HYBRIDOMA TECHNOLOGY

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MILESTONES IN IMMUNOLOGY

1796 Where Immunology Began

EDWARD JENNER is rightly described as the "Founding Father of Immunology". He is best known for his experiments on the smallpox vaccine and the trials he carried out to prove its protective value. His work began a pathway of discovery of the immune system, how it works and how it can be exploited to the benefit of man. Scientists from all over the world have contributed to these discoveries. Many have received Nobel Prizes in recognition of the importance of their contribution.

1885 The Spread of Vaccination

LOUIS PASTEUR discovered how to prepare and use attenuated disease-causing microbes as vaccines against cholera in chickens, and anthrax and rabies in animals and man. In 1885 he gave the first rabies vaccination to a young boy, Joseph Meister, who had been savaged by a rabid dog. The boy survived and vaccination became a well-established way of preventing disease.

1901 Antibodies Protect against Disease

EMIL VON BEHRING and SHIBASABURO KITASATO discovered that antibodies against diphtheria and tetanus poisons could be given to patients to cure them from these diseases. Von Behring was awarded the first Nobel Prize for Medicine for this work on serum therapy.

1905 Immune Responses to Tuberculosis Described

ROBERT KOCH developed a way to make pure cultures of bacteria. He discovered the cholera bacterium. He also identified the bacillus that causes tuberculosis (TB) and described the host response to it.

1908 Cells and Antibodies are Important in Immunity

ELIE METCHNIKOFF and PAUL EHRLICH shared the Nobel Prize for their work. Metchnikoff was the first to observe cellular phagocytosis and suggest its protective importance. Ehrlich developed stains for, and described cells in the blood. He put forward the first idea of antibodies as molecular chains on the surface of cells.

1913 The Immune System can Cause Disease

CHARLES RICHET worked on anaphylaxis in his studies with Paul J Portier on the body's response to toxins. He was one of the first to demonstrate that the protective effects of the immune system could also cause great damage to the body.

1919 Antibody and Complement Work Together to Kill Bacteria

JULES BORDET discovered that complement was involved in lysis of red cells and was fixed by antibody in immune reactions, leading to bacteria being killed. His findings were later used to develop a test for syphilis.

1930 Discovery of the Human Blood Groups as Tissue Antigens

KARL LANDSTEINER discovered the ABO blood groups and Rhesus Factor. His research paved the way for successful blood transfusions. He also made major contributions to our understanding of the way in which antibody molecules combine with antigen and of the specificity of antibodies at the chemical level.

1951 Vaccine against Yellow Fever

MAX THEILER showed that yellow fever is caused by a virus, and that growing the virus in culture so weakened the strain that it would not cause disease when injected into humans. Instead it acts as a vaccine to protect against infection.

1957 Development of Antihistamine Drugs for the Treatment of Allergy

DANIEL BOVET found that many of the unpleasant symptoms of allergy are caused by histamine which produces inflammation. He developed drugs which blocked the action of histamine (antihistamines).

1960 Immunological Tolerance to "Self": The Central Role of Lymphocytes in Immunity

F. MACFARLANE BURNET and PETER MEDAWAR were awarded the Nobel Prize for their work on immunological tolerance and cellular immunity. Their work focused attention on lymphocytes as the key players in the immune response.
MEDAWAR discovered that the immune system is responsible for the rejection of organ transplants. With Rupert Billingham and Leslie Brent he showed that if cells from one mouse were introduced to the immune system of another mouse early in life, they would be accepted as "self" and not rejected, a condition defined as " immunological tolerance".
MACFARLANE BURNET proposed the clonal selection theory for antibody production which transformed ideas on cellular immunity. He also contributed to the understanding of self-tolerance by proposing that immune cells which recognise "self" molecules are destroyed early in their development.

1972 The Structure of the Antibody Molecule is Unravelled

RODNEY PORTER and GERALD EDELMAN described the chemical structure of antibody molecules. They deduced how they have a constant region and two sites which bind to antigen. They were also able to explain how variations in the amino acid sequence of individual antibodies results in different binding shapes allowing them to bind to many different antigens.

1977 The Development of Sensitive Tests to Measure Hormones Using Antibodies

ROSALIND YALLOW working with Soloman Berson discovered the association of autoantibodies with insulin-resistant diabetes. She developed a very sensitive method for measuring the concentration of hormones in blood, using specific antibodies and a radioactive antigen. This "immunoassay" method for hormones had enormous clinical benefit for patients with hormonal problems. She was the first woman immunologist to win the Nobel Prize.

1980 The Genes that Control the Antigen Presenting Molecules

BARUJ BENACERRAF, GEORGE SNELL and JEAN DAUSSET demonstrated the importance of the genes which govern the antigen presenting molecules on cell surfaces: the Major Histocompatibility Complex genes. These control the immune response to infection and are also very important in transplant rejection.

1984 Advances in Understanding how the Immune System is Controlled

NIELS K. JERNE was recognized for his important theoretical contributions to the understanding of how the immune system is controlled. His ideas about antigens selecting the appropriate antibody-bearing cells paved the way for Burnet's clonal selection theory.

1984 Development of Monoclonal Antibodies

CESAR MILSTEIN and GEORGE KOHLER were, in this same year, recognized for their development of the technique for making monoclonal antibodies. These are now a tool used widely in medicine, research and industry.

1987 How the Antibody Genes Provide Diversity

SUSUMU TONEGAWA worked on the organisation of antibody genes and demonstrated how so many antibody patterns could be produced by such a limited number of genes. His ideas were also very important in understanding the structure and formation of the T cell receptor.

1991 Advances in Transplantation Immunology

E. DONAL THOMAS and JOSEPH MURRAY are the latest in a long line of immunologists to be awarded the Nobel Prize. They received it for their work on transplantation immunology.

