Immunology

Jianzhong Chen, PhD

Institute of Immunology

Zhejiang University

References 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 Introduction of Immunology Brief History of Immunology

Introduction of Immunology

Introduction of Immunology Concept of Immunity Immune Response Immune Cells Tissues and Organs of the Immune System Immunopathology

Immunity1.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 MoleculesInnate immunityResponds

rapidly No memoryNo or low

specificity

Physical barriersPhagocytes

(PMNs and macrophages)Natural killer

cells

Humoral factorsComplementAcute phase

ProteinsCytokines

Adaptive immunityResponds

Slowly MemoryHighly specific

T cellsB cellsDendritic cells

AntibodiesCytokinesGranzymes

Innate immunity mechanism of recognition

Pathogen associated molecules patterns(PAMPs ） :LPS,DNA,RNA,Protein

Danger-associated molecular patterns (DAMPS):DNA,HSP

Pattern recognition receptors (PRR): Toll-like receptor(TLR) ,C-lectin recptor(CLR),RIG-I-Like recptor(RLR),NOD-like Receptor(NLR)

Innate Immunity

Polly Matzinger

Adaptive immune response

Links between innate and adaptive immunity

Cells of immune system

Lymphocytes1.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.

Antigen presenting cells (APC)

1. Dendritic cells (DC): powerful in antigen processing and presentation.

2. Macrophage: powerful in antigen processing and destruction, but low in antigen presentation.

Introduction

Antigen presenting cellsIntroduction

Natural killer cells (NK)1. 5-10% of blood lymphocytes, LGL

2. express neither T-cell nor B-cell

antigen receptors

Introduction

Phagocytic cells

(Lung) Macrophage Attacking E. coli

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

Introduction

Phagocytic cells

monocyte neutroph

il

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

Pathogen associated molecules patterns(PAMPs ） :LPS,DNA,RNA,Protein

Danger-associated molecular patterns (DAMPS):DNA,HSP

Pattern recognition receptors (PRR): Toll-like receptor(TLR) ,C-lectin recptor(CLR),RIG-I-Like recptor(RLR),NOD-like 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 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 havingchildren inhale powders made from thecrusty skin lesions of patients recoveringfrom smallpox

Edward Jenner (1749-1823) Jenner vaccination

Ali Maali

Why Can we eradicate the smallpox?

• No animal reservoir • Lifelong immunity • Subclinical cases rare • One serotype • Effective vaccine • Major commitment by governments

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.

Von Behring (1854~1917) discovered the antitoxin and the principles of antiserum therapy. He established one of the first corporations to product immunologic products.

Robert Koch (1843~1910)

for his investigations and discoveries in relation to tuberculosis"

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.

Paul Ehrlich (1854~1915).

Selective theories(Paul Ehrlich,1900 ） The binding like the fitting of a lock with key,the side-chain 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

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

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"

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".