foundations 1 forgotten concepts (copy) (copy)

what is the makeup of cartilage?

5% chondrocytes, 95% ECM

ECM: water, collagen and elastic fibers, proteoglycans, multiadhesive glycoproteins

makeup of bone

35% organic components (cells and organic matrix)

65% organic mineral crystals (calcium phosphate as hydroxyapatite crystals)

true or false: fibrocartilage cannot be repaired

FALSE - it has limited repair capability, but can be repaired

how does damaged perichondrium regenerate?

differentiation of perichondrial cells - limited regeneration capabilities

what are the steps to intramembranous ossification, after osteoblasts deposit osteoid?

collagen fibers are oriented randomly, forming woven (immature) bone

collagen fibers are replaced by lamellar bone

what are the requirements for endochondral ossification? (5)

1. cartilage model

2. interstitial and appositional growth of cartilage

3. erosion of cartilage

4. vascularization

5. bone deposition by osteoblasts and osteocytes

what are the five zones of growth at the epiphyseal growth plate during bone development?

zone of resorption, zone of calcified cartilage (dying chondrocytes), zone of hypertrophy, zone of proliferation, zone of reserve cartilage

what chemical is secreted by hypertrophying chondrocytes to promote vascular invasion?

VEGF

how is endochondral ossification regulated (nutritional and hormonal)

nutritional: calcium; oxygen and vitamin C (collagen)

hormonal: IGF-1 (stimulates chondrocyte proliferation) and FGF (inhibits chondrocyte proliferation)

what are the treatments for osteoporosis?

anti-RANKL antibodies, diet (vitamin D, calcium), bisphosphonates, HRT

which of the following is associated with type IV collagen: hyaline cartilage, elastic cartilage, epithelium, or bone?

epithelium

how are the origins of osteoblasts and osteoclasts different?

osteoblasts originate from osteoprogenitor cells (mesenchymal cells)

osteoclasts originate from macrophages

what is the difference between azurophilic and specific granules?

azurophilic (primary) granules are equivalent to lysosomes and are found in all leukocytes (granulocytes and agranulocytes)

specific (secondary) granules contain specific enzymes for each cell type and are only found in granulocytes (basophils, neutrophils, and eosinophils)

what is the largest blood cell?

monocyte

purkinje fibers are interspersed with what organelle along the periphery?

ribosomes; also have lysosomes and lipofuscin granules near them on staining

what are the unique functions of the endothelial cells of arterioles, venules, and capillaries?

arteriole - regulate BP

venule - regulate inflammation and immunity

capillary - transport nutrients, angiogenesis, express ACE-1t

true or false: both arteries and veins have an internal elastic lamina

FALSE - only arteries have an internal elastic lamina (located in tunica intimate)

the artery wall of muscular arteries is predominantly what layer?

tunica media

where in the artery is the outer elastic lamina located?

tunica media

what kind of CT comprises tunica adventitia?

dense irregular CT - type 1 collagen

true or false - capillaries do not have all three layers of vessel

TRUE - capillaries only have tunica intima - no media or adventitia

where in the body are each type of capillary found?

continuous - lungs, CNS, CT, muscle tissues

fenestrated - kidney, endocrine, intestines

sinusoids - liver, bone marrow, spleen

what are the different therapies for HTN, and where do they act in the body?

ACE inhibitors - arterioles

angII-R antagonists - arterioles

beta-blockers - heart and arterioles

diuretics - kidney

LDL receptor is degraded when bound to what molecule?

PCSK9

how does PCSK9 work? why is this important for cholesterol management?

when LDL receptor is bound to PCSK9, the receptor is degraded, decreasing LDL endocytosis; PCSK9 inhibitors inhibit degradation of LDL receptor and enhance clearance of LDL from blood

what blood vessel structure is analogous to the endocardium?

tunica intima

true or false: there are elastic fibers in large veins like the vena cava?

