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Course: Immunology
Lecturer: Dr. Weam Saad
Lecture: Introduction to Immunology
Introduction to Immunology as a Science
The immune system is the body’s biological defense mechanisms
that protect against foreign invaders. Only in the last century, the
components of that system and the ways they work were discovered and
found.
The true roots of the study of the immune system were
from 1796 when an English physician, Edward Jenner, discovered a
method of smallpox vaccination. He noted that dairy workers who
contracted cowpox from milking infected cows were resistant to smallpox
(they didn’t get infected during work with infected cows).
In 1796, the scientist Jenner injected a young boy with material from
a milkmaid who had an active case of cowpox. After the boy recovered from
his own resulting cowpox, Jenner inoculated him with smallpox; the boy
was immune (didn’t show disease clinical signs). After Jenner published
these results Jenner's vaccination spread rapidly.
It was Louis Pasteur who established the cause of infectious
diseases and the medical basis for immunization. First, Pasteur wrote his
germ theory of disease, the concept that disease is caused by a
microorganisms. In 1880, Pasteur discovered that aged cultures of cholera
bacteria lost their power to induce disease in chickens but can cause
immunity against the disease when injected. He also used attenuated
(weakened) cultures of anthrax and rabies to vaccinate against those
diseases.
Another historical development by Louis Pasteur, in 1884, Pasteur
used weakened cultures of Bacillus anthracis, the causative agent of
anthrax, and inactivated sample from the spinal cords of rabbits infected
with the rabies virus to produce immunity to anthrax and rabies. Pasteur’s
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method started the development of other active immune protective vaccines
like oral poliomyelitis vaccine that developed by Albert Sabin in the 1950s.
The American scientists Theobald Smith (1859–1934) and Daniel
Salmon (1850–1914) showed in 1886 that bacteria killed by heat could also
induce immunity.
In 1888, Pierre-Paul-Emile Roux (1853–1933) and Alexandre
Yersin (1863–1943) showed that diphtheria bacillus produced a toxin that
the body responded to it by producing an antitoxin.
Emil von Behring and Shibasaburo Kitasato found a similar
toxin-antitoxin reaction in tetanus in 1890. Von Behring discovered that
small doses of tetanus or diphtheria toxin produced immunity, and that this
immunity could be transferred from animal to animal by serum. Von
Behring concluded that the immunity happened by substances produced in
the blood, which he called antitoxins, or antibodies.
Hans Buchner (1850–1902) in 1893 discovered another important
blood substance called complement (Buchner’s named it alexin), and Jules
Bordet in 1898 found that this complement enabled the antibodies to
combine with antigens (foreign substances) and destroy or eliminate them.
Karl Landsteiner was able to use this specific antigen-antibody reaction
(that each antibody reacted only against a specific antigen) to distinguish
the different blood groups (ABO System Grouping).
A new element was introduced during the 1880s by the Russian
microbiologist Elie Metchnikoff. He discovered cell-based immunity:
white blood cells (leucocytes), which Metchnikoff called phagocytes (cells
that ingested and destroyed foreign particles).
A theory of immunity was written by Paul Ehrlich in the 1890s; he
said: “side-chain” theory explained that antigens and antibodies combine
chemically in fixed ways, like a key fits into a lock.
Until this time, the immune responses were seen as beneficial and
necessary to protect human body from infectious agents. But, in 1902,
Charles Richet and Paul Portier showed that extreme immune reactions in
test animals (laboratory animals used in experiments), had become sensitive
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to antigens by previous exposure. This phenomenon of hypersensitivity,
called anaphylaxis, showed that immune responses could cause damage to
the body itself. Hypersensitivity to antigens also explained allergies, this
term was named by Pirquet in 1906.
Much more was learned about antibodies in the middle of twentieth
century, including the fact that they are proteins of the type gamma globulin
portion in plasma and they are produced by plasma cells; their molecular
structure was also found.
An important advance in Immunochemistry came in 1935 when
Michael Heidelberger and Edward Kendall (1886–1972) developed a
method to detect and measure amounts of different
Immunity: active,
passive, and delayed.
A cellular research showed that there are two types of lymphocytes;
B-lymphocytes, which secrete antibody, and T-lymphocytes, which
regulate the B-lymphocytes and also kill foreign substances directly (killer
T cells) or stimulate macrophages to do so (helper T cells). Lymphocytes
recognize antigens by characteristics on the surface of the antigen-carrying
molecules.
Knowledge about the immune system’s role in rejection of
transplanted tissue became extremely important as organ transplantation
became surgically important. Peter Medawar’s work in the 1940s showed
that such rejection was an immune reaction to antigens on the foreign tissue.
Donald Calne showed in 1960 that immunosuppressive drugs (drugs
that suppress immune responses), able to reduce transplant rejection, and
these drugs were first used on human patients in 1962.
In the 1940s, George Snell discovered in mice a group of tissue-
compatibility genes, the MHC, which played an important role in
controlling acceptance or resistance to tissue grafts.
Autoimmune reaction, in which the body has an immune response to
its own substances, also may be a cause of a number of diseases, like
multiple sclerosis. During 1960s, Ion Gresser discovered that the protein
interferon acts against cancerous tumors during cancer treatment
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experiments. After the development of genetically engineered interferon in
1980s; that made it available for treatment of cancer.
The
invention
of
monoclonal
antibodies
in
the
mid-
1970s was a
grate and effective method to
fight one of
the most serious immune system disorders, AIDS.
The cytokines, proteins produced by the body that help the immune
system cells to communicate with each other and activate them to fight
infection. The researches on cytokines opened new windows to improve
treatment of difficult diseases like cancers and AIDS.