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ANAT2241 Histology: Basic & Systematic Integumentary System Dr. Reza Shirazi Department of Anatomy, School of Medical Sciences Faculty of Medicine & Health, UNSW Sydney [email protected] Image by Dr John Abramyan, University of Michigan Resources Recommended reading: Textbook chapter...

ANAT2241 Histology: Basic & Systematic Integumentary System Dr. Reza Shirazi Department of Anatomy, School of Medical Sciences Faculty of Medicine & Health, UNSW Sydney [email protected] Image by Dr John Abramyan, University of Michigan Resources Recommended reading: Textbook chapter (Wheather's online): Skin Textbook chapter (Junqueira’s Basic Histology: Text and Atlas, 16e online): Skin University of Michigan Histology and Virtual Microscopy Learning Resources Chapman Histology https://www.youtube.com/channel/UCvSvCkHjCbHn8aGd6OPno_A/featured Learning Objectives 1. To understand the structure and function of integumentary system 2. To know the microscopic structure of the epidermis, dermis and hypodermis 3. To know the histological differences between hairy (thin) and glabrous (thick) skin 4. To know the formation and histology of skin appendages: eccrine and apocrine sweat glands, sebaceous glands, hairs and nails 5. To know the histological features of Pacinian and Meissner corpuscles. Skin (Integument or Cutaneous Layer) The largest single organ of the body Composed of: 1- Epidermis: an epithelial layer 2- Dermis: a layer of connective tissue (Hypodermis or subcutaneous tissue: a loose connective tissue layer usually containing pads of adipocytes; Corresponds to the superficial fascia of gross anatomy) Appendages of skin (Integumentary System): • Hairs • Nails • Sebaceous glands • Sweat glands Specific Functions of the Skin 1- Protective: 2- Sensory 3- Thermoregulatory 4- Metabolic 5- Sexual signaling (X45; thin skin. Dermatoglyphs: Fingerprints and Footprints The dermal-epidermal interdigitations are of the pegand-socket variety in most skin Well-formed ridges and grooves in the thick skin of the palms and soles, which is more subject to friction Forming distinctive patterns unique for each individual, appearing as combinations of loops, arches, and whorls Epidermis A stratified squamous keratinized epithelium composed of cells called keratinocytes Other much less abundant cell types in epidermis (non-keratinocyte cells): 1- Melanocytes: pigment-producing cells 2- Langerhans cells: antigen-presenting cells 3- Merkel cells: tactile epithelial cells Major distinction between thick skin (found on the palms and soles) and thin skin (found elsewhere on the body): • Thickness of the epidermal layer in thin skin: 75 to 150 μm • Thickness of the epidermal layer in thick skin: 400 to 1400 μm (1.4 mm) Thickness of full skin on the scalp: about 1.5 mm Thickness of full skin on the back: about 4 mm a: (X100; H&E; Skin) Epidermis (X45; thin skin. (X65; Thick skin. Layers of Epidermis The epidermis consists of four layers of keratinocytes (or five layers in thick skin): 1- Basal layer (stratum basale) 2- Spinous layer (stratum spinosum) 3- Granular layer (stratum granulosum) 4- Stratum lucidum (found only in thick skin) 5- Stratum corneum (X240; H&E; Layers of epidermis in thin skin. • EP: epidermal ridges or pegs • DP: dermal papillae • D: dermis • B: stratum basale • S: stratum spinosum • G: stratum granulosum • C: stratum corneum Basal Layer (Stratum Basale) A single layer of basophilic cuboidal or columnar cells on the basement membrane Characterized by intense mitotic activity Contains, along with the deepest part of the next layer, progenitor cells for all the epidermal layers An important feature of all keratinocytes in the stratum basale: the cytoskeletal keratins (intermediate filaments) Stratum germinativum: 1- Stratum basal 2- Some cells of stratum spinosum just above the stratum basale Basal Layer (Stratum Basale) Spinous Layer (Stratum Spinosum) Normally the thickest layer, especially in the epidermal ridges Containing tonofibrils composed of keratin filaments Appearance of many short “spines” or prickles at the cell surface (X400; PT; Stratum spinosum of thick skin. • Arrow: cytoplasmic projections (X8,400; TEM of a single spinous keratinocyte. • Arrows: surface projections (X40,000; Detail of the desmosomes joining two cells showing intermediate filaments associated with desmosomes Granular Layer (Stratum Granulosum) Consists of three to five layers of flattened cells: • Undergoing the terminal differentiation process of keratinization • Cytoplasm filled with intensely basophilic masses called keratohyaline granules Keratohyaline granules: • Dense masses of filaggrin and other proteins associated with the keratins of tonofibrils • Linking them further into large cytoplasmic structures (X560; H&E; Stratum granulosum and stratum lucidum in thick skin. • S: stratum spinosum • G: stratum granulosum • L: stratum lucidum • C: stratum corneum Granular Layer (Stratum Granulosum) Characteristic features in cells of the granular layer: -Golgi-derived lamellar granules containing various lipids and glycolipids • Undergo exocytosis • Producing a lipid-rich, impermeable layer around the cells (a major part of the skin’s barrier against water loss) (X560; H&E; Stratum granulosum and stratum lucidum in thick skin. • S: stratum spinosum • G: stratum granulosum • L: stratum lucidum • C: stratum corneum Stratum Lucidum Present only in thick skin A thin, translucent layer of flattened eosinophilic keratinocytes held together by desmosomes Features of the keratinocytes in stratum lucidum: • Flattened eosinophilic cells • No nuclei and organelles • Cytoplasm consists almost exclusively of packed keratin filaments embedded in an electron-dense matrix (X560; H&E; Stratum granulosum and stratum lucidum in thick skin. • S: stratum spinosum • G: stratum granulosum • L: stratum lucidum • C: stratum corneum Stratum Corneum 15-20 layers of squamous, keratinized cells filled with filamentous keratins Keratin filaments: • Synthesized during cell differentiation in the immature layers • As they form, keratin tonofibrils become heavily massed with filaggrin and other proteins in keratohyaline granules (X560; H&E; Stratum granulosum and stratum lucidum in thick skin. • S: stratum spinosum • G: stratum granulosum • L: stratum lucidum • C: stratum corneum Stratum Corneum Epidermis Color of the Skin The color of the skin is the result of: 1- Keratinocytes’ content of melanin 2- Carotene 3- Number of blood vessels in the dermis Melanocytes • A specialized cell found among the cells of the basal layer and in hair follicles • One melanocyte accumulates for every five or six basal keratinocytes • Attached by hemidesmosomes to the basal lamina • Lacking attachments to the neighboring keratinocytes • Several long irregular cytoplasmic extensions from each melanocyte cell body penetrate the epidermis, running between the cells of the basal and spinous layers and terminating in invaginations of 5-10 keratinocytes (X400; H&E; Melanocytes. • M: melanocytes • D: dermis (X400; H&E; Ultrastructure of a melanocyte. • BL: basal lamina • G: Golgi complexes • MG: melanin granules • CE: cytoplasmic extension • K: keratinocyte Melanin Synthesis Melanin Granules in Keratinocytes The neighboring keratinocytes phagocytose the tips of these dendrites Then keratinocytes take in the melanosomes Keratinocytes transport them toward their nuclei Melanosomes accumulate within keratinocytes as a supranuclear cap that prior to keratinization: • Absorbs and scatters sunlight, protecting DNA of the living cells from the ionizing, mutagenic effects of UV radiation Darkening of the skin (tanning) Darkening of the skin, or tanning, after exposure to solar radiation 1- A physicochemical reaction darkens pre-existing melanin 2- At the same time, acceleration of the melanin synthesis Langerhans Cells Antigen presenting cells (APCs) Derived from monocytes Represent 2%-8% of the cells in epidermis Typically located more superficially than melanocytes, in the stratum spinosum Usually most clearly seen in the spinous layer Cytoplasmic processes extend from these dendritic cells between keratinocytes of all the layers, forming a fairly dense network in the epidermis Microorganisms cannot penetrate the epidermis without alerting these dendritic cells and triggering an immune response (X40; Immunostaining of the skin; antibodies against langerin/CD207 and keratin. • Yellow: Langerhans cells • Green: keratin of the epidermis and follicles • F: hair follicles • E: epidermis (X200; Immunostaining of face-on view of an epidermal sheet; antibodies against langerin/CD207. • Network of the Langerhans cells Langerhans Cells (X300; Langerhans Cells. Merkel Cells (Epithelial Tactile Cells) Low-threshold mechanoreceptors (modified keratinocytes) essential for sensing gentle touch Abundant in highly sensitive skin like that of fingertips and at the bases of some hair follicles Difficult to distinguish from melanocytes by routine microscopy Have synaptic contacts with the expanded terminal discs of unmyelinated afferent fibers penetrating the basal lamina Dermis A layer of connective tissue that supports the epidermis and binds it to the subcutaneous tissue (hypodermis) The thickness of the dermis varies with the region of the body and reaches its maximum of 4 mm on the back Interdigitation of dermal papillae (irregular surface of the dermis) with epidermal pegs or ridges (projections of the epidermis) A basement membrane always occurs between the stratum basale and the dermis and follows the contour of the interdigitations between these layers Sublayers of the Dermis Sublayers of the Dermis 1- Papillary layer • A thin layer beneath epidermis • Includes the dermal papillae • Consists of loose connective tissue, 2- Reticular layer • Much thicker • Consists of dense irregular connective • Presence a network of elastic fibers, providing elasticity to the skin (X100; Weigert elastic stain; Elastic fibers of dermis. • Darkly stained fibers: elastic fibers • Eosinophilic bundles: collagen bundles A rich network of blood and lymphatic vessels in Dermis 1- Subpapillary (superficial) plexus: • Between the papillary and reticular dermal layers • Sends capillary branches extend into the dermal papillae 2- Deep plexus: • Lies near the interface of the dermis and the subcutaneous layer • Containing larger blood and lymphatic vessels Functions of the dermal vasculature: 1- Nutritive function 2- Thermoregulatory function A rich network of blood and lymphatic vessels in Dermis Innervation of the Dermis The dermis is also richly innervated Sensory afferent nerve fibers: • Forming a network in the papillary dermis and around hair follicles • Ending at epithelial and dermal receptors Autonomic effector nerves (postganglionic fibers of sympathetic ganglia) innervating: • Dermal sweat glands • Smooth muscle fibers No parasympathetic innervation is present in skin Hypodermis: Subcutaneous Layer or Superficial Fascia Consists of loose connective tissue containing numerous adipocytes With extensive vascular supply: • Promotes rapid uptake of insulin or drugs injected into this tissue Sensory Receptors Skin functions as an extensive receiver for various stimuli from the environment Diverse sensory receptors are present in skin: • Simple nerve endings with no Schwann cell or collagenous coverings (unencapsulated receptors) • More complex structures with sensory fibers enclosed by glia and delicate connective tissue capsules (encapsulated receptors) Sensory Receptors Unencapsulated Receptors 1- Tactile cells (or Merkel cells) • Associated with a disc or expanded axonal ending • Function: § Tonic receptors for sustained light touch § Sensing an object’s texture 2- Free nerve endings • In the papillary dermis • Extending into lower epidermal layers • Associated with Merkel cells • Function: § Respond primarily to high and low temperatures (thermoreception), pain (nociception), and itching (pruritus) § Important tactile receptors 3- Root hair plexuses: • A web of sensory fibers surrounding the bases of hair follicles in the reticular dermis • Function: § Detects movements of the hairs Encapsulated Receptors Phasic mechanoreceptors responding rapidly to stimuli on the skin Four are recognized in human skin, although only the first two are seen in routine preparations: 1- Meissner corpuscles 2- Lamellated (pacinian) corpuscles 3- Krause end bulbs • Have extremely thin, collagenous capsules penetrated by a sensory fiber • Found primarily in the skin of the penis and clitoris where they sense low-frequency vibrations 4- Ruffini corpuscles • Have collagenous, fusiform capsules • Stimulated by stretch (tension) or twisting (torque) in the skin • Detecting tissue distortion Meissner Corpuscles Consisting of sensory axons winding among flattened Schwann cells Elliptical structures arranged perpendicular to the epidermis in the dermal papillae Numerous in the fingertips, palms, and soles but decline slowly in number during aging after puberty Function: • Stimulated by light-touch or low-frequency stimuli against skin temporarily deform their shape (X150; H&E; Meissner’s corpuscles) • DP: dermal papilla