FALSE

in what layer of the artery are atherosclerotic plaques found?

tunica intima

summarize the time course of an immune response to infection

macrophage recognizes PAMP, phagocytoses bacterium, and presents antigen on MHC II

BCR binds antigen on bacterium as well, phagocytoses bacterium, and presents a different antigen on MHC II

TFH recognizes bacterial epitope and is activated by macrophage

TFH also recognizes foreign epitope on MHC II on B cell surface and secretes cytokines to stimulate B cell maturation/differentiation

B cell divides into plasma (secrete antibodies) and memory cells

antibodies bind to bacterium; Fc receptors on macrophages also bind antibodies

what are PRRs?

PAMP recognition receptors on the surface of and within cells involved in innate immunity in; in phagocytic cells, when PAMPs bind to PRRs, stimulates phagocytosis, killing, and/or inflammation

what are the five key properties of adaptive immunity?

specificity (recognize specific antigens)

diversity (numerous pathogens recognized)

memory

self-limitation (prevents chronic inflammation)

tolerance (prevents autoimmunity)

what are the principal functions of the five main antibody classes?

IgA: tissue fluid and blood (monomer); secretions (tears, airways, intestines) (dimer)

IgD: transmembrane B cell receptor (not secreted)

IgE: bound to receptor on mast cell and basophil

IgG: most common antibody; in blood, lymph, and tissue fluid

IgM: transmembrane B cell receptor (monomer); blood and mucous (pentamer)

what do TCRs do?

epitope receptor that binds one specific epitope when presented by antigen-presenting cell on MHC II; can only recognize epitopes bound to MHC

what is the time course for an immune response?

within minutes: inflammation, complement activation, phagocytosis, and pathogen destruction

within hours: interaction between dendritic cells and T cells (antigen recognition, adhesion, co-stimulation, T cell proliferation, differentiation) and activation of antigen-specific B cells

within days: formation of effector and memory T cells; interaction of T cells with B cells and formation of germinal centers to produce effector and memory B cells; antibody production

a few days: emigration of effector lymphocytes from peripheral lymphoid organs; effector cells and antibodies eliminate pathogen

true or false: B cells can recognize full-size antigens without MHC

TRUE - B cells are the only cells that do not need MHC proteins with bound non-self epitopes to recognize non-self

what is the difference between antigen presentation to TH1 cells and TFH cells?

TH1 cells recognize epitopes on APCs and secrete cytokines to stimulate APC to kill pathogen

TFH cells recognize epitopes on APCs (like TH1), but interaction stimulates TFH cell to help B cell mature and differentiate

explain the steps involved in TFH cells stimulating B cells

TFH is previously educated by APC

BCR on B cell recognizes epitope on surface of antigen, causing B cell to internalize and process antigen

B cell displays a different antigen (not pathogen epitope) on MHC II to TFH

TFH recognizes internal epitope from B cell on MHC II and secretes cytokines that stimulate B cell maturation

(CD8 proteins/TCRs) recognize epitopes presented by MHC I to Tc cells?

TCRs - TCR recognizes and CD8 stabilizes

what does Ki67 do?

regulates global gene expression and promotes carcinogenesis; increased Ki67 staining suggests altered gene expression and nucleolar activity

why is pompe disease considered a lysosomal storage disease?

the deficient enzyme, alpha-1,4-glucosidase, is a lysosomal enzyme needed for glycogen utilization

what happens to LDL and the LDL receptor once it enters the cell?

LDL receptor is recycled, and LDL is degraded in lysosome to release free cholesterol

what is the normal function of lamin proteins?

form nuclear lamina, an intermediate filament layer that organizes heterochromatin and helps regulate gene expression

what are the functions of the smooth ER?

lipid synthesis, detox reactions (via cytochrome P450), and Ca2+ storage

where in the cell are cytochrome P450 enzymes stored?

RER and SER

true or false: the nucleolus is involved in RNA synthesis

TRUE - synthesis of rRNA

what specific surface molecule is the basis of positive or negative clonal selection of lymphocytes?

