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135 Cards in this Set
- Front
- Back
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how can mitochondrial dysfunction lead to both apoptosis and necrosis?
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apoptosis: release of cytochrome c
necrosis: inability to generate ATP, increased intracellular pH, loss of Na/K pump activity |
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what ion is a major cause of necrosis?
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increased intracellular Ca
leads to enzyme activation (membrane and nuclear damage) increases mitochondrial permeability (bad!) |
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at a cellular level, what are the mechanisms of REVERSIBLE cell injury?
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loss of ADP
increased cell pH loss of membrane transport (edema) membrane detachment glycogen depletion |
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at a cellular level, what are the mechanisms of IRREVERSIBLE cell injury?
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membrane damage (phospholipases, ROS)
release of lysozomal enzymes large Ca influx |
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coagulation necrosis: characteristics
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cell outlines preserved
can be ischemic or hemorrhagic types without nuclei |
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liquefactive necrosis
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liquefaction by lysozomal enzymes or neutrophils
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caseous necrosis
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variant of coag necrosis: acellular cheese like material
(TB and Histoplasma) |
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fat necrosis:
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unique to the adipose around pancreas
pancreatic lipase saponifies TGs |
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Fibrinoid necrosis
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limited to small vessels
deposition of fibrous material inn vessel wall |
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what are the 3 possible nuclear changes in a NECROTIC cell?
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karylosis (fading of nucleus)
pyknosis (shrinkage of nucleus) karyorrhexis (nuclear fragmentation) |
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how do viruses inhibit apoptosis?
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they express caspase inhibitors
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what is the difference between intrinsic and extrinsic apoptosis?
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intrinsic: controlled by Bcl-2, lead to mitochondrial release of cyt c
extrinsic: Fas and TNF receptor activation. they converge on executioner caspases |
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how does Bcl-2 work?
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it prevents the formation of Bax/Bak pores in the mitochondria which allow release of cytochrome c.
net result: Bcl-2 is anti-apoptotic (there are antagonists of bcl-2!) |
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how is acute inflammation differentiated from chronic inflammation?
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acute: neutrophil invasion
chronic: lymphocyte and/or monocyte invasion |
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what is the difference between an exudate and a transudate?
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transudate: extravascular fluid due to increased hydrostatic pressure (low protein content)
exudate: extravasc fluid due to increased vascular permeability (high protein content) with inflammatory cells |
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serous exudate:
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lowest protein content (of exudates)
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fibrinous exudate:
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with fibrin and other proteins
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purulent exudate:
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exudate with neutrophils
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what are the 2 vasoactive substances increasing vascular permeability?
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histamine and serotonin
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what are the components of a granuloma?
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core of highly activated macrophages (with lots of cytoplasm: so they're called "epithelioid cells", may fuse to become multinucleate "giant cells")
rim of lymphocytes possibly fibrotic ring and necrotic center |
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leukocytes exit the blood stream at...
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post capillary venules
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what is the function , mechanism, and location of the selectins?
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they mediate ROLLING
they all have N terminal lectin binding domains (they bind CHO) L selectin is on leukocytes, P and E selectin are on endothelial cells |
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what is the funciton and location of Integrins?
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They are responsible for strong adhesion and integration into tissue
Mac-1 is on monocytes and neutrophils LFA-1 is on lymphocytes both Mac-1 and LFA-1 bind ICAM-1 (on endothelial cells) |
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how is integrin activity controlled?
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The Ig cell adhesion molecules (principally ICAM-1) expression is controlled by CYTOKINES
binding affinity of the Integrins with ICAM is inc reased by CHEMOKINES on endothelial surface binding chemokine receptors on rolling leukocytes |
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IL-8 is chemotactic for...
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neutrophils
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CCL5 is chemotactic for...
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lymphocytes
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IFN-gamma is a cytokine increasing
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phagocytosis and killing (macrophages)
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what is the difference between resolution and restitution?
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resolution: complete reduction of inflammatory processes
restitution: return only to normal fx level |
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restitution requires...
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regenerative capacity of the tissue (
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what is the major stimulatory molecule for angiogenesis?
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VEGF
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what is the major stimulatory molecule for fibrogenesis?
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TGF-beta
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what is granulation tissue
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the sub-terminal tissue in scar formation
fibroblasts secreting collagen highly vascularized (numerous small tissues) |
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what is the difference between
fibrinous: fibrous: |
fibrinous: containing fibrin (insoluble protein made from fibrinogen...i.e. clots)
fibrous: containing fibrobasts and collagen |
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proliferation of endometrium during menstrual cycle is an example of...
