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. Abbas, A, K. et.al, Cellular and Molecular
  Immunology (6th ed., 2007), Chapters 1 2
• 2. Male D., J. Brostoff, D. B Roth, and I. Roitt
  Immunology, 7th ed., 2006.

2
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

• 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 the Immunology.

3
Evaluation

• For the Immunology Section
• Examination gt 70
• Attendance Class performance gt 30

4
Outline

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

5
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)

Vaccination (also called Immunization)ltVaccinia
6
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

7
Eradication of smallpox
Edward Jenner
8
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


9
Outline

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

10
Key concepts about immunity-I
1. The immune system has evolved to (1) Protect
against the invading pathogens (or foreign
substances) and to (2) Maintain tissue
homeostasis. Meanwhile, microbes have
evolved to survive in the host. 2. The immune
system (in vertebrates) 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 the older
host defense system - Existed in both
Invertebrates Vertebrates - Provides the
initial defense against infections -
Activates and Programs adaptive immune
responses
11
Key concepts about immunity-II
5. Adaptive immunity evolved later -
Existed only in Vertebrates - Provides the
more potent and diverse defense 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

12
Overview of immune responses
13
Innate vs Adaptive immunity
The immune system has the ability to recognize
some self components -The Normal condition gt
prevent self-recognition -The Pathological gt
occur self-recognition
14
Phagocytosis by innate immunity-I

• Cells w/ phagocytic ability Macrophage,
  Neutrophil, Dendritic cells.
• 2. Phagocytosis serves two key functions
• (1) Killing microbes
• (2) Antigen (Ag) Presentation

15
Phagocytosis during innate immunity-II
Inflammation gt A hallmark of innate immunity gt
Local accumulation of immune cells molecules
against microbes gt Function to eliminate
infections but often cause tissue damage
diseases gt Link to the development of many
diseases, e.g. Cancer, Cardiovascular
disease, .etc.
16
The Pioneer of Innate immunity Elie Mechnikov

• The Discovery of Phagocytosis
• The Nobel Laureate in Medicine 1908

17
The Pioneer of Humoral immunity Paul Ehrlich

• The Discovery of Antibody functions
• The Nobel Laureate in Medicine 1908

18
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)
19
Overview of adaptive immune responses
20
Outline

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

21
Features of Adaptive immunity
(107 109)
22
Specificity, Memory, and Homeostasis of Adaptive
Immunity
23
Clonal expansion of lymphocytes
24
Types of adaptive immunity
1. Humoral immunity gt Molecules in body
fluid, ex. 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, ex. viruses,
bacteria
For innate immunity, it also includes Humoral
Cellular components for immune defense
25
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
26
Serum therapy gt Humoral immunity Passive
immunity Serum (Ab) from animals recovered from
diphtheria infection gt Naïve animals gt
Resistant to diphtheria infection
27
Key concepts in innate immunity
1. The innate immune system mainly recognizes
common structures shared by classes of
microbes. 2. Microbial common structures gt
Pathogen-Associated Molecular Patterns
(PAMPs), eg. LPS, Peptidoglycan, Microbial
DNA RNA. 3. Receptors that recognize
PAMPs are called Pattern- Recognition
Receptors (PRRs). 4. PRRs are encoded in
germline DNA gt limited Diversity 5. PRRs may
also recognize components from injured or dead
host cells gt Autoimmune diseases
28
Examples of Pattern-Recognition Receptors (PRRs)
29
Toll-like Receptors
30
Locations of Different PRRs
Body fluids -Soluble PRRs Cellular PRRs - Cell
surface - Endosomes - Cytosol
31
Soluble Pattern Recognition Receptors-Complement
activation pathways
32
Epithelial barriers prevent the entry of microbes
33
Cellular components of the immune system will be
discussed extensively in Lecture 2.
34
Failure of the immune system
Ineffective response -Immunodeficiency Overactive
response -Hypersensitivity Auto-reactive
response -Autoimmunity
35
Outline

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

36
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

37
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 occasions but not others?
38
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.
39
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)