The Nobel Prize is awarded annually for achievements in physics, chemistry, physiology or medicine, literature, and peace. The prizes were first awarded in 1901 in accordance with Alfred Nobel's will. The 1901 prizes in physiology or medicine were awarded to Emil von Behring for his work on diphtheria antitoxin and Paul Ehrlich for his work on immunity and chemotherapy. Subsequent prizes have been awarded for major advances in understanding the immune system, including discoveries of monoclonal antibodies, the major histocompatibility complex, immune tolerance, and the roles of dendritic cells and innate immunity.

1. Prepared By:
V.Madhukar

2.  The Nobel Prize is a set of annual international
awards bestowed in a number of categories by Swedish
and Norwegian committees in recognition of
academic, cultural and/or scientific advances. The will
of the Swedish inventor Alfred Nobel established the
prizes in 1895.
 The prizes in Physics, Chemistry, Physiology or
Medicine, Literature, and Peace were first awarded in
1901

3. Name(Age) Year Location Field of Work
Emil von Behring
(60)
1901 Germany Diptheria Antitoxin
Paul Ehrlich(54) 1908 Germany Adaptive Immunity, Autoimmunity
Ilya
Mechnikov(63)
1908 France Phagocytosis and The macrophage
Jules Bordet(49) 1919 Belgium Complement system in Immune system
Karl
Landsteiner(62)
1930 Vienna Human Blood Types Discovery
Macfarlane
Burnet(61)
1960 Australia Theory Of Immune Tolerance
Peter Medawar(45) 1960 UK Experiments On Immune Tolerance
Gerald
Edelman(43)
1972 USA Chemical Structure of Immunoglobulin
Rodney Porter(55) 1972 UK Chemical Structure of Immunoglobulin

4. Jean Dausset(64) 1980 France Human MHC
George Snell(77) 1980 USA Mouse MHC
Baruj
Benacerraf(60)
1980 USA MHC Immune-Response Genes
Niels Jerne(73) 1984 Switzerland Theory of Immunity
Cesar Milstein(57) 1984 UK Monoclonal Antibodies
Georges
Kohler(38)
1984 Switzerland Monoclonal Antibodies
Rolf
Zinkernagel(52)
1996 Switzerland CMI and MHC Restriction
Peter Doherty(56) 1996 Australia Cellular Immune Defense
Bruce Beutler(54) 2011 USA Activation of Innate Immunity
Jules
Hoffmann(70)
2011 France Activation of Innate Immunity
Ralph
Steinman(67)
2011 Canada Dendritic Cell and its Role in Adaptive
Immunity

5. Behring and Kitasato jointly published their classic paper, "Ueber das
Zustandekommen der Diphtherie-Immunität und der Tetanus-Immunität
bei Thieren" ("The Mechanism of Immunity in Animals to Diphtheria and
Tetanus").
One week later, Behring alone published another paper dealing with
immunity against diphtheria and outlining five ways in which it could be
achieved. These reports announced that injections of toxin from
diphtheria or tetanus bacilli led animals to produce in their blood
substances capable of neutralizing the disease poison.
Behring and Kitasato dubbed these substances ANTITOXINS.
Furthermore, injections of blood serum from an animal that had been
given a chance to develop antitoxins to tetanus or diphtheria could confer
immunity to the disease on other animals, and even cure animals that
were already sick.


7. Ehrlich, then a relatively obscure German scientist, had been awarded
the Nobel Prize in Medicine. He shared the honor with the much more
famous but now almost forgotten Ilya Mechnikov for their work on Immunity.
Paul Ehrlich :
Paul Ehrlich worked with Robert Koch on serum research and then also
worked with Emil Behring on Diptheria. He is well known for works in
autoimmunity and adaptive immunity.
Ehrlich after working with Koch and Behring devoted himself to
chemotherapy. His aim was, as he put it, to find chemical substances which
have special affinities for pathogenic organisms, to which they would go, as
antitoxins go to the toxins to which they are specifically related, and would
be, as Ehrlich expressed it, «magic bullets» which would go straight to the
organisms at which they were aimed.