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physiologic hyperplasia
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hypertyroidism and post-surgical adhesions are examples of...
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pathologic hyperplasia
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cardiomegaly is an example of
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pathologic cell hypertrophy
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loss of wolffian ducts during embyogenesis of female fetuses is an example of...
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physiologic ATROPHY (they persist even though they're tiny)
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muscle wasting as a result of denervation is an example of
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atrophy
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hypoplasia is...
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incomplete development of an organ
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agenesis/aplasia is:
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failure of an organ to develop at all
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atresia is:
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failure of the hollow portion of an organ to form (esophagus, trachea, fallopian tube without lumen)
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dysplasia is:
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disorganization of normal cellular uniformity (pre-neoplastic sign)
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what are the two components of neoplasms?
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parenchyma (the neoplastic cells of origin)
stroma (the desmoplastic fibroblasts, this is what you feel in a lump) |
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how do the appearance of individual cells vary between benign and malignant neoplasms?
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benign: well differentiated (look like cell of origin)
malignant: poorly differentiated (variable appearance) |
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the suffix -oma refers to
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benign neoplasms
(except for lymphoma, which is malignant) |
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when do benign neoplasms become concerning?
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compression of vital organs (meningioma)
interference with normal fx (leiomyoma of uterus) hormone production (insulinoma) malignant potential (adenomatous polyp in colon) |
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at a cellular level, what features strongly suggest malignant neoplasm?
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pleomorphism of nuclei/cells
bizarre mitotic figures hyperchromatic nuclei |
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carcinoma:
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malignant neoplasm of epithelial origin
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sarcoma:
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malignant neoplasm of mesenchymal origin
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carcinomas most often metastasize by traveling through...
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lymphatics
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kidney and colon cancers most often metastasize by traveling though...
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hematogenous path
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what is the difference between tumor grade and tumor stage?
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grade: an expression of the differentiation of the tumor
stage: an expression of the extend of spread of a tumor |
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asbestos exposure puts a person at high risk for...
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mesothelioma (cancer of pleural lining, encases lung, BAD!!) and bronchogenic carcinoma
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arsenic exposure puts a person at risk for what type of cancer?
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skin cancer
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aniline dye exposure puts a person at risk for what type of cancer?
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bladder cancer
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unopposed estrogen puts a person at risk for what type of cancer?
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endometrial cancer
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exposure to Epstein-Barr virus puts a person at risk for
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Burkitt's lymphoma
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exposure to H. Pylori puts a person at risk for...
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gastric lymphoma
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exposure to Hepatitis B/C virus puts a person at risk for...
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hepatocellular carcinoma
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Carcinoembryonic antigen (CEA):
marker for- sensitivity and specificity- |
marker for: GI cancers (also can be breast, liver, lung cancers)
can use to follow disease progression limitation: low specificity |
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Alpha-fetoprotein (AFP)
marker: |
marker for: hepatocellular carcinoma
germ cell tumors of yolk sac-differentiation |
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CA 125
marker: |
marker for: ovarian carcinomas
(also benign and malignant uterine tumor) can have helpful or misleading values if tracked post-op |
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CA19-9
marker for: |
pancreatic cancer
(also elevated in colorectal carcinoma, gastric carcinoma) |
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Prostate Specific Antigen
sensitivity and specificity |
great sensitivity
moderate specificity (also elevated in prostatitis, benign prostatic hyperplasia) |
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why is PSA good as a screening agnet?
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although it has moderate specificity, it has great sensitivity
also, prostate cancer usually begins peripherally and patients won't experience urinary retention until late in disease process |
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what are normal PSA levels?
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0-4 ng/mL
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when taking a FNA on a palpable mass, what is an easy indicator of metastatic squamous carcinoma?
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just 1 giant squamous cell is diagnostic of metastatic squamous carcinoma
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why is histology better than cytology?
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it allows you to grade, stage, and characterize neoplasms
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on histology, how can you ID a sarcoma?
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usually spindle cells without intercellular bridges (desmosomes) like carcinomas have
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what are teh advantages of IHC in ID of neoplasms?
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can ID cell of origin (espcially for hematopoietic origin)
can also inform pharm treatment by specific markers |
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a cancer becomes detectable at how many cells?
kills you at how many cells? |
10^9 cells
10^12 cells |
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which gene type is never a cause of a familial cancer syndrome?
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oncogenes. They are + function genes, you only need one for activity. It doesn't hold with the loss of heterogeneity mechanism of familial cancer syndromes
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mutations in p53 are associated with...
