Systems 5b.txt

• alkyl radicals, fuck with DNA
• dacarbazine (purine)
• cisplatin: sulfur groups

• mimic metabolites of nucleic acids effect S phase
• inhibit enzymes or produce incorrect code
• methotrexate: DHF reductase inhibitor
• mercatopurine: purine mimic
• 5-fluoruracil: pyrimidine analouge

abberrant fatty acid synthesis incorporated to cell membranes

• streptomyces cytotoxin bind DNA inhibit cell division
• dactinomycin: G-C intercalater
• doxorubicine: inhibit replication, topoisomerase
• bleomycin: DNA scission & fragmentation (G2 and M phases)
• mitomycin: cross-link DNA

• antimicrotubule agent, arrest metaphase
• vinblastine
• vincristine

• disrupt tubulin (tubules) normal dynamic reoganization of microtuble network
• paclitaxel & docetaxel

• synergy
• intermittent
• alternating non-cross resistant regamin
• bone marrow transplantation or peripheral stem cell reinfusion.

• alcohol, tobacco, HPV, radiation
• chewing quids of betel
• non-fitting dentures

• surgery, radiation
• chemo: cisplatin, 5-flurouracil, carboplatin, paclitaxel
• tumor growth factors: EGFR

• tyrosine kinase dimerize to activate overexpression in many HNSCC
• EGFR Abs & tyrosine kinase inhibitors

• Gleevec (imantinib) bcr:abl, gastrointestinal stromaltumors
• Iressa: getitinib: non-small cell lung
• Tarceva (erlontinib): non small cell lung and pancreatic cancer

• oral mucositis
• xerostomia
• taste dysfunction
• TMJ dysfunction
• dental and skeletal growth or dev anomalies

• innate: non-spec, no memory, fast, granulocytes-monocytes, invariant, Non-MHC
• adaptive: specific, memmory, delayed, lymphocytes, variant, MHC restricted

dendritic, monocyte/macrophage, B cells

• 1. binding T Cell receptor in context of MHC I or II
• 2. Co stimulation (CD28 T, B7 APC)
• 3. activation through secreted cytokines
• activate, survive, differentiate

RAG1 RAG2 recombinase (only adaptive)

• MHC I: CD8 T cells, 9AA peptides
• MHC II: CD4 T cells, 13-14 peptides

• TH1: IF-gamma, IL-2 activate macrophages
• TH2: IL 4,5,6,10, activate B cells
• TH17: IL-17, oral cavity, stim & recruit PMN
• Treg: TGF-beta regulate/anti-inflammatory
• can recruit & stim PMNs

• select good cells
• delete auto cells

• 1. neutralization
• 2. opsonization
• 3. activation of complement

• genetically altered
• hyperplasia
• dysplasioa
• in situ
• metastasis

carcinoma

sarcoma

-blastomas

DNA seq variation, can be responsible for individual variability

transmitted to every cell

clonal descendents only affected.

• evade apoptosis
• self-sufficient growth signals (oncogenes)
• insensitive to anti-growth (tumor suppressor)
• angiogenesis
• limitless replication: (telomerase activation)
• tissue invasion (metastasis)

• proliferation genes normally regulated by growth signals, cell-cell or extracellular matrix interactions
• growth factors: PDGF, FGF, EGF
• signal transducers: ras, src, abl
• signal effectors: myc, fos, jun
• oncogene: mutant allele of proto-oncogene (self sufficient)
• dominant gain of function

respiratiory, urogentital, GI, glands(lacrimal, salivary, mammary)

protooncogene that has a point mutation to be constitutively active (pancreas 100%, colon 50%, lung, AML (30%))

• tranlocation of 9 to 22 overactive tyrosine kinase
• philadelphia (CML)
• FISH diagnosis
• treat w/ gleevec (binds to BCR/ABL)

• human epithelial growth factor 2 (tyrosine kinase) breast cancer
• treat w/ herceptin
• FISH diagnosis

• brakes on cell growth, protect inappropriate cell division
• recessive loss of function-> cancer (usually both copies to be deleterious)
• deletion (loss of heterozygosity) most common
• missense(1 bp), nonsense(premature stop), frameshifts(insertions or microdeletions)

epigenetic, lead to inactivation of gene, occurs nearly every neoplasm

uniparental disomy, normal allele deleted, mutated duplicated

• inhibits cell cycle until ready
• binds E2F (prevents G1 to S) until phosphorylated
• mutations prevents binding

DNA damage/stress detector

DNA repair genes, lead to breast or ovarian cancers

MLH1, MSCH2, MSH6

400m2 vs 2.5 for skin

• microfold specialized lymphoid follicle-associated dever adntgens across
• found in GI tract(adenoids, tonsils, small intestin, colon, rectum)

• exlude antigens
• tight junctions, air or fluid flow, mucus (glycocalyx), pH, microvillae

• collectins: prevent colonization & entry
• defensins: antimicrobial
• TLR & NODs: ID microbes as foreign, activate NFkB which signal epithelial to secrete cyto and chemokines

• c-type lectins SP-A, SP-D (surfactant proteins)
• complement mannose binding

Surfactant proteins recognize sialic acid and galactose

• PMNs
• paneth cells (intestinal crypts)
• eptithelial (UG & respiratory tract)

tonsils and adenoids ring of lymphoid tissues around entrance of gut and airway

lymph node analogue of B cells not as many T cells in GALT

• enter peyers patches via CCR7 and L-selectin
• activate
• drain to lymph nodes
• activated T cells w/ CCR9 go to lamina propria of small intestine

IgA-bind and neutralize (all over, from laminal propria, endosomes or lumen)

IgG>>IgM

• IgA dimerize via J chain
• attach to poly-Ig receptor to be trancytosed to lumen

CCL20 and CCL9 (direct dendritic to microbe) (DCs can reach trough tight junctions