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Immunology

Introduction to IMMUNOLOGY COURSE • Subject Agenda* Theoretical part (Lecture): 14.01—-18.03—-22.

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04. 2013 Practical part (Labwork) • Study Materials: Textbook (David Male and Ivan Roitt-2006-DIR; Abul Abbas-2007AA), Clips and Internet search • [email protected] com. Pass: btiu12345 • Evaluation – Midterm Exam, Final Exam, Labwork – Assignment (Home-work, Topic-oriented-In-class discussion, Readand-Present Practice) Contact me at: R501, IU Building; or via email: [email protected] edu. vn NTTH-HCMIU-IMMUN-2013 Introduction to IMMUNOLOGY- An X soup What is Immunology? What is Immune System (IS)? • History of Immunology • Cells and Soluble Mediators of IS= ? • Immune Response- Pathogens (Ags): Innate and Adaptive Immunity- Collaboration NTTH-HCMIU-IMMUN-2013 Introduction to IMMUNOLOGY What is Immunology? What is Immune System (IS)? Immunology is the study of our protection from foreign macromolecules or invading organisms and our responses to them. Foreign macromolecule/ Antigen –— Immunogen: e. g. virus protein, worm, parasite Everything that should not be in my body

Immune System: Molecules, cells, tissues and organs which provide nonspecific and specific protection against Microorganisms; Microbial toxins and Tumor cells Crucial to human survival NTTH-HCMIU-IMMUN-2013 History of Immunology • Experiential Immunology period • Experimental Immunology period • Modern Immunology period Immunology act as an independent subject (1970s) NTTH-HCMIU-IMMUN-2013 I. Experiential Immunology period (the 17th century- the middle of 19th century) In ancient times, many serious infection diseases, such as smallpox, plague and cholera etc, caused innumerable people dead.

Plague !!! — Black Death Disease NTTH-HCMIU-IMMUN-2013 Story of Plague port of Weymouth. The Black Death was one of the most devastating pandemics in human history, peaking in Europe between 1348 and 1350, and killing between 75 million and 200 million people Wikipedia Yersinia pestis NTTH-HCMIU-IMMUN-2013 Figure 1. Photomicrographs demonstrating the high bacterial burden of Y pestis in various organs. Top left, A: Tissue Gram stain of a lymph node reveals the profusion of neutrophils and large clumps of Gram-negative coccobacilli characteristic of Y pestis (Brown-Hopps, original ? 00). Large clusters of bacteria (arrows) are found in the alveolar spaces (top right, B), adrenals (bottom left, C), and kidneys (bottom right, D) [hematoxylin-eosin, original ? 400]. Chmura et al. 2003, CHEST, Painful Lymphadenopathy and Fulminant Sepsis in a Previously Healthy 16-Year-Old Girl NTTH-HCMIU-IMMUN-2013 ~ 430 B. C: Peloponesian War, Thucydides describes plague – the ones who had recovered from the disease could nurse the sick without getting the disease a second time NTTH-HCMIU-IMMUN-2013 In 1670, Chinese medical practitioners : variolation

Edward Jennar —-An English physician He discovered that cowpox vaccination protected against smallpox in 1796 NTTH-HCMIU-IMMUN-2013 Vaccine- Vaccination Vaccine: A preparation of microbial antigen, often combined with adjuvants,that is administered to individuals to induce protective immunity against microbial infections. Vaccination: A general term for immunization against infectious diseases,orginally derived from immunization against smallpox which uses the Vaccinia virus. NTTH-HCMIU-IMMUN-2013 NTTH-HCMIU-IMMUN-2013 Why do they not want to play with my kids? NTTH-HCMIU-IMMUN-2013 II.

Experimental Immunology period (the middle of 19th century-the middle of 20th century) 1. Active immunity In the middle of 19th century R. Koch —-Isolated and cultured bacteria successfully Pasteur —-Infectious diseases were caused by pathogens In 1880, Pasteur —-Anti-cholera live-attenuated vaccine (old culture of Chicken V. cholera) —-Artificial active immunity Robert Koch Active immunity: The form of adaptive immunity that is induced by exposure to a foreign antigen and in which the immunized individual plays an active role in responding to the antigen. Louis Pasteur(1822-1895) NTTH-HCMIU-IMMUN-2013 . Passive immunity In the late eighties of 19th century Roux and Yersin: Diphtheria was caused by exotoxin produced by C. diphtheriae The discovery of diphtheriae antitoxin and bactericindins Antitoxin—-Antibody (Ab); Exotoxin—-Antigen (Ag) Study on reaction of Ag and Ab in vitro —-Serology In 1890,Von Behring and Kitasato —-diphtheriae antitoxin was applied in treatment of Diphtheria —- Artificial passive immunity Passive immunity: The form of immunity to an antigen that is established in one individual by transfer of antibody or lymphocytes from another individual who is immune to that antigen.