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Li-Fraumeni syndrome (very high risk for all sorts of cancers)
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mutation in APC gene are associated with...
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Familial adenomatous polyposus and colon cancer
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what are the 7 characteristics of cancer cells?
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1. genomic instability
2. self sufficiency of growth signals 3. resistance to growth inhibition 4. limitless replication potential 5. resistance to apoptosis 6. sustained angiogenesis 7. tissue invasion and metastasis |
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what is the function of the normal BRCA1 protein?
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DNA repair
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what is the function of the Rb gene?
what controls it |
it is a strong inhibitor of the transition between G1 and S.
transition allowed when Rb is inhibited by phosphorylation by CDK4/Cyclin D |
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how does HPV lead to cancer?
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its proteins are oncogenic
E6: inactivates p53 E7: inhibits Rb |
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what are protooncogenes?
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genes of signal transduction pathways, anti-apoptosis factors, transcription factors
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HER2: function and role in cancer
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it is an epidermal growth factor overexpressed in many breast cancers
herceptin inhibits it |
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what is the function of the bcr-abl protein?
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it is an unregulated tyrosine kinase induces cell growth
inhibited by gleevac |
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what is the mutation associated with burkitt's lymphoma?
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c-myc mutation, heavy chain promoter translocated in front of myc protein (a growth transcription factor)
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Ras is a...
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oncogene
overactivated by a point mutation |
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JAK2 is a...
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oncogene
overactivated by a point mutation |
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what are the two most important tumorigenesis sensors?
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p14 and p16 (both located on the Ink4 gene locus)
when p14 and p16 are activated, they activate p53 and Rb, respectively. |
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what is the function of MDM-2?
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p53 acts as a transcription factor for its transcription
when there isn't DNA damage MDM-2 protein proteolyzes p53 when there is DNA damage, MDM-2 is phosphorylated (inactivated) |
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normal cells become senescent after how many doublings?
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~60
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what is the cause and consequence of acute promyelocytic leukemia?
trx? |
cause: translocation to make a PML retinoic acid receptor
consequence: DIC because the dying cells cause coagulation trx: all-trans retinoic acid induces terminal differentiation of leukemia cells |
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loss of what gene greatly increases likelihood of metastasis?
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loss of E-cadherin (it allows cells to slough and move away)
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which HPV subtypes are the high risk types?
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HPV16 and HPV18
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people with humoral immunodeficiency are susceptible to...
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infection by encapsulated bacteria
sinopulmonary disease |
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people with cellular immunodeficiency are susceptible to...
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low grade opportunistic fungi, viruses
growth retardation increased change of cancer malignancy |
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what is the best source for information on primary immune deficiencies?
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"Primary Immune deficiencies"
updates from the International Union of Immunological Societies Expert Committee Published in J of Allergy and Clin. Immunology |
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what mutations cause SCID?
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all of the interleukin receptors have a common gamma chain, without activity at all the IL receptors you have SCID
also, loss of adenosine deaminase leads to toxic buildup of adenosine...very toxic to T cells in particular |
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what is the cause of Hyper IgM?
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mutation in CD40L
B cells are present, produce lots of IgM but can't class switch so all of the other types of Ig are not present |
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what is the cause of X-linked agammaglobulinemia?
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mutation in gene for a cytoplasmic tyrosine kinase (btk)
B cells and Ig markedly decreased infections with pyogenic bacteria |
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what are the characteristics of common variable immunodeficiencies?
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decrease in at least 2 Ig types
IgM =< normal recurrent pyogenic bacterial infection |
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what are the symptoms of DiGeorge syndrome?
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agenesis of thymus
huge decrease in CD-8 T cells susceptible to fungal and viral infections |
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what is the cause of Wiskott-Aldrich Syndromme
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mutated X linked gene leads to decline in T cells and platelets
IgM down IgA and IgE up |
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what is the cause of APECED?
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defect in deletion of self-reactive T cells- autoimmunity
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what are the disorders of phagocytes?
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CGD: defect in respiratory burst
LAD: Leukocyte adhesion deficiency (delayed cord separation and infection) |
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deficiencies in "early" complement components lead to...
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SLE like syndromes, rheumatoid like disease, and infections
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deficiencies in "late" complement components leads to...
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SLE like diseases
susceptibility to neisseria meningitidis infection |
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what is responsible for HIV binding to T cell?
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gp120: binds CCR on T cell
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what is responsible for HIV's ability to penetrate the T cell membrane?
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gp41
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how does HIV get access to T cells?
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it binds APCs and "hitches a ride" to T cells
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what components are necessarily for HIV to infect T-cells?
