Overview

Conduction portion: § Nasal cavities § Pharynx § Larynx § Trachea § Bronchi § Bronchioles Respiratory portion: § Respiratory bronchioles § Alveolar ducts § Alveoli

Respiratory epithelium: § Ciliated cells* § Brush cells (microvilli) § Goblet cells § Basal cells (capable of mitosisà regenerate lining of resp tree) § Endocrine cells (peptide hormones & catecholamines) *Kartagener’s disease

Epithelium

Lamina propria

Submucosa

Function

Nasal cavities

Nasal mucosa

Respiratory: Pseudostratified, ciliated, columnar (with goblet cells)

Highly vascular CT, with serous and mucus glands; thin walled veins

*humidify (transfer heat to inspired air) *trap particles

Olfactory mucosa

Thicker, Æ goblet cells

Pure serous glands Centrally projecting nerve fibers

Receptors for sense of smell

See histopath web site: “M1 histology” for images

Vocal cords

True

Stratified squamous on-keratinizing

*contains skeletal mm *inserts into vocal ligament

false

Respiratory epithelium

Trachea

Respiratory epithelium: pseudostratified, ciliated with goblet cells

*Thick basement membrane * dense CT with longitudinal layer of elastic fibers (divides lam prop from submucosa)

*Loose CT with fat cells and mixed muco-serous glands *trach cartilag rings *smooth mm btwn rings *adventia: CT

Lung

1 ° Bronchus

Rep epth: less tall, contains fewer goblet cells *mast cells

Lam prop: more dense, large amount of elastin in more superficial layers

¯ # sero-mucous glands cartilage-flattened plates (Æ ring like!) small # lymphocytes in adventitia: “diffuse mucosa-associated lymphoid tis”

3 ° (segmental) bronchus

Tall columnar Æ much pesudostratification ¯ # goblet cells

¯ # glands

Few reg cartilg plates Submucosa merges with adventitia

Bronchioles

Simple columnar, ciliated, ¯ # goblet cells

clara cells: secrete glycosaminoglycans & contain P450 to metab airborne toxins

Æ cartilage! Spiral smooth muscle

Clinical correlation: instability of bronchiolar smooth mm à leads to contraction and airway narrowing è ASTHMA

Terminal bronchioles

Simple cuboidal Æ goblet cells

Smallest diameter of pure conducting resp tree

Respiratory portion

Resp bronchioles

Æ goblet cells ciliated cuboidal cells clara cells

Alveolar Duct

Alveolar Sac

Alveoli

Type I pneumocytes: alveolar lining (simple squam epth), connected by tight junctions; Æ mitotic ability Type II pneumocytes: synthesize surfactantà stored in lamellar bodies; Ö mitotic abilityè replace both type I and type II pneumocytes Alveolar macrophages* Alveolar pores (pores of Kohn)

