Histo Lab Connective

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Connective tissues

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bind structures together, form a framework andsupport for organs and the body as a whole, store fat, transportsubstances, protect against disease, and help repair tissuedamage.

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Connective tissues

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resists stress in your bones. It provides or helpsin immunity. It organizes tissues and metabolic processes.

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Connective tissues

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provides a matrix that supports and physicallyconnects other tissues and cells together to form the organs of thebody

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Interstitial fluid of connective tissue

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gives metabolic support to cells as the medium fordiffusion of nutrients and waste products.

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embryonic mesenchyme

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All connective tissues originate from ______, atissue developing mainly from the middle layer of the embryo, themesoderm.

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mesenchyme

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consists largely of viscous groundsubstance with few collagen fibers

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Mesenchymal cells

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are undifferentiated and have largenuclei with prominent nucleoli and fine chromatin.

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Mesenchymal cells

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They are often said to bespindle shaped with their scanty cytoplasm, andare extended as two or more thin cytoplasmicprocesses

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Mesenchymal cells

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migrate from their site oforigin in the embryo, surrounding andpenetrating developing organs

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stem cells

blood, the vascularendothelium, and the muscle.

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In addition to producing all types of connective tissueproper and the specialized connective tissue like boneand cartilage, the embryonic mesenchyme includes

____ for other tissues such as ____

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protein fibers and ground substance

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extracellular matrix of the connective tissue includes

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Ground substance

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a complex of anionic, hydrophilicproteoglycans, glycosaminoglycans (GAGs), and multiadhesive glycoproteins (laminin, fibronectin, and others)

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Ground substance

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This is a watery, rubbery, unstructured materialthat fills in the spaces between cells andprotects cells from their surroundings.

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Ground substance

gags or theglycosaminoglycans.

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It is flexible, made of starch and proteinmolecules mixed with water and proteoglycansfrom each sprouts lots and lots of long, starchystrands called the ___

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ECM

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The major constituent of connective tissue is your __

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EXTRACELLULAR MATRIX

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It consists of different combinations of protein fibers suchas collagen and elastic fibers and ground substance.

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therapeutic repair and organ regeneration

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Mesenchyme-like cells remain present in some adult connectivetissues are being investigated as possible sources of stem cells for

___

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multipotent

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some cells in mesenchyme are ___ (they havethe potential to differentiate to different cells)

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Tooth pulp and adipose tissue

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Mesenchymal-like cells remain present in some adultconnective tissues.○ Examples:

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Fibroblasts

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are the key cells in connective tissue proper

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Fibroblasts(fibrocytes)

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Extracellular fibers and ground substance

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Plasma Cells

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Antibodies

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Eosinophilicleukocytes

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Modulate allergic/vasoactive reactions anddefense against parasites

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Lymphocytes

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Various immune/defense functions

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Neutrophilicleukocytes

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Phagocytosis of bacteria

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Macrophages

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Phagocytosis of ECM components anddebris; antigen processing and presentationto immune cells; secretion of growth factors,cytokines, and other agents

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Mast Cells andBasophilicLeukocytes

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Pharmacologically active molecules (eg,histamine)

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Adipocytes

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Storage of neutral fats

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Fibroblast

Plasma Cells

Lymphocytes

Eosinophilic Leukocytes

Neutrophilic Leukocytes

Macrophage

Mast Cells and Basophilic Leukocytes

Adipocytes

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CELLS OF CONNECTIVE TISSUES

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FIBROBLASTS

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the most common cells in connective tissue proper

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FIBROBLASTS

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produce and maintain most of the tissue’s extracellularcomponents

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FIBROBLASTS

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synthesize and secrete collagen (the most abundantprotein of the body) and elastin

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active

quiescent

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Fibroblast: The __ cellFibrocyte: The __ cell

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fibroblasts

spindle

eosinophilic

collagen

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The __ typically have a large active nucleieosinophilic cytoplasm that tapers off in both directions along theaxis of the nucleus; it is usually referred to as __ shape● The nuclei are clearly seen, but the __cytoplasmic processes resemble the ___ bundlesthat fill the ECM and are two difficult to distinguish in anystaining

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Active

Inactive

fibrocytes

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fibroblasts were the both active and quiescent fibroblastsmay sometimes be distinguished as of this section of the dermis.● ___ fibroblasts have a large euchromatic nuclei andbasophilic cytoplasm● ____ fibroblasts or the ___ are smaller withheterochromatic nuclei