NTTH-HCMIU-IMMUN-2013 3. Mechanism of protective immunity Cell mediated immunity(CMI) —–1883-1884, Metchnikoff: Microorganisms were engulfed and destroyed by phagocytic cells Humoral immunity(HI) —-1897,Ehrlich: Ab in serum played important roles in protective immunity Both HI and CMI were very important for protective immunity, Ab in serum could promote the phagocytosis of phagocytic cells —- 1903, Wright & Douglas 4. Study on immune-pathology & immune disease In 1902, Richet and Portier—-Anaphylaxis Pirquet and Shick—-Hypersensitivity In 1903,

Arthus—-Arthus phenomenon In 1906, Pirquet —- Allergy In 1907, Donath and Landsteiner —-Autoantibody cause autoimmune disease NTTH-HCMIU-IMMUN-2013 5. Study on antigen In the early of 20th century, Landsteiner studied on antigenic determinant (epitope) —-ABO blood type 6. Study on immunochemistry In 1938,Tiselius and Kabat —-Ab is ? globulin In the fifties of 20th century, Porter and Edelmen, —-Molecular structure of Ab: 4 peptides 7. Study on immune tolerance: No positive response to specific Ag In 1945, Oven found natural immune tolerance In 1953, Medawar set up animal model of acquired immune tolerance in newborn period. . Hypothesis for Ab formation Templates postulate (1930,Breinl and Haurowitz) Variable folding postulate (1940,Pauling) Natural selection postulate (1955,Jerne) Clonal selection theory (1959, Burnet):- Clone: a group cells that stem from identical cell NTTH-HCMIU-IMMUN-2013 III. Modern Immunology period (the middle of 20th century-the 21th century) 1. Study on immune system In 1957, Glick Fabricius found out that Chicken without bursa can not produce Ab —-B cell In 1961,Good and Miller —- Cell mediated immune of new born mice whose thymus were taken away are defective —-T cell 2.

Study on monoclonal antibody —-In 1975, Kohler and Milstein 3. Study on immune genetics —-In 1978, genetic control of antibody diversity —-Discovery of accurate mechanism of immune response on gene level (MHC, TCR , BCR) 4. Study on molecular mechanism of T/B lymphocyte activation and signal transduction 5. Study on effective mechanism of immune cells NTTH-HCMIU-IMMUN-2013 6. Study on clinical immunology Organ transplantation; Autoimmune disease; Tumor immunology; Infectious diseases 7.

Study on applied immunology Preparation of monoclonal antibody and genetic engineering antibody; Preparation of recombinant cytokines; Study on DNA vaccine; Study on treatment with immune cells 8. New techniques of modern immunology and application Separation of immune cells; Protein analysis technique; Phage display technique; Preparation of new animal model NTTH-HCMIU-IMMUN-2013 NTTH-HCMIU-IMMUN-2013 NTTH-HCMIU-IMMUN-2013 The immune system Immune system Innate (non-specific) immunity Adaptive (specific) immunity Anatomic barriers (Skin,mucous membranes) •Physological barriers (temperature, pH) •Phagocytic Barriers (cells that eat invaders) •Inflammatory barriers (redness, swelling, heat and pain) •Antigen specificity •Diversity •Immunological memory •Self/nonself recognition NTTH-HCMIU-IMMUN-2013 Our immune systems generate an almost infinite variety of cells and substances Foreign Recognition Memory Upon 2° exposure produces enhanced response Effector Response To eliminate or neutralize particle *In some cases, the IR fails to function; at other times, the IR can turn on its host

NTTH-HCMIU-IMMUN-2013 Humoral and cellular immunity (antibody mediated or cellular) NTTH-HCMIU-IMMUN-2013 B cells Surface bound antibody Antibody secreting B cell Antigen B-cell Soluble antibodies, circculate in the body NTTH-HCMIU-IMMUN-2013 Antibody secreting B cell B-cell Virus killed NTTH-HCMIU-IMMUN-2013 Discussion Topics 1. Why do warm-blooded, long-lived animals require particularly complex immune defense? – p4-DIR 2. Why would removal of Ag lead to the decline in an immune response? – p14-DIR And many more to explore in the DIR textbook

Home works P18-DIR NTTH-HCMIU-IMMUN-2013 The real ones Crawling Macrophage Neutrophil and DCs NTTH-HCMIU-IMMUN-2013 Introduction to IMMUNOLOGY- An X soup • What is Immunology? What is Immune System (IS)? • History of Immunology • Cells and Soluble Mediators of IS= ? • Immune Respone- Pathogens (Ags): Innate and Adaptive Immunity- Collaboration Read DIR-page 1-18 NTTH-HCMIU-IMMUN-2013 Once upon a time… There was a WARGAMES OF THRONES- MATTER OF “LIVE OR DIE” HAS IT ALREADY ENDED? NO, IT IS JUST A BEGINNING… NTTH-HCMIU-IMMUN-2013

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