NK Macrophages

本章大綱 1. Hematopoiesis ( 造血 ) 2. Cells of the Immune System 3. Organs of the Immune System

Hematopoiesis

Locations of hematopoiesis Hematopoietic stem cell (HSC) Embryonic stage: Yolk sac  fetal liver  spleen (3 rd to 7 th month)  bone marrow

Self-renew differentiate (embryonic stem cells, ES cells)

Clinical Use of Hematopoietic Stem Cells 1. Providing a functional immune system to individuals with a genetically immunodeficiency. 2. Replacing a defective hematopoitic system with a functional one (i.e. anemia). 3. Restoring the hematopoitic system of cancer patients after treatment with high doses of chemo- therapeutic agents or radiation.

Autologous : The recipient is also the donor. Syngeneic : The donor is the identical twin of the recipient. Allogeneic : The donor and the recipient are not genetically identical within the same species. Xenogeneic : The donor and the recipient are from different species.

Bone-Marrow Transplantation

Cells for transplantation Bone-marrow cells Peripheral blood cells Umbilical-cord blood cells (Cord Blood) Stem-cell transplantation

Cells of the Immune System

Normal Adult Blood-Cell Count __________________________________ Cell type Cells/mm 3 % ___________________________________________________________________________________________________________________________ Red blood cells 5.0 x 10 6 Platelets 2.5 x 10 5 Leukocytes 7.3 x 10 3 Neutrophil 50 – 70 Lymphocyte 20 – 40 Monocyte 1 – 6 Eosinophil 1 – 3 Basophil < 1 ____________________________________________

- Lymphoid Cells B lymphocytes, T lymphocytes, Null Cells (natural killer, NK cells) -Mononuclear Phagocytes Monocytes, Macrophages, dendritic cell - Polymorphonuclear Cells (PMN) or granulocytic cells or granulocytes Neutrophils, Eosinophils, Basophils, Mast cells, Dendritic cells

Lymphoid Cells - 20% - 40% of the body’s white blood cells - 99% of the cells in the lymph - ~ in the human body - Circulate in the blood and lymph - Migrate into the tissue spaces and lymphoid organs

T Lymphocytes: Thymus B Lymphocytes: Bursa of Fabricius ( 黏液囊 ) or Bone Marrow

T Lymphocyte Markers T cell receptor (TCR) CD4/CD8 CD B7 CD signal transduction

B Lymphocyte Markers Immunoglobulin (Ig) B220 (CD45R) MHC Class II CR1 (CD35) & CR2 (CD21) Fc  RII (CD32) B7-1 (CD80) & B7-2 (CD86) CD40

Fate of antigen-activated small B lymphocytes Short half life 1-2 week

Null Cells - Most are large, granular lymphocytes called natural killer (NK) cells. - Against tumor cells and cells infected with some virus. - Constitute % of the lymphocytes in human peripheral blood. - NK T cells

Mononuclear Phagocytes - Monocytes circulating in the blood - Macrophages in the tissues

Macrophages are 5- to 10-fold larger than monocytes and contain more organelles, especially lysosomes

Macrophages -Alveolar macrophages in the lung -Histiocytes in connective tissues -Kupffer cells in the liver -Mesangial cells in the kidney -Microglial cells in the brain - Osteoclasts in bone

Functions of Macrophages - Phagocytosis - Antimicrobial and cytotoxic activities - Antigen processing and presentation - Secretion of factors

Granulocytic Cells (granulocytes) - Neutrophils:phogocytosis - Eosinophils: against parasite - Basophils: nonphagocytosis; allergic

Two lobed Eosin red

One lobed Methylene blue

Dendritic Cells - Arises from the myeloid and lymphoid lineages. -Presenting antigen to T H. -MHC class II and B7 co-stimulatory

Skin, mucousorgans MHC class II B7

Organs of the Immune System

Primary (central) lymphoid organs - Provide appropriate microenvironments for the development and maturation of lymphocytes. -thymus, bone marrow Secondary (peripheral) lymphoid organs - Trap antigen from tissues or vascular spaces and are sites where mature lymphocytes can interact effectively with that antigen. - lymph nodes, spleen, mucosal-associated lymphoid tissues (MALT), e.g., gut-associated lymphoid tissue (GALT).

Tertiary lymphoid tissue - Cutaneous-associated lymphoid tissues Lymphatic System ( 淋巴系統 ) - Once mature lymphocytes have been generated in the primary lymphoid organs, they circulate in the blood and lymphatic system, a network of vessels that collect fluid that has escaped into the tissues from capillaries of the circulatory system and ultimately return it to the blood.

Lymphatic Vessels

The Human Lymphoid System secondary primary 鎖骨下靜脈 胸導管

The thymus stromal cells: maturation lobule +,-, selection

Bone Marrow Human, mice: bone marrow Cattle, sheep: fetal spleen, ileal peyer’s patch Rabbit: gut associated tissue, appendix Birds: bursa of fabricius

A Lymph Node (1) B, dendritic, Macrophage T, dendritic Plasma cells

A Lymph Node (2) Ag Primary follicle Ag Secondary follicle Germinal centers Lymphocytes migrate from blood

The Spleen Blood borne antigen

The Spleen (1) ( 血管神經出入口 ) Ag

The Spleen (2) MΦ, RBC Lymphocytes, MΦ T cells

Mucosal-Associated lymphoid tissue (MALT) Tonsils Appendix Peyer’s patches - contain a large population of Ab-producing plasma cells

Tonsils ( 上顎 ) ( 舌 ) (咽)(咽)

Peyer’s Patch contain intraepithelial lymphocytes IELs B cells, plasma cell, activated T H cells & m 

Structure of M Cells Basolaternal plasma membrane

Production of IgA Ab in the Gut

Use M cells to infection Polio virus Salmonella species Vibrio cholerae

Cutaneous-associated Lymphoid Tissue

( 八目鰻 )

本章大綱 1. Hematopoiesis ( 造血 ) 2. Cells of the Immune System 3. Organs of the Immune System