Week 3 Flashcards
b cell location
follicles. Stained immunohistochemical cd20
t cell location
perifollicular. stained immunohistochemical. cd3
Use of HLA testing?
Screen for disease risk and test for transplantation workup (MHC1 match better prognosis)
Problems distinguishing b-lymphocyte prolif from monoclonal (neoplastic) Use what?
B-lymphocyte immunoglobluin gene rearangement analysis
TCR gene rearrangement analysis
check if population of neoplastic t lympocytes have same TCR gene rearrangement. Helps determine neoplastic prolif
flow cytometry
quantifies fluorescent tagged cells. MUST USE FRESH UNFIXED TISSUE/BLOOD
Normal lymph flow cytometry
85% t cell, 15% b cell. 1.5% more kappa than lambda
In situ hybridization
used to stain lambda or kappa lights chains. If both stain, its polyclonal
Protein electrophoresis
Checks gamma peak looking for a spike or not.
immunofixation electrophoresis
used to detect what type of M-spike there is if long skinny peek on protein electrophoresis
waldenstroms macroglobulinemia shows up how?
M spike in gamma regoin and kappa restriction
5 pillars of cancer treatment?
surgery, chemo, radiation, target therapies to specific changes on cancer cell and now immunotherapy
Atopy
Predisposition to develop immediate hypersensitivy reaction. 50% atopic people have family with allergies
Localized allergic reaction examples and how to diagnose
sinusitis, bronchial asthma, food allergies, urticaria. Find offending agent by using skin prick allergy test
Treatment of localized allergic reaction
avoid offending agent, medications (steroids, antihistamines, etc), or immunotherapy (desensitization therapy)
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<p>define system anaphylaxis</p>
life threatening systemic allergic reaction. Typicall find fall in BP, bronchospasms and laryngeal edema
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<p>causes of systemic anaphylaxis</p>
drugs (penecillin), food (peanuts) insect toxins (bee sting) or latex allergy
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<p>treatment for anaphylaxis</p>
IM EPI!
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<p>What is desensitization therapy?</p>
used with honeybee allergy for example, give repeated injections with higher doses. Body makes more IgG that can bind to allergin and prevent binding to mast cell
<p><p>Pemphigus vulgaris</p></p>
<p><p>HS type 2. antibodies against desmoglein found in desmosomes of the epidermis. result is massive blisters</p></p>
<p><p>goodpasture syndrome</p></p>
<p><p>HS type 2 antibodies against basement membrane of glomerular .LINEAR PATTERN OF DEPOSITION</p></p>
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<p>reason for type 3 HS damage</p>
antigen antibody complex FORM, DEPOSITION on vessel walls and lead to tissue damage when cleared out. by COMPLEX MEDIATE IMFLAMMATION
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<p>How to detect disease activity in HST-3</p>
Check levels of c3 as they are burned up with course of disease
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<p>Key feature of HST-3 and reason for different manifestations</p>
FIBRINOID NECROSIS - replacement of damaged vessel walls. Lupus is example of HST3 IF IN SKIN. various antigen and site of deposition leads to DIFFERENT CLINICAL MANIFESTATIONS
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<p>Example of immune complex deposition</p>
LUPUS AND POSTSTROPTOCOCCAL GLOMERULONEPHRITIS make GRANULAR DEPOSITS resulting in kidney damage!
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<p>type 4 hypersensitivity</p>
DELAYED response of t cells from antigen. cd4 releases cytokines after repeat exposure, leading to inflamation and tissue injury
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<p>examples of type 4 hypersensitivy</p>
TB skin test. poison ivy, nickel exposure.
> Granuloma formation
macrophages enter epithelial following cytokine activity. Becomes histiocytes and surround infection to contain it.
large dense pink circles
<p>caseating granuloma caused from TB. CENTRAL NECROSIS</p>
oncogenes are?
oncogenes are similar to pro-oncogenes and express oncoproteins. only need ONE allele to activate. promote cell growth with absense of signals
RAS oncogene does what
when mutated its permanently active leading to cell stimulation
why test for her-2/neu?
if this epidermal growth factor receptor is present, can be treated by monoclonal antibodies!
Why test for KRAS mutation?
if present, pathway is active without the EGFR signal so it cant be treated like her2/neu
If BCR-ABL is found?
CML! philly 22. incrased growth. This is a oncogene
Inheritad mutation in BRCA1/2?
BRCA regulates DNA repair. if BOTH are lost may get breast, prostate or ovary cancer. auto domin
Inherited mutation in APC?
APC stops nuclear transciption. If both alleles are lost, get familial polypsos (colorectal carcinoma). auto domin
Warburg effect?
cancer cells shift to aerobic glycolyis to make more cell required intermediates
BCL-2 overexpression?
BCL2 prevents cytochrome c release from mito. If increased it prevents cell death and can lead to follicular lymphoma.
hereditary nonpolyposos colon cancer syndrome
defect in DNA repair. born with one, other mutated later in life. auto dominant
New cancer classification system?
No longer classified by anatomy but by THERAPEUTIC TARGETS
platelet activating factor
released by mast cells AND macrophages. platelet aggragation and contract pulmonary smooth muscles
Epi treatment dosing. Other treatment for anaphylaxis
.01mg/kg IM in leg (hold for 10 seconds if pen) use 1:1000 mixture.
give oxygen, monitor vitals, benadryl, albuterol. give IV if bp does not rise.
.3 max in children, .5 in adults!
Adult epipen is preset to .3 mg/kg
Cell kill hypothesis
CCS drugs follow first order kinetics and kill PROPORTION of tumor cells at given dose
radiation recall reaction
Common causes?
erythema and desquamation of skin at sites of prior radiation therapy
Most common with ANTHRACYCLINE (doxo)
recruitment in antineoplastics
CCNS used for log kill, makes cancer go to Go, CCS given to kill rapidly dividing cells
synchrony with antineoplastics
Ability of CCS to make cells go into same cell division at same time. results in more sensitive to drugs. Time delivery of second drug.
folic acid
if low?
When to give it?
folate supplement. more stable.
If low, get megaloblastic anemia and NUERAL TUBE DEFECT. No neural damage
Give only after b12 is stable, otherwise will mask neuro defects (anemia comes before neuro damage in b12 defiency)
leucovorin
replaces folate therapy
does not need DHFR
B12
low due to malabsorption
cant give oral
neuro damage
b12 supplements
Hydroxycobalamin (also used for cyanide poisoning)
-stays in circ longer due to plasma bound
cyanocabalamin
reduced folate carrier
low affinity high capacity transport for folate
leuco >folate > metho
reduced expression is PRIMARY resistance
Important at PHARM levels
leucovorin rescue (form of rescue therapy)
if RFC expression is low, need to increase methotrexate levels. Give leucovorin to feed normal cells that wont have DHFR working anymore
folate receptor
high affinity low capacity system found on specific tissues (lungs kidney, placenta). transport folate at low levels.
Important at PHYSIOLOGICAL CONC.
polyglutamation
folate is polyglutamated by folypolyglutamate synthase (FPGS). Needed to retain it and increase affinity for thymidylate synthase
Example of SELECTIVE TOXICITY
Trimethoprim
inhibits BACTERIAL DHFR
Sulfamethoxazole
inhibits dihydropteroate synthase in bacteria. works synergisit with trimethoprim
dihydropyrimidine dehydrogenase
degrades 5-fu in liver. If deficient, increased sensitivity to drug
pyrimidine monophosphate kinase
converts UMP to UDP. important in resistance to 5-fu
rate limiting step in DNA synthesis?
thymiddylate syntahase. dUMP to dTMP