Inset: A higher magnification of a Meissner’s corpuscle. (X320) Lamellated (Pacinian) Corpuscles Large oval structures Structure: • An outer capsule: 15-50 thin, concentric lamellae of flattened Schwann cells and collagen • A highly branched, unmyelinated axon surrounded by the capsule Function: • Sensing coarse touch, pressure (sustained touch), and high-frequency vibrations Location: • Deep in the reticular dermis and hypodermis • In the connective tissue of organs located deep in the body, including the wall of the rectum and urinary bladder (X85; Pacinian corpuscles) • N: nerves • Arrow: The neural portion Hair Elongated keratinized structures Form within epidermal invaginations called hair follicles All skin has at least minimal hair except the glabrous skin of: • Palms • Soles • Lips • Glans penis • Clitoris • Labia minora Hair Follicle Derived from the epidermis but extending deep into the dermis Hair bulb: • A terminal dilation in the growing hair follicle Hair papilla: • A dermal papilla inserting into the base of the hair bulb • Contains a capillary network required to sustain the hair follicle • Covered by the keratinocytes continuous with those of the basal epidermis § Forming the matrix of the elongating hair root Cells of the hair bulb matrix proliferate, take up melanin granules, and undergo keratinization to differentiate as the three concentric layers of the hair b: (X70; H&E; A longitudinal section of a hair root and bulb) c (X260; SEM; A hair shaft emerging at the stratum corneum Hair Follicle Keratinocytes of the hair bulb: • Generally similar to those in the basal and spinous layers of epidermis • Divide rapidly in a matrix region immediately around the dermal papilla and then undergo keratinization, melanin accumulation, and terminal differentiation to form the hair • Receiving melanosomes from the melanocytes in the hair bulb matrix • Cells in the hair root matrix differentiate with variable amounts and types of keratin (X140; H&E; The base of a hair follicle) • DP: dermal papilla • CTS: connective tissue sheath • IRS: internal root sheath • ERS: external root sheath • G: glassy membrane • CO: cortex (X140; H&E; Hair root) • M: medulla • CO: cortex • CU: cuticle • IRS: internal root sheath • ERS: external root sheath • G: glassy membrane • CTS: connective tissue sheath (X150; fluorescent antibodies against laminin in basal laminae; Longitudinal section through rat whisker follicle) • DP: dermal papilla • CO: cortex • CU: cuticle • RS: internal and external root sheaths • G: glassy membrane Hair In most thick hairs: 1- Medulla: formed by moderately keratinized cells 2- Cortex: formed by heavily keratinized cells 3- Cuticle: a thin layer of heavily keratinized cells Hai Follicle Epithelial root sheath: • Continuous with the outermost cells of the hair bulb • Separated from dermis by glassy membrane (an acellular hyaline layer which is the thickened basement membrane) 1- Internal root sheath • Completely surrounds the initial part of the hair root • Degenerates above the level of the attached sebaceous glands 2- External root sheath • Covers the internal sheath • Extends all the way to the epidermis, where it is continuous with the basal and spinous layers Connective tissue sheath: • Surrounding dermis Arrector Pili Muscle A small bundle of smooth muscle cells Extends from the midpoint of the fibrous sheath to the dermal papillary layer Nail Hard plates of keratin on the dorsal surface of each distal phalanx Produced by a similar process of keratinization Parts of the nail: 1- Nail root 2- Nail plate (X100; Mallory Trichrome; The base of a hair follicle) • PNF: proximal nail fold • E: eponychium • NR: nail root • NP: proximal region of the nail plate • DNM: dorsal nail matrix • VNM: ventral nail matrix • NB: nail bed • D: dermis Nail Root • The proximal part of the nail • Covered by a fold of skin, from which the epidermal stratum corneum extends as the cuticle, or eponychium • Forms from the nail matrix in which cells divide, move distally, and become keratinized in a process somewhat similar to that of the stratum corneum and hair • Matures and hardens as the nail plate (X10; Photomicrograph of a sagittal section of distal phalanx with a nail) • PNF: proximal nail fold • E: eponychium • NR: nail root • NP: proximal region of the nail plate • DNM: dorsal nail matrix • VNM: ventral nail matrix • NB: nail bed • D: dermis Nail