Overview of Immunology: From Historical Perspectives to Modern Techniques

 
 
Introduction
 
Immunology and Immune system
To rid the body of foreign particles (microbial
and otherwise) and abnormal cells
Immunis, meaning “exempt”
Two main function is-
Recognition
Response
 
Overview of immunology
 
Innate Immunity:
 
Fast-acting
 
Less specific recognition
 
Early during evolution
 
e.g. barriers to infection such as skin and mucus surfaces
Adaptive Immunity:
 
Specificity
 
Distinguish antigens sometimes present from those always present
 
Memory and Recall
Cells of the immune system
 
Leukocytes originating from haemopoietic cells
Communication with other systems
 
Endocrine system
 
Central nervous system
 
Skeletal system
Disruption of the Immune System
 
Allergy
 
Autoimmunity
 
Immunodeficiency
 
 
Historical perspective
 
Earliest written reference to the phenomenon of immunity can be traced back to
Thucydides, the great historian of the Peloponnesian War.
The case was Plague in Athens, in 430 BC
The first recorded attempts to induce immunity deliberately were performed by the
Chinese and Turks 
in the 15
th
 century.
Various reports suggested that the dried crusts derived from smallpox pustules
were either inhaled into the nostrils or inserted in to the small cuts in the skin
A technique called variolation
 
In 1718, Lady Mary Wortley Montagu, the wife of the British ambassador to
Constantinople, observed the positive effects of 
variolation
 
on the native
population and had the technique performed on her own children.
 
The method was significantly improved by the English physician 
Edward Jenner
, in
1798
.
Intrigued by the fact that milkmaids who had contracted the mild disease cowpox
were subsequently immune to smallpox, which is a disfiguring and often fatal
disease, Jenner reasoned that introducing fluid from 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.
 
The induction of immunity to cholera:
Louis Pasteur 
had succeeded in growing the bacterium thought to cause fowl
cholera in culture and then had shown that chickens injected with the cultured
bacterium developed cholera.
After returning from a summer vacation, he injected some chickens with an old
culture.
The chickens became ill, but, to Pasteur’s surprise, they recovered.
Pasteur then grew a fresh culture of the bacterium with the intention of injecting it
into some fresh chickens.
But, as the story goes, his supply of chickens was limited, and therefore he used
the previously injected chickens.
Again to his surprise, 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 protect
against the disease.
He called this attenuated strain a 
vaccine 
(from the
Latin 
vacca
, meaning “cow”), in honor of Jenner’s work
with cowpox inoculation.
 
In 1885, Pasteur administered his first vaccine to a
human, a young boy who had been bitten repeatedly
by a rabid dog. The boy, Joseph Meister, was
inoculated with a series of attenuated rabies virus
preparations. He lived and later became a custodian
at the Pasteur Institute.
 
From 
Harper’s Weekly 
29:
836;
courtesy of the National Library of Medicine
 
Relationship between two Great
Scientists who contributed significantly to
immunology
 
Although Koch and Pasteur were contemporaries, they were intensely competitive
and actually bitter enemies--of course, the outbreak of the Franco-Prussian war
(1870) did nothing to cement their relationship.
In a trenchant example of how not to behave toward a colleague at a scientific
meeting, Koch made his way to the podium following Pasteur’s lecture and said:
“When I saw in the program that Monsieur Pasteur was to speak today...I attended
the meeting eagerly, hoping to learn something new...I must confess that I have
been disappointed, as there is nothing new in the speech which Monsieur Pasteur
has just made...”
 
First insights into mechanics of immunity…
 
1880’s
- Metchnikoff
discovered phagocytic
cells that ingest microbes
and particles
cells conferred immunity
 
1890
- von Behring and
Kitasato discovered blood
sera could transfer
immunity
liquid of blood conferred
immunity
 
Q: Which confers immunity…
 
cells or serum?
 
Emil von Behring
 
S. Kitasato
 
Elie Metchnikoff
 
1930’s – early techniques made it easier to
study 
humoral
 elements [than cellular
ones].
 
-discovery of active component of blood –
  
gamma globulin “protein”
 
1950’s – discovery of T and B cells
Later discoveries linked lymphocytes to
both cellular and humoral immunity
 
A:
 
Both cells and serum contribute to immunity
!
 
Understanding specificity of antibody for antigen took years
 
Early 1900’s
-
Landsteiner revealed
antibody could be
produced vs. most any
organic compound
 
Last 20 yrs
- Antibody
specificity reveals
unlimited range of
reactivity – also to
newly synthesized
chemicals!
 
