Introduction to The Immune System

1
Introduction to The Immune System

• Pin Ling (? ?), Ph.D.
• ext 5632 lingpin_at_mail.ncku.edu.tw
• References
• 1. Male D., J. Brostoff, D. B Roth, and I. Roitt
  
• Immunology, 7th ed., 2006.
• 2. Abbas, A, K. et.al, Cellular and Molecular
• Immunology (6th ed., 2007), Chapters 1
  2

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Keys toward Learning Immunology

• Lectures gt Deliver the Key Concepts of
  Immunology.
• Workbook gt Apply the Knowledge from Immunology
  to the Solutions of clinical problems.
• Textbook reading gt Help learn the details and
  build up the comprehensive knowledge of immunology

1. What we teach is the current knowledge about
Immunology. 2. Some may stand forever and
Some may change in the future. 3. So Keep
your mind Open! You could be the next One to
make a breakthrough in Immunology.
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Outline

• The Origin of the Immune Concept
• Overview of Immunity to Microbes
• Features Components of Innate Adaptive
  Immunity
• Summary Question

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The Origin of Immune Concept-I

• The term Immunity
• gt Latin word Immunitas gt Protection from
  legal prosecution (Roman senators)
• Biological definition gt Protection from
  infectious diseases
• 2. The concept of immunity gt existed in ancient
  Greek Chinese gt the experienced view
• The scientific view of immunity gt Edward Jenner
  (1796)
• Observation gt Milkmaids generally get No
  Smallpox
• Hypothesis gt Pus from vaccinia (cowpox)
• gt Protect milkmaids from smallpox
• Test gt Inoculate materials from cowpox pus
• gt Protect a young boy from smallpox
• (Protective immunity)

Vaccinia gt Vaccination (also called Immunization)
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The Origin of Immune Concept-II

• 4. The concept of Immunity developed gradually
  over time through many scientific findings
• gt Robert Koch (1905 Nobel Laureate) gt
  Infectious
• diseases caused by microorganisms
• gt Louis Pasteur gt Vaccines against cholera
  rabies
• gt These clinical successes gt The search of
  underlying mechanism of Protection of Infectious
  Diseases
• gt The development of Immunology
• Advances in technology (e.g., Cell culture,
  Monoclonal Ab, Flow cytometry, Genetic
  engineeringetc) have facilitated our
  understanding of the immune system and its
  functions.
• Descriptive Science gt Experimental Science

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Table 1-2. Features of Innate and Adaptive Immunity
Table 1-2. Features of Innate and Adaptive Immunity
The first vaccination against smallpox
Exudate from a cowpox pustule on the hand of
milkmaid Sarah Nelmes was inserted into scratches
on the arms of James Phipps, May 14, 1796.
This table lists the major characteristics and components of innate and adaptive immune responses. Innate immunity is discussed in much more detail in Chapter 2.
Adopted from www.ebinrushed.com/history/images/his
tory_7.jpg
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Eradication of smallpox
Edward Jenner
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Table 1-1. Effectiveness of Vaccines for Some Common Infectious Diseases
Table 1-1. Effectiveness of Vaccines for Some Common Infectious Diseases
Table 1-1. Effectiveness of Vaccines for Some Common Infectious Diseases
Table 1-1. Effectiveness of Vaccines for Some Common Infectious Diseases
Disease Maximum number of cases (year) Number of cases in 2004 Percent change
Diphtheria 206,939 (1921) 0 -99.99
Measles 894,134 (1941) 37 -99.99
Mumps 152,209 (1968) 236 -99.90
Pertussis 265,269 (1934) 18,957 -96.84
Polio (paralytic) 21,269 (1952) 0 -100.0
Rubella 57,686 (1969) 12 -99.98
Tetanus 1,560 (1923) 26 -98.33
Haemophilus influenzae type B 20,000 (1984) 16 -99.92
Hepatitis B 26,611 (1985) 6,632 -75.08