Plate • Bound to a bed of epidermis (nail bed) which contains only the basal and spinous epidermal layers • Continuous growth in the matrix pushes the nail plate forward over the nail bed (which makes no contribution to the plate) at a rate of about 3 mm/mo for fingernails and 1 mm/mo for toenails • The distal end of the plate becomes free of the nail bed at the epidermal fold called the hyponychium Skin Glands Three major types of exocrine glands in the skin: 1- Sebaceous glands: secrete oily sebum into the space around the hair root 2- Eccrine sweat glands: with thermoregulatory function emptying their secretion onto the skin surface via sweat pores 3- Apocrine sweat glands: secrete a more protein-rich sweat into the follicles of hair in skin of the axillae and perineum Skin Glands: Sebaceous Glands Embedded in the dermis over most of the body, except in the thick, glabrous skin of the palms and soles More abundant in the face and scalp Branched acinar glands with several acini converging at a short duct that usually empties into the upper portion of a hair follicle In certain hairless regions, such as the penis, clitoris, eyelids, and nipples, sebaceous: ducts open directly onto the epidermal surface Secrete oily sebum into the space around the hair root (X122; H&E; A pilosebaceous unit) • D: ducts • S: sebocytes • H: hair (X400; H&E; A sebaceous glands) • C: gland’s capsule • S: sebocytes • H: hair Skin Glands: Sebaceous Glands The acini of sebaceous glands: classic example of holocrine secretion • Releasing sebum as the main secretory product Sebocytes: • Large, lipid-producing cells filled with small fat droplets No myoepithelial cells Pilosebaceous unit: • A hair follicle and its associated sebaceous glands Eccrine Sweat Glands Develop as long epidermal invaginations embedded in the dermis Most numerous on the foot soles Collectively the 3 million eccrine sweat glands of the average person approximately equal the mass of a kidney and produce as much as 10 L/d Innervation: via cholinergic fibers Function: • Thermoregulation • Auxiliary excretory organs, eliminating small amounts of nitrogenous waste and excess salts Components of the eccrine sweat glands: 1- Secretory part: generally more pale-staining than the ducts 2- Ducts • Both parts with irregular stratified cuboidal appearance (X320; H&E; Eccrine sweat glands) • S: secretory components • D: ducts Eccrine Sweat Glands: Secretory Part Consists of an unusual stratified cuboidal epithelium with three cell types 1- Clear cells • Produce the sweat 2- Dark cells • Irregular pyramidal cells • The granules undergo merocrine secretion to release a mixture of glycoproteins with bactericidal activity 3- Myoepithelial cells • Located on the basal lamina • Contract to move the watery secretion into the duct (X200; Mallory trichrome; Eccrine sweat glands) • S: secretory components • D: ducts (X200; TEM; Secretory portion of the eccrine sweat gland) • BL: basal lamina • M: myoepithelial cells • D: dark cells • C: clear cells • IC: intercellular canaliculi • L: lumen Eccrine Sweat Glands: Ducts Consist of two layers of more acidophilic cells: At the epidermis, each duct merges with the stratum basale and sweat flow continues in a spiraling channel through the five epidermal strata to an excretory sweat pore in the skin surface Apocrine Sweat Glands Found in skin of the axillary and perineal regions Their development depends on sex hormones and is not complete and functional until after puberty Gland’s name is controversial since it apparently involves both merocrine and apocrine secretion Innervation: via adrenergic nerve endings Products: • A protein-rich product mixed with sebum • Sex pheromones (in a reduced or vestigial capacity in humans) • Slightly viscous secretion is initially odorless but may acquire a distinctive odor as a result of bacterial activity (X45; Apocrine sweat glands) Inset: Higher magnification of secretory component Apocrine Sweat Glands Components: 1- Secretory components: • Much larger lumens than those of the eccrine sweat glands • Have both myoepithelial cells and a single, eosinophilic cell type in a simple epithelium (cuboidal or columnar) 2- Ducts: • Like those of the eccrine glands but usually open into hair follicles at the epidermis (X200; Mallory trichrome; Apocrine sweat glands) • S: secretory portion • D: ducts • H: hair follicles Apocrine Sweat Glands Blood and Lymphatic tissue ANAT2441: Histology JOYCE EL-HADDAD [email protected] @orientatewithjoyce Lecture Outline - Function of blood - formation of blood - Formed elements of blood - Lymphoid organs Learning Outcomes 1. To identify the cellular components of blood and understand their functions. 