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cell cyclingand mitotic activity

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Growth Factors: influences growth and differentiation● Adults: Fibroblasts rarely undergo division● If in need of more Fibroblasts, GF stimulates ____

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Myofibroblasts:

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Fibroblasts involved in wound healing○

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Myofibroblasts:

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They have a well-developed contractilefunction and are○ Smooth muscle + fibroblast

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irregular scar

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Spaces left after injuries, especially in tissues whose cells dividepoorly or not at all (eg, cardiac muscle), are filled by connectivetissue, forming dense ____ tissue

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wound contraction

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Myofibroblast activity is important for the phase of tissue repaircalled

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ADIPOCYTES

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“fat cells”● found in the connective tissue of many organs.●

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ADIPOCYTES

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specialized for cytoplasmic storage of lipid as neutral fats● production of heat

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Adipose Connective Tissue

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● serves to cushion and insulate the skin and other organs.

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MACROPHAGES; MONONUCLEAR PHAGOCYTESYSTEM

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Phagocytosis● especially abundant at sites of inflammation

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MACROPHAGES; MONONUCLEAR PHAGOCYTESYSTEM

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secrete growth factors important for tissue repair

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MACROPHAGES; MONONUCLEAR PHAGOCYTESYSTEM

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function in the uptake, processing, and presentation ofantigens for lymphocyte activation

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MACROPHAGES; MONONUCLEAR PHAGOCYTESYSTEM

pinocytotic and phagocytic

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Irregular surface with pleats, protrusions, andindentations, features related to their active _____activities.● They generally have well-developed Golgi complexesand many lysosomes

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Histiocytes

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● macrophage in the connective tissues

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Monocytes

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precursor cells of macrophages

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Monocytes

early embryonic

mononuclear phagocyte system

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formed in the yolk sac during ____development circulate and become resident indeveloping organs throughout the body, comprising agroup of related cells called the ___

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Monocyte

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Blood

Precursor of themacrophages

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Macrophage

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Connective tissue,lymphoid organs,lungs, bonemarrow, pleural andperitoneal cavities

Production of cytokines,chemotactiv factors andseveral molecules thatparticipate ininflammation (defense),antigen processing, andpresentation

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Kupffer cell

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Liver (perisinusoidal)

Same as macrophages

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Microglial cell

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Central nervoussystemSame as macrophages

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Langerhans cells

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Epidermis of skin

Antigen processing andpresentation

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Dendritic cell

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Lymph nodes,spleen

Antigen processing andpresentation

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Osteoclast (fromfusion of severalmacrophages

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Bone

Localized digestion ofbone matrix

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Multinucleargiant cell(Several fusedmacrophages)

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In connective tissueunder variouspathologicalconditions

Segregation anddigestion of foreignbodies

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Monocytes

Macrophage

Kupffer cells

Microglial cells

Langerhans cells

Dendritic cells

Osteoclasts

Multinuclear giant cell

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cells of themononuclear phagocyte system

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multinuclear giant cells

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When adequately stimulated, macrophages may increase in sizeand fuse to form ___, usually found only inpathologic conditions.

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MAST CELLS

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oval or irregularly shaped cells of connective tissue,between 7 and 20 μm in diameter, filled with basophilicsecretory granules that often obscure the central nucleus●

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MAST CELLS

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localized release of many bioactive substancesimportant in the local inflammatory response, innateimmunity, and tissue repair

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MAST CELLS

Perivascular mast cell

Mucosal mast cell

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Numerous in the ff locations:○ near small blood vessels in skin and mesenteries(__)○ tissue that lines digestive and respiratory tracts(___)

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Mast Cells

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Granules are poorly preserved by fixatives● Displays metachromasia● Difficult to identify in routinely prepared slides

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Immediate Hypersensitivity Reactions

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Allergic reaction caused by the release of certainchemical mediators stored in mast cells

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Immediate Hypersensitivity Reactions

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Occur within a few minutes after the appearance of anantigen in an individual previously sensitized to thatantigen

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Heparin

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a sulfated GAG that acts locally as an anticoagulant

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Histamine

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promotes increased vascular permeability and smoothmuscle contraction

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Serine Proteases

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activate various mediators of inflammation

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Chemotactic Factors

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attracts Eosinophil and Neutrophil leukocytes

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Cytokines

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polypeptides directing activities of leukocytes and othercells of the immune system

