Lecture 5: Cell Birth & Cell Death

neoplasia

Irreversible proliferation of cells: proliferation continues even in the absence of an external stimulus

hashimoto disease (hypothyroidism)

apoptosis of thyroid cells (low T3/T4 levels)

fatigue, dry skin, “feeling down”

symptoms of Hashimoto disease

CPID, smokers (chronic damage to epithelial cells)

metaplasia clinical correlation

dysplasia of exocervix

Hashimoto disease

most common form of hypothyroid disease (opposite of Grave’s disease)

Fas ligand (when Fas receptor on lymphocytes bind to lignad, lymphocytes undergo rapid apoptosis)

at immunologically “privileged” sites (eye, testes), the vascular endothelial cells express

Bcl pro and anti-apoptotic

the ratio of what determines apoptosis in the mitochondria?

intrinsic pathway of apoptosis

Burkitt’s lymphoma reveals molecules and mechanisms for

physiologic activators/inducers of apoptosis

TNF, FasL, growth/survival factor withdrawal, glucocorticoids

damage-related activators/inducers of apoptosis

viral infection, heat shock, toxins, tumor suppressors, oxidants/free radicals

therapy-associated activators/inducers of apoptosis?

UV/gamma irradiation, chemotherapeutic drugs

irreversible

is neoplasia reversible or irreversible?

apoptosis (cysts on surface, large empty spaces)

polycystic kidney disease is an example of too much

reversible

is hyperplasia reversible or irreversible?

reversible

is metaplasia reversible or irreversible?

reversible

is dysplasia reversible or irreversible?

benign
malignant

what are the 2 major forms of neoplasia?

benign

loss of proliferation controls only (stays in place):

malignant

loss of both proliferation and positional controls

regeneration

1-for-1 replacement of lost cells by the same cell type

physiological (helpful)

regeneration is always pathological/physiological

regeneration

hyperplasia

metaplasia

dysplasia

what are 4 reversible altered proliferative states?

regeneration

endothelial regrowth following vascular surgery is an example of:

regeneration

liver regrowth after donating or receiving a transplant is an example of:

hyperplasia

increase in the number of cells in a tissue; cells are fully differentiated. Can be physiological (helpful) or pathological (harmful)

hyperplasia

Grave's disease (hyperthyroidism) is an example of thyroid _________

hyperplasia (helpful version)

an increase in hematopoietic cells in bone marrow following severe blood loss or changes in altitude is an example of ______

hyperplasia

an increase in smooth muscle cells in the arterial wall in atherosclerosis or following vascular surgery (restenosis) is an example of ________

metaplasia

adaptive substitution of one cell type for another

metaplasia

Replacement of ciliated columnar epithelium by stratified squamous epithelium in response to chronic inflammation (eg. chronic pelvic inflammatory disease or smoking) is an example of ________

dysplasia

activated metabolic pathways for proliferation; loss of orientation in a tissue. Abnormal appearance of cells

cancer

cervical dysplasia as seen on a Pap Smear in women may be an early sign of _______

“benign”

uterine fibroids are a ________ neoplasia of smooth muscle cells. most common tumor of women (affects black women disproportionately)

apoptosis

what cellular even has a critical role in determining the presence of syndactyly/polydactyly or not?

uterine fibroids

symptoms: abnormal, heavy bleeding; pain/pressure; fertility problems

apoptosis

polysistic kidney disease occurs when there is too much ________

malignant (crossing the boundary)

cancer = ____________ neoplasia

critical for maintaining homeostasis (cell proliferation = cell death)

why have apoptosis?

apoptosis

tissues with greatest frequencies of cell proliferation also exhibit the greatest frequency of _________, including thymus, spleen, small intestine, epidermis, ovarian follicles

necrosis

________ is triggered by sustained ischemia, physical, or chemical trauma.

cells swell, organelles damaged, chromatin randomly degraded

inflammation (cells lyse, organelles destroyed)

necrosis causes

apoptosis

_________ is triggered by specific signals that activate specific genes. cells shrink, organelles intact, chromatin degraded systematically.

phagocytosis (membrane blebs, cell contents retained)

apoptosis causes

induction
modulation
execution

what are the 3 phases of apoptosis?

intrinsic pathway of apoptosis

the modulation step of apoptosis only exists in which pathway?

Bcl proteins

the modulation phase of apoptosis is regulated by:

extrinsic pathway of apoptosis

TNF-α is an activator for which pathway?

extrinsic pathway of apoptosis

Fas is an activator for which pathway?

extrinsic pathway of apoptosis

in which pathway of apoptosis do proteins bind to a cell receptor that directly activates caspase cascade?

intrinsic pathway of apoptosis

growth/survival factor withdrawal is an activator for which pathway?

intrinsic pathway of apoptosis

a viral infection is an activator for which pathway?

intrinsic pathway of apoptosis

heat shock is an activator for which pathway?

intrinsic pathway of apoptosis

toxins and free radicals are activators for which pathway?

intrinsic pathway of apoptosis

UV/gamma irradiation and chemotherapeutic drugs are activators for which pathway?

executioner caspases

caspases followed by endonucleases; caspases are directly responsible for blebbing:

mitochondria

where are all the Bcl proteins located?

cytochrome c

what molecule comes out of mitochondrial channels during the intrinsic apoptosis pathway that will initiate executioner caspases?

bcl proteins

If the apoptotic signal utilizes the intrinsic (mitochondrial) pathway, the process may be modulated (either enhanced or dampened) by:

extrinsic pathway of apoptosis

death receptors activating the caspase cascade is a feature of which pathway?

intrinsic pathway of apoptosis

which pathways can be modulated either up (pro-apoptotic) or down (anti-apoptotic) by the Bcl family proteins?

caspases followed by endonucleases

the chief executioners of the cell in both the intrinsic and extrinsic pathways for apoptosis:

FAS receptor (undergo rapid apoptosis upon entering priveleged sites)

immunologic immunity ("privilege") is conferred on sites like the eye and testis because immune cells (lymphocytes) constitutively express:

restenosis (smooth muscle cell hyperplasia) following balloon angioplasty

what is this depicting?