2. To describe the tissue morphology of a lymph node and the features of the cortex, medulla, trabeculae, medullary cords and sinusoidal system. Centrifuged blood sample Plasma composition Plasma ~55% Water 92% Transports organic and inorganic molecules, cells, platelets, and heat Plasma proteins 7% Other solutes Buffy coat <1% 1% Platelets Blood clot formation and tissue repair White blood cells Neutrophils (60 -70%) Monocytes (3-10%) Red blood cells Eosinophils (1-4%) Red blood cells ~45% Lymphocytes (20 -40%) Basophils (0 -1%) LM of bone marrow obtained via needle biopsy from the medullary cavity L typi Two are a (Ba) stain lymp has cyto (RBC elem a un and with bico 690 Blood • • • Blood is specialized connective tissue Consists of cells that circulate in a fluid known as plasma Average volume of blood ~ 4-6 L depending on body composition Function of blood is: o to transport oxygen and nutrients to the lungs and tissues. o form blood clots to prevent blood loss o carry cells that are immune in nature o deliver waste products to the kidneys and liver, which filter and clean the blood. 168 Blood and Bone Marrow Blood formation (Haemopoiesis) Timeline Main source of Haemopoiesis PE RBC First few weeks of gestation Yolk sac 6 weeks of development Liver and spleen 6-7 months of fetal life Bone marrow LM of a bone marrow smear at low (Above) and high (Right) magnifications. The smear, made from a bone marrow aspirate, shows details of hematopoiesis. Hematopoietic cells of the erythroid lineage at different stages of development in B include a proerythroblast (Pr), basophilic erythroblast (BE), and early polychromatophilic erythroblast (PE). Mature erythrocytes (RBC) and two unidentifiable cells (arrows) are also seen. Above: 8×; Right: 2000×. Wright’s. Pr BE https://radiopaedia.org/articles/yolk-sac He Childhood Bone marrow (most of the skeleton) Adult life Bone marrow (axial skeleton, femur, LM of a bone marrow biopsy specimen at low (Above) and high (Right) magnifications. The solid core of tissue contains bone marrow and humerus) and bony trabeculae (arrows). Normal bone marrow consists of a heter- FC Bo ogeneous population of cells in various stages of differentiation. Clusters of tightly packed hematopoietic cells (He) sit between large adipocytes (FC) and bony trabeculae (Bo). Adipocytes look empty because of lipid extraction during specimen preparation. Above: 8×; Right: 200×. H&E. 7.11 METHODS OF STUDYING BONE MARROW Smears and trephine needle biopsy (for preparation of bone than smears for elucidating cell details but provide a panoramic view of bone marrow and its normal architecture. They are also Haemopoiesis • Bone marrow is the site of haematopoiesis after birth. Because most blood cells are short-lived, they need continuous replacement. • All mature blood cells derive from pleuripotential stem cells in bone marrow • Colony-forming unit (CFUs) committed to erythroid lineage production contain progenitor cells known as colony-forming unit-erythrocytes (CFU-E). In other words, these are the cells that turn into the erythrocytes. • Granulocyte and monocyte cell lines develop from one progenitor cell known as the colony-forming unitgranulocyte-monocyte (CFU-GM). In other words, these are the cells that turn into the leukocytes. • Cells of the lymphocyte lineage are generated from colony-forming unit-lymphocytes (CFU-L). • Progenitor cells for megakaryocytes produce colonies that contain colony-forming unit-megakaryocytes (CFU-Me). En Erythrocytes (red blood cells) • • • • • • Anucleated biconcave discs A biconcave shape provides a large surface area for primary functions like transporting O2 from lungs to tissues and returning CO2 from tissues to lungs for elimination The iron containing protein hemoglobin in RBCs accounts for their red color Highly flexible and malleable as they travel in narrow capillary lumina 99% of formed elements of blood and have a lifespan in circulation of 120 days RBCs lose their nucleus at the end stages of erythropoietic development in bone marrow. * RBC * 5µm Electron micrograph (EM) of an erythrocyte in the lumen of a capillary. The RBC lacks organelles. Its uniformly granular density is due to the presence of hemoglobin. An endothelium (En) surrounds the capillary, sectioned transversely. Note how the RBC completely fills the lumen. 