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Phospholipid precursor

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converted to prostaglandins, leukotrienes, and otherimportant lipid mediators of the inflammatory response

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Heparin

Histamine

Serine Proteases

Chemotactic Factors

Cytokines

Phospholipid precursor

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Molecules released from mast cells’ secretorygranules

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antigens and allergens

300,000

cross-linked

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mast cell secretion of those granules is triggered by re-exposure tocertain ___● molecules of the immunoglobulin E antibody or the IgEantibody produced in an initial response to an allergen,such as a pollen or a bee venom, are bound to surfacereceptors for IgE of which ___ are present per mastcell● Second exposure: the IgE molecules bind this antigenand the few IgE receptors very rapidly become

___.

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PLASMA CELLS

10-20

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lymphocyte-derived, antibody-producing cells

average life span is only __ days

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LEUKOCYTES

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From circulating blood cells, they leave blood bymigrating between the endothelial cells of venules toenter connective tissue● Most leukocytes function in connective tissue only for afew hours or days and then undergo apoptosis

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Neutrophils, lymphocytes, monocytes, eosinophils and basophils

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LEUKOCYTES example

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Inflammation

chemical mediators

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begins with the local release of ____● These substances act on local blood vessels, mast cells,macrophages, and other cells to induce eventscharacteristic of inflammation

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Pain

chemical mediators

sensory

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___ is due mainly to the action of the ___ onlocal ___ nerve endings. All these activities help protect andrepair the inflamed tissue

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1) Collagen2) Reticular3) Elastic

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FIBERS

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FIBERS

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fibrous components of connective tissue are elongatedstructures formed from proteins that polymerize aftersecretion from fibroblasts

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Collagen ● Reticular ● Elastic fibers

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Three Main Types of Fibers

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COLLAGEN

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most abundant protein in the human body – almost 30%of the dry weight.●●

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COLLAGEN

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It is the key element of all connective tissues, as well asthe different epithelial basement membranes and theexternal laminae of your muscle and nerve fibers.

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COLLAGEN

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form various extracellular fibers, sheets, and networks, allof which extremely strong and resistant to normalshearing and tearing forces

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I,II, III

IV

VII

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Fibrillar collagens: ● Network or sheet-forming collagens: ● Linking/anchoring collagens:

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Collagen type I

collagen fibers

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, the most abundant and widely distributedcollagen, forms large, eosinophilic bundles usually called __

.

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Collagen type I

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Fibrils assemble to form large, extremely strong collagenfibers that may be further bundled by linking collagensand proteoglycans

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Collagen Type 2

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(present in cartilage) Occurs as fibrils but does not formfibers or bundles.● Sheet-forming coll

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Collagen Type 2

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Sheet-forming collagen type IV subunits assemble as alatticelike network in epithelial basal laminae.

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Collagen

slow

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turnover and renewal in normal connective tissue isgenerally a very __but ongoing process.

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stable

high

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In some organs, such as tendons and ligaments, thecollagen is very ____, whereas in others, as in theperiodontal ligament surrounding teeth, the collagenturnover rate is __.

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Ehlers-Danlos typeIV

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Faulty transcriptionor translation ofcollagen type III

Aortic and/orintestinal rupture

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Ehlers-Danlos typeVI

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Faulty lysinehydroxylation

Increased skinelasticity, rupture ofeyeball

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Ehlers-Danlos typeVII

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Decreaseprocollagenpeptidase activity

Increase articularmobility, frequentluxation

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Scurvy

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Lack of vitamin C,a requiredcofactor for prolylhydroxylase

Ulceration of gums,hemorrhages

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Osteogenesisimperfecta

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Change of 1nucleotide ingenes for collagentype I

Spontaneousfractures, cardiacinsufficiency

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keloid

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A _ is a local swelling caused by abnormally large amountsof collagen that form in scars of the skin.

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RETICULAR FIBERS

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Found in delicate connective tissue of many organs,notably in the immune system● consist mainly of collagen type III, which forms anextensive network (reticulum) of thin fibers for the supportof many different cells

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RETICULAR FIBERS

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Periodic acid-Schiff (PAS) positive

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RETICULAR FIBERS

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contain up to 10% carbohydrate as opposed to 1% inmost other collagen fibers.

