Histology: Vesicles, Inclusion, Cytoskeleton

Front 1

Endosomes

Back 1

-vesicles that pinch off of the plasma membrane

-lipid bilayer contains plasma membrane proteins

-lumen contains extracellularcomponents.

-three types ofendocytosis:

1.Pinocytosis: nonspecific intake ofsmall molecules.

2.Receptor-mediatedendocytosis: specific uptakeusing receptors.

3.Phagocytosis: uptake of largemolecules and organisms.

Front 2

Lysosomes

Back 2

-membrane-bound organelles involved in intracellular digestion.

-Lysosomal proteins:

--mostly enzymes

--produced by the rER → processed in the Golgi apparatus.

-Lysosomes that bud fromthe trans-Golgi:

--small

--typically have a dense stain in electronmicrographs

--barely visible on LM

-Lysosomes released from the Golgi-apparatus ultimately fuse with a structure tobe degraded:

-endosome, phagosome, senile organelle.

--size and appearance of lysosomesat this stage varies widely→ most have dark clumps within them=digested material.

Front 3

Secretory granules

Back 3

-products of the rER / Golginetwork.

-contents vary, dependingon the specific function of the cell.

-EM: clustered nearthe plasma membrane on side of the cell they will be released.

-lumen: duct into which these cells secrete the contentsof their secretory granules (SG).

-Note: extensive rER will be present in cells with lots of SG (Golgi is not as apparent)

-present in cells that use regulated secretion – secretion in response to asignal. (Cells that secrete constitutively (constantsecretion), will have few or no visible secretory granules.)

Front 4

Peroxisomes

Back 4

(aka microbodies)

-contain oxidativeenzymes → detoxification and oxidation of long-chain fattyacids

→ prominent inliver cells.

-In all species except humans,they can be identified by a single colloid density in electron micrographs.

-peroxisomal proteins are synthesized in the cytosol and imported into theperoxisome

-initialstructural vesicle that will become a peroxisome arises as a bud from thesmooth endoplasmic reticulum.

Front 5

Lipid droplets

Back 5

-droplets of lipid within the cytoplasm(no kidding).

-tend to beround,

-accommodate their shape to other components in the cell.

-various size → typically fairly large (larger than mitochondria)

-density varies with staining inelectron micrographs.

-mostcells have one or a few lipid droplets,

-prominent in two cell types:

1.Steroid secreting cells that usethe lipids as substrates for hormone production.

2.Adipose cells, which are storingenergy.

Front 6

lipid droplets

Back 6

-pale cytoplasm

-washed away during tissue preparation

*one principle you should understand now:

-Cells that produce steroid hormones have abundant lipid droplets

-cells that secrete peptide or protein hormones (e.g. insulin) have abundant RERand Golgi.

Front 7

Cytoskeletal elements

Back 7

cytoskeleton: composed of thread-like proteins involved in activities suchas cell structure and intracellular trafficking. There are three major components of thecytoskeleton:

1. microtubules

-centrioles

2. microfilaments

3. intermediate filaments

Front 8

Microtubules

Back 8

hollow tubes, ~25nm in diameter

-EM: appear as parallel double lines in longitudinal sections and as rings in cross section

-major function:

-organelle movement with thecell,

-movement of cilia and flagella

-movement of chromosomes duringmitosis/meiosis (major component of mitotic spindle)

-Agents that disrupt microtubule dynamics:

1. preventing microtubule formation (vincaalkaloids or colchicine)

2. inhibiting microtubule disassembly (Taxol)

→ interrupt mitosis→ targetdividing cells → and are effective chemotherapies to treat cancers.

Front 9

Microfilaments

Back 9

solid tubes, 5nm in diameter

-can only be seen in cells throughspecialized staining techniques.

-function: involved in cell motilityand shape, major components of microvilli.