11,500×. RBC 2µm 7.3 ULTRASTRUCTURE AND FUNCTION OF ERYTHROCYTES RBCs are anucleate biconcave discs that are highly flexible and malleable as they travel in narrow capillary lumina. They make up 99% of the formed elements of blood and have a lifespan in circulation of about 120 days. Numbers of RBCs per liter of blood usually average 5 × 1012 in men and 4.5 × 1012 in women. In the human embryo, RBCs are initially nucleated, up to 7 weeks of gestation. During final stages of erythropoietic development in bone marrow, RBCs lose the nucleus and almost all organelles except the cytoskeleton and then enter the circulation. Because RBCs lack a nucleus but have a plasma membrane, they are more containing protein hemo color. Hemoglobin rapid jugated protein containi globin. Heme is a porphy of hemoglobin in whole 12-16 g/dl for females. S abnormalities, including occur in humans. C A deficiency of RBCs and types of which exist. Corr Immune System LYMPHOCYTES Function: provide defense of the body against invasion of foreign material from both outside and inside the body A Neutrophil. Ne Neutrophils • Neutrophils are the most numerous leukocytes and constitute 60%-70% of the leukocyte count. • The nucleus has a distinctive morphology and many forms (polymorphonuclear leukocytes), with a clump-like pattern and three to five lobes connected by fine chromatin strands. • Immature neutrophils show only slight nuclear lobulation; older cells have more, dark-staining lobes. A Neutrophil. • • • RBC Blood and Bone Marrow B Neutrophils are actively motile and function outside the circulation. After they develop in bone marrow, they stay in the bloodstream for 8-12 hours. Neutrophil numbers increase in acute bacterial infections. 161 Ne Ne RBC * C RBC GC LMs of neutrophils in blood smears. The young neutrophil (Ne) in A has a U-shaped, darkly stained nucleus. The neutrophil in B is more mature; its * Eosinophils • Eosinophils make up a small proportion of leukocytes in peripheral blood: 1%-4% of the leukocyte count. • Eosinophils circulate in the bloodstream for 6-8 hours; once they migrate to connective tissues, their lifespan is 8-10 days. • Their nucleus is typically bilobed. • Cytoplasm extremely eosinophilic. 162 Blood and Bone Marrow Eosinophil. • The cells phagocytose antigen-antibody complexes and parasites, and elevated cell numbers occur in parasitic infections and allergic responses such as hay fever and asthma. Eo RBC LM of an eosinophil in a blood smear. The distinctive, closely packed eosinophilic granules fill the cytoplasm of the eosinophil (Eo). The usually bilobed nucleus has an irregular shape. This granular leukocyte has a larger diameter than that of the erythrocytes (RBC). 1350×. Wright’s. Basophils • The least numerous leukocytes, account for less than 1% of the leukocyte count • The nucleus is often irregular in shape or bilobed. • Distinctive specific granules that are intensely basophilic and fill the cytoplasm. • Basophils closely resemble mast cells of connective tissue • Basophil. .The motile basophils are involved in allergic reactions and increase in number in many clinical conditions such as hay fever, urticaria (hives), chronic sinusitis, and some leukemias. • Blood and Bone Marrow Ba RBC An elevated basophil count in peripheral blood rarely occurs in most benign conditions. An increasing basophil count can suggest worsening of disease SG LM of a basophil in a blood smear. The easily recognized basophil (Ba) has many large basophilic specific granules that are blue. The nucleus, being masked by the granules, is less evident. The erythrocytes (RBC) are smaller than the basophil. 1200×. Wright’s. Monocytes • Monocytes are agranular leukocytes that are immediate precursors to cells of the monocytemacrophage system (aka Mononuclear Phagocytic System) • They usually circulate in the bloodstream for only 1-3 days and perform almost all functions outside the circulation. These actively motile cells enter connective tissues to become macrophages (or phagocytes). Monocyte. • Each cell has a nucleus that varies in form and may have an oval, kidney, or horseshoe shape Blood and Bone Marrow LM of a monocyte in a blood smear. A monocyte (Mo) nucleus is highly indented and less densely stained than that of lymphocytes. Throughout the light blue cytoplasm are many faintly stained granules, so the cytoplasm looks dusty. The monocyte is twice as large as the erythrocytes (RBC). 