alveolar macrophage

type II pneumocyte with lamellar body

emphysema

	Structure	Function	EM
Perioxisomes Detail of secondary lysosome with engulfed material within it. 1 = Limiting membrane; 2 = Matrix; 3 = partly digested material.		Lysosomes Know the lysosome storage diseases
Glycogen EM of hepatocyte illustrating size relationships between glycogen particles (1 and 2) and ribosomes of the RER (3). Know the glycogen storage diseases I, II, III, V		Golgi apparatus Details of a Golgi apparatus (body) showing the forming face (1); aturing face (2); saccules (3) and secretory vesicles (4) budding from the saccules. The Golgi complex typically lies adjacent to the nucleus. 5= centriole. Functions: 1. distribution center of proteins and lipids from ER to the plasma membrane, lysosomes, and secretory vesicles 2. modifies N-oligosaccharides on asparagines 3. Adds )-oligosaccharides to serine and threonine residues 4. Proteoglycan assembly from proteoglycan core proteins 5. Sulfation of sugars in proteoglycans and of selected tyrosine on proteins 6. addition of mannose-6-phospate to specific lysosomal proteins, which targets the protein of the lysosome	Clinical: I-cell disease is caused by the failure of addition of mannose-6-phospate to lysosome proteins, causing these enzymes to be secreted outside the cell instead of being targeted to the lysosome.
Mitochondria Details of mitochondria. 1 = External envelope; 2 = Cristae; 3 = Matrix (the more electron-dense material); 4 = Granules within the matrix. Know what metabolic processes occur in the mitochondria		ER: smooth High magnification of a network of smooth endoplasmic reticulum. Unlike rough endoplasmic reticulum, which usually occurs in flat sheets, this organelle comprises interconnected tubules (1). 2 = Mitochondrion; 3 = Free ribosomes, seen either singly or as Polyribosomes (polysomes). SER is the site of steroid synthesis and detoxification of drugs and poisons
Nucleus & Nucleolus Transmission electron micrograph of nucleus similar to the one in the previous figure. The nucleolus (3) shows an internal structure. The chromatin is predominately euchromatin with heterochromatin which is typically located close to the nuclear envelope and is discontinuous at the nuclear pores. Mitochondria (2) are seen in the surrounding cytoplasm.
Cilia Tangential section of cilia showing the structural transitions that occur between the shaft of the cilia (upper right) and the basal bodies (lower left) which give rise to the cilia. Cross-cuts of cilia showing the typical 9X2 +2 arrangement of microtubules within the cytoplasm (ring of 9 doublets plus 2 single microtubules in the center). The cell membrane envelopes each cilium.		EM of cilia cut longitudinally. (A few microvilli are on the neighboring cell to the left, for a size comparison.) Notice that each cilium is rooted in a barrel-like basal body. The dense lines extending from the basal bodies and up into the cilia are microtubules. The unit membrane of the cell continues up over each cilium. *Remember Kartagener’s

		Cell-cell junctional structures	Structure	Function	EM
	Cell-cell adhesions	Tight junctions “zona occludens”		Selective barrier: tight seal between two cells, so anything that needs to travel between lumen and basal lamina needs to go through the cells Extends around the entire perimeter of the cell
		Gap junction “nexus” connexins *skin *osteocytes *astrocytes *cardiac m *smooth mm *endocrine		Found in cells requiring rapid communication between neighboring cells; eg., heart cells. A conexon is the pore created by connexins to form a channel through which camp, aa’s and small molecules can pass
		Adhering Junctions: Adhesion belt “Zonula adnerens” cadherins, actin Desmosomes “macula adnerens” cadherins è intermediate filaments		Involve two glycoproteins connecting two cells; cytoskeletal filaments (actin/intermediate) bound to intracellular attachment proteins, then connected to cadherin moleculesà join the two cells together Attachment plaque Tonofiliments

characteristics of the immune system A. Specificity 1.The immune system discriminates among antigens, even when their structures are closely related. 2.Antigens include large molecules in isolation or displayed on cells. 3.Small molecules or haptens can be antigens too if coupled to large molecules (for example, poison ivy toxin). 4.The specificity of the immune response depends on the selective proliferation and differentiation of clones of lymphocytes, each displaying distinct antigen receptors. 5.There are two types of lymphocytes: B lymphocytes (bone marrow-derived) and T lymphocytes (thymus-derived). B. Memory 1.After encountering an antigen, the body is primed to recognize it on subsequent exposures. 2.In addition to antibody-secreting plasma cells, long-lived memory lymphocytes are produced in response to antigen. 3.Memory lymphocytes proliferate quickly upon secondary exposure to the antigen. C. Enhanced response on secondary exposure 1.The secondary response to an antigen occurs faster, is larger, and is more specific. 2.Immunologic memory and enhanced secondary response make vaccination possible. D. Distinction between self and non-self 1.The immune system can respond to foreign antigens without responding to self Ag’s 2.Self-nonself discrimination is learned in the thymus. 3.When the immune system recognizes self Ag’s as foreign, autoimmune dx may result. 4.Immunological tolerance is the lack of response to a foreign antigen because it is recognized as self by the immune system. E. Genetic control 1.The immune system is under the control of genes in the major histocompatability complex (MHC). 2.Histocompatability (or transplantation) Ag’s are glycoproteins encoded by MHC genes 3.Histocompatibility Ag’s confer the identity "self" on cells on which they are located. 4.Some types of histocompatibility antigens are present on all cells of the body, and function in the immune response to virally-infected cells. 5.Other types of histocompatibility antigens participate in the presentation of antigens to lymphocytes by antigen-presenting cells (APCs).

