Download of innate immunity

Introduction to The Immune
System
• Pin Ling (凌 斌), Ph.D.
ext 5632; [email protected]
• 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.
Keys toward Learning Immunology
•
Lectures => Deliver the “Key Concepts” of
Immunology.
1. What we teach is the current knowledge about
Immunology.
Workbook
Apply
2.•Most
would stand=>
forever
andthe
Some“Knowledge”
may change infrom
the
Immunology to the “Solutions” of clinical
future.
problems.
3. So Keep
your mind Open! You could be the next “One” to
make a breakthrough in the Immunology.
•
Textbook reading => Help learn the
details and build up the comprehensive
knowledge of immunology
Evaluation
For the Immunology Section:
• Examination => 70 %
• Attendance & Class performance
=> 30%
Outline
• The Origin of the Immune Concept
• Overview of Immunity to Microbes
• Features & Components of Innate &
Adaptive Immunity
• Summary & Question
The Origin of Immune Concept-I
1. The term “Immunity”
=> Latin word “Immunitas” => Protection from legal
prosecution (Roman senators)
Biological definition => Protection from infectious
diseases
2. The concept of immunity => existed in ancient Greek &
Chinese
=> Vaccination
the experienced
viewcalled Immunization)
Vaccinia
=>
(also
3. The medical view of immunity => Edward Jenner (1796)
Observation => Milkmaids generally get No Smallpox
Hypothesis => Pus from vaccinia (cowpox)
=> Protect milkmaids from smallpox
Test => Inoculate materials from cowpox pus
=> Protect a young boy from smallpox
(Protective 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.
Adopted from www.ebinrushed.com/history/images/history_7.jpg
The Origin of Immune Concept-II
4. The concept of “Immunity” developed gradually over time
through many scientific findings:
=> Robert Koch (1905 Nobel Laureate) => Infectious
diseases caused by microorganisms
=> Louis Pasteur => Vaccines against cholera & rabies
=> These clinical successes => The search of underlying
mechanism of “Protection of Infectious Diseases”
=> The development of “Immunology”
5. Advances in technology (e.g., Cell culture, Monoclonal Ab,
Flow cytometry, Genetic engineering…etc) have facilitated
our understanding of the immune system and its functions.
“Descriptive Science” => “Experimental Science”
Eradication of smallpox
Edward Jenner
Vaccines for common infectious diseases
Still no effective vaccines for many infectious microbes,
e.g., HCV, HIV, Dengue virus…..etc
Outline
• The Origin of Immune Concept
• Overview of Immunity to Microbes
• Features & Components of Innate &
Adaptive Immunity
• Summary & Question
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 (damaged cells or cancer).
Meanwhile, microbes (outside) and tumors (inside) have evolved to
survive in the host.
2. The immune system (in vertebrates) consists of (1) Innate
immunity and (2) Adaptive immunity
=> An integrated system of host defense
=> Cells & molecules function cooperatively
Antigen-presenting cells => Lymphocytes => Effector cells
3. Innate immunity is evolutionally the more conserved host defense
system:
- Existed in both Invertebrates & Vertebrates
- Provides the first line of defenses against infections
- “Activates” and “Programs” adaptive immune responses
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
Better
Understanding of Immunology
infection
 Help manipulate immune responses
6. 
The
immune
may problems
fail => Immunodeficiency,
Solve
thesystem
medical
Hypersensitivity, & Autoimmune diseases.
7. Normal immune responses can be obstacles in medical
cases, e.g., organ transplantation
Overview of immune responses
Innate vs Adaptive immunity
The immune system has the ability to recognize
some self components:
- The Normal condition => prevent self-recognition
- The “Pathological Conditions” => occur self-recognition
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
Phagocytosis during innate immunity-II
Inflammation:
1. A “Hallmark” of innate immune response (Call for help)
2. 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.
