Transcript IMMUNOLOGY

Immunology
Jianzhong Chen, PhD
Institute of Immunology
Zhejiang University
References
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何维 主编。《医学免疫学》第二版 ，人民卫生出
版社 2010
金伯泉 主编。《医学免疫学》第五版 人民卫生出
版社 2008
Abbus A K, et al. Cellular and Molecular Immunology.
7th Edition,Elsevier Saunders . 2012
Janeway C A, et al. Immunobiology. 8th ed. Garland
Science Publishing . 2012
Content
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Introduction of Immunology
Brief History of Immunology
Introduction of Immunology
Introduction of Immunology
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Concept of Immunity
Immune Response
Immune Cells
Tissues and Organs of the Immune System
Immunopathology
Immunity
1.Immunity: : Meaning the state of protection from infectious disease.
In 430BC, a plaque in Athens, Those who recovered from the
plaque would not contact the disease a second time.
2. Agents: microorganisms (viruses, bacteria etc) and their products,
foods, chemicals, pollen, tumor cells, etc.
3.Immune system: immune tissues and organs, immune cells,
immune molecules
4.Immune response: collective and coordinated response to the
introduction of foreign substances.
5.Immunology: study the structure of immune system and its
functions.
Immune Response
 Innate immune response
natural immune response
non-specific immune response
 Adaptive immune response
acquired immune response
specific immune response
The innate and adaptive immune response
Characteristics
Cells
Molecules
Innate immunity
Responds rapidly
No memory
No or low
specificity
Physical barriers
Phagocytes (PMNs
and macrophages)
Natural killer cells
Humoral factors
Complement
Acute phase
Proteins
Cytokines
T cells
B cells
Dendritic cells
Antibodies
Cytokines
Granzymes
Adaptive
immunity
Responds Slowly
Memory
Highly specific
Innate immunity mechanism of
recognition
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Pathogen associated molecules
patterns(PAMPs）:LPS,DNA,RNA,Protein
Danger-associated molecular patterns
(DAMPS):DNA,HSP
Pattern recognition receptors (PRR): Tolllike receptor(TLR) ,C-lectin
recptor(CLR),RIG-I-Like recptor(RLR),NODlike Receptor(NLR)
Innate Immunity
Polly Matzinger
Adaptive immune response
Links between innate and adaptive immunity
Cells of immune system
Lymphocytes
1.Lymphocytes (except NK cells) are wholly
responsible for the specific immune recognition
of pathogens, so they initiate adaptive immune
responses.
2.Lymphocytes are derived from bone-marrow
stem cells.
3.B lymphocytes develop in the bone marrow.
T lymphocytes develop in the thymus.
Introduction
Antigen presenting cells (APC)
1.
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Dendritic cells (DC): powerful in antigen
processing and presentation.
Macrophage: powerful in antigen processing and
destruction, but low in antigen presentation.
Introduction
Antigen presenting cells
Introduction
Natural killer cells (NK)
1. 5-10% of blood lymphocytes, LGL
2. express neither T-cell nor B-cell
antigen receptors
Phagocytic cells
(Lung) Macrophage Attacking E. coli
Introduction
Phagocytic cells
Monocytes (blood)/Macrophages (tissues)
functions: 1. remove particulate antigens
2. take up, process and present
antigenic peptides to T cells
distribution: Kupffer cells in the liver
microglial cells in the brain
Phagocytic cells
monocyte
neutrophil
Phagocytic cells
Polymorphonuclear granulocytes
1.neutrophils; basophils; eosinophils
2.neutrophils are short-lived phagocytic cells
multilobed nucleus; 10-20 m
3.neutrophils have a large arsenal of antibiotic
proteins
granules: lysosomes; lactoferrin
Innate immunity mechanism of
recognition
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Pathogen associated molecules
patterns(PAMPs）:LPS,DNA,RNA,Protein
Danger-associated molecular patterns
(DAMPS):DNA,HSP
Pattern recognition receptors (PRR): Tolllike receptor(TLR) ,C-lectin
recptor(CLR),RIG-I-Like recptor(RLR),NODlike Receptor(NLR)
Innate Immunity
Polly Matzinger
Tissues and organs of the immune
system
Primary (or central) lymphoid organs
bone marrow
thymus
Secondary (or peripheral) lymphoid organs
spleen
lymph nodes
Mucosal-associated lymphoid tissue (MALT)
Mucosal immune system (MIS)
1.non-encapsulated lymphoid tissue in the
lamina propria and submucosal areas of the
gastrointestinal, respiratory and
genitourinary tracts.
2. tonsil, appendix, Peyer’s patches
3. B cell
IgA
IEL
Adaptive immune ( T cell)
4. function: local (mucosal) immunity
Mucosal-associated lymphoid tissue (MALT)
Immunopathology
Hypersensitivity
- overactive immune response
Immunodeficiency
- ineffective immune response
Autoimmunity
- inappropriate reaction to self antigens
Brief History of Immunology
Brief History of Immunology
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1. Empirical Immunology(AD1700-1900)
2. Scientific Immunology(1900-1950s)
3. Modern Immunology(1960s-Present)
Documents show that as
early as AD 1000,
the ancient Chinese
custom existed of having
children inhale powders
made from the
crusty skin lesions of
patients recovering
from smallpox
Edward Jenner (1749-1823)
Jenner vaccination
Ali Maali
Why Can we eradicate the
smallpox?
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• No animal reservoir
• Lifelong immunity
• Subclinical cases rare
• One serotype
• Effective vaccine
• Major commitment by governments
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Lious Pasteur (1822~1895).
The genius of Pasteur
carried him to the solution
of many problems: the
spoilage of beers and wines,
with the accompanying
pasteurization process; the
discovery of anaerobic
bacteria, virus vaccines,
and attenuation of
virulence; and studies of
spontaneous generation.
His studies in
immunology have
rightly earned him the
position as father of
the science.
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Von Behring
(1854~1917)
discovered the
antitoxin and the
principles of
antiserum
therapy. He
established one of
the first
corporations to
product
immunologic
products.
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Robert Koch
(1843~1910)
for his
investigations
and discoveries
in relation to
tuberculosis"
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Elie Metchnikoff
(1845~1916)
converted his
discoveries of
phagocytosis into a
doctrine that gained
many disciples from
his coterie of students.
He shared the Nobel
Prize with Ehrlich in
1908.
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Paul Ehrlich
(1854~1915).
Selective theories(Paul
Ehrlich,1900） The
binding like the fitting of
a lock with key,the sidechain specificity was
determined before its
exposure to Ag, and the
Ag selected the
appropriate side-chain
receptor.
He shared the Nobel
Prize with Metchnikoff
in 1908.
Clonal selection theory and
immune tolerance
The clonal selection hypothesis
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Rodney R. Porter
(1917~1985) shared
the Nobel Prize in
Physiology and
Medicine with
Edelman in 1972.
• Gerald M. Edelman
(1929~) was only 43
years of age when he
shared the Nobel Prize
with Porter in 1972.
MHC
Monoclonal Ab and
Antibody Diversity
Susumu Tonegawa is
a Japanese Scientist who
won the Nobel Prize for
physiology or medicine in
1987 "for his discovery of
the genetic principle for
generation of antibody
diversity"
Peter C. Doherty
Rolf M. Zinkernagel
”for their discoveries concerning the specificity of
the cell mediated immune defence”
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" and the other half to
Ralph M. Steinman "for his discovery of the dendritic cell and its role
in adaptive immunity".