BCRs and TCRs - generated at random through genetic recombination

how are stem cell niches maintained in the thymus and red bone marrow?

specific cell-cell interactions between stem cells and stroll cells

outline the steps of B cell education in red bone marrow

immunoglobulin (Ig) genes recombine in pro-B and pre-B cells (antigen independent)

H and L chains form IgM in plasma membrane (each IgM has single, unique antigen specificity)

IgM is BCR that is tested for self-reactivity (if self-reactive, apoptosis)

B cells expressing IgM that is not self-reactive survive, exit bone marrow as immature, naive B cells

describe the process of recombination to produce antibody diversity in B cells (and TCR diversity in T cells)

segments (V, J, D, C) of genes for Ig proteins are randomly selected and joined together to generate sequence diversity in variable regions

where in the thymus are epithelioreticular cells?

thymus stroma

true or false: reticular cells and reticular fibers are present in the thymus

FALSE - only cells present in thymus are thymocytes, epithelioreticular cells, macrophages, and fibroblasts/CT cells (capsule only)

where do positive and negative selection of double positive thymocytes occur? what cell is responsible for antigen presentation?

thymus cortex - epithelioreticular cells

where does negative selection of single positive thymocytes occur? what cell is responsible for antigen presentation?

thymus medulla (prevents self-reactivity) - macrophages, dendritic cells, and epithelioreticular cells

what is the structure of the blood-thymus barrier? why is the blood-thymus barrier important

structure (innermost to outermost) endothelial cells with basal lamina, connective tissue with cells and ECM, epithelioreticular cells with basal lamina

blocks foreign antigens from entering thymus, ensuring that TCR selection is based on recognition of self-epitopes presented by MHC on APCs

outline the lymph flow in the lymph node

afferent vessel → subcapsular sinus → trabecular sinus → medullary sinus → efferent vessel

what is the function of reticular fibers in the lymph node?

filters and traps substances in lymph

promotes movement and interaction of immune cells that mediate immune reactions and surveillance

what is the difference between FDCs and DCs? give an example of a DC

FDCs - present in germinal centers, hold and display antigen-antibody complexes (not MHC II) for developing B cells with Fc receptors that bind and hold antibody-antigen complexes

DCs - professional APCs (example: activated Langerhans cell that becomes interdigitating DC) that phagocytose and process foreign antigens, migrate to secondary lymphoid tissues, and present epitopes bound to MHC II to educate and activate mature, naive T cells

how do mature T cells form?

form in secondary lymphatic tissues (deep cortex in lymph node) following antigen presentation by DC

antigen presentation also activates mature T cells to form effector cells

true or false: all sinus spaces in lymph nodes are lined with HEVs

FALSE - sinus spaces are lined with simple epithelium, only certain parts of lymph node are lined with HEVs

why are FDCs not considered true APCs?

FDCs bind antibodies with bound antigens (not on MHC II), they do not interact with T lymphocytes, and they only present self-epitopes bound to MHC I

what are Hassal’s corpuscles?

only found in thymus and formed by epithelioreticular cells

what leukocyte is present in the lymph node medullary sinus but not the medullary cord?

eosinophils

what leukocyte is present in the lymph node medullary cord but not the medullary sinus?

plasma cell

which cells are transported in lymph? which cells are not transported in lymph?

in lymph: APCs, lymphocytes, macrophages (do not enter blood), neutrophils, eosinophils

never in lymph: mast cell, plasma cell (do not enter blood)

what are some common causes of lymphangitis?

streptococcal bacteria, insect or spider bite, fungus, virus

what are the defining features of diffuse lymphatic tissue? (3)

no CT capsule, no afferent lymphatic supply, reticular cells/fibers not always present

where in the lungs is BALT?

CT that supports bronchi

describe the blood circulation in the spleen

splenic artery → trabecular artery → central artery (in PALS) → penicillin arterioles → macrophage-sheathed capillaries → splenic cord (open circulation) → splenic sinus (closed circulation) → trabecular vein → splenic vein

what cells are present in splenic cords?

macrophages, neutrophils, platelets, and reticular cells

what is the most abundant form of MALT?