Disease Maximum number of cases (year) Number of cases in 2004 Percent change
Diphtheria 206,939 (1921) 0 -99.99
Measles 894,134 (1941) 37 -99.99
Mumps 152,209 (1968) 236 -99.90
Pertussis 265,269 (1934) 18,957 -96.84
Polio (paralytic) 21,269 (1952) 0 -100.0
Rubella 57,686 (1969) 12 -99.98
Tetanus 1,560 (1923) 26 -98.33
Haemophilus influenzae type B 20,000 (1984) 16 -99.92
Hepatitis B 26,611 (1985) 6,632 -75.08


Disease Maximum number of cases (year) Number of cases in 2004 Percent change
Diphtheria 206,939 (1921) 0 -99.99
Measles 894,134 (1941) 37 -99.99
Mumps 152,209 (1968) 236 -99.90
Pertussis 265,269 (1934) 18,957 -96.84
Polio (paralytic) 21,269 (1952) 0 -100.0
Rubella 57,686 (1969) 12 -99.98
Tetanus 1,560 (1923) 26 -98.33
Haemophilus influenzae type B 20,000 (1984) 16 -99.92
Hepatitis B 26,611 (1985) 6,632 -75.08


This table illustrates the striking decrease in the incidence of selected infectious diseases for which effective vaccines have been developed.Adapted from Orenstein WA, AR Hinman, KJ Bart, and SC Hadler. Immunization. In Mandell GL, JE Bennett, and R Dolin (eds). Principles and Practices of Infectious Diseases, 4th ed. Churchill Livingstone, New York, 1995, and Morbidity and Mortality Weekly Report 531213-1221, 2005.
This table illustrates the striking decrease in the incidence of selected infectious diseases for which effective vaccines have been developed.Adapted from Orenstein WA, AR Hinman, KJ Bart, and SC Hadler. Immunization. In Mandell GL, JE Bennett, and R Dolin (eds). Principles and Practices of Infectious Diseases, 4th ed. Churchill Livingstone, New York, 1995, and Morbidity and Mortality Weekly Report 531213-1221, 2005.
This table illustrates the striking decrease in the incidence of selected infectious diseases for which effective vaccines have been developed.Adapted from Orenstein WA, AR Hinman, KJ Bart, and SC Hadler. Immunization. In Mandell GL, JE Bennett, and R Dolin (eds). Principles and Practices of Infectious Diseases, 4th ed. Churchill Livingstone, New York, 1995, and Morbidity and Mortality Weekly Report 531213-1221, 2005.
Vaccines for common infectious diseases
Still no effective vaccines for many infectious
microbes, e.g., HCV, HIV, Dengue virus..etc
Disease Maximum number of cases (year) Number of cases in 2004 Percent change
Diphtheria 206,939 (1921) 0 -99.99
Measles 894,134 (1941) 37 -99.99
Mumps 152,209 (1968) 236 -99.90
Pertussis 265,269 (1934) 18,957 -96.84
Polio (paralytic) 21,269 (1952) 0 -100.0
Rubella 57,686 (1969) 12 -99.98
Tetanus 1,560 (1923) 26 -98.33
Haemophilus influenzae type B 20,000 (1984) 16 -99.92
Hepatitis B 26,611 (1985) 6,632 -75.08


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Outline

• The Origin of Immune Concept
• Overview of Immunity to Microbes
• Features Components of Innate Adaptive
  Immunity
• Summary Question

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Intracellular extracellular pathogens
Immune responses are adapted to different types
of pathogen.
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Key concepts about immunity-I
1. The immune system has evolved to serve two
major functions (1) Protect against the
invading pathogens (or foreign substances)
(2) Maintain tissue homeostasis (damaged cells or
cancer). Meanwhile, microbes (outside) and
tumors (inside) have evolved to survive in
the host. 2. The immune system (in mammals)
consists of (1) Innate immunity and (2)
Adaptive immunity gt An integrated system
of host defense gt Cells molecules
function cooperatively Antigen-presenting
cells gt Lymphocytes gt Effector cells 3.
Innate immunity is evolutionally the more
conserved host defense system (1) Existed
in both Invertebrates Vertebrates (2)
Provides the first line of defenses against
infections, and (3) Activates and
Programs adaptive immune responses
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Key concepts about immunity-II
5. Adaptive immunity evolved later -
Existed only in Vertebrates - Provides the
more potent and diverse defenses against
infections - Develops as a response to
infection and adapts to the infection 6. The
immune system may fail gt Immunodeficiency,
Hypersensitivity, Autoimmune diseases. 7.
Normal immune responses can be obstacles in
medical cases, e.g., organ transplantation