Front 10

Intermediate filaments

Back 10

solid tubes, 10nm in diameter

-function: unclear, though it is likelythat, at least for the keratins in skin, they are involved in resistance toshear force at the level of the tissue.

-mice were created with a deletion in akeratin intermediate filament protein → prone to skin blisters (similar to a human conditionknown as epidermolysis bullosasimplex)

Front 11

Centrioles

Back 11

-paired organelles

-composed of microtubules arranged in 9 triplets

-interphase cells: centrioles located in the center of the cell, part of thecentrosome,

Front 12

Lysosomal Storage Diseases

Back 12

-disruption of digestive function → accumulation of undigestedmaterial within the cell → inhibits normal cellularfunction

-Tay-Sach’sdisease

-gangliosides accummulate

Front 13

secretory granules in pancreatic ß cells

Back 13

We have alreadylooked at these cells from the pancreas that demonstrated cytoplasmicbasophilia. Recall that they are

-organized into acini

-lumen at the center of each acinus

-portion of the cell adjacent tothe acinus is highly eosinophilic → this is due to the numerous secretorygranules contained in these cells.

→ these (and other epithelia) cells are polar:

-apical side: faces lumen=theside of the cell with the secretory granules.

-basal side: side nearest the connective tissue=cytoplasmic basophilia.

Front 14

inclusions (artifacts)

Back 14

1. lipid droplets

2. glycogen

3. pigments

Front 15

pigments

Back 15

- cellular deposits.

-melanin: deposited in skin cells, provides theepithelial cells of the epidermis protection against ultraviolet radiation.

-H&E stainedslide, but the pigment is not stained by this method; it is visible naturally(which is the definition of a pigment).

-Other pigments youwill encounter underly potential pathology:

--lipofuscin granules

--hemosiderin

Front 16

glycogen

Back 16

-complex carbohydrate most likely present in all cells, but abundant in the liver and skeletal muscle.

-electron micrographs:

--appears as clusters of dense round particles

--often associated with smooth endoplasmic reticulum, which has at least one of the enzymes for glycogen metabolism on its membrane.

-- looks like clusters of ribosomes. Each individual glycogen particle is approximately the same size and shape as a ribosome. However, glycogen will cluster, ribosomes do not

Front 17

hemosiderin

Back 17

-Small amounts ofhemosiderin exist normally in many cell types involved in red blood cellbreakdown:

--macrophages,

--spleen

--liver

-accumulates within cells as a yellow-brown pigment

-can bespecifically visualized using Prussian blue

-Excess hemosiderincan occur either as a localized or systemic process:

--Localized hemosiderin accumulation: occurs during bruising, whenhemorrhaging results in accumulation of hemosiderin within macrophages. The different states of iron duringhemoglobin breakdown are reflected in the colors that appear during bruisehealing.

-- Systemic hemosiderinaccumulation:iron overload→ excess iron in the diet orexcess hemolysis; hemosiderin accumulates largely in the liver, bone marrow, spleen,and lymph nodes, although it also increases in other organs such as thepancreas and kidneys.

Front 18

lipofuscin granules

Back 18

aging cells( liver and heart) often exhibityellowish-brown near the nucleus(blue arrow), which are electron-dense in electron micrographs (redarrow). These granules are not harmful,but commonly accumulate within the cell in response to oxidative stress, and,therefore, are suggestive of underlying pathology.

Front 19

centrosome

Back 19

-complex of proteins from which radiate the microtubule network

organizes the microtubule network → also called the microtubule-organizing center (MTOC)

-During mitosis, centrioles are duplicated, and each pair migrates to opposite poles of the cell

-intracellulartrafficking of vesicles: In this regard,the centrosome is indeed the “center” of the cell, adjacent to theGolgi apparatus. Newly processedproteins are packaged in the trans Golgi, and move from the center of the celloutward along these microtubule tracks to various destinations. Incoming vesicles from endocytosis also movetoward the centrosome, some eventuallyreaching the Golgi apparatus for processing.