Immunology/Cells of the Immune System

Hematopoiesis

Stem cells, like the stem of a plant, are cells that branch off into other cell types (hence the name). Hematopoiesis is the generation of blood cells in the bone marrow. Hematopoietic Stem Cells (HSCs) are cells within the bone marrow that maintain their own population through cell division while branching off some daughter cells to form subspecialized sets of cell-types.

During the embryonic stage however, humans do not yet have long bones but are still able to accomplish hematopoesis. The yolk sac acts as the site of hematopoiesis for the first several months of gestation, and in the second and third trimesters the fetal liver and spleen take over hematopoietic duties. Gradually, during the final trimester, the hematopoetic duties are handed over to the long bones of the fetus.

By parturition, hematopoiesis has become localized to the bone marrow itself. Most cells can multiply via division into cells like themselves, and thus are known to be unipotent. If a cell can differentiate into any cell type, it is called totipotent; a zygote's first dividing cells, and some embryonic stem cells (ES cells) are totipotent. HSCs are known as pluripotent or multipotent, meaning they can reproduce themselves (creating a store of unending stem cells) while having other cell-types branch off of their foundation stem, becoming several other types of cells.

The following is a list of the final differentiated types of cells that HSCs can become:

• Hematopoietic Stem Cell (HSCs renew their stocks)
• Lymphoid Progenitor Cell
  • Natural Killer Cell (NK Cell)
  • Dendritic Cell
    • Monocyte-derived dendritic cell
    • Plasmacytoid dendritic cell
  • T Cell Progenitor
    • CD4+ T Helper Cell
    • CD8+ T Cytotoxic Cell
  • B Cell Progenitor
• Myeloid Progenitor Cell
  • Mast Cell
  • Dendritic Cell
  • Granulocyte-Monocyte Progenitor Cell
    • Monocyte
    • Neutrophil (leukocytosis is high neutrophils and is used clinically to indicate infection; also known as polys, segs, and PMNs, Polymorphonucleophages)
  • Eosinophil Progenitor Cell
    • Eosinophil
  • Basophil Progenitor Cell
    • Basophil
  • Megakaryocyte
    • Platelets
  • Erythoid Progenitor Cell
    • Erythrocyte (RBC)

All of these cell types are created in the bone marrow. Throughout the body's tissues, monocytes and B cells can specialize further. B cells will become

• plasma cells (effector B cells)
• memory B cells

Monocytes can become any of the following vimentin+ cells:

• circulating blood monocytes
• cardiac failure cells (in alveoli)
• alveolar macrophages
• epithelial macrophages
• Mesangial Cells (in the kidney glomerulus)
• Kupffer Cells (in liver)
• Ito Cells (in liver)
• histiocytes (in connective tissue)
• Microglial cells (in brain)
• Osteoclasts (in lamellar bone)

NK1-T cells are a special set of rapid-response cells that have TCRs but interact with CD1 rather than MHC-I or MHC-II. These cells are a sort of NK cell/T cell hybrid. When activated, NK1-T cells recruit both cytotoxic T cells and B cells.

Returning to the bone marrow itself, certain growth factors and cytokines must be present in cell microenvironments in order for these cells to go down one differentiation pathway or another. Much like the stroma (supportive tissue) of an organ, the stromal cells of the bone marrow assist in hematopoiesis both by creating a scaffolding upon which the stem cells grow and differentiate while also secreting factors that influence and encourage growth.

Apoptosis

Apoptosis is programmed cell death via disintegration of the cell into membrane-bound pieces which are then phagocytized. The purpose of apoptosis is to destroy cells in an ordered way without releasing the possibly toxic intracellular chemicals and components into the extracellular tissue. Necrosis is death of a cell based on injury or disease and does not employ similar safeguards. Several genes act to influence apoptosis. They include:

• Apoptosis Inhibitors
  • bcl-2
  • bcl-X long
• Apoptosis Enhancers
  • bax (inhibits bcl-2)
  • bcl-X short (inhibits bcl-X long)
  • caspases
  • fas

T Cell Responses

T cells can initiate several different responses.

• TH1 Response--mostly inflammatory, recruits T cells and macrophages
• TH2 Response--mostly antibody-mediated, recruits B cells

Certain cells act to suppress a T cell-mediated response, and are known as suppressor T cells. It is unknown whether there is an actual Ts subpopulation or if Tc and Th cells simply act in a suppressor role in some cases.

Natural Killer Cells

NK cells act to attach to IgG antibodies on the surface of cancerous or virus-infected cells. In this way, they connect the humoral (B cell) and cell-mediated responses. For this reason, NK cells are central to something known as antibody-dependent cell-mediated cytotoxicity (ADCC).

Macrophage Responses

Macrophages phagocytize foreign invaders after chemotaxic factors lure the macrophages to sites of infection. Certain factors that attach to the invading cells (e.g. antibodies) or break open the invading cells' walls (e.g. complement system) act as opsonins (from a Greek word for "tasty'). Opsonization is thus the alteration of a foreign invader to make it more palatable to the macrophage's reactions. Macrophages release certain compounds call Reactive Oxygen Intermediates (ROIs) to kill invading cells in something known as the respiratory burst. ROIs include H2O2 and oxygen radicals. Melanocytes are important in the degradation of these compounds, which act to destroy invader DNA but also endanger host DNA at times; for this reason melanocytes are found in the skin, where they neutralize radicals caused by UV light; interestingly melanocytes are also found in the dark internal esophagus, where they function to destroy radicals produced by acid reflux out of the stomach. Macrophages also release certain compounds like lysozyme, defensin peptides (which form holes in cell membranes, much like complement) and tumor necrosis factor alpha (which can kill certain cancer cells). Macrophages also secrete certain complement proteins (although the liver produces most complement proteins) and interleukins, which help in the inflammatory response.

Chronic granulomatous disease is a genetic malfunction where the body does not produce NADPH oxidase. This retards the macrophages' ability to create Reactive Oxygen and Nitrogen Intermediates (ROIs & RNIs), predisposing afflicted patients to infections.

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