• Better Understanding of Immunology
• Help manipulate immune responses
• Solve the medical problems

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Overview of immune responses
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Innate vs Adaptive immunity
The immune system has the ability to recognize
some self components - The Normal condition gt
prevent self-recognition - The Pathological
Conditions gt occur self-recognition
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Phagocytosis by innate immunity-I
1. Cells w/ phagocytic ability Macrophage,
Neutrophil, Dendritic cells. 2. Phagocytosis
serves two key functions (1) Killing
microbes (2) Antigen (Ag) Presentation
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Elie MechnikoffThe Pioneer of Innate Immunity
1. The Discovery of Phagocytes Phagocytosis 2.
The Nobel Laureate in Medicine 1908
Adopted from Nature Immunology, July 2008
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Paul Ehrlich One of the pioneers of humoral
adaptive immunity
1. The Discovery of Antibody functions 2.
The Nobel Laureate in Medicine 1908
The development of modern Immunology in 20th
century mainly centers on understanding the
Adaptive Immune System.
Adopted from Nature Immunology, July 2008
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Interaction between innate and adaptive immunity
1. Innate immunity gt Ag presentation (by
Dendritic cells) 2. Adaptive immunity gt Ag
recognition (by T B lymphocytes)
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Interaction between innate and adaptive immunity
1. Innate immunity gt Ag presentation
(by infected cells) 2. Adaptive immunity
gt Ag recognition (by T B lymphocytes)
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Overview of adaptive immune responses
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Outline

• The Origin of Immune Concept
• Overview of Immunity to Microbes
• Features Components of Innate Adaptive
  Immunity
• Summary Question

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The principle cells of the immune system
Cellular components of the immune system will be
discussed extensively in Lecture 2.
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Features of Adaptive immunity
(107 109)
(vaccination)
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Specificity, Memory, and Homeostasis of Adaptive
Immunity
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Principle of Vaccination
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Clonal expansion of lymphocytes
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Antigens, Epitopes, Antibodies

• Antigens (immunogens) initiate adaptive immune
  responses.
• 2. Antigens may contain several different
  Epitopes for recognition by lymphocyte receptors
  or antibodies

