Biomolecular Engineering II:

Engineering of Immunity
 The most familiar application of biomedical
engineering in immunology is the development of
vaccines.

 The development of vaccines that are both safe and

effective has been one of the great achievements of
modern medicine. Smallpox, polio and influenza are
now in control.
 Many vaccines work by enhancing the formation of
Abs within the body of the vaccine recipient.

 Abs are specialized proteins that can inactivate

pathogens directly, or mark them for destruction by
other elements of the immune system
 Antigens, Abs, and mAbs

 Ab molecules are proteins that carry out important

functions in the immune system. The most
important property of an Ab is its ability to bind to
an antigen (Ag), or specific chemical.

 Ab molecules bind to chemical targets on the surface

of pathogens, such as bacteria or viruses.
 Antigens, Abs, and mAbs

 The target chemical to which an Ab binds is called an

Ag.

 An Ag can be a protein, a polysaccharide, or even a

small molecule that is attached to a larger carrier.

 Abs are produced by specialized cells of the immune

system that are differentiated forms of circulating
white blood cells called B cells.
 Antigens, Abs, and mAbs

 A B cell is stimulated to produce an Ab by an

encounter with a foreign Ag.

 Whenstimulated by an Ag, the B cell matures into an

Ab-producing cell, called a plasma cell.
Examples of therapeutic mAbs that have been
approved for use in the United States
 What are Abs?

 The basic Ab molecule is shaped like a “Y,” with two

Ag-binding sites at the top of the arms of the “Y” and
an effector region within the base of the “Y” .
 What are Abs?

 Therefore: the basic Ab contains:

1) two identical Ag-binding regions, which are formed by variable
regions from a light and a heavy chain.

2.) one effector region, which is formed by conserved regions of

the two heavy chains.

By binding to cell receptors and other immune molecules, the

effector region is responsible for producing class-specific
functions.
 What are Abs?

 The Ag-binding sites of all Ab molecules include

amino-acid sequence contributions from both the
heavy and light chains.

 Within the variable regions of the heavy and light

chains are hypervariable regions (called
complementary determining regions, or
CDRs). It is the composition of these CDRs that
determine the Ag-binding specificity of each Ab.
 Clinical uses of Abs

 In 1890, von Behring and Kitasato demonstrated

that immunity to certain diseases could be provided
to non-immune individuals by the transfer of serum.

 This demonstration was critical in uncovering the

role of Abs in the immune response; it was also the
first example of passive immunization in
animals.
 Clinical Uses of Abs

 In passive immunization, Abs that are manufactured

outside of the recipient’s body are administered to an
individual, usually to prevent an infectious disease.

 Passive immunization is a method of disease

prophylaxis: Prophylaxis is a term that refers to
a medical procedure that is intended to prevent a
disease, rather than cure a disease that is already
established.
 Immunotherapy with Ab-toxin conjugates

 The development of mAb–toxin conjugates as cell-

selective cytotoxic agents has been vigorously
pursued over the last several decades

 Immunotoxins are designed by selecting mAbs that

are produced to bind to components of cells, such as
receptors on the surface of cancer cells.
 Immunotherapy with Ab-toxin conjugates

 Whereas conventional chemotherapy drugs are toxic

to normal cells as well as diseased cells,
immunotoxins should selectively bind to diseased
cells, making chemotherapy safer and more effective.

 Immunotoxin therapy can lead to tumor regression

and increased survival in animals bearing solid
tumors. But human applications of immunotoxin
therapy have developed slowly
Vaccines
 Vaccines

 Vaccines currently protect individuals around the

world from debilitating or life-threatening diseases
including smallpox, polio, and hepatitis.
 Vaccines that prevent common diseases of
childhood have dramatically reduced mortality
during the early years of life.
 Vaccines can be produced to treat infectious diseases
that are caused byviruses, bacteria, parasites, or
other infectious agents. Usually, vaccines are used as
prophylaxis.
 Viral Diseases

 Viruses are tiny,disease-causing agents—usually on

the order of 100nmin diameter (although size varies
greatly among virus families)—that can only multiply
within cellular host.

 In general, a virus consists of genetic material, which

can be DNA or ribonucleic acid (RNA), surrounded
by a protective, glycoprotein coat called a capsid.
Some viruses have complex capsid structures that
include an envelope, or phospholipid-rich
membrane.
 Pop Quiz

 1. Are large, Y-shaped proteins that are used in the

immune system to identify and counteract invaders
such as viruses.

A. Antibodies B. Antigen
C. Antiserum D. Adjuvants
 Pop Quiz

 2. Substance that is introduced to the body that can

stimulate the production of Abs.

A. Antibodies B. Antigen
C. Antiserum D. Adjuvants
 Pop Quiz

 3. In ________, Abs that are manufactured outside

of the recipient’s body are administered to an
individual, usually to prevent an infectious disease.

A. Vaccination
B. Immuno-therapy
C. Passive Immunization
D. Avidity
 Pop Quiz

 4. A term that refers to a medical procedure that is

intended to prevent a disease, rather than cure a
disease that is already established.

A. Antibodies
B. Prophylaxis
C. Vaccination
D. mAbs
 Pop Quiz

 5. ____ currently protect individuals around the

world from debilitating or life-threatening diseases
including smallpox, polio, and hepatitis.

 A. Vaccines
 B. Immuno-therapy
 C. Prophylaxis
 D. mAbs