GALT

what cells are present in the medullary cords and medullary sinuses of the lymph node?

medullary cords: B cells, plasma cells, macrophages

medullary sinuses: endothelial cells, macrophages

what three cell-cell junction types make up the junctional complex in the intestinal epithelium? what specific proteins make up each junction?

tight junction (occludins and claudins), zonula adherens (cadherins), desmosome (desmocolin and desmoglien)

which cellular proteins regulate mitosis/the cell cycle? which cellular proteins regulate apoptosis?

mitosis: cyclins and CDKs

apoptosis: Bcl-2, p53, caspases

true or false: epithelial polarity is reprogrammed after mitosis

FALSE: epithelial polarity (sustained by junctional complexes) remains intact during mitosis and apoptosis

true or false: stem cells have tight junctions

TRUE - and tight junctions are retained after mitosis

list the layers of the alimentary canal, from interior (lumen) to exterior

mucosa (epithelium, lamina propria, muscularis mucosa), submucosa, muscularis externa (inner circumferential layer and outer longitudinal layer), serosa (mesothelium + CT)/adventitia

blood arrives at the liver in two ways. what are the names of the vessels, and what percentage of arriving blood is contained in each?

hepatic portal vein: 75%

hepatic artery: 25%

how does the liver regenerate?

hepatocytes and endothelial cells can divide, kupffer cells will differentiate from monocytes; stem cells are also present in zone 1

where are kupffer cells in the liver?

line sinusoidal capillaries and phagocytose foreign organisms and aged RBCs

which conditions would you expect damage to zone 3 of the liver?

heart disease (or any disease that decreases overall oxygen concentration/blood movement)

alcohol

Tylenol

what is the organization of the cortical kidney lobe?

lobules with a centralized medullary ray and bordered by interlobular vessels

large medullary pyramid collects urine

what are the parts of the kidney nephron?

renal corpuscle (glomerulus and bowman’s capsule), proximal tubules (convoluted and straight), distal tubules (convoluted and straight), thin tubules

what makes up the filtration apparatus of the renal corpuscle? how are substances filtered?

fenestrated capillaries and podocytes

fenestration of glomerular endothelial cell lets all molecules except blood cells through

basal lamina of glomerulus prevents large protein filtration

slit membranes between pedicels of podocytes prevents medium-sized protein filtration

where in the nephron is glucose resorbed?

from proximal convoluted tubule to peritubular capillary

list the blood flow in the kidney (until the glomeruli capillaries)

renal artery → interlobar artery → arcuate artery → interlobular artery → afferent arterioles → glomeruli (cortical and juxtamedullary)

list the blood flow in the cortical glomeruli

capillaries (cortical glomeruli) → efferent arterioles → peritubular capillaries → interlobular vein → renal vein

list the blood flow in the juxtamedullary glomeruli

capillaries (juxtamedullary glomeruli) → efferent arterioles → vasa recta → arcuate vein → interlobar vein → renal vein

list the flow of urine starting at the glomeruli (cortical and juxtamedullary)

bowman’s space → proximal convoluted tubule → proximal straight tubule → thin segment → thick ascending limb → distal convoluted tubule → connecting tubule → collecting duct → calyx

what cells synthesize the basement membrane of the glomerulus?

podocytes and endothelial cells

what structures does the neuroectoderm form?

CNS and retina

what structures do neural crest cells form?

PNS ganglia and their axons, Schwann cells, skull and jaw bones (intramembranous ossification)

what structures does ectoderm form?

epidermis, hair, sweat glands, ear canal (pharyngeal cleft 1)

what structures does somatic mesoderm form?

limb skeleton, lateral and ventral body wall

what structures does splanchnic mesoderm form?

GI tract wall, heart, blood and lymphatic vessels, early blood cells

what structures does intermediate mesoderm form?

kidneys

what structures does paraxial mesoderm form?

axial skeleton, skeletal muscles of trunk and limbs, dermis of back

what structures does endoderm form?

epithelial lining of pharynx; small intestine; epithelial tissues of liver, tonsils, thymus, auditory tube

what is the difference between disruption and dysplasia?

disruption refers to initially normal development interrupted by extrinsic factors (deformation is a type of disruption where the extrinsic factor is physical force)

dysplasia refers to abnormal development at the cell and/or tissue level

what space is the epiblast next to? what space is the hypoblast next to?

epiblast is next to amniotic cavity, hypoblast is next to yolk sac

in the US, birth defects affect ~__% of newborns each year, and birth defects account for ~__% of infant deaths

birth defects affect ~3% of newborns annually and account for ~20% of infant deaths (leading cause of infant death)