Tissue

blood

2007-12-23T12:09:00.000-08:00

Blood is a highly specialized tissue produced in the bone marrow in a process called hematopoiesis. Blood contains red blood cells (a=erythrocytes) and white cells (leukocytes, b=neutrophil, c=eosinophil, d=lymphocyte) circulating in plasma accompanied by platelets, plasma proteins, and other dissolved substances.

[] Hemopoiesis [] Hematopoiesis - high-resolution version (837 KB) [] tem basophil [] tem eosinophil [] tem eosinophil [] tem small lymphocyte [] tem monocyte [] tem neutrophil engulfing Candida []

bone marrow

2007-12-23T09:26:00.000-08:00

Hematopoiesis (production of blood) occurs in the bone marrow, which is located within the hollow interior of bones, predominantly in flat bones and long bones. []Gray's, labeled photomicrograph, diagram []

The tissue within bone marrow is differentiated as 'red' marrow (erythropoiesis, thrombopoiesis, production of WBC) and 'yellow' marrow, which contains fat cells. The proportion of 'yellow marrow' increases with the accumulation of fat cells during the individual's life span, though reversion to red marrow is possible in response to blood loss.

normal [] bone marrow section [] bone marrow section 2 [] bone marrow smear []

In addition to hematopoietic stem cells (HSC), mesenchymal stem cells (hMSC) are located around the central sinus of the bone marrow and have the potential to differentiate into osteoblasts, chondrocytes, myocytes, and other cell types. Bone marrow stem cells have also been demonstrated to aid in the regeneration of adipocytes, hepatocytes, lung, alimentary canal, skin, and endothelial cells. Side population cells (SP's) are believed to be present in skeletal muscle, and thus scientists hypothesize that SP's express plasticity by contributing to hematopoiesis as well as skeletal muscle tissue.

fibrinolytic system

2007-12-19T15:51:00.000-08:00

The fibrinolytic system dissolves fibrin blood clots, acting in reverse to the coagulation system.

▼ε-aminocaproic acid : antifibrinolytics : fibrin clots : fibrin degradation products : fibrinolysis : kringle domains : PAI-1, PAI-2 : plasmin : plasminogen : plasminogen activator inhibitors : serine proteases : serpins : thrombolytic agents : tissue plasminogen activator (PLAT, tPA) : tranexamic acid : uPA : urokinase : urokinase receptor : zymogen ▼

Plasminogen, the inactive, zymogen form of plasmin, is incorporated into fibrin clots as they form. Cleavage of plasminogen by tissue plasminogen activator (PLAT, tPA) and urokinase converts plasminogen to the active serine protease plasmin form. Acting as a serine protease, the kringle domains of plasmin bind to arginine and lysine residues and cleave fibrin into fibrin degradation products (fibrinolysis).

Tissue plasminogen activator (PLAT, tPA) is a serine protease secreted by cells of the arteriolar endothelium. Urokinase, also termed urokinase-type plasminogen activator (uPA), is also a serine protease that contains a serine protease domain, a kringle domain, and a growth factor domain. The serpins, plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) irreversibly inhibit the protease (peptidase) activity of tPA and uPA.

In the extracellular matrix, urokinase binds to the urokinase receptor, tethering urokinase to the cell membrane. Through its interaction with the urokinase receptor, urokinase participates in cell adhesion, migration, and cellular mitotic pathways. It appears that tissue degradation following plasminogen activation facilitates tissue invasion and contributes to establishment of tumor metastasis, making urokinase an attractive potential target for anticancer inhibitors. Urokinase is employed as a thrombolytic agent in the treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE). Both urokinase and recombinant tissue plasminogen activator (PLAT, tPA) are employed in treatment of myocardial infarction (MI), and recombinant PLAT is used in treatment of acute stroke (CVA, cerebrovascular accident).