1350×. Wright’s. Mo RBC 1 Platelets Blood and Bone Marrow opoiesis 169 Thrombocytopoiesis (Megakaryocytopoiesis) poietic Cell Cell Hematopoietic Stem Cell CFU-Meg blast Megakaryoblast 166 Blood and Bone Marrow Platelets. Promegakaryocyte RBC hocyte Thymus • Platelets are motile cytoplasmic fragments enveloped by a plasma membrane • They arise from megakaryocytes in bone marrow and appear as plate-like structures without nuclei. • Platelets play a major role in blood coagulation Pl Megakaryocyte En 1µm T-Lymphocyte Platelets EM of two platelets and part of an erythrocyte (RBC) in the lumen of a blood vessel. The platelets (Pl) contain several dense, membrane-bound granules. One platelet seems to adhere (arrows) to the vessel’s endothelium (En). 15,000×. Pl T-Lymphocyte Platelets T-Lymphocyte nce, main cell types seen in bone marrow smears topoiesis (center, right), and megakaryocyesemble lymphocytes. Except for megakaryocytes, es, nuclear density increases, and special features cific granules (eosinophilic, basophilic, or on rate and survival and maturation of progenitor Pl En Lymphocytes Lymphocytes Organs B Cells* T Cells* NK cells Dendritic cells (antigen presenting cell) Diffuse Lymphatic Tissue (S) Lymph Nodes (S) Spleen (S) Thymus (P) Bone Marrow (P) P= Primary lymphatic organ S = Secondary lymphatic organ * Plus different types of these cells. Lymphocytes - B cells are more numerous than T cells - B cells > Plasma cells > production and secrete of antibodies - T cells recognise invaders, activate the immune response, kill infected or abnormal cells, coordinate immune functions, and establish immunological memory to provide long-term protection against recurring threats. Take home: Smooth cytoplasm = low/no activity Rough/grainy cytoplasm = high activity – protein synthesis Lymphocytes When lymphocytes are active, that is when their morphology will change e.g. Plasma “Clockface” nucleus • Heterochromatin: tightly packed form of DNA (dark) • Euchromatin: loosed packed form of DNA (light) • Activated B cell > plasma B cells that is secreting antibodies B vs T cell Plasma B cell Cytotoxic T cell Lymphoid Organs qDiffuse Lymphatic Tissue (S) qLymph Nodes (S) qSpleen (S) qThymus (P) Diffuse Lymphatic Tissue • Mucosal Associated Lymphoid Tissue (MALT) • Initiate immune responses to specific antigens encountered along all mucosal surfaces – enlarge. • Not enclosed by a connective tissue capsule • Located in the underlying lamina propria of epithelial lining Different locations, different name: NALT - Nasal Associated Lymphoid Tissue BALT - Bronchus Associated Lymphoid Tissue GALT - Gut Associated Lymphatic Tissue Think about the epithelial lining covering the nasal cavity, upper resp tract and GIT Lymphatic follicles in the ileum Transport gut lumen organisms and particles to immune cells across the epithelial barrier. Most numerous in the ileum of the small intestine LYMPH NODES: Function In lymph vessel pathways “filter” (surveillance) lymph Immune - detect infections from peripheral tissues • skin, respiratory tract, gastrointestinal tract, etc. Return interstitial fluid to circulation Primary or secondary? LYMPH NODES: Structure Location throughout the entire body - concentrated in axilla, groin, lung, gastrointestinal tract mesenteries Small (1 mm - 2 cm) encapsulated organ. In lymph vessel pathways “filter” lymph • Afferent - towards node (A - arrives at the node) • Efferent - away from node (E - exits the node) LYMPH NODES 1 Afferent lymphatic vessel 2 Subcapsular sinus 3 Trabecular sinus 4 Medullary sinus 5 Efferent lymphatic vessel Afferent lymphatic vessels → subcapsular sinus → trabecular sinuses → medullary sinuses → efferent lymph vessel (hilum) @orientatewithjoyce @orientatewithjoyce @orientatewithjoyce • High endothelial venules (HEVs) are different from regular blood vessels. • They have a high endothelial cell layer with cuboidal or columnar morphology, as opposed to the flat endothelial cells found in typical capillaries. • This specialized endothelium allows for interactions between lymphocytes and endothelial cells, which is essential for lymphocyte extravasation (leakage).