Organ B cells T cells Thymus Æ cortex medulla Lymph node -nodules outer cortex -paracortex inner cortex Spleen -nodules white pulp -PALS white pulp

Lymph Node

There are two types of follicles visible by light microscopy Primary follicles: are densely basophilic; contain large #s of resting lymphocytes which express numerous specific immunoglobulin molecules on their cell surfaces; none have bound antigen or have received T cell help. Secondary follicles: contain lighter staining germinal centers; the lymphocytes are transcribing and translating many genes as a result of antigen- dependent diff’n; germ centers contain numerous lymphoblasts and lymphocytes with mitotic figures b/c antigen-stimulated proliferation of the responding lymphocytes is also occurring.

Tonsil

Lingual, pharyngeal, and tubal tonsils (or adenoids). Palatine Macrophages are the chief antigen-presenting cells of the tonsil, just as dendritic cells are the chief antigen-presenting cells of the lymph node. Tonsillar macrophages are often referred to as imparting a "starry sky" appearance to this lymphoid tissue.

GI tract: GALT

Gut-Associated Lymphatic Tissue M-Cells sample the intestinal contents and present a specific antigen to immature lyphocytes Lymphocytes migrate to lymph nodes, where they mature Mature lymphocytes are carried by the thoracic duct to the blood and return to the intestine Mature lymphocytes differentiate into plasma cells that secrete specific IgA antibodies into the lamina propria The majority of IgA with the lamina propria enters the blood and reaches the liver sinusoids IgA within the sinusoids binds to receptors on hepatocytes and is endocytoses. AT the bile canaliculi, IgA is released into the biliary tract, in combination with a portion of its receptor (secretory piece), as secretory IgA Secretory IgA enters the intestinal lumen with the bile

This slide shows an isolated, single primary lymph nodule in the wall of the stomach stained dark purple because of the small lymphocyte accumulation. Such nodules are often found in the wall of tracts that exit to the outside and represent a first line of defense against foreign substances that might enter the body via these routes. Nodules like this in the GI tract are thought to be one source of B-type lymphocytes producing IgA antibodies.

Peyer’s Patch

Unencapsulated lymphoid tissue found in lamina propria and submucosa of small intestine. Covered by single layer of cuboidal enterocytes (Æ goblet cells) with specialized M cells interspersed. M cells take up antigen. Stimulated B cells leave Peyer’s patch and travel through lymph and blood to lamina propria of intestine, where they differentiate to IgA-secreting plasma cells. IgA receives protective secretory component, then is transported across epithelium to gut to deal with intraluminal antigens.

Spleen

FUNCTIONS OF THE SPLEEN: 1. It destroys defective red and white blood cells. 2. It sequesters monocytes from blood à helps develop into macrophages. 3. It stores 1/3 of the platelets in the body as a reserve. 4. It removes lymphocytes from blood & is a site of Ag-dep T & B cell dif’n OVERALL ORGANIZATION * outer connective tissue capsule with trabeculae projecting into the organ *Red pulp is a large area of erythrocyte concentration consists of splenic sinuses and splenic cords. * White pulp is made of diffuse and nodular lymphoid tissue, and is associated with arteries *Both red and white pulp are made of reticular meshworks much like those of lymph nodes. -reticular cells are fibroblast-like & are joined by cytoplasmic processes. -reticular fibers made by these cells are collagen QUESTION: WHICH AREA OF THE SPLEEN HAS THE MOST CELLS, RED OR WHITE PULP?