Conversely, antifibrinolytics, such as aminocaproic acid (ε-aminocaproic acid) and the more potent tranexamic acid are employed as inhibitors of fibrinolysis. They act by blocking the lysine-binding site in the kringle domains on plasminogen, and are employed in treatment of menorrhagia, excessive post-operative bleeding, and bleeding dyscrasias.

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tags [Tissue] [fibrinolysis] [metastasis] [DVT] [PE] [MI] [CVA] [thrombolytic agent] [antifibrinolytics]

germinal centers

2007-12-18T19:06:00.000-08:00

Germinal centers are important in humoral immunity, and comprise collections of activated B lymphocytes within non-thymus lymphoid tissue. Germinal centers are histologically distinct, lighter-stained centers within lymph nodules and other lymphoid tissues. [] micrograph, micrograph 2, germinal center with 'tingible body macrophages', Nodule with Germinal Center 1, Nodule with Germinal Center 2, histology, HHH atlas, diffuse and mucosa associated lymphoid tissue with germinal centers[].

Upon antigenic activation, B cells migrate to follicules where they undergo monoclonal expansion in the vicinity of follicular dendritic cells (FDC). Within three days, activated B cells mutate their antibody-encoding DNA, generating diverse clones in the germinal centre (VDJ recombination).

Follicular dendritic cells, acting as APCs, stimulate the B cells to express surface antibodies (as centrocytes) in a state of potential apoptosis, competing for FDC survival signals in a process that is considered to be dependent on the affinity of surface immunoglobulin for presented antigen (affinity maturation).

Functional B-cells receive differentiation signals from helper T cells in a process that involves isotype switching (for example, from IgM to IgG). This interaction with T cells is believed to prevent the generation of autoreactive antibodies.

Activated B cells either continue to proliferate as centroblasts (recycling hypothesis) or differentiate either into specific-antibody-producing plasma cells or into memory B cells primed to be rapidly activated by subsequent contact with the cognate antigen []diagram[].

GC morphology is specific for different stages of the proliferation/differentiation. In early stages, a network of FDCs is packed with proliferating B cells. By day 4, GCs exhibit separation into dark and the light zones, containing proliferating cells and B cells undergoing selection. After day 10, the zones dissappear. After 3 weeks, GC development typically terminates.

'Tingible body macrophages' contain phagocytosed cellular debris.

Progressive transformation of germinal centers (PTGCs) are larger than regular germinal centers and comprise mainly mantle zone lymphocytes with remnants of large germinal center cells. Mantle zones are obscured, and interfollicular areas typically contain small lymphocytes with a few immunoblasts. PTGC are usually found in the lymph nodes of patients with reactive follicular hyperplasia, though association with nodular lymphocyte predominant Hodgkin lymphoma has been described.[images]

a-infiltrations

2007-12-16T16:35:00.000-08:00

A-Deistic
Adeistic
Black Out
cosmic
Eine Kleine Nattermusing
eMusings
eVolition
Galaria
Godborygmi
Godspell Follies
Gray Matters
MetaThoughts
Mimble Wimble
Naturalism
BLogodaedaly
palimpsest
Salient
Science of Evolution
Sechuam
Sintheist
Tabula Flexuosa
The Scarlet A
Weltschauung

kinin system

2007-12-14T15:10:00.000-08:00

The kinin system, or kinin-kallikrein system, or kininogen-kallikrein-kinin system plays a role in inflammation, coagulation, sodium homeostasis, sensations of pain, cardioprotective effects of preconditioning, and control of blood pressure. K-k-k mediators induce vasodilation, prostaglandin biosynthesis, tissue remodeling through regulation of proteases, and pathophysiologies. The kallikrein-kinin system is complex, with several bioactive peptides that are formed in many different compartments.

