Download Overview of the Immune System

Chapter 1
Overview of the Immune System
Sept 19 & 21, 2006
你需要學習的問題：
• 什麼叫做免疫力 (immunity)?
• 免疫力有哪兩大類?
• 什麼叫做先天性免疫力 (innate immunity)?
• 什麼叫做適應性免疫力 (adaptive immunity)?
• 先天性免疫反應由哪些成員組成? 有何特色?
• 適應性免疫反應由哪些成員組成? 有何特色?
• 先天性免疫力與適應性免疫力如何分工及合作?
• 當免疫系統失常時，有哪些後果?
Outlines
1. Historical Perspective 歷史的回顧
2. Early Studies of Humoral and Cellular Immunity
早期關於體液性及細胞性免疫力的研究
3. Theoretical Challenges 學理上的爭議
4. Infection and Immunity 感染及免疫力
5. Innate and Adaptive Immunity
先天性及適應性免疫力
6. Immune Dysfunction and its Consequences
免疫失常及其後果
The immune system evolved to protect
multicellular organisms from pathogens.
- Pathogens are diverse.
- The immune system is highly adaptable.
There are two systems of immunity:
- Innate immunity
- Adaptive immunity
Two systems collaborate to protect the body.
How to protect? - recognition & response
拉丁文 - immunis: exempt
英文- immunity:
the state of protection
from infectious disease
Historical Perspective
Peloponnesian War (431 – 404 B.C.)
伯羅奔尼撒戰爭
Thucydides 修西迪底斯 (希臘將軍及歷史學家):
Only those who had recovered from
the plague could nurse the sick
because they would not contract the
disease a second time.
免疫學的發展與微生物學及
疫苗的應用有很密切的關聯
15th Century: Chinese and Turks
Inhale the dried crusts derived from smallpox pustules
into the nostrils (吹花) or insert into small cuts in the skin.
-Variolation (種牛痘)
18th Century: Jenner (1798)
Milkmaids who had contracted cowpox (a mild disease)
were subsequently immune to smallpox (a disfiguring and
often fatal disease).
Jenner introduced fluid from a cowpox pustule into people.
Louis Pasteur (巴斯德，1822 - 1895)
The chicken which were injected with
fowl cholera bacterium (old culture)
survived from a subsequent injection
of fresh culture of bacteria.
- Aging had weakened the virulence of the pathogen.
- An attenuated (weakened) strain could protect the
chickens against the disease.
Vaccine 疫苗
- vacca, meaning cow, in honor of
Jenner’s work
1881, vaccination of the sheep with heat-attenuated
anthrax bacilli (Bacillus anthracis,炭疽)
1885, Pasteur administered the first vaccine
to a human, a young boy who had bitten by
a rabid (rabies 狂犬病) dog.
Early Studies of Humoral
and Cellular Immunity
Mechanism of Immunity:
Early studies revealed humoral
and cellular components of the
immune system.
Humoral Immunity
[Serum]: Serum from animals previously
immunized to bacteria could transfer
the immune state to unimmunized
animals
g-globulin (gG)
immunoglobulin (Ig)
antibody (Ab, 相對於 antigen [Ag])
Because immunity was mediated by antibodies
contained in body fluid (known as humors), it was
called humoral immunity.
Cellular Immunity
[Phagocytes]: Certain white blood cells were
able to ingest microorganisms
and other foreign material.
Metchnikoff (1883) demonstrated that cells
contribute to the immune state of an animal.
He hypothesized that cells, rather than serum
components, were the major effector of
immunity.
- Cell-mediated Immunity
Theoretical Challenges
Is humoral or cell-mediated immunity
responsible for the protection?
The full immune response requires both cellular and
humoral responses.
The lymphocyte was identified as the cell responsible
for both cellular and humoral immunity due to the
improved cell culture techniques in 1950’s.
T lymphocyte – derived from the thymus mediated
cellular immunity
B lymphocyte – derived from bone marrow,
responsible for humoral immunity
How is the immunological specificity
generated?
- the selective theory
Ehrlich (1900) – side-chain theory
Jerne, Talmadge, Burnet (1950s) – clonal-selection theory
- the instructional theory
Breinl & Haurowitz (1930) – antigens serve as templates
Pauling (1940s) – protein folding
Infection and Immunity
- The immune system evolves to protect
organisms from pathogens.
- An effective defense relies heavily on the
nature of the individual microorganism.
- The immune system must deal with all
types of microbes and has evolved
multiple strategies for combating the
invasion of pathogens.
Pathogens representing the major categories
of microorganisms causing human diseases
Viruses - rotavirus
Bacteria - Pseudomonas
Fungi – Candida albicans
Parasites - filaria
想一想：
人類在200多年前已懂得使用疫苗，為何
至今仍無法利用疫苗對抗許多傳染病?
Innate and Adaptive
Immunity
Innate Immunity (1)
- A set of disease-resistance mechanisms that are
present before the onset of infection and not
specific to a particular pathogen
- Respond immediately. It is the 1st line of
defense during the critical period just after
the host’s exposure to a pathogen.
Innate Immunity (2)
- Consist of cellular and molecular components
that recognize classes of molecules peculiar
to frequently encountered pathogens.
- Barriers (skin, mucosa, acids, sweat, tears,
etc.), phagocytic cells (macrophages,
neutrophils, etc.) and antimicrobial
components (lysozyme, interferon,
complement, collectins, etc.)
Innate Immunity (3)
- Many of the molecules involved in innate
immunity have the property of pattern
recognition – the ability to recognize a given
class of molecules.
- Members with pattern recognition ability
may be soluble (lysozyme, complement
components,..) or cell-associated receptors,
such as Toll-like receptors (TLRs).
red cell
Macrophages attacking Escherichia coli
The bacteria are phagocytized and breakdown products secreted. The
monocyte has been recruited to the vicinity of the encounter by
soluble factors secreted by the macrophage.
Adaptive Immunity
- Occurs within 5 or 6 days after the initial
exposure to an Ag.
- Displays a high degree of specificity.
- Exposure to the same Ag some time in the
future results in a memory response:
respond more quickly, stronger, and often
more effective in neutralizing and clearing
the pathogen.
- Lymphocytes & antibodies (Ab)
Adaptive and innate immunity do not
operate independently of each other; they
function as a highly interactive and
cooperative system, producing a total
response more effective than either could
alone.
Major components barriers (e.g.,
skin);
phagocytes;
pattern
recognition
molecules
Lymphocytes;
antigen-specific
receptors; antibodies
The Hallmarks (表徵) of Adaptive Immunity:
1. Antigenic specificity
2. Diversity
3. Immunological memory
4. Self-nonself recognition
Distinctive Membrane Molecules
on Lymphocytes
T lymphocyte
B lymphocyte
T cell
receptor
T helper (TH) cell
T cytotoxic (TC) cell
Antigen is Recognized Differently
by B and T Lymphocytes
B lymphocytes: recognize an antigenic
determinants, or epitope
T lymphocytes: recognize peptide epitopes
associated with a major
histocompatibility complex
(MHC) molecule on the
surface of a self-cell
The MHC Molecules Bind Antigenic Peptides
Cooperation between T lymphocytes and
antigen-presenting cells
Mf
T cell
Association of an antigen-presenting cell (APC)
with a T lymphocyte
Numerous T Lymphocytes Interact
with a Single Macrophage
L
M
L
L
Clonal Selection of Lymphocytes
Immunological Memory – Ab response
Overview of
the T cell and
B cell
Responses
Immune Dysfunction
and Its Consequences
- Allergy and Asthma
過敏、氣喘
- Autoimmune disease
自體免疫疾病
- Immunodeficiency
免疫缺陷 (先天、後天)
- Graft rejection and
graft-versus-host (GVH) disease
移植排斥、移植物抗宿主疾病
Questions:
1. What is innate immunity ?
2. What is adaptive immunity ?
3. What components does the innate branch of the
immune system consist of ?
4. What components does the adaptive branch of the
immune system consist of ?
5. How do innate and adaptive immunity interact
and cooperate?