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61 Cards in this Set

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How does a nucleus typically appear with H&E stain? Why?
Nucleus typically appears blue/pruple, as hematoxylin is a basic dye which stains acidic structures.
Give examples of different shapes/sizes of nuclei found in the following cell types:
satellite cell
smooth mm
endothelial cell
monocyte or eosinophil
neutrophil or megakaryocyte
Hepatocyte: round
Neuron: large
Satellite cell: small
Smooth muscle cell: long
Endothelial cell: thin
Monocyte, eosinophil: bilobed
Neutrophil, megakaryocyte: multilobed
Give examples of cells with the following numbers of nuclei:

None: red blood cells.
1: most cells
2: some hepatocytes
2-3: cardiac muscle cells
many: osteoclast, skeletal muscle fiber
How can the location of the nucleus be used for:

1) Tissue identification
2) Direction of secretion in gland
3) Orientation of tissue
1) Tissue identification: central vs. peripheral nucleus, can tell cardiac vs. skeletal muscle

2) Apical nucleus vs. basal nucleus: the secretory products are closest to the secretory membrane (i.e. nucleus are displaced).

3) Orientation of tissue: inner circular vs. outer longitudinal smooth muscle layer in muscularis externa in gut.
What does the nucleus contain?
Chromatin: nucleic acids + proteins.

Nucleic acids = DNA, or RNA (mRNA, rRNA).
Proteins = histones or others, i.e. transcription factors, kinetochore proteins.
What are the 2 types of chromatin?
1) Heterochromatin: (~10%), electron dense, transcriptionally inactive, appears dark under EM.

2) Euchromatin: (~90%) appears light under EM, 2 forms, active (10% and inactive 90%...active is being transcribed).
How is DNA arranged?
Wound around histones like a spool. These are small globular proteins with many + charged aa. DNA is coiled 2x around each histone, such that histones + 2 turns of DNA = 1 nucleosome. Continuous stretches are called chromosomes.
What happens to the second X chromosome in females?

How is this represented?
One becomes permanently inactive as the gene products of both are not required.

This is found as a small, dark mass of heterochromatin adhering to the nuclear membrane, called a Barr body.
Which chromosomes have genes which encode rRNA?

Where are these visible?

Nucleolus, the site of ribosome production.
What are the 3 zones of the nucleolus and what do they contain?
1) fibrillar centre: DNA not actively being transcribed.

2) Dense fibrillar component: RNA being synthesized

3) Granular component: maturing ribosomal precursor components.
What is the nuclear envelope?

What is the inner nuclear membrane supported by?

What are nuclear pores? What are the size limitations?
Double membrane structure bounding nuclear contents.

Inner nuclear membrane is supported by a meshwork of intermediate filaments - the nuclear lamina.

Nuclear pores span the envelope, allowing passage of molecules b/w nucleus and cytoplasm.

Size limitations: small molecules <9nm pass through pores passively, large molecules <26nm must be actively transported.
What is the cell cycle?
Cell cycle: Growth (G1) --> Synthesis (S) = genome replication --> Growth 2 (G2) --> (M) Mitosis (division).
What happens in prophase?

What is the hallmark?
Centrioles move to the opposite poles
Fragmentation of nuclear envelope
Disappearance of nucleolus
Chromatin condensation

Hallmark: chromatin condensation - the dark staining chromatin beings to condense.
What happens in metaphase?

What is the hallmark?
Chromosome condensation complete
Microtubules attach to kinetochore proteins on chromosome
Chromosomes move to cell equator

Hallmark: see chromosomes lining up at equator.
What happens in anaphase?

What is the hallmark?
Sister chromatids split apart and move to poles
Cell membrane begins to constrict at equator.

Hallmark: separation of chromatin to daughter poles.
What occurs in telophase?

What is the hallmark?
Cell membrane separation is complete.
Nuclear envelope reassembles
Nucleolus reappears

Hallmark: > 2 separation b/w bands of chromatin
What are the 2 main type of cell death? What is the difference?
Apoptosis and necrosis.

Apoptosis: cell death resulting from a normal process.

Necrosis: cell death as a result of tissue damage. Associated with inflammation, usually involving large portions of organs.
What are the 3 different histological appearances of necrosis?
Pyknosis: condensation of chromatin into dense, small mass.