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gp120 to bind to CD4
CCR5 on T cell as a co-receptor gp41 for entry into T cells |
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what neoplasms are associated with AIDS?
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Kaposi sarcoma (skin papules)
B cell non-hodgkin lymphoma brain lymphoma uterine cervical cancer |
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mutations at what gene provide protection against HIV infection?
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CCR5 (it is the co-receptor for HIV T cell entry)
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how can an HIV infected patient keep the infection at bay?
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CD8 T cells can produce a factor called Cellular Anti-viral Factor (CAF) that blocks HIV replication in CD4 cells without killing the CD4 cells
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how does amyloid appear on staining?
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fibrils form misfolded linked beta sheets
pinkish takes up Congo reddish orange apple green with polarized light |
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where is the best play to take a biopsy to diagnose an amyloidosis?
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fat biopsy
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what are some of the main causes of secondary amyloidosis?
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chronic inflammation
rheumatic autoimmune diseases |
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what should you always consider on ddx of unexplained organ failure or unexplained organomegaly
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amyloidosis
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type I hypersensitivity rxns
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IgE antibody mediated huge release of histamine. Anaphylaxis
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type II hypersensitivity rxns
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antibody mediated
cytotoxic: opsonization/complement deposition non-cytotoxic: against ECM proteins (pemphigus) or against receptors (Myasthenia Gravis) |
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type III hypersensitivity rxns
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Ag-Ab complex deposition. Serum sickness.
fever, urticaria, renal dysfx |
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type IV hypersensitivity rxns
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delayed type cell mediated. TB skin test
Acute transplant rejection and GVHD |
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what is the process of thymic T cell selection?
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all cells have MHC I, dendritic cells and macrophages have MHC II
T cells that react too strongly to MHC are deleted (negative selection), T cells that reaction somewhat to MHC are selected (positive selection) |
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what 2 mechanisms prevent selection of self reactive CD8 T cells?
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chronic stimulation of T cells favors apoptosis
MHC presentation without co-stimulatory signals (by normal host cells) to an unactivated T cell causes anergy of the T cell |
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a loss of what part of the apoptotic pathway can cause autoimmunity?
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Fas or FasLn (can cause autoimmune lymphoproliferative syndrome)
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which complement components can cause autoimmunity, and how can that happen?
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C2 and C4 especially
seems paradoxical! but...early complement is important for opsonization of apoptotic bodies. without clearance, the apoptotic bodies are immunogenic and lead to autoimmunity |
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what is Chronic Discoid Lupus?
how is it diagnostically different |
a subtype of SLE
Skin manifestations ONLY has ANA but no anti-dsDNA-Abs |
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what kind of antibodies do you get in Drug-induced lupus?
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anti-histone Abs
DO NOT have anti-dsDNA-Abs |
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what are the important diagnostic tests for RA?
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Rheumatoid factor: an autoantibody against denatured IgG
good sensitivity, not great specificity anti-CCP Ab: not great sensitivity, great specificity |
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what are the main symptoms of scleroderma?
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CREST
Calcinosis (thickening of skin and vasculature) Raynaud's phenomenon (vasospasm in hands) Esophageal dysmotility Sclerodactyly Telangectasia |
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what is the pathogenesis of systemic sclerosis (Scleroderma)?
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fibrosis of skin, vasculature, GI tissues
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what are the diagnostic autoantibodies of systemic sclerosis (scleroderma)
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anti-Scl-70 Ab
Anti-centromere Abs |
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what is the pathogenesis of Sjogren's syndrome?
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T cell infiltration of lacrimal and salivary glands. Xerostomia and keratoconjunctivitis sicca
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what is the difference between raynaud's phenomenon and raynaud's syndrome?
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phenomenon: small artery vasospasm leading to discoloration of hands due to cold or stress
disease: cryglobulins that agglutinate and gel at cold temperatures leading to the same phenomenon |
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anti-ANCA antibodies are present in which two conditions?
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wegener's granulomatosus
microscopic polyangitis |
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what are the symptoms of Kawasaki disease?
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MI
Fever Swollen hands and feet with desquamating rash eye redness strawberry tongue |
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what are the symptoms of polyarteritis nodosa?
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microaneurysms of small-med vessels
skin, joint, heart, sometimes renal involvement |
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how does polyarteritis nodosa differ from Microscopic Polyangiitis?
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MPA has renal and pulmonary involvement (always) and anti-ANCA
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cerebral infarction causes what type of necrosis?
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liquefactive because it activates autocatalytic enzymes
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