Bone marrow

Bone marrow is the flexible tissue in the interior of bones. In humans, red blood cells are produced in the heads of long bones in a process known as hematopoiesis. On average, bone marrow constitutes 4% of the total body mass of humans; in an adult weighing 65 kilograms (143 lb), bone marrow accounts for approximately 2.6 kilograms (5.7 lb). The hematopoietic component of bone marrow produces approximately 500 billion blood cells per day, which use the bone marrow vasculature as a conduit to the body's systemic circulation. Bone marrow is also a key component of the lymphatic system, producing the lymphocytes that support the body's immune system. Bone marrow transplants can be conducted to treat severe diseases of the bone marrow, including certain forms of cancer. Additionally, bone marrow stem cells have been successfully transformed into functional neural cells, and can also potentially be used to treat illnesses such as inflammatory bowel disease and, in some cases, HIV.

Marrow types
A femoral head with a cortex of cortical bone and medulla of trabecular bone. Both red bone marrow and a focus of yellow bone marrow are visible. The two types of bone marrow are medulla ossium rubra (red marrow), which consists mainly of hematopoietic tissue, and medulla ossium flava (yellow marrow), which is mainly made up of fat cells. Red blood cells, platelets and most white blood cells arise in red marrow. Both types of bone marrow contain numerous blood vessels and capillaries. At birth, all bone marrow is red. With age, more and more of it is converted to the yellow type; only around half of adult bone marrow is red. Red marrow is found mainly in the flat bones, such as the pelvis, sternum, cranium, ribs, vertebrae and scapulae, and in the cancellous ("spongy") material at the epiphyseal ends of long bones such as the femur and humerus. Yellow marrow is found in the medullary cavity, the hollow interior of the middle portion of long bones. In cases of severe blood loss, the body can convert yellow marrow back to red marrow to increase blood cell production.

Stroma
The stroma of the bone marrow is all tissue not directly involved in the marrow's primary function of hematopoiesis. Yellow bone marrow makes up the majority of bone marrow stroma, in addition to smaller concentrations of stromal cells located in the red bone marrow. Though not as active as parenchymal red marrow, stroma is indirectly involved in hematopoiesis, since it provides the hematopoietic microenvironment that facilitates hematopoiesis by the parenchymal cells. For instance, they generate colony stimulating factors, which have a significant effect on hematopoiesis. Cell types that constitute the bone marrow stroma include:

fibroblasts (reticular connective tissue) macrophages adipocytes

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osteoblasts osteoclasts endothelial cells, which form the sinusoids. These derive from endothelial stem cells, which are also present in the bone marrow.

Macrophages contribute especially to red blood cell production, as they deliver iron for hemoglobin production.

Bone marrow barrier

The blood vessels of the bone marrow constitute a barrier, inhibiting immature blood cells from leaving the marrow. Only mature blood cells contain the membrane proteins required to attach to and pass the blood vessel endothelium. Hematopoietic stem cells may also cross the bone marrow barrier, and may thus be harvested from blood.

Mesenchymal stem cells

The bone marrow stroma contains mesenchymal stem cells (MSCs), also known as marrow stromal cells. These are multipotent stem cells that can differentiate into a variety of cell types. MSCs have been shown to differentiate, in vitro or in vivo, into osteoblasts, chondrocytes, myocytes, adipocytes and beta-pancreatic islets cells. MSCs can also transdifferentiate into neuronal cells.

Red marrow parenchyma

Cellular components
. Cellular constitution of the red bone marrow parenchyma[ Average Group Cell type fraction Myeloblasts 0.9% Promyelocytes 3.3% Neutrophilic myelocytes 12.7% Eosinophilic myelocytes 0.8% Neutrophilic metamyelocytes 15.9% Myelopoietic Eosinophilic metamyelocytes 1.2% cells Neutrophilic band cells 12.4% Eosinophilic band cells 0.9% Segmented neutrophils 7.4% Segmented eosinophils 0.5% Segmented basophils and mast cells 0.1%
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Reference range 0.2-1.5 2.1-4.1 8.2-15.7 0.2-1.3 9.6-24.6 0.4-2.2 9.5-15.3 0.2-2.4 6.0-12.0 0.0-1.3 0.0-0.2

Pronormoblasts Erythropoietic Basophilic normoblasts cells Polychromatic normoblasts Orthochromatic normoblast Megakaryocytes Plasma cells Other cell Reticular cells types Lymphocytes Monocytes

0.6% 1.4% 21.6% 2.0% < 0.1% 1.3% 0.3% 16.2% 0.3%

0.2-1.3 0.5-2.4 17.9-29.2 0.4-4.6 0.0-0.4 0.4-3.9 0.0-0.9 11.1-23.2 0.0-0.8

In addition, the bone marrow contains hematopoietic stem cells, which give rise to the three classes of blood cells that are found in the circulation: white blood cells (leukocytes), red blood cells (erythrocytes), and platelets (thrombocytes)

Compartmentalization
Biological compartmentalization is evident within the bone marrow, in that certain cell types tend to aggregate in specific areas. For instance, erythrocytes, macrophages, and their precursors tend to gather around blood vessels, while granulocytes gather at the borders of the bone marrow.

Lymphatic role
The red bone marrow is a key element of the lymphatic system, being one of the primary lymphoid organs that generate lymphocytes from immature hematopoietic progenitor cells. The bone marrow and thymus constitute the primary lymphoid tissues involved in the production and early selection of lymphocytes. Furthermore, bone marrow performs a valve-like function to prevent the backflow of lymphatic fluid in the lymphatic system.

Diseases of the bone marrow

The normal bone marrow architecture can be damaged or displaced by aplastic anemia, malignancies such as multiple myeloma, or infections such as tuberculosis, leading to a decrease in the production of blood cells and blood platelets. The bone marrow can also be affected by various forms of leukemia, which attacks its hematologic progenitor cells. Furthermore, exposure to radiation or chemotherapy will kill many of the rapidly dividing cells of the bone marrow, and will therefore result in a depressed immune system. Many of the symptoms of radiation sickness are due to damage sustained by the bone marrow cells. To diagnose diseases involving the bone marrow, a bone marrow aspiration is sometimes performed. This typically involves using a hollow needle to acquire a sample of red bone marrow from the crest of the ilium under general or local anesthesia.

Cutaneous associated lymphoid tissue

he skin is an important anatomic barrier to the external environment,and its large surface area makes this tissue important in nonspecific(innate)defenses.The epidermal (outer)layer of the skin is composed largely of specialized epithelial cells called keratinocytes.These cells secrete a number of cytokines that may function to induce a local inflammatory reaction.In addition,keratinocytes can be induced to express class II MHC molecules and may function as antigen-presenting cells.Scattered among the epithelial-cell-matrix of the epidermis are Langerhans cells,a type of dendritic cell,which internalize antigen by phagocytosis or endocytosis.The Langerhans cells then migrate from the epidermis to regional lymph nodes,where they differentiate into interdigitating dendritic cells.These cells express high levels of class II MHC molecules and function as potent activators of naive Helper cells.

The epidermis also contains so-called intraepidermal lymphocytes.These are similar ti the intraepithelial lymphocytes of MALT in that most of them are CD8 plus cells,which have limited diversity for antigens that enters through the skin and some immunologist believe that they may play a role in combating antigens that enter through skin.The under-laying dermal layer of the skin contains scattered CD4 plus and CD8 plus T cells and macrophages.Most of these dermal T cells were either previously activated cells or are memory cells.