kinninogens
● high-molecular weight kininogen (HMWK)
● low-molecular weight kininogen (LMWK)
● T-kininogen (in rats)
vasoactive peptides
● bradykinin (BK),
● kallidin (KD)
● [des-Arg] kinins and B1 receptors
___ ● actions mediated through autacoids such as eicosanoids, NO, and endothelium-derived hyperpolarizing factor
___ ● hydrolyzed by a group of kininase peptidases (diagram)
kinin receptors (GPCR)
● B1 and B2
kininogenase enzymes
● pre-kallikrein
● kallikreins
● aminopeptidases
kininase enzymes
● kininase I
● angiotensin converting enzyme (ACE, or kininase II)
● carboxypeptidase N
● neutral endopeptidase

Kininogens:
● produced predominantly in liver (HMWK), also locally in other tissues (LMWK)
● produced by alternative splicing of a single gene product
● release kinins upon protease hydrolysis by kininogenases
● cofactors in coagulation pathway
● inhibit cysteine protease enzymes
● participate in inflammatory acute phase response

Tissue and plasma kallikreins are serine proteases that liberate vasoactive-peptide kinins (BK and KD) from the kininogens. Kallikreins are synthesized in vascular tissue and the liver. HMKW has no intrinsic catalytic activity, acts as a cofactor for coagulation and inflammation, and yields the nonapeptide bradykinin upon plasma kallikrein lysis. LMWK is produced locally in many tissues, and releases the decapeptide kallidin (KD) on lysis by tissue kallikrein. Bradykinin peptides can also be generated by aminopeptidase-mediated cleavage of kallidin peptides. Trypsin, plasmin, and some snake venoms release kinins. (diagram)

In immune and inflammatory responses, factor XIIa is activated by charged surfaces (bacterial lipopolysaccharide, oligosaccharides, connective tissue proteoglycans, or damaged basement membranes). In the presence of factor XIIa, pre-kallikrein (PK) is cleaved to plasma kallikrein which acts upon HMWK to release the vasoactive nonapeptide, bradykinin. Plasma kallikrein also converts inactive factor XII to active XIIa, participating in a positive feedback loop. The cleavage of bradykinin from HMWK is highly localized since pre-kallikrein and substrate (HMWK) circulate as a complex.

Bradykinin (BK) is has the sequence Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, and various kininases attack different amino acid positions.(diagram) The decapeptide kallidin has the sequence Lys-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg, which is equivalent to bradykinin with an extra amino acid (lysine) in the number one position.

Kallidin, or Lys-bradykinin, is released by the action of tissue kallikrein on LMWK. Tissue kallikrein is found in many tissues, either as the active enzyme or as a precursor requiring activation. Unlike plasma kallikrein, which acts upon HMWK as preferred substrate, tissue kallikrein can release kallidin from either HMWK or LMWK. Kallidin can subsequently be converted directly into bradykinin through the action of aminopeptidases present in both the plasma and on the surface of epithelial cells.

Kinins act via type 1 (B1) or type 2 (B2) kinin receptors. (diagram). The B2 receptor normally predominates, whereas B1 receptors are induced by tissue injury (myocardial ischaemia, inflammation). Bradykinin acts on the B receptors: B2 >> B1.

Almost all cells express GPCR-type kinin receptors, which mediate the activities of both bradykinin and kallidin. Receptor stimulation causes:
● increased vascular permeability
● relaxation of venular smooth muscle
● hypotension
● contraction of intestinal smooth muscle
● contraction of smooth muscle in airways (increasing airway resistance)
● stimulation of sensory neurons (pain)
● alteration of ion secretion by epithelial cells
● production of nitric oxide
● release of cytokines by leukocytes
● release of eicosanoids from various cell types.

Because they elicit such a broad spectrum of activity, kinins have been implicated in many pathophysiologies including pain, sepsis, asthma, symptoms associated with rhinoviral infection, rheumatoid arthritis, and a wide variety of other inflammatory diseases.

