Dendritic cell, an antigen-presenting cell Sept 24, 2002

Overview of Immune Responses

1. Historical Perspective 歷史上的回顧

2. Innate (Nonspecific) Immunity 天賦性免疫

3. Adaptive (Specific) Immunity 適應性免疫

4. Comparative Immunity 比較免疫學

5. Immune Dysfunction and its Consequences 免疫失調及其後果

Recognition

Response – Effector Response

Memory 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 修西的底斯 ( 希臘歷史學家 ): Only those who had recovered from the plague could nurse the sick because they would not contract the disease a second time.

15th Century: Chinese and Turks

Inhale the dried crusts derived from smallpox pustules ( 膿皰 ) into the nostrils 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

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 strain could protect the chickens against the disease.

Vaccine 疫苗 - vacca, meaning cow, in honor of Jenner’s work

Vaccinate 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.

Mechanism of Immunity

Humoral and Cellular 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.

Humoral and Cellular Immunity

[Phagocytes]: Certain white blood cells were able to ingest microorganisms and other foreign material.

Metchnikoff (1908) hypothesized that cells, rather than serum components, were the major effector of immunity. - Cell-mediated Immunity

In the 1950’s, the lymphocyte was identified as the cell responsible for both cellular and humoral immunity.

T lymphocyte – derived from the thymus mediated cellular immunityB lymphocyte – derived from bone marrow, responsible for humoral immunity

Innate (nonspecific) Immunity

Innate immunity - A set of disease-resistance mechanisms that are 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.

- macrophages

Adaptive immunity

- Displays a high degree of specificity.- Occurs within 5 or 6 days after the initial exposure to an Ag.- 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 & Ab

Adaptive and innate immunity do not operate independently of each other; they function as a highly interactive and cooperative system, producinga total response more effective than either could alone.

Innate (nonspecific) Immunity

1. Anatomic barriers: skin, mucous membranes

2. Physiological barriers: temperature, low pH, chemical mediators

3. Phagocytic/endocytic barriers

4. Inflammatory barriers

Attachment

Phagocytosis of Bacteria

Ingestion

Fusion of phagosomeand lysosome

Digestion

Release of digestion products from the cell

Initiators of Inflammation

Invading microorganisms

Damaged cells in response to tissue injury

Plasma enzyme system

Products of various white blood cells

1. Vasodilation – an increase in the diameter of blood vessels

2. An increase in capillary permeability exudate 滲出液 edema 水腫

3. Influx of phagocytes from the capillaries into the tissues margination 邊緣化 extravasation or diapedesis 血球滲出 chemotaxis 趨化

Signs of Inflammation:

redness swelling heat pain loss of function

Inflammatory Response

Adaptive (specific) Immunity

Antigen specificity 抗原特異性

Diversity 多樣性

Immunological memory 免疫記憶

Self/nonself recognition 自我 / 非我辨認

Distinctive Membrane Molecules On Lymphocytes

B lymphocyte T lymphocyte

(T helper cell) (T cytotoxic cell)

T Cell ReceptorCluster of Differentiation 4