8. Ehrlich had, like so many other discoverers before him, to battle with
much opposition before Salvarsan or Neosalvarsan (more than 900 tests
were performed) were accepted for the treatment of human syphilis; but
ultimately the practical experience prevailed and Ehrlich became famous
as one of the main founders of chemotherapy.
Ilya Mechnikov
It was at Messina in a private laboratory that he discovered the
phenomenon of phagocytosis with which his name will always be
associated. This discovery was made when Mechnikov observed, in the
larvae of starfishes, mobile cells which might, he thought, serve as part
of the defenses of these organisms and, to test this idea, he introduced
into them small thorns from a tangerine tree which had been prepared as
a Christmas tree for his children. Next morning he found the thorns
surrounded by the mobile cells, and, knowing that, when inflammation
occurs in animals which have a blood vascular system, leucocytes escape
from their blood vessels, it occurred to him that these leucocytes might
take up and digest bacteria that get into the body.

10. His discovery that the bacteriolytic effect of acquired specific antibody is
significantly enhanced in vivo by the presence of innate serum
components which he termed alexine (but which are now known
as complement). This mechanism became the basis for complement-
fixation testing methods that enabled the development of serological
tests for syphilis. The same technique is used today in serologic testing for
countless other diseases.
Together with Gengou (in 1906), he cultivated B.pertussis and laid the
foundations of the generally accepted opinion that this organism is the
bacterial cause of whooping cough. In addition to his being an
acknowledged world authority in many branches of bacteriology, Bordet
was considered to be a great exponent and worker on immunology.

12. After leaving school, Landsteiner studied medicine at the University of
Vienna, graduating in 1891. Even while he was a student he had begun to
do biochemical research and in 1891 he published a paper on the
influence of diet on the composition of blood ash.
In 1875 Landois had reported that, when man is given transfusions of the
blood of other animals, these foreign blood corpuscles are clumped and
broken up in the blood vessels of man with the liberation of
haemoglobin. In 1901-1903 Landsteiner pointed out that a similar reaction
may occur when the blood of one human individual is transfused, not
with the blood of another animal, but with that of another human being,
and that this might be the cause of shock, jaundice, and haemoglobinuria
that had followed some earlier attempts at blood transfusions.

13. His suggestions, however, received little attention until, in 1909, he
classified the bloods of human beings into the now well-known A, B, AB,
and O groups and showed that transfusions between individuals of
groups A or B do not result in the destruction of new blood cells and that
this catastrophe occurs only when a person is transfused with the blood of
a person belonging to a different group. Earlier, in 1901-1903, Landsteiner
had suggested that, because the characteristics which determine the
blood groups are inherited, the blood groups may be used to decide
instances of doubtful paternity.
To the end of his life, Landsteiner continued to investigate blood groups
and the chemistry of antigens, antibodies and other immunological
factors that occur in the blood. It was one of his great merits that he
introduced chemistry into the service of serology.

15. Using the concept of self, Burnet introduced a hypothesis about the
situation where the body failed to make antibodies to its own components
(autoimmunity) and by extension the idea of immune tolerance. He
proposed that
if in embryonic life expendable cells from a genetically distinct race are
implanted and established, no antibody response should develop against
the foreign cell antigen when the animal takes on independent existence
Burnet was, however, unable to prove this experimentally. Peter
Medawar, Rupert E. Billingham and Leslie Brent did find support for
Burnet's hypothesis in 1953 when they showed that splenocytes could be
engrafted by intravenous infusion into mice in utero or just after birth and
that when these mice matured, they could accept skin and other tissues
from the donor but not from any other mouse strain. Burnet and Medawar
were co-recipients of the 1960 Nobel Prize in Physiology or Medicine for
this work, as it provided the experimental basis for inducing immune
tolerance, thereby allowing the transplantation of solid organs.

17. Responding to external threats such as disease-causing microorganisms,
protein antibody molecules are released by specialized immune cells into
the blood stream to disarm the threat. Their mode of attack is target
recognition: millions of different molecules can be created, each with a
different binding site, which can identify distinctive proteins on their
specifically assigned foe with pinpoint accuracy.
A long-standing question in the field was how an almost identical-
looking collection of antibody proteins can, at the same time, have the
capacity to target specifically any one of an almost infinite range of
foreign agents.

18. Gerald Edelman and Rodney Porter independently took similar
approaches to deciphering their structure, both realizing that the best
way in which to grasp the finer aspects of such large molecules was to
split them into smaller, more manageable pieces. Their deconstruction
methods differed.
Porter used a protein-cleaving enzyme that fragmented an antibody
molecule into its functional subsections.
Edelman's approach destroyed antibody function by using chemicals to
break the bridge-like bonds that keep the constituent protein chains
together, his procedure relying on the finding that copious quantities of
antibodies are produced by cancerous versions of white blood cells.

20. While fighting off infectious agents, our immune defences must take
extreme care not to avoid harming any cells belonging to its own host.
Achieving this requires a sophisticated self-identification system, and this
is centred on a collection of genes called the major histocompatibility
complex, or MHC, which encode proteins known collectively as
histocompatibility antigens. Each individual carries a unique combination
of these antigens on the surface of their cells, providing a form of
biological ID system for distinguishing one individual from another.

21. George Snell discovered the first components of the MHC in the 1940s
through their role in rejecting transplants in mice. At that time, the
search for genetic factors that reject tumour transplants had been
narrowed down to a number of possible locations on mouse
chromosomes .
On closer inspection, what appeared to be a single gene in the
neighbourhood turned out to be a surprisingly large number of genes that
were closely linked together.
Around a decade later, Jean Dausset uncovered the first compatibility
antigen in humans. He noticed that a patient receiving several
transfusions of ABO compatible blood still suffered an unexpected
immune reaction. Dausset discovered that in this case antibodies were
being launched against white blood cells belonging to the donor only, and
that these antibodies in the patient’s serum triggered a similar reaction in
half the samples of white blood cells taken from other people. He called
the factor responsible MAC, and this turned out to be the first of a series
of human leukocyte antigens, or HLAs.

22. Experiments by Baruj Benacerraf in the 1970s provided the first indication
that immune reactions are controlled by genes. Benacerraf was surprised
to discover that different strains of guinea pigs launched different levels of
attack towards the same foreign antigen, and he traced the cause to what
he termed immune response genes.
Baruj Benacerraf George Snell Jean Dausset

23. The important contribution of theory and practice in shaping our
understanding of the body's immune system. The hypotheses formulated
by Niels Jerne presented a clearer image of the way in which a diverse
range of antibodies can be engaged to fight an invader. Georges Köhler
and César Milstein constructed perpetual antibody-production lines that
have become an essential laboratory tool for researchers worldwide.
Milstein had developed cancerous forms of antibody-producing cells that
grew and multiplied forever, but which churned out antibodies of
unknown specificity; while Köhler had tweaked normal antibody-
producing cells to produce specific antibodies, but they survived for a few
days only in culture.

24. Combining forces, the neat trick they came up with was to fuse a normal
antibody-producing cell with a tumour cell, forming a hybrid that was
both immortal and could create a specific antibody. Köhler and Milstein's
technique for creating any single predetermined type of so-called
monoclonal antibody on demand has led to many medicine and
biomedical applications, from creating more reliable probes for blood and
tissue typing tests, to designing completely new therapeutic strategies for
diseases such as cancer.
Niels Jerne Cesar Milstein Georges Kohler

25. Viruses, such as those that cause the common cold or flu, are a
particularly devious form of intruder to tackle. Once they enter their host,
these infectious agents find cells to hide in while they reproduce in order
to infiltrate more targets. Fortunately for us our internal defence system
has a trick up its sleeve to seek out this hidden threat. It recruits a
specialized form of white blood cell, T killer lymphocytes, that can
identify and destroy virus-infected cells, and yet can somehow leave
normal healthy cells unharmed.

