May public health problems and consumers compliances are related to food quality and safety. The application of food hygiene standards and regulations need to strengthen to reduce the burden of foodborne diseases on public health and to protect the consumers from adulteration.

1. Lecture 1

2. History of Immunology
 The discipline of immunology grew out of the observation that
individuals who had recovered from certain infectious diseases
were, there after, protected from the disease.
 Perhaps the earliest written reference to the phenomenon of
immunity can be traced back to Thucydides, the greatest
historian of the Peloponnesian war.
 In describing, a plague in Athens, he wrote in 430 BC that only
those who had recovered from the plague could nurse the sick,
because they would not contract the disease a second time.

3. Conti………
 The first recorded crude attempts to induce immunity deliberately
were performed by the Chinese and Turks in the 15th century.
 Various reports suggest that the dried crusts derived from smallpox
pustules were either inhaled into the nostrils or inserted into small cuts
in the skin (a technique called variolation).
 In 1718, Lady Mary Wortely Montagu, the wife of British Ambassador
to Constantinople, observed the positive effects of variolation on the
native population and had the technique applied to her own children.

4. Conti……..
 The technique was significantly improved by the English physician,
Edward Jenner in 1798.
 Intrigued, of the fact, those milkmaids who had contracted cowpox (a
mild disease) were subsequently immune to smallpox. Jenner reasoned
that introducing fluid from a cowpox pustule into people might protect
them from smallpox.
 To test this idea, he inoculated an 8-year-old boy with fluid from a
cowpox pustule and later intentionally infected the child with
smallpox.

5. Conti………
 As predicted, the child did not develop smallpox. Jenner’s technique of
inoculating with cowpox to protect against
 smallpox spread quickly through Europe. Even though, the
immunology was born in the 18th century with the practice of
variolation and of Jenner’s vaccination, it became a true science only in
the 19th century.
 Beginning in 1880, the world witnessed a veritable torrent of progress,
stimulated both by Pasteur and his students and by Robert Koch and
his group.

6. Conti………
 The magnificent contribution was done by Pasteur, Roux,
Metchnikoff and Bordet on the one hand and those of Koch,
Pfeiffer and Ehrlich on the other.
 Louis Pasteur showed with his work on fowl cholera, anthrax and
rabies that these organisms once attenuated, could be used
specifically to protect the individual against the disease that they
caused. From this, extraordinary series of investigations were
born, the modern science of immunology.

7. Conti……..
 In 1885, Pasteur administered the first vaccine to a human,
a young boy, who had been bitten repeatedly by a rabid dog
(Fig. 1.1).
 Emil von Behring and Kitasato in 1890, inoculated toxins of
diphtheria and tetanus to animals, to produce neutralizing
antitoxin serum. They introduced passive immunization in
modern medicine for which von Behring was awarded
Nobel Prize in 1901.

8. Fig. 1.1: Wood engraving of Louis Pasteur watching Joseph Meister
receiving the rabies vaccine by a third person (From Harper’s weekly
29:836; Courtesy of National Libraryof Medicine)

9. Conti……..
 The phagocytic theory was first to be conceptualized in 1880 by a
Russian zoologist named Elie Metchnikoff. He hypothesized that
the basis of inflammation was the cellular reaction.
 Vascular and nervous reactions were secondary. He further
suggested that the elimination or destruction of invaders was the
sole function of phagocytic cells. Subsequently, many workers
proposed the presence of soluble substances (humoral factors),
which were bactericidal.

10. Conti……..
 Finally in 1903, Almroth Wright and Stewart Douglas
discovered a humoral component known as opsonin,
which makes the target bacteria palatable for phagocytosis.
 In 1908, Metchnikoff and Ehrlich shared the Nobel Prize
for the respective studies of cellular and humoral factors in
host defense. Ehrlich proposed side-chain theory of
antibody formation and antibody function.

11. Conti……….
 In 1905, von Pirquet and Schick published a brilliant series
of studies on children treated with horse diphtheria
antiserum, which led to untoward reaction.
 They then introduced the concept that all the events in
immunological reactivity might not be beneficial to the
host and they named the disease caused by the immune
response to horse protein ‘serum sickness’ a term still in
use.

12. Conti……….
 In the same decade Arthus, Proteir and Richet described the
cutaneous vasculitis and anaphylaxis in animals.
 In 1913, Charles Richet received the Nobel Prize in recognition
to his work on anaphylaxis.(Is a severe, potentially life-
threatening allergic reaction)
 Pfeiffer discovered the phenomenon of in vivo cytolysis of Vibrio
cholerae much earlier (1894–1895), following intraperitoneal
inoculation of V. cholerae in an immunized guinea pig.

13. Conti………..
 This early experiment led to the understanding of
complement-mediated cytolysis by Pfeiffer and later
Buchner and Bordet. Jules Bordet was honored with the
Nobel Prize in 1919 for his work on complement.
 Being successful in passive immunization against
diphtheria and tetanus von Behring applied this
conception in tuberculosis and failed miserably.

14. Conti………
 Robert Koch also had to accept the failure in providing immunity
against tuberculosis.
 Ultimately, Albert Calmette and Camille Guérin, the French scientists
found out an effective vaccine Bacille Calmette-Guérin (BCG) for
tuberculosis (1921).
 The vaccine had been prepared from the attenuated strain of
Mycobacterium bovis.
 Twentieth century witnessed phenomenal advances in understanding
the immunological concepts.

15. Conti………
 As the subjects grew, a number of diseases were assigned to
immunological causes (immunopathological disorders) and
ultimately the subject was offered a separate status.
 The practice of transfusion of blood from man to man was risky
and unpredictable, until the discovery of blood groups by Karl
Landsteiner. In recognition of his outstanding (great) work of
elucidating the blood groups and Rh factor, he was awarded
Nobel Prize in 1930.