THE ROAD AHEAD

The impact of immunology on human health and welfare has been immense since Jenner's first steps along the road in 1796. About three-quarters of all human diseases involve the immune system in one way or another.
Immunology is now far more than the study of infection and the making of new vaccines. Immunological research is providing new approaches for the diagnosis and treatment of cancer, autoimmune disease, immunodeficiency and allergies and has been a major contributor to the successful development of transplant surgery.

THE INNATE AND ADAPTIVE IMMUNITY

Our daily activities expose us to a number of health threatening microbes which are the major agents of diseases. But, let us ask ourselves how comes we don't fall sick often? This brings us back to the concept of immunity. As previously discussed, immunity is comprised of two major parts, the innate and adaptive immunity.

The two parts of the immune system, one is less specific (innate) but quite necessary and the other more specific (adaptive). The innate immunity forms the first line of defense and exists before encountering the pathogens. This type of immunity is comprised of four types of defensive barriers namely; anatomic barriers (skin and mucous membranes), physiologic barriers (temperature, pH and chemical mediators), phagocytic barriers (blood monocytes, neutrophils and tissue macrophages) and the fourth inflammatory barriers.

The adaptive immunity which is more specific is triggered following an antigenic challenge to an organism. The key players in adaptive immunity are the lymphocytes, antibodies and other molecules they produce. This kind of immunity has four characteristics; antigenic specificity, diversity, immunologic memory and self/nonself recognition. It displays antigenic specificity in a sense that it is capable of distinguishing even minor differences between antigens. The diversity is seen where the immune system can generate a fairly huge diversity in its recognition molecules capable of recognizing many unique structures among foreign molecules. The immune system also has memory, that it can easily remember the foreign molecule which it had previously encountered. And the good thing about the immune system is the ability to recognize self from nonself molecules which prevents the body from attacking itself.

Having seen what the innate and adaptive immunity is, we need to know what happens when we are exposed to pathogenic microbes. And what is real happening to our bodies? I mean to the immune system.
..To be continued....

IMMUNOLOGY OVERVIEW

The immune system is a system of defence that protect the animals from being diseased. It is composed of molecules and cells that works in concert to eliminate or neutralize the foreign pathogenic microbes or molecules that have invaded the animal's body. The system is diverse and highly complex.

Functionally, the immune response can be divided into two phases; namely recognition pahes and response phase. In recognition phase the immune system is highly specific in the sense that it can distinguish pathogens and discriminate between the foreign molecules and body's own cells and proteins. Response phase follows recognition, after the immune system has recognised the foreign molecules it respond by eliminating or neutralizing the organism. This is called effector response. When the body is encountering the organism for the second time the immune response is much more stronger than the previuos one, so the system eliminates the pathogen and prevent disease. This is called memory response

Immunity in vertebrates is divided into two, the innate immunity (primitive),which is existing in an animal's body, and the adaptive immunity which is the evolved system of specific response. The two works together to provide a high degree of protection.

In some cases, the immune system fails to protect the body as a consequense of some deficiency in its components; at other times it becomes an aggressor and turns against its own host. This introduces the concept of autoimmunity.

Historical perspective of Immunology

The term immunity originates from a Latin word immunis meaning "exempt". Thus, immunity literally means the state of protection from infectious diseases.

Edward Jenner, an English physician in 1798, convinced by the fact that milkmaids who had contracted the mild disease cowpox were subsequently immune to smallpox, he thought that introduction of fluid from a cowpox pustule into people (i.e. inoculation) might confer protection from smallpox. He tested his idea by inoculating an eight years old boy with fluid from cowpox pustule and later he challenged the boy with smallpox, the boy did not develop smallpox. This was the beginning of studies on immunity.

Loius Pasteur, basing on the ideas of Jenner, was the person who coined the word vaccine (Latin, vacca, means "cow") in honor of Jenner's work with cowpox inoculation. He did his experiment by injecting chickens with an old culture af bacterium thought to cause fowl cholera, the chickens became ill but later they recoverd. Again he injected the same chickens with a freshly grown culture of the bacterium, the chickens were completely protected from the disease. Pasteur hypothesized and proved that aging had weakened the virulence of the pathogen, and that such an attenuated strain might be administered to confer protection against the disease. He called the attenuated strain vaccine.

Pasteur did another experiment, he attenuated the bacterium causing anthrax (Bacillus anthracis) by heat and inoculated into one group of sheep and left other group uninoculated. He then challenged the two groups of sheep with unattenuated bacterium. The group of sheep that were previuosly inoculated with attenuated bacterium survived and while sheep from the other group all died.

In 1885, Pasteur administered his firdt vaccine to a human, a young boy who had been bitten by a rabid dog. The boy, Joseph Meister, was inoculated with a series of attenuated rabies virus preparations, and he lived. These experiments marked the evolution of the displine of immunology.

BRIEF INTRODUCTION TO IMMUNOLOGY

Immunology is both the study of the human immune system and the field of medicine that treats diseases of the immune system. Immunity is the body's ability to resist a disease, and the immune system is a bodywide network of interacting systems: bone marrow, white blood cells, the entire lymph system and even the skin. Immunology dates back to ancient civilizations, as it has long been known that certain individuals are naturally immune to some diseases, and that survivors of certain diseases are immune to the disease they survived. Since the immune system is so broad, encompassing everything from blood cells to skin, immunology is a very broad field of study. The treatment of disorders as simple as common allergies and as complex as AIDS all fall under the immunology category.

It deals with, among other things, the physiological functioning of the immune system in states of both health and disease, malfunctions of the immune system in immunological disorders, the physical, chemical and physiological characteristics of the components of the immune system in vitro, in situ, and in vivo.