What is a DNA topoisomerase?
unwinding of DNA for transcription
Topoisomerase-1 (scl-70) antibodies are seen in scleroderma and crest
what is translation?
building of a protein out of amino acids from mRNA template.
Antibodies to tRNA synthetase (anti-jo-1-antibiodies) are seen in dermatomyositis
what are centromeres?
they link the sister DNA
anticentromere antibodies are seen in Crest Syndrome
What does tumor supressor gene P53 do?
prevents entry into S phase (synthesis)
losing it opens the gate to synthesis
implicated in osteosarcoma, rhabdomyosarcoma dn chondrosarcoma
pRB-1 Retinoblastoma protein
undergoes progressive cell cycle regulated phosphorylation
targets E2f: a transcription factor that regulates genes important for cell cycle control
Agarose Gel electrophoresis
Northern Blot: detects RNA
Western Blot: detects Protein
Southern Blot: Detects DNA
cytogenic analysis is used to dtect chromosomal translocations
t(x;18) synovial sarcoma
t(11;22) Ewings Sarcoma
t(12:16) myxoid liposarcoma
t(12;22) in clear cell sarcoma
what is silencing RNA?
Blocks transcription of mRNA in order to study results of genes loss of function.
How does the innate system recognize pathogens?
Pathogen-associated molecular patterns (PAMPs) on microbes are recognized by TLRs on innamte immune system cells (macrophages and dendritic cells)
There is an upregulation of NF_KB transcription factor, resulting in release of immune mediators (PRP enzymes)
Arachadonic acid is released from cell membtanes making prostaglandins and leukotrienes
What is the immununology term for anyphylaxitic shock?
IgE-type 1 hypersensitivity reaction
What are some disease examples of autoimmunity, where the epitopes are "self"?
Anti-RNP-mixed connective tissue
anti-histone- drug induced lupus
anti-RO and anti LA--sjogrens
HLA gene on chromosome 6
can be rearranged to make an antigen specific receptor on APCs for a billion or more different epitopes
associated with (PAIR)
Type 1 hypersensitivity
Mediated by IgE
mast cell degranulation-histamine
Food and drug allergies
Type II hypersensitivity
Mediated by IgM or IgG
cytotoxic, antibody mediated response
Heparin induced thrombocytopenia
Type III hypersensitivity
Immune complex mediated ) antigen/antibody
Type IV hypersensitivity
cell-mediated (no antibodies)
helper T-cells activate cytotoxic cells and macrophages to attack tissue
Type 1 diabetes
type iV response to orthopedic implants
initiates acute phase response
induces bone loss through activation of osteoclasts via RANK/RANKL pathway
induces synthesis of acute phase proteins from liver
is key to growth and survival of multiple myeloma cells
what makes staph resistant to PCN?
b-lactamase bla gene
what gene makes staph MRSA
penicllin-binding protein 2a
fibronectin in staph increased adhesions to titanium
what is the technical name for biofilm?
what is the cytotoxin for ca MRSA?
Panton-Valentine leukocidin cytotoxin (PVL)
pore forming toxin specific to neutrophils
list some clinically relevant bacterial toxins?
Endotoxin-gram negative lipopolysaccharide
Exotoxin-Clostridium perfringens-lecithinase-tissue destroying alpha toxin
accounts for the myonecrosis and hemolysis of gangrene
Clostridium tentani toxin
tetanospasmin--blocks inhibitory nerves
lockjaw or muscle spasm
blocks acetylchonine release
activate 20% of T-cells
massive cytokine release
Group A strep_ M protein
S. auress-TSS toxin 1
located on staphylococcal chromosome cassette mobile element-Carry IV
encodes for penicllin-binding protein 2A, which has low affinity for b-lactam antibiotics
Community acquired MRSA
Bacteris have smaller SCCmec genetic elements
almost all have PVL cytotoxin
gamma-hemolysin-a pore forming toxin that can lyse PMNs
At risk grous are athletes, IV drug abusers, homelss, military recruits, prisoners
INfection of dermis and lymphatics
Group A streph
peau de orange
tx with PCN or erythromycin