General description of blood circulation through the spleen 1. Blood enters the spleen by way of the splenic arteries passing through the hilus. 2. Splenic arteries branch into the trabeculae as trabecular aa. 3. Trabecular arteries leave the trabeculae and run through the white pulp as central arteries 4. Central arteries are surrounded by the periarteriolar lymphatic sheath or PALS which is lymphatic tissue. 5. Central arteries leave the white pulp and pass into the marginal zone between the red pulp and the white pulp and terminate into the reticular meshwork of the cords. 6. On periphery, the marginal zone blends into cords of red pulp. 7. Blood flows through the splenic cords, then through the interendothelial slits of splenic sinuses. 8. Blood flows from the splenic sinuses into the pulp veins. 9. Pulp veins empty into the trabecular veins. 10. Trabecular vv empty into the splenic vv à leave the spleen.

Rod cells form the walls of splenic sinuses which are long anastomozing venous channels. *They are a unique endothelium with a unique fenestrated basement membrane. * Rod endothelial cells are elongate with tapered ends and lie parallel to the long axis of the sinus. * They are joined by junctional complexes along their lateral surfaces *They are separated by thin slit like spaces *They lie on a fenestrated basement membrane that looks almost like a net. Gaps between the rod cells and in the fenestrated basement membrane permit blood cells to pass directly through. Thus, a large fraction of the splenic circulation is open, not closed Note that not all splenic circulation is open; some blood circulates through the spleen rapidly in a closed circulatory system rather than passing through splenic sinuses.

Thymus

The thymus is the site of antigen-independent differentiation for T lymphocytes, as the bone marrow is for B lymphocytes.

Hassell's corpuscles : concentrically wound epithelial reticular cells— Æfunctional, but specifically mark the thymic medulla.

*A young child's thymus is filled with cells and very active *The thymus reaches its greatest weight at puberty. *After puberty, the organ begins to involute, and cortical lymphocytes and epithelial reticular cells are progressively replaced by fat.

Skeletal		Longitudinal	Cross Section			Smooth vs. Skeletal
Smooth muscle
Cardiac muscle
				Contract Stretch A band: ÆD ÆD I band: ¯ (shorten) (lengthen) H band: ¯ Z disks: à ß ß à			Conctracting Sarcomere
								thick white: perimysium little white: endomysium

	Skeletal	Cardiac	Smooth
Nuclei	Multinucleated; Peripheral	Multinucleated; central	Single nucleus; central
Banding	Actin & myosin form distinctive bands	Actin & myosin form distinctive bands	Acting & myosin; Æ bands
Z disks	Ö	Ö	Æ; Ö cytoplasmic dense bodies (equivalent to Z disks) –contain a -actinin
T tubules	T tubules @ A-I junction; triads present	T tubules @ Z disk; diads present (T tubule flanked by one cisterna of sarcoplasmic reticulum)	Æ T tubules; Æ diads or triads; caveolae are present (equivalent to T tubule)
Cellular junctions	Æ	Intercalated disks: fascia adnerens, desmosomes, & gap junctions	Gap junctions
Neuromuscular junctions	Ö	Æ present; contraction is intrinsic (heart beat is myogenic)	Æ; contraction is intrinsic, neural, or hormonal
Ca 2+ -binding	Troponin	Troponin	Calmodulin
Regeneration	Limited; satellite cells	Æ ; injured cardiac myocytes are generally replaced by connective tissue	High

Phagocytic Cell	Light Microscope	EM	Misc
Langerhans Cells (5% of cells in skin) Found in stratum spinosum Contain Birbeck granules Antigen-presenting cells in the bone marrow
Kupffer Cells (Liver) Macrophages derived from circulating monocytes Found in liver sinusoids Demonstrate phagocytic activity
Alveolar Macrophages
Microglia Originate in mesoderm Arise from monocytes phagocytic
Tonsilar Macrophages “Starry Sky”