Karyorrhexis: fragmentation nucleus

Karyolysis: disappearance of nucleus (loss of chromatin staining).
Define apoptosis.

At what level does it occur?

What is the morphological appearance?
Apoptosis: energy dependent process of programmed cell death.

Occurs at the level of the single cell or in a small group of cells, NOT accompanied with inflammation.

Morphological: chromatin condenses and fragments. Rest of the cell shrinks and fragments into membrane bound vesicles called APOPTOTIC bodies which are phagocytosed by neighbouring cells.
Name the sites of blood cell production during development? In adults?

Where is yellow marrow found? Red marrow?
Yolk sac, liver, spleen, bones. Adults = bone marrow. This is in red marrow.

Yellow marrow - in diaphyses of long bones, mainly adipose. Red marrow = cancellous (spongy) bone. - form-fitting, irregular bones.
What are the components and proportions of blood?

What are the granular leukocytes? Agranular?
Plasma: 55-60%, this is 90% H2O, called serum after clotting, 1% = buffy coat, 35-45% = RBC in females, 40-50% in male.

Granular: neutrophils (40-75%), eosinophils and basophils.

Agranular: lymphocytes (25-30%) and monocytes.
Outline the stages of erythropoiesis.

How long does it take?
Erythropoiesis: proerythroblast --> basophilic erythroblast (contains many ribosomes), --> polychromatophilic erythroblast --> orthochromatophilic erythroblast (normoblast) (cell loses ribosomes, nucleus becomes very condensed and dark) --> reticulocyte (nucleus has been ejected)

7 days total.
What proportion of reticulocytes are usually found in circulation?
0.6-2%. Become fully mature in 48 hours.
Where does white blood cell functioning occur?

What is the process of white blood cell migration called?

What type of granules do wbc contain? What do they stain with?
In connective tissue.

Process = diapedesis. This involves molecular interactions between membranes of blood cells and endothelial cells.

Granules: azurophilic granules - stain with azure dye.

% 40-75
Lobe: multilobed, less with age.
Function: phacogytose organisms during acute phase of infection.
Storage: in bone marrow by loose attachment to sinusoidal endothelium. Drawn out in response to infection.
Lifespan: day in circulation before entering connective tissue, then 1-4 days before apoptosis.

% 2-4
Lobe: bilobed with eosinophilic granules.
Function: phagocytize antigen-antibody complexes. Secrete "major basic protein" to destroy HELMINTHES! Secrete factors (histaminase) to modulate inflammatory response.

%: <1%
Nucleus: irregular, but obscured by show-stealing metachromatic granules.
Function: membrane binds IgE, granules contain histamine and mediators of inflammation
What is the progression of granulopoiesis?
Myeloblast --> promyelocytes (primary granules appear), --> myelocytes (specific granules appear, LAST MITOSIS), --> metacmyelocyte (post mitotic) --> mature granulocyte.


%: 2-8%
Size: 2-3x > rbc
Nucleus: large, eccentric, kidney-shaped, slightly basophilic cytoplasm
Time: circulate for < 1 day before leaving circulation to become phagocytes...macrophages, Langerhans cells, Kupffer cells, dendric cells, osteoclasts.
Role: phagocytosis and APC to T lymphocytes, can fuse to form giant cells.

Sequence: APC phagocytizes invading organisms, the antigen is digested and displayed on membrane for presentation to T cells, which are then activated to respond, migrating to the site of infection.

Special features?

What are the 3 main sub-types?
%: 25-30%
Special: only lymphocyte to re-enter circulation after leaving it, only mature wbc that can proliferate.

3 types: B cells, T cells an NK cells.
What is the role of B lymphocytes?
Role: secrete antibodies to a specific antigen. Have Fc receptors on membranes to bind with antibody (immunoglobulin).

Antigen binds to antibody = B cell proliferates giving B memory and plasma cells.

Plasma cells secrete antibody specific for antigen.

Cannot fully respond without T helper cell activation.
What is the role of T helper cells?
Express CD4+ antigens. Proliferate and secrete cytokines that stimulate the response of other lymphocytes to same antigen, e.g. B cells.
What is the role of cytotoxic T cells?
Express CD8+ antigens. These attack antigen associated with cell membranes and destroy by secreting PERFORINS or inducing apoptotic pathway
Where is major histocompatability complex molecule I found?