26. Investigating how mice are protected against infection from a viral agent
that can cause the disease meningitis, they were surprised to find that
virus-killing T lymphocytes taken from a mouse could only execute their
destructive effect in infected cells belonging to the same strain. Doherty
and Zinkernagel proposed that lymphocytes ignored infected cells in
other strains because they need to simultaneously recognize two distinct
signals on their suspected target – a specific molecule belonging to the
concealed virus, and a specific protein marker found on all host cells that
signifies that it belongs to itself. Closer inspection revealed that the virus'
molecule actually distorts the host's marker protein by attaching to it, and
this altered self protein informs the T lymphocytes that the cell is
infected.
Doherty and Zinkernagel's findings finally unmasked the true purpose of
these self-recognition protein molecules, the major histocompatibility
antigens.
Why these proteins create a barrier to transplantation was far from
obvious, but the discoveries of Doherty and Zinkernagel revealed that this
is merely an unavoidable side-effect of their true biological function.
Acting as a surveillance system to distinguish self from non-self, these
major histocompatibility antigens allow immune cells to make their
crucial life-or-death decision in the face of numerous threats.

28. The Nobel Prize in Physiology or Medicine 2011 was divided, one half
jointly to Bruce A. Beutler and Jules A. Hoffmann "for their discoveries
concerning the activation of innate immunity"
The other half to Ralph M. Steinman "for his discovery of the dendritic cell
and its role in adaptive immunity".
Ralph Steinman :
Steinman’s early research in collaboration with Cohn was an attempt to
understand the white cells of the immune system that operate in a variety
of ways to spot, apprehend, and destroy infectious microorganisms and
tumor cells. In 1973, Steinman and Cohn discovered dendritic cells, a
previously unknown class of immune cells that constantly formed and
retracted their processes. This discovery changed the field of
immunology.

29. For the next four decades, until his death in 2011, Steinman’s laboratory
was at the forefront of dendritic cell research. He and his colleagues
established that dendritic cells are critical sentinels of the immune
system that control both its innate and adaptive responses - from
silencing to actively resisting its challenges. He also showed that dendritic
cells are the 2 main initiators of T cell-mediated immune responses.
His most recent studies were focused on the interface of several diseases
with the immune system and included clinical studies using dendritic
cell- and immune-based vaccines and therapies for such medical
conditions as graft rejection, resistance to tumors, autoimmune diseases,
and infections. In 2010, he initiated at The Rockefeller University Hospital
a phase I clinical trial with the first dendritic cell-targeted vaccine against
HIV.
Diagnosed with pancreatic adenocarcinoma in March 2007, Steinman
believed that dendritic cells had the potential to fight his aggressive
tumor. With many collaborators and leading-edge technology, he
designed dendritic cell-based immunotherapies for himself that he
thought might also advance medical science.

30. Bruce Beutler and Jules Hoffmann :
Beutler and Hoffman helped to elucidate innate immunity. That’s the
non-specific array of initial responses by the body’s immune system that
can recognize invading microorganisms as being foreign and try to
destroy them.
Dr.Hoffman found in fruit flies, and Dr.Beutler subsequently discovered
in mice, a crucial protein-binding mechanism that helps the immune
system recognize invaders and trigger an immune response against them.
Together, these discoveries made it possible to develop new vaccines to
fight infections and to encourage the immune system to attack tumors.

32.  Oxford Kuby J(1997) Immunology- WH Freeman and
Company
 Ivan M Roit(1994) Essential Immunology- Blackwell
Scientific Publications
Links:
 www.nobelprize.org
 www.nature.com (Nature Immunology)

33. “What I have achieved is a single stone from the
beach of Knowledge, There is more to explore!”
- Albert Einstein
THANK YOU! And
Lets Explore. . .