Historical Perspective

of Immunology

MIC 317-L1
Overview of the Immune System

• The immune system evolved to protect

multicellular organisms from pathogens.
• It is highly adaptable, defends the body against
invaders as diverse as the tiny ( ̴30 nm),
intracellular virus that causes polio and as large as
the giant parasitic kidney worm, which can grow to
over 100 cm in length and 10 mm in width.
• This diversity of potential pathogens requires a
range of recognition and destruction mechanisms
to match the multitude of invaders.
• To accomplish this feat, vertebrates have evolved a
complicated and dynamic network of cells,
molecules, and pathways.
• Organisms causing disease are termed pathogens,
and the process by which they induce illness in the
host is called pathogenesis.
• The human pathogens can be grouped into four
major categories based on shared characteristics:
viruses, fungi, parasites, and bacteria.
• Some of the shared characteristics that are
common to groups of pathogens, but not to the
host, can be exploited by the immune system for
recognition and destruction.
Our enemies (pathogens)
Our soldiers of the immune system
Supporting components of the immune system
Supporting components of the immune system
Supporting components of the immune system
Fight between the invaders and the
immune components
Historical Perspective of Immunology
• The discipline of immunology grew out of the
observation that individuals who had recovered
from certain infectious diseases were thereafter
protected from the disease.
• The Latin term immunis, meaning “exempt,” is
the source of the English word immunity, a state
of protection from infectious disease.
• Perhaps the earliest written reference to the
phenomenon of immunity can be traced back to
430 BC.
• In describing a plague in Athens, it was found that
only those who had recovered from the plague
could nurse the sick because they would not
contract the disease a second time.
 Early Vaccination Studies
• The first recorded attempts to
deliberately induce immunity
were performed by the
Chinese and Turks in the
fifteenth century.
• They were attempting to prevent smallpox, a
disease that is fatal in about 30% of cases and that
leaves survivors disfigured for life.
• Reports suggest that the dried crusts derived from
smallpox pustules were either inhaled or inserted
into small cuts in the skin (a technique called
variolation) in order to prevent this disease.
• In 1718, Lady Mary Wortley Montagu observed
the positive effects of variolation on the native
Turkish population and had the technique
performed on her own children.
• The English physician Edward Jenner later made a
giant advance in the deliberate development of
immunity, again targeting smallpox.
•In 1798, intrigued by the fact that milkmaids
who had contracted the mild disease cowpox
were subsequently immune to the much more
severe smallpox, Jenner reasoned that
introducing fluid from a cowpox pustule into
people (i.e., inoculating them) might protect
them from smallpox.
• To test this idea, he inoculated an eight-year-old
boy with fluid from a cowpox pustule and later
intentionally infected the child with smallpox.
• As predicted, the child did not develop smallpox.
• In a classic experiment performed in 1881,
Pasteur first vaccinated one group of sheep with
anthrax bacteria (Bacillus anthracis) that were
attenuated by heat treatment.
• He then challenged the vaccinated sheep, along
with some unvaccinated sheep, with a virulent
culture of the anthrax bacillus.
• All the vaccinated sheep lived and all the
unvaccinated animals died.
• These experiments marked the beginnings of the
discipline of immunology.
• The experimental work of Emil von Behring and
Shibasaburo Kitasato in 1890 gave the first insights
into the mechanism of immunity, earning von
Behring the Nobel Prize in Physiology or Medicine
in 1901.
• Von Behring and Kitasato demonstrated that
serum—the liquid, noncellular component
recovered from coagulated blood—from animals
previously immunized with diphtheria could
transfer the immune state to unimmunized
animals.
• In 1883, even before the discovery that a serum
component could transfer immunity, Elie
Metchnikoff , another Nobel Prize winner,
demonstrated that cells also contribute to the
immune state of an animal.
• He observed that certain white blood cells, which
he termed phagocytes, ingested (phagocytosed)
microorganisms and other foreign material.
• Noting that these phagocytic cells were more
active in animals that had been immunized,
Metchnikoff hypothesized that cells, rather than
serum components, were the major effectors of
immunity.
• The active phagocytic cells identified by
Metchnikoff were likely blood monocytes and
neutrophils.
 Humoral Immunity

• In search of the protective agent of immunity,

various researchers in the early 1900s helped
characterize the active immune component in
blood serum.
• This soluble component could neutralize or
precipitate toxins and could agglutinate (clump)
bacteria.
• During the 1930s, mainly through the efforts of
Elvin Kabat, a fraction of serum first called gamma
globulin (now immunoglobulin) was shown to be
responsible for all these activities.
• The soluble active molecules in the
immunoglobulin fraction of serum are now
commonly referred to as antibodies.
• Because these antibodies were contained in body
fluids (known at that time as the body humors),
the immunologic events they participated in was
called humoral immunity.
 Cell-Mediated Immunity

• A controversy developed between those who held

to the concept of humoral immunity and those
who agreed with Metchnikoff ’s concept of
immunity imparted by specific cells, or cell-
mediated immunity.
• The relative contributions of the two were widely
debated at the time.
• It is now obvious that both are correct—the full
immune response requires both cellular and
humoral (soluble) components.
• With the emergence of improved cell culture and
transfer techniques in the 1950s, the lymphocyte
was identified as the cell type responsible for both
cellular and humoral immunity.
• We now know that cellular immunity is imparted
by T cells and that the antibodies produced by B
cells confer humoral immunity.