Both bradykinin and kallidin can be degraded by a variety of plasma and cell surface enzymes (kininases), the commonest of which are kininase I, kininase II (angiotensin converting enzyme, ACE), and carboxypeptidase N. In the plasma, kininase I forms [des-Arg] kinins by cleaving the C-terminal arginine from both bradykinin and kallidin. The [des- Arg] kinins act as agonists of B1 receptors (in some species) and have been implicated in the pathophysiology of chronic inflammation.

Towards understanding the kallikrein-kinin system: insights from measurement of kinin peptides. Campbell DJ. Braz J Med Biol Res. 2000 Jun;33(6):665-77. [Free Full Text Article]

tags [Tissue] [kinin-kallikrein] [pain] [vasodilators]

lymphoid system

2007-12-13T01:11:00.000-08:00

Components of the lymphoid system are:
● immune cells – B cell lymphocytes and plasma cells, dendritic cells, granulocytes, macrophages, monocytes of mononuclear phagocyte system (MPS), T cell lymphocytes
● lymph ducts and vessels and lymph nodes (right)
[] histopathology []
● lymphoid organs including reticuloendothelial system – bone marrow, (lymph nodes), mucosa-associated lymphoid tissue, Peyer's patches, spleen, thymus, tonsils, vermiform appendix

The reticuloendothelial system or mononuclear phagocytic system comprises a range of cells that are capable of phagocytosis, including macrophages and monocytes. Phagocytosis is an innate rather than an adaptive immune process. The phagocytic cells either circulate in the blood or are attached to various connective tissues such as pulmonary alveoli, liver sinusoids, skin, spleen, and joints.

The RES functions to provide phagocytic cells for both the inflammatory response and immune responses (primary RES) and to remove pathogens and senescent cells from circulation (secondary RES)

The reticuloendothelial system (RES) includes:
● primary (central) lymphoid production organs – bone marrow, thymus
● secondary (peripheral) lymphoid function organs – circulating monocytes, histiocytes located in many tissues, Kupffer cells of the liver, "Littoral cells" of the spleen, mucosa-associated lymphoid tissue (MALT), which is subdivided into bronchus-associated lymphoid tissue (BALT) and gut-associated lymphoid tissue (GALT), Peyer's patches.

o-o index of tissue micrographs [] germinal centers [] fluorescence microscopy dendritic cell uptake of dying cells within spleen [] micrograph red pulp of spleen [] micrograph splenic red pulp [] micrograph spleen cells (mouse) DAPK2 stained [] micrograph white pulp, splenic nodule [] micrograph white pulp infiltrate with Langhans giant cell [] histopathology spleen Gaucher's disease [] micrograph gallery cell surface antigens [] Virtual Histology Main []

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tags [Tissue] [lymphoid] [reticuloendothelial] [lymph nodes] [thymus]

thymus

2007-12-05T16:01:00.000-08:00

The thymus is a lobulated lymphoid organ that is important in the development of T lymphocytes.

Each thymic lobule comprises a darker staining outer cortex and a lighter staining inner medulla. The cortex is composed of dense lymphoid tissue that lacks nodules. The medulla stains more lightly than the cortex because the medullary stroma is less heavily infiltrated with lymphocytes than is the cortex.

The thymic medulla contains Hassall's corpuscles, which are flattened, concentrically arranged keratinizing epithelial cells thatare strongly acidophilic (staining pink with H & E). Degenerate cells are found at the center of the Hassall's bodies. Thymic stromal cells are not reticular cells, and they differ from those of other lymphatic tissue in being epithelial (endodermal) in origin. They are large, pale cells (epithelial-reticular cells) within the medulla. They do not make reticular fibers and are attached to each other through desmosomes.

ectoderm

2007-11-20T21:04:00.000-08:00

Outer embryological layer.

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mesoderm

2007-11-20T11:11:00.000-08:00

Middle embryological layer.

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endoderm

2007-11-20T10:41:00.000-08:00

Inner embryological layer.