Karl Landsteiner
 
Edward Jenner
 
Born on May 17, 1749, in Berkeley, Gloucestershire, England, Died Jan. 26,
1823.
        As a teenager, while learning to be a physician, he heard a young farm
girl tell a doctor that she could not contract smallpox because she had once
had cowpox (a very mild disease).  This started him thinking about a
vaccine.
       After years of experimenting, on May 14, 1796, Edward Jenner carried
out a famous experiment on a healthy 8-year-old boy, James Phipps, with
cowpox.  He took material from a burst pustule on the arm of Sarah Nelmes
who had apparently contracted cowpox.  He then deliberately exposed the
boy to virulent variola virus two months later and found that the child was
protected, showing only a mild inflammation around the site where the
variola was injected.
        Some record shows that in 1789 he had already experimented
vaccination on his own son, then aged one-and-a-half, with the swine pox,
followed by conventional smallpox inoculation.
A CRIME??
 
Sarah Nelmes’ hand
 
 
Louis Pasteur (1822-1895)
Stereochemistist: molecular asymmetry
 
Fermentation and silk worker disease
 
Germ Theory of disease
 
Attenuated vaccines for cholera, anthrax, and rabies
 
On July 4, 1886, 9-year-old Joseph Meister was bitten
repeatedly by a rabid dog. Pasteur treated him with his
attenuated rabies vaccine two days later.  Meister
survived.
 
Joseph Meister later become a gatekeeper for the Pasteur
Institute.  In 1940, when he was ordered by the German
occupiers to open Pasteur's crypt, Joseph Meister
refused and committed suicide!
 
 
Emil Adolf von Behring (1854 – 1917)
 
Awarded first Nobel Prize in physiology, 1901
 
Student of Koch
 
With Kitasato and Wernike, discovered anti-toxin   for
Diphtheria and Tetanus and applied as therapy.
 
Paul Ehrlich (1854 – 1915)
Developed a series of tissue-staining dyes including
that for tubercle bacillus.
  Worked with Koch.  Developed anti-toxin
(Diphtheria) and hemalysis
 
   Side-chain theory of antibody formation:
"surface receptors bound by lock & key; Ag
stimulated receptors"
   Shared 1908 Nobel Prize with Metchnikoff.
 
 
Elie Metchnikoff  (1845-1916)
 
·   Formed the basis of leukocyte phagocytosis.
·   Birth of cellular immunology
Shared Nobel Prize with Ehrlich in 1908
 
Milstein (b. 1927) and K
ö
hler (1946-1995)
 
 
   Monoclonal antibody
 
 
Susumu Tonegawa (b. 1939)
 
Cloning of the Immunoglobulin gene
 
1987 Nobel prize for his discovery of "the genetic
principle for generation of antibody diversity".
 
 
Peter C. Doherty and Rolf M. Zinkernagel
 
       Two signals
        1996 Nobel Prize for their discoveries concerning
         "the specificity of the cell-mediated immune defence".
 
 
Source: Immunology by Richard et al.,
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Immunology is the study of the immune system, its functions, and responses to various stimuli. The field traces back to ancient times, with historical figures like Thucydides and Edward Jenner contributing to its development. From innate immunity to adaptive responses, the immune system plays a crucial role in fighting infections, allergies, and autoimmunity. Understanding the evolution of immunology helps in appreciating modern techniques used to induce immunity, like vaccination.

  • Immunology
  • Immune system
  • Historical perspective
  • Adaptive immunity
  • Vaccination

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  1. Mr. Bhartendu Vimal (Asst. Professor) CoF, Kishanganj BASU, Patna

  2. Introduction Immunology and Immune system To rid the body of foreign particles (microbial and otherwise) and abnormal cells Immunis, meaning exempt Two main function is- Recognition Response

  3. Overview of immunology Innate Immunity: Adaptive Immunity: Specificity Distinguish antigens sometimes present from those always present Memory and Recall Cells of the immune system Leukocytes originating from haemopoietic cells Communication with other systems Endocrine system Central nervous system Skeletal system Disruption of the Immune System Allergy Autoimmunity Immunodeficiency Fast-acting Less specific recognition Early during evolution e.g. barriers to infection such as skin and mucus surfaces

  4. Historical perspective Earliest written reference to the phenomenon of immunity can be traced back to Thucydides, the great historian of the Peloponnesian War. The case was Plague in Athens, in 430 BC The first recorded attempts to induce immunity deliberately were performed by the Chinese and Turks in the 15th century. Various reports suggested that the dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted in to the small cuts in the skin A technique called variolation In 1718, Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolationon the native population and had the technique performed on her own children.

  5. The method was significantly improved by the English physician Edward Jenner, in 1798. Intrigued by the fact that milkmaids who had contracted the mild disease cowpox were subsequently immune to smallpox, which is a disfiguring and often fatal disease, Jenner reasoned that introducing fluid from 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.

  6. The induction of immunity to cholera: Louis Pasteur had succeeded in growing the bacterium thought to cause fowl cholera in culture and then had shown that chickens injected with the cultured bacterium developed cholera. After returning from a summer vacation, he injected some chickens with an old culture. The chickens became ill, but, to Pasteur s surprise, they recovered. Pasteur then grew a fresh culture of the bacterium with the intention of injecting it into some fresh chickens. But, as the story goes, his supply of chickens was limited, and therefore he used the previously injected chickens. Again to his surprise, the chickens were completely protected from the disease.

