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.

15 th 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 ) 18 th 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.

1890s start to understand the mechanism of immunity Emil von Behring antitoxin/serum diphtheria

Mechanism of Immunity

Electrophoresis of serum proteins (Tiselius & Kabat, 1939) untreated treated

Humoral and Cellular Immunity [Serum]: Serum from animals previously immunized to bacteria could transfer the immune state to unimmunized animals  -globulin (  G) (1930s) 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 immunity B lymphocyte – derived from bone marrow, responsible for humoral immunity

Innate (Nonspecific) Immunity 天賦性免疫 Adaptive (Specific) Immunity 適應性免疫

Innate (nonspecific) Immunity

Innate immunity - A set of disease-resistance mechanisms that are not specific to a particular pathogen. - Respond immediately. It is the 1 st line of defense during the critical period just after the host’s exposure to a pathogen. - macrophages

Innate (nonspecific) Immunity 1. Anatomic barriers: skin, mucous membranes 2. Physiological barriers: temperature, low pH, chemical mediators 3. Phagocytic/endocytic barriers 4. Inflammatory barriers

dermis 皮酯腺

Phagocytosis of Bacteria

Inflammatory Response

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

Initiators of Inflammation Invading microorganisms Damaged cells in response to tissue injury Plasma enzyme system Products of various white blood cells

Innate (nonspecific) Immunity 1. Anatomic barriers: skin, mucous membranes 2. Physiological barriers: temperature, low pH, chemical mediators 3. Phagocytic/endocytic barriers 4. Inflammatory barriers

Adaptive (specific) Immunity

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

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

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.

Distinctive Membrane Molecules On Lymphocytes B lymphocyteT lymphocyte (T helper cell) (T cytotoxic cell)

Naïve B cell Memory B cellEffector B cell + Ag (plasma cell) Antibody

T Cell Receptor Cluster of Differentiation 4

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

Clonal selection of lymphocytes

In a strain A animal

NK Macrophages