Role in immunity?
MHC 1 = expressed on all cells of an individual.

MHC II: Only on APC.

Role: T helper cells respond to antigen presented by APC in MHC II complex. Activated cytotoxic T cells attack a cell that does not have MHC1 or those that have MHC I with antigen.
What is the function of NK cells?
Attack and destroy virus infected cells and some transformed cells without apc. Contain little cytoplasm.
What is the function of platelets?
Function: lifespan of < 10 days, function in hemostasis by adhering to collagen of subendothelial connective tissue of the TUNICA INTIMA and release contents.

Promotes aggregation, vasoconstriction, clot formation and retraction, tissue repair.

Attracted to sub-endothelial connective tissue.
What are megakaryocytes?

Where are they found?

What do they do?
Platelet producing cells, very large, multi-lobed polyploid nucleus.

Found in bone marrow associated with sinuses.

Extend processes into sinuses and shed platelets directly via fragmentation.
What are the primary lymphatic organs?

What occurs here?
Bone marrow and thymus.

Here, lymphocytes of each clone acquire the ability to recognize 1 specific foreign molecule (acquire immunocompetence).
How is the diversity of the immune reaction achieved?

What happens to the slackers?
Diversity: achieved by random rearrangement of the gene segments encoding the antigen receptors.

Slackers are destroyed!
What happens in the bone marrow?
-T and B lymphocytes develop
-B lymphocytes develop immunocompetence (antigen specificity)
-T lymphocytes go to thymus gland where they develop immunocompetence.
Describe the structure of the thymus.
Thymus: 2 irregular lobes surrounded by connective tissue with a connective tissue septae, located in superior anterior mediastinum.

2 parts: cortex (outer, darker staining part containing many small lymphocytes) and medullla (inner, lighter staining part with few lymphocytes).
What are the epithelial reticular cells?

How are they connected to each other?
Epithelial cells (from endoderm of 3rd pouch) lining capsule, covering trabeculae in capillaries in the cortex and medulla. These create the blood-thymus barrier and secrete growth factors for T cell growth and differentiation.

Connected to each other by desmosomes. Where they line the capsule and cover septae and vessels and they are connected by tight junctions.
How do T cells develop immunocompetence?

What happens to those that don't express TCR?
T cells express antigen-specific T cell receptors (TCR) on cell membranes.

Those that don't express TCR undergo apoptosis and are phagocytosed by macrophages.
Where do mature immunocompetent T lymphocytes go?
Migrate to the medulla and leave the thymus through post-capillary venules and efferent lymphatic capillaries to colonize secondary tissues and organs.
What are Hassall's corpuscules useful for?
Identifying thymus. These are circular, eosinophillic staining bodies, reticular cells are filling with keratin.
List 3 secondary lymphatic tissues and organs.
1. Diffuse lymphatic tissue. These are collections of lymphocytes in the connective tissue underlying the epithelium of respiratory, digestive and genitourinary systems.

e.g. lymph nodules (follicles) -spherical clusters of lymphocytes lighter staining germinal centres from cores of nodules. Here, activated lymphocytes beginin to differentaite into effector forms.

-nodules in pharynx

Peyer's patches
-nodules in distal ileum

2. Lymph nodes

3. Spleen
What is the role of lymph nodes?

Describe the structure of lymph nodes and outline the flow pathway of lymph.
Filters for antigen detection in lymph. Dendtritic cells carry antigents to nodes in afferent lymph. Sinuses contain reticular fibers, reticular cells and macrophages. Antigen entering nodes is captured and presented by macrophages.

Structure: fibrous connective tissue capsule with penetrating septae. Reticular cells and fibers form a meshwork between trabeculae supporting sinuses in the cell and node.

Sinuses are afferent lymphatics emptying into subscapular sinuses then to cortical sinuses to medullary sinuses to efferent lymphatics. B and T cells leave in efferent lymph.
What is the major cell type in each of the following?