Alphabetic links to Glossary items:◦ A ◦ B ◦ C ◦ D ◦ E ◦ F ◦ G ◦ H ◦ I ◦ J ◦ K ◦ L ◦ M ◦ N ◦ O ◦ P ◦ Q ◦ R ◦ S ◦ T ◦ U ◦ V ◦ W ◦ X ◦ Y ◦ Z ◦ o-o animation index o-o diagram index o-o image index o-o micrograph index o-o table index o-o sem/tem index o-o video index .

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hematopoiesis

2007-10-17T19:11:00.000-07:00

Hematopoiesis is the production of blood cells, a developmental process located in the (red) bone marrow, though some cells mature elsewhere. For example, T lymphocytes are so named because they mature in the thymus, and antigenic stimulation of B lymphocytes to become plasma cells typically takes place in the periphery.

The process of haematopoiesis occurs in several stages, and is controlled by at least 11 growth factors. The first stage involves the differentiation of a pluripotential stem cell into a committed progenitor, which is followed by maturation of committed progenitors in distinct pathways.

[] labelled photomicrograph of bone marrow, diagram of adult stem cell plasticity, diagram of stem cell versus progenitor cell []

Stem cell stage:

pluripotential hematopoietic stem cell

↓ --------------------↓

common myeloid progenitor----or----common lymphoid progenitor

The common myeloid progenitor can generate:

● proerythroblasts (pronormoblasts) → erythropoiesis

● myeloblasts → granulopoiesis

● monoblasts → monocytopoiesis

● megakaryoblasts → thrombopoiesis

The common lympoid progenitor can generate:

● lymphoblasts → lymphopoiesis

Committed progenitor stage to mature cell : granulopoiesis

common myeloid progenitor

↓

myeloblast

↓

B/E/N promyelocyte

↓---↓---↓

B/E/N myelocyte

↓---↓---↓

B/E/N metamyelocyte

↓---↓---↓

B/E/N band

↓---↓---↓

basophil, eosinophil, neutrophil

↓ -----------------------

mast cell -----------------------

Committed progenitor stage to mature cell : lymphopoiesis

common lymphoid progenitor

↓

lymphoblast

----------------------------------------↓ rearrangements H: D-J → H: V-DJ

prolymphocyte

-----------------↓ rearrangements L: V-J --------------------------↓

small lymphocyte------or----- natural killer cell (large granular lymphocyte)

------------↓ IgM→IgD ---------↓------------------------------------ ↓

------B lymphocyte--or-- T lymphocyte

------------↓----------------------------------------------------------- ↓

--------plasma cell------------------------------------------lymphoid dendritic cell

Development of mature B lymphocytes from multipotent progenitors requires the coordinated activities of a number of transcriptional regulatory proteins, including EBF, Pax-5, and E2A.

E2A proteins function in early B lineage development to regulate B lineage-specific gene expression as well as B cell survival. E2A-encoded proteins are involved in the differentiation of a number of cell types, and they are especially important in lymphocyte development.

The E2A gene encodes E47 and E12, which are basic-helix-loop-helix (bHLH) transcription factors that bind DNA either as homodimers or as heterodimers with other bHLH proteins. Such bHLH DNA binding activity in the B-lineage comprises E47 homodimers. Development of thymocytes mainly involves heterodimers of E47 and a related bHLH protein, HEB. Thymocytic E2A protein expression is required to initiate T-cell differentiation. During the development of thymoctyes, E-proteins and their antagonists, Id2 and Id3, regulate T-lineage specific gene expression and TCR rearrangement. E2A and Id proteins block thymocytic maturation in the absence of pre-TCR expression, and pre-TCR signaling acts to promote development in part by inhibiting E2A activity. [l]

Committed progenitor stage to mature cell : monocytopoiesis

common myeloid progenitor

↓

monoblast

↓

promonocyte

↓

monocyte

↓ ----↓

macrophage or myeloid dendritic cell

Committed progenitor stage to mature cell : erythropoiesis

common myeloid progenitor