  7. Pasteurhypothesized and proved that aging had weakened the virulence of the pathogen and that such an attenuated strain might be administered to protect against the disease. He called this attenuated strain a vaccine (from the Latin vacca, meaning cow ), in honor of Jenner s work with cowpox inoculation. In 1885, Pasteur administered his first vaccine to a human, a young boy who had been bitten repeatedly by a rabid dog. The boy, Joseph Meister, was inoculated with a series of attenuated rabies virus preparations. He lived and later became a custodian at the Pasteur Institute. From Harper s Weekly 29:836; courtesy of the National Library of Medicine

  8. Relationship between two Great Scientists who contributed significantly to immunology Although Koch and Pasteur were contemporaries, they were intensely competitive and actually bitter enemies--of course, the outbreak of the Franco-Prussian war (1870) did nothing to cement their relationship. In a trenchant example of how not to behave toward a colleague at a scientific meeting, Koch made his way to the podium following Pasteur s lecture and said: When I saw in the program that Monsieur Pasteur was to speak today...I attended the meeting eagerly, hoping to learn something new...I must confess that I have been disappointed, as there is nothing new in the speech which Monsieur Pasteur has just made...

  9. First insights into mechanics of immunity Emil von Behring 1880 s- Metchnikoff discovered phagocytic cells that ingest microbes and particles cells conferred immunity S. Kitasato 1890- von Behring and Kitasato discovered blood sera could transfer immunity liquid of blood conferred immunity Q: Which confers immunity cells or serum? Elie Metchnikoff

  10. A:Both cells and serum contribute to immunity! 1930 s early techniques made it easier to study humoral elements [than cellular ones]. -discovery of active component of blood gamma globulin protein 1950 s discovery of T and B cells Later discoveries linked lymphocytes to both cellular and humoral immunity

  11. Understanding specificity of antibody for antigen took years Karl Landsteiner Early 1900 s- Landsteiner revealed antibody could be produced vs. most any organic compound Last 20 yrs- Antibody specificity reveals unlimited range of reactivity also to newly synthesized chemicals!

  12. Edward Jenner Born on May 17, 1749, in Berkeley, Gloucestershire, England, Died Jan. 26, 1823. As a teenager, while learning to be a physician, he heard a young farm girl tell a doctor that she could not contract smallpox because she had once had cowpox (a very mild disease). This started him thinking about a vaccine. out a famous experiment on a healthy 8-year-old boy, James Phipps, with cowpox. He took material from a burst pustule on the arm of Sarah Nelmes who had apparently contracted cowpox. He then deliberately exposed the boy to virulent variola virus two months later and found that the child was protected, showing only a mild inflammation around the site where the variola was injected. After years of experimenting, on May 14, 1796, Edward Jenner carried vaccination on his own son, then aged one-and-a-half, with the swine pox, followed by conventional smallpox inoculation. Some record shows that in 1789 he had already experimented Sarah Nelmes hand A CRIME??

  13. Louis Pasteur (1822-1895) Stereochemistist: molecular asymmetry Fermentation and silk worker disease Germ Theory of disease Attenuated vaccines for cholera, anthrax, and rabies On July 4, 1886, 9-year-old Joseph Meister was bitten repeatedly by a rabid dog. Pasteur treated him with his attenuated rabies vaccine two days later. Meister survived. Joseph Meister later become a gatekeeper for the Pasteur Institute. In 1940, when he was ordered by the German occupiers to open Pasteur's crypt, Joseph Meister refused and committed suicide!

  14. Emil Adolf von Behring (1854 1917) Awarded first Nobel Prize in physiology, 1901 Student of Koch With Kitasato and Wernike, discovered anti-toxin for Diphtheria and Tetanus and applied as therapy.

  15. Paul Ehrlich (1854 1915) Developed a series of tissue-staining dyes including that for tubercle bacillus. Worked with Koch. Developed anti-toxin (Diphtheria) and hemalysis Side-chain theory of antibody formation: "surface receptors bound by lock & key; Ag stimulated receptors" Shared 1908 Nobel Prize with Metchnikoff.

  16. Elie Metchnikoff (1845-1916) Formed the basis of leukocyte phagocytosis. Birth of cellular immunology Shared Nobel Prize with Ehrlich in 1908

  17. Milstein (b. 1927) and Khler (1946-1995) Monoclonal antibody

  18. Susumu Tonegawa (b. 1939) Cloning of the Immunoglobulin gene 1987 Nobel prize for his discovery of "the genetic principle for generation of antibody diversity".

  19. Peter C. Doherty and Rolf M. Zinkernagel "the specificity of the cell-mediated immune defence". Two signals 1996 Nobel Prize for their discoveries concerning

  20. Stem Cell Lymphoid cell line Myeloid cell line Polymorpho -nuclear leucocytes Monocytes B T NK Macrophages Neutrophils Eosinophils Basophils Specific Innate

  21. Source: Immunology by Richard et al.,

  22. Thank you

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