Elie Mechnikoff:The Pioneer of Innate Immunity
1. The Discovery of Phagocytes & Phagocytosis
2. The Nobel Laureate in Medicine 1908
Adopted from Nature Immunology, July 2008
Paul Ehrlich: One of the fathers of humoral
adaptive immunity
1. The Discovery of
Antibody functions
2. The Nobel
The development of modern Immunology
in 20th century
Laureate in
mainly centers on understanding the Adaptive
Medicine 1908
Immune System.
Adopted from Nature Immunology, July 2008
Interaction between innate and
& adaptive immunity
1. Innate immunity => Ag presentation (by Dendritic cells)
2. Adaptive immunity => Ag recognition (by T & B lymphocytes)
Overview of adaptive immune responses
Outline
• The Origin of Immune Concept
• Overview of Immunity to Microbes
• Features & Components of Innate
& Adaptive Immunity
• Summary & Question
Features of Adaptive immunity
(107 ~ 109)
(vaccination)
Specificity, Memory, and Homeostasis
of Adaptive Immunity
Clonal expansion of lymphocytes
Types of adaptive
immunity
1. Humoral immunity
=> Molecules in body fluid,
e.g. Antibody (Ab)
=> Key player => B cells
=> Target
extracellular
For
innate
immunity, it
microbes
& toxins
Cellular
components
for
2. Cell-mediated immunity
=> Key player => T cells =>
regulate other immune
cells
=> Target intracellular
microbes, e.g. viruses,
bacteria
also includes Humoral &
immune defense
Active vs. Passive immunity
Active immunity => A host response to a microbe (Ag)
=> specific and long-term immune defense (memory)
Passive immunity => Adoptive transfer of Ab or lymphocytes
specific for a microbe (or Ag)
=> specific, instant but transient immune defense
Serum therapy => Humoral immunity &
Passive immunity Serum (Ab) from animals
recovered from diphtheria infection
=> Naïve animals => Resistant to diphtheria
infection
Innate vs. Adaptive Immune Recognition
Adaptive immune recognition:
1. Antigen (Ag) receptors on T & B lymphocytes.
2. These Ag receptors generated by “somatic gene recombination”
3. 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.
The “Renaissance” of innate immunity
In 1989, Janeway => Immune
recognition of microbes => Detection of
conserved molecular patterns, referred
to PAMPs (Pathogen-Associated
Molecular Patterns) with features:
Charles A. Janeway, M.D.
Yale Univ.
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
The “Renaissance” of innate immunity-II
In 1996, Hoffmann’s group
 Toll functions as a PRR
in Drosophila
Julie A. Hoffmann, Ph.D.
Strasbourg, France
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.
Key concepts in innate immunity
1. The innate immune system mainly recognizes common
structures shared by classes of microbes, => Pathogen
Associated Molecular Patterns (PAMPs), e.g., LPS,
Peptidoglycan, Microbial DNA & RNA.
2. Host receptors that recognize PAMPs are called PatternRecognition Receptors (PRRs), which are encoded in
“Germline” DNA=> 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 => Autoimmune diseases
Examples of PatternRecognition Receptors
(PRRs)
Toll-like Receptors
Locations of
Different PRRs
Body fluids
-Soluble PRRs
Cellular PRRs
- Cell surface
- Endosomes
- Cytosol
Soluble Pattern Recognition ReceptorsComplement activation pathways
Epithelial barriers prevent the
entry of microbes
Cellular components of the immune
system will be discussed extensively
in Lecture #2.
Failure of the immune system
1. Ineffective response
- Immunodeficiency
2. Overactive response
- Hypersensitivity
3. Auto-reactive
response
- Autoimmunity
Outline
• The Origin of Immune Concept
• Overview of Immunity to Microbes
• Features & Components of Innate &
Adaptive Immunity
• Summary & Question
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 PatternRecognition 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
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?
The End & Thank you
Interaction between innate and
& adaptive immunity
1. Innate immunity
=> Ag presentation
(by infected cells)
2. Adaptive immunity
=> Ag recognition
(by T & B lymphocytes)
The Interface between innate and
adaptive immunity
Beutler, B. et al., Nat Immunology 2004