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Types of adaptive immunity
1. Humoral immunity gt Molecules in body
fluid, e.g. Antibody (Ab) gt Key player
gt B cells gt Target extracellular
microbes toxins 2. Cell-mediated immunity
gt Key player gt T cells gt regulate
other immune cells gt Target
intracellular microbes, e.g. viruses,
bacteria
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Functions of different types of lymphocyte
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Active vs. Passive immunity
Active immunity gt A host response to a microbe
(Ag) gt specific and
long-term immune defense (memory) Passive
immunity gt Adoptive transfer of Ab or
lymphocytes
specific for a microbe (or Ag)
gt specific, instant but transient immune
defense
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Serum therapy gt Humoral immunity Passive
immunity Serum (Ab) from animals recovered from
diphtheria infection gt Naïve animals gt
Resistant to diphtheria infection
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Innate vs. Adaptive Immune Recognition
Adaptive immune recognition 1. Antigen (Ag)
receptors on T B lymphocytes.2. These Ag
receptors generated by somatic gene
recombination3. They recognize diverse Antigens
(peptides) from microbes or non-self.
Innate immune recognition Q How do host cells
recognize invading pathogens at the first
place? Scientists have no answer to this until
the end of the 20th century.
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The Renaissance of innate immunity
In 1989, Janeway gt Immune recognition of
microbes gt Detection of conserved molecular
patterns, referred to PAMPs (Pathogen-Associated
Molecular Patterns) with features 1. Invariant
among a given class of microbes. 2. Have
essential roles in microbial physiology.
3. Recognized by receptors of the innate
immune system, called PRRs
(Pattern-Recognition Receptors). 4. Innate
immunity regulates adaptive immunity
Charles A. Janeway, M.D. Yale Univ.
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The Discovery of Toll and Toll-like receptor (TLR)
Cell. 1996 Sept 20 86(6)973-83 The
dorsoventral regulatory gene cassette
spatzle/Toll/cactus controls the potent
antifungal response in Drosophila adults.
Lemaitre B, Nicolas E, Michaut L, Reichhart JM,
Hoffmann JA. Institut de Biologie Moleculaire at
Cellulaire, UPR 9022 du Centre National de la
Recherche Scientifique, Strasbourg, France
Nature 388, 394 - 397 (24 July 1997) A human
homologue of the Drosophila Toll protein signals
activation of adaptive immunity.Medzhitov R,
Preston-Hurlburt P, Janeway CA Jr.Section of
Immunobiology, Yale University School of
Medicine, New Haven, Connecticut 06520-8011, USA.
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Key concepts in innate immunity
1. The innate immune system mainly recognizes
common structures shared by classes of
microbes, gt Pathogen Associated Molecular
Patterns (PAMPs), e.g., LPS, Peptidoglycan,
Microbial DNA RNA. 2. Host receptors that
recognize PAMPs are called Pattern-
Recognition Receptors (PRRs), which are encoded
in Germline DNAgt limited Diversity. 3.
Innate immunity not only provide the first line
of defenses but link to the program of
adaptive immunity. 4. PRRs may also recognize
components from injured or dead host cells gt
Autoimmune diseases
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Toll-like Receptors
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Locations of Different PRRs
Body fluids -Soluble PRRs Cellular PRRs - Cell
surface - Endosomes - Cytosol
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Soluble Pattern Recognition Receptors-Complement
activation pathways
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Functions of Complement
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Epithelial barriers prevent the entry of
microbes
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Failure of the immune system

• 1. Ineffective response
• - Immunodeficiency
• 2. Overactive response
• - Hypersensitivity
• 3. Auto-reactive response
• - Autoimmunity

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Outline

• The Origin of Immune Concept
• Overview of Immunity to Microbes
• Features Components of Innate Adaptive
  Immunity
• Summary Question

43
SUMMARY

• 1. Protective immunity against microbes is
  mediated by the
• early response of innate immunity and the
  later response of
• adaptive immunity.
• 2. Innate immune responses are initiated by
  recognition of
• common microbial structures (PAMPs) by
  Pattern-
• Recognition Receptors (PRRs) on innate
  immune cells.
• - Provide the first line of host defense
• - Activate and regulate the adaptive immunity
• 3. Adaptive immune responses are initiated by
  recognition of
• foreign antigens by specific lymphocytes.
• - Provide more potent, specific (Ag), broad
  protection
• - Develop immune memory for the next exposure
• - Feedback regulate innate immunity

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Questions
1. Why is it necessary to vaccinate against
tetanus only every 10 years, though
antibodies against the toxoid disappear from the
circulation within a year? 2. Why is the
vaccine against tetanus always effective, whereas
the vaccine against influenza protects on
some epidemics but not others?
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Table 1-2. Features of Innate and Adaptive Immunity
Table 1-2. Features of Innate and Adaptive Immunity
The End Thank you
This table lists the major characteristics and components of innate and adaptive immune responses. Innate immunity is discussed in much more detail in Chapter 2.
46
Phagocytosis during innate immunity-II

• Inflammation
• A Hallmark of innate immune response (Call for
  help)
• Local accumulation of immune cells molecules
  against microbes
• 3. Function to eliminate infections but often
  cause tissue damage diseases
• 4. Link to the development of many diseases,
  e.g., Cancer,
• Cardiovascular disease, .etc.