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RETICULAR FIBERS

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occur in the reticular lamina of basement membranesand typically also surround adipocytes, smooth muscleand nerve fibers, and small blood vessels

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Argyrophilic

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Came from the Greek word Argyros (silver)

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black

impregnation

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Reticular fibers are seldom visible in hematoxylin andeosin (H&E) preparations but are characteristicallystained __ after __ with silver salts

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ELASTIC FIBERS

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thinner than the type I collagen fibers and form sparsenetworks interspersed with collagen bundles in manyorgans, particularly those subject to regular stretching orbending

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darker

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Fibers may be difficult to discern in H&E stain tissue but elastin has adistinct __ staining appearance with other stainingprocedures.

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Elastic Lamellae

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Fenestrated sheets of elastin found in the wall of largeblood vessels, especially arteries.

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Fibrillin

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Glycoprotein essential for the formation of elastic fibers● Secreted by fibroblasts

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Microfibrils

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act as scaffolding upon which elastin is then deposited

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Elastin

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accumulates around the microfibrils, eventually makingup most of the elastic fiber, and is responsible for therubberlike property

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Desmosine

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● Amino acid found uniquely in elastin

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Elastase

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Pancreatic enzyme capable of elastin hydrolysis

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Marfan syndrome

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Mutations in the fibrillin genes result in ____, adisease characterized by a lack of resistance in tissues rich inelastic fibers.

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interstitial fluid

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Water in the ground substance of connective tissue isreferred to as ___ and has an ion compositionsimilar to that of blood plasma.

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Ground substance

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filling the space between cells and fibers in connectivetissue.

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one third

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It is estimated that __ of the body’s plasmaproteins are normally found in the interstitial fluid ofconnective tissue

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Ground Substance

Glycosaminoglycans (GAGs)○ Proteoglycans○ Multi-adhesive Glycoproteins

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a highly hydrated (with much bound water), transparent,complex mixture of three major kinds of macromolecules:

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Ground Substance

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allows diffusion of small molecules and, because it isviscous, acts as both a lubricant and a barrier to thepenetration of invaders

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GLYCOSAMINOGLYCANS (GAGs)

hexosamine

uronic

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(also called mucopolysaccharides) are long polymers ofrepeating disaccharide units, usually a ___ and

___ acid

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glucosamine

galactosamine

glucuronate

iduronate

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GLYCOSAMINOGLYCANS (GAGs)

The hexosamine can be ___ or ____,and the uronic acid can be ___ or ___

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Hyaluronan

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Hyaluronate or hyaluronic acid● Largest and most ubiquitous GAG

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Hyaluronan

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Forms a viscous, pericellular network that binds aconsiderable amount of water, giving it an important rolein allowing molecular diffusion through connective tissueand in lubricating various organs and joints.

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Dermatan Sulfate● Chondroitin Sulfates● Keratan Sulfate● Heparan Sulfate

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FOUR MAJOR GAGs

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PROTEOGLYCANS

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consist of a core protein to which are covalentlyattached various numbers and combinations of thesulfated GAGs

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PROTEOGLYCANS

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Synthesized on the RER● distinguished by their diversity, which is generated in partby enzymatic differences in the Golgi complexes

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Perlecan

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key proteoglycan in all basal laminae

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Aggrecan

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One of the best-studied proteoglycans● very large, having a core protein heavily bound withchondroitin and keratan sulfate chains

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Hurler, Hunter,Sanfilippo, and Morquio

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The lack of specific hydrolases in the lysosomes has been foundto be the cause of several disorders, including the __ syndromes

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MULTIADHESIVE GLYCOPROTEINS

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all have multiple binding sites for cell surface integrinsand for other matrix macromolecules●

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MULTIADHESIVE GLYCOPROTEINS

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large molecules with branched oligosaccharide chainsand allow adhesion of cells to their substrate

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Laminin

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with binding sites for integrins, type IV collagen, andspecific proteoglycans, providing adhesion for epithelialand other cells

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Fibronectin

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synthesized largely by fibroblasts● provides specific binding sites for integrins and isimportant both for cell adhesion and cellular migrationthrough the ECM

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Edema

blood

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__ is the excessive accumulation of interstitial fluid inconnective tissue. This water comes from the __ , passingthrough the capillary walls that become more permeable duringinflammation and normally produces at least slight swelling

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Hydrostatic Pressure

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caused by the pumping action of the heart, which forceswater out across the capillary wall

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Osmotic Pressure

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produced by plasma proteins such as albumin, whichdraws water back into the capillaries

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greater

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Hydrostatic pressure is ____ than the colloid (?) osmoticpressure.