Corticomedullary junction:
Medulla (medullary cords)
Cortex: nodules, mainly B lymphocytes
Corticomedulally junction: T cells
Medulla: lymphocytes, plasma cells.
List the contents of the lymph node.
Reticular fibers (contain collagen)
Reticular cells (make reticular fibers)
Dendritic cells
Plasma cells (in inner medulla)
Sinuses (carry lymph through node)
Blood supply
What are the roles of the spleen?

Describe the structure.
-Detect and respond to blood born antigen
-Remove aged RBC and platelets

Structure: fibroelastic connective tissue capsule with penetrating septae, Meshwork of reticular fibers between trebeculae support the pulp.
What are the 2 types of pulp comprising the spleen. Give contents/functions.
White pulp: contains central arteries, T lymphocytes in periarterial sheath along central arteries, and B lymphocytes in follices along central lines.

Red pulp: splenic sinusoids, splenic cords (b/w the sinusoids), arterioles, blood cells, and reticular cells. Macrophages and reticular cells present antigens to lymphocytes in white pulp.
Describe the components of the extracellular matrix of bone.

What are the 3 main cell players in bone?
2 components: Mineral and ORganic.

Mineral: 70% of weight, Ca++ and P in hydrxyapatite. Gives rigidity and storage for minerals.

Organic: (osteoid part). Resilience. Type I collagen, glycoproteins, proteolglycans, bind cytokines and growth factors.

Osteoblasts, osteocytes, osteoclasts.

Derived from?
Factor Required?
Derived from - progenitor cells
Location - surface of bone matrix
Job - production of osteoid and calcification
Appearence - basophilic cytoplasm because it is screting, may be cuboidal when active or flattened when not active.

Factor: CBFA1

Derived from?
Derived from: osteoblasts surround by bone matrix.

Location: in lacunae of bone matrix, surrounded by unmineralized matrix.

Job: maintain the matrix, death of these leads to bone reabsorption. Connected to adjacent osteocytes y CANALICULI, processes form gap junction channels.
May also sense mechanical stress and coordinate adjustment response.

Derived from?
Derived from: fusion of mononuclear cells in bone marrow under influence of M-CSF and RANKL.

Location: bone surfaces, in depressions called Howship's lacunae (resorption lacunae)

Appearance: multinucleated (5-10) with eosinophlic cytoplasm.

Job: Attach to bone matrix with suction, secreate proteins to demineralize the matrix, and break down organic components.
What is bone remodelling?

What is Wolff's Law?
Process of bone resorption and deposition, ensure health and strength. Osteoclasts break down matrix, growth factors and cytokines bound in matrix are released and stimulate osteoblasts to make new matrix.

Osteoblast > clast = increasing bone mass/hypertrophy.
Blast < clast = bone mass loss/atrophy

Wolff's Law: every change in form and function of a bone is followed by change in internal architecture.
What happens when serum Ca++ levels fall?
Parathryroid glands release PTH.
PTH stimulates osteocyte activity, promoting osteocytic osteolysis.
PTH stimulates osteoblasts and bone marrow stromal cells to upregulate M-CSF and RANKL expression.
Osteoclast numbers up, activity up, Ca released to serum.
What happens when serum Ca++ levels are increased?
Calcitonin is released by the thryoid. This acts directly on osteoblasts to increase activity, extract Ca++ from serum, to decrease serum Ca++ levels.
Describe the 2 types of bone arrangement.
1) Cancellous/Spongy/Traecular Bone:
-Composed of branching and anastomosing spicules (trabeculae) which are cross-bridged to add strength. Found in irregulary shaped bones and epiphyses. Hematopoietib bone marrow between trabeculae.

2) Compact/Cortical/Lamellar Bone:
-Periphery, thick, have osteocytes in haversian systems (osteons).
Haversian System: explain.
-Found in compact bone
-Haversian canals run parallel to the long axis of bones
-Canal contains blood vessels, nn, osteoblasts, connective tissue and progenitor cells.
-Lacunae with osteocytes are in rings around the canal.
Canaliculi connect osteocytes with Haversian canal.
-Lamellae of matrix is between rings of osteocytes.
What is woven bone?
-Found at sites of rapid bone deposition, the lamellar nature of compact bone is not found because collagen fibers are randomly arranged. Will be replaced by stronger, resilient Haversian system. Haven't had a chance to organize! Immature form of compact bone!