History and overview of immunology

History and Overview of Immunology

Prof M.I.N. Matee

Department of Microbiology and ImmunologySchool of Medicine

MUCHS

BIOL 495:Introduction to Immunology

Immunology stems from L.- immunis = “exempt;” Eng. = protection from disease

•To rid the body of foreign particles (microbial and otherwise) and abnormal cells

Our Immune system involves the interplay between our Non-specific and our Specific Immune

responses

Overview of Immune System

•Innate Immunity:Fast-acting Less specific recognitionEarly during evolution e.g. barriers to infection such as skin and mucus surfaces

•Adaptive Immunity:SpecificityDistinguish antigens sometimes present from those always presentMemory and Recall

•Cells of the immune systemLeukocytes originating from bone marrow stem cells

•Communication with other systemsEndocrine systemCentral nervous systemSkeletal system

•Disruption of the Immune SystemAllergyAutoimmunityImmunodeficiency

Psychoneuroimmunology

Our immune systems generate an almost infinite variety of cells and substances

Foreign Recognition

Effector Response Memory

To eliminate or neutralize

particle

Upon 2° exposureproduces enhanced response

*In some cases, the IR fails to function; at other times, the IR can turn on its host

towards modern times…

1798 –Edward Jenner noticed immunity bestowed to milkmaids – injected fluid from cowpox blister into skin of patient (orphan or prisoner)

1989- WHO announced smallpox was eradicated from the world

War on smallpox…

Louie Louie…

1879- discovered that old bacterial cultures of Pasteurella lost virulence. Referred to injection of weakened culture a “vaccine” in honor of Jenner

1881- He applied the same technique vs. anthrax

….and then rabiesPasteur inoculating sheep at Msr. Rossignol’s farm – May, 1881

Louis Pasteur

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 cellsLater 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 Köhler (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".

Cells of the Immune System

• All the cells of the Immune System are leucocytes and originate in the bone marrow from a common precursor, the pluripotent stem cell.

• Some cells are mature when they leave the marrow.

• Other cells complete their differentiation outside the marrow.

Stem Cell

B

Basophils

Polymorpho-nuclear

leucocytes

Neutrophils

Eosinophils

Macrophages

Monocytes

Lymphoidcell line

Myeloid cell line

T

NK

Specific

Innate

Reading List:

• • Chapter 2, History of Immunology, by P.M.H. Mazumdar, in

Fundamental Immunology, Ed: WE Paul. 5th Edition, 2003• • Silverstein AM. 2001. The end of immunology? Nat Immunol

2:893-895.

• Silverstein AM. 2003. Darwinism and immunology: from Metchnikoff to Burnet. Nat Immunol. 2003 Jan;4(1):3-6.

• Available for photocopying at the Office of Molecular Genetics, Microbiology and Immunology, Room 727.

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