 is that it binds strongly to a
glycoprotein on the surface of HIV.
• Through this binding to CD4, an HIV can enter and
infect T cells and cause AIDS.

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TcR Complex
• Figure 31.15 Interaction between helper T cells and
antigen-presenting cells.

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Cytokines
Cytokines: Glycoproteins that are produced by one cell
and alter the function of another cell.
• Cytokines have no antigen specificity.
• They are short-lived and are not stored in cells.
• They are released in bursts in response to all manner
of insult or injury.
• They travel and bind to specific cytokine receptors on
the surface of macrophage and B and T cells and
induce cell proliferation.
• One set of cytokines are the interleukins (ILs).
• Macrophages secrete IL-1 upon bacterial infection.

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Classes of Cytokines
Cytokines are classified by the secondary structure of
their polypeptide chains:
1. Four a-helical segments;
• An example is IL-2, which activates other B and T cells
and macrophages.
2. Only b-pleated sheets in 2° structure;
• An example is tumor necrosis factor (TNF).
3. Both a-helical and b-pleated sheets segments;
• An example is epidermal growth factor (EGF).
4. A subgroup called chemotactic cytokines
(chemokines);
• They attract leukocytes to the site of infection or
inflammation.
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Action of Cytokines
• When a tissue in injured, leukocytes are rushed to the
inflamed area.
• Cytokines help them migrate out of blood vessels to
the site of injury.
• Cytokines are also major players in:
Chronic inflammations.
Autoimmune diseases.
Asthma and other forms of allergic inflammation.
Transplant rejection.

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How to Recognize Self
One of the major problems facing body defenses is how
to recognize a foreign body as “not self” and avoid
attacking “self”.
Selection of T and B cells:
• T and B cells are specific and have memory.
• T cells mature in the thymus gland.
• During maturation, those T cells that fail to interact
with MHC and thus cannot respond to foreign antigens
are eliminated through a selection process.
• T cells that express receptors TcR that are prone to
interact with normal self antigens are also eliminated
through a selection process.

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T Cells
Figure 31.16(a) and (b)
A two-stage process
leads to the growth
and differentiation of T
cells.

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T Cells
• Figure 31.16(c) A two-stage
process leads to the growth and
differentiation of T cells.

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How to Recognize Self
Selection of T and B cells (cont’d)
• The maturation of B cells in the bone marrow depends
on their engagement with their receptors, BcR, with
antigen.
• Those B cells that are prone to interact with self
antigens are eliminated before they leave the bone
marrow.
• Many signaling pathways control the proliferation of B
cells.

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How to Recognize Self
Discrimination of the cells of the innate system:
• Natural killer cells and macrophages have no specific
targets and no memory of what epitopes signal danger.
• Still, they must discriminate between normal and
abnormal cells.
• Innate immunity cells have activating receptors and
inhibitory receptors on their surfaces.
• An inhibitory receptor recognizes the epitome of a
normal cell, binds to it, and prevents activation of killer
cells or macrophages.
• When a macrophage encounters a foreign antigen, the
antigen binds to the activating receptor; this binding
prompts the macrophage to destroy the antigen.

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How to Recognize Self
Autoimmune diseases:
• In spite of the safe guards to prevent acting against
“self”, some parts of the immune system may go awry.
Autoimmune diseases include:
The skin diseases psoriasis and eczema.
Myasthenia gravis.
Rheumatoid arthritis.
Multiple sclerosis.
Insulin-dependent diabetes.
Allergies.
Crohn’s disease.

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How to Recognize Self
Autoimmune diseases (cont’d)
• The major drugs for treating autoimmune diseases are
the glucocorticiods, the most important of which is
cortisol.
• The glucocorticoids regulate the synthesis of cytokines
either by interacting directly with their genes or
indirectly through transcription factors.
• Macrolid drugs, such as cyclosporine A and rapamycin,
bind to receptors in the cytosol and, through
secondary messengers, inhibit the entrance of nuclear
factors into the nucleus.
• The absence of nuclear factors prevents transcription
of cytokines.

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Chapter 31 Immunochemistry

End
Chapter 31

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