16. Conti……….
 The concept of immunocomplexes and their important
contribution to immunopathology, came with the development
of radioactive tracers and immunofluorescent dyes. With these
tracers and dyes, foreign proteins were tagged and followed, after
they were injected into the body and their ultimate pathologic
consequences were explored.
 It was impossible to understand the function of the cells in the
immune response with the limited techniques available in the
early part of the century.

17. Conti……….
 Lymphocytes were noted and their importance speculated, but
these monotonously similar looking cells were difficult to study.
The development of immunofluorescent techniques (Coons and
his colleagues, 1942) allowing for the localization of the unique
products, the introduction of modern protein chemistry and the
use of cell culture techniques helped to a great extent, in
understanding the vast complexity of the defense system.

18. Conti……….
 Successions of theories were put forwarded from time to time, to
explain the specificity, memory and other features of immune
responses.
 Most credit went to Rodney R Porter and Gerald M Edelman in
elucidating the structure of antibody. Edelman showed that the
immunoglobulin molecule had polypeptide chains, two heavy
and two light. For their outstanding contribution, they were
awarded Nobel Prize in 1972.

19. Conti……..
 The existence of the markers of the biological individuality
(histocompatibility antigens) was first suggested by Gore in 1937.
 Snell, in 1948, showed that the mouse H-2 locus is genetically complex.
Dausset identified the human leukocyte antigen (HLA) locus or major
histocompatibility complex (MHC).
 Benacerraf showed that genes of HLA determining loci may control
immune response.
 In 1980, Snell, Dausset and Benacerraf were awarded Nobel Prize for
their respective contribution in the field.

20. Conti……….
 Niels Jerne was awarded Nobel Prize in 1984, for his
contributions in immunology, the most fundamental of his role
in developing the concept of clonality and for his description of
the idiotype network in the regulation of immune response. An
ingenious method for large scale production of monoclonal
(monospecific) antibody (mAb) against any desired antigen was
developed by Georges E Kohler, Cesar Milstein and Niels K Jerne
in 1975.

21. Conti……..
 They produced a hybrid cell by fusing antibody-forming cell with
a myeloma cell. The production of mAb by hybridoma technique
created a revolution in the field of immunology in opening up
various researches, diagnostic and therapeutic procedures.
 In recognition of their work, they were awarded Nobel Prize in
1984.
 Another, Stalwart (Susumu Tonegawa) was honored by Nobel
award in 1987 for his study on genetics of antibody production.

22. Conti……..
 Murray and Thomas were awarded Nobel Prize in the year 1990
for their work ‘Use of immunosuppressive drugs in
transplantation’.
 Doherty and Zinkernagel were also honored by Nobel award in
1996 for the work ‘Role of MHC in antigen recognition by T cells’.
In 2002, Sydney Brenner, Robert H Horvitz and JE Sulston were
awarded Nobel Prize for ‘Genetic regulation of organ
development and cell death (apoptosis).’

23. Conti………
 The immunology as a subject has grown immensely in the last
100 years. Louis Pasteur, Metchnikoff, Ehrlich, Bordet and many
others contributed importantly and critically to the birth and
robust development of the science of immunology.
 The amount of detail knowledge that has been accumulated has
already reached paroxysmal proportion and the rate of
accumulation, far from abating, is itself increasing.

24. Conti……….
 But the most discouraging fact is that the theoretical explosion
of knowledge has not been able to make significant contribution
to the management of situation as important as allergy, organ
transplantation and autoimmune diseases and even, ironically,
anti-infectious diseases.
 If, there has been some progress that results from the practical
aspect of pure scientific knowledge, it is the domain of
vaccinology.

25. Conti……..
 The control of number of diseases that cause significant mortality and
morbidity has made outstanding progress, but there remains a crying
need for vaccine against others.
 Every year millions of death, throughout the world, are caused by
tuberculosis, malaria and acquired immune deficiency syndrome
(AIDS), the diseases for which there are no effective vaccines.
 It is hoped that the immunologists of today, using the tools of
molecular and cellular biology, genomics, proteomics, will make
inroads into preventing these diseases.

26. Conti……….
 As it had happened, it is expected that the world would
witness further explosion of knowledge in immunology in
coming decades.
 Concerted efforts are needed to be directed in the subjects
such as tumor immunology, autoimmunity and
vaccinology to develop strategies for protection against
many crippling diseases.

27. Conti………..
 Eventually what has evolved as a precise and powerful tool
created by nature to ensue continued survival of the
species, would perhaps be manipulated to yield better
quality of life (Table 1.1).

28. Table 1.1 Nobel Prize winners in the field of immunology
Year Name Discovery
1901 Emil von Behring Serum antitoxin
1905 Robert Koch Cellular immunity to tuberculosis
1908 Paul Ehrlich Theories of immunity
1908 Metchnikoff Phagocytosis
1913 Richet Anaphylaxis
1919 Jules Bordet Immunity (work on complement)
1930 Landsteiner Blood group
1960 Burnet and Medawar Immunological tolerance
1972 Edelman and Porter Nature and structure of antibody

29. Conti………
1977 Yalow Radioimmune assays
1980 Benacerraf, Snell and
Dausset
Major histocompatibility
complex (MHC) genes
and transplantation
1984 Milstein, Kohler and Jerne Monoclonal antibody
1987 Susumu Tonegawa Genetics of antibody
production
1990 Murray and Thomas Use of immunosuppressive
drugs in
transplantation
1996 Doherty and Zinkernagel Role of MHC in antigen
recognition of T cells
2002 Sydney Brenner, H Robert
Horvitz
and JE Sulston
Genetic regulation of organ
development and cell
death (apoptosis)