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 pustulesinto 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

-globulin (G) 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).

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.

red cell

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., Lymphocytes; skin); antigen-specific phagocytes; receptors; antibodies pattern recognition molecules

The Hallmarks ( 表徵 ) of Adaptive Immunity:

1. Antigenic specificity

2. Diversity

3. Immunological memory

4. Self-nonself recognition

Distinctive Membrane Molecules on Lymphocytes

B lymphocyte T lymphocyte

T helper (TH) cell T cytotoxic (TC) cell

T cell receptor

Antigen is Recognized Differentlyby 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

Association of an antigen-presenting cell (APC) with a T lymphocyte

T cellM

Cooperation between T lymphocytes and antigen-presenting cells

Numerous T Lymphocytes Interact with a Single Macrophage

M

L

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?