Title: Previously on Bio308
1Previously on Bio308
Signaling cascades
Large intracellular signaling proteins
Types
2nd Messengers
IP3
DAG
Ca
Nucleotides
Similarities
Advantages
Coordination
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3Next on Bio 308
Graves disease Comparing information from
other situations and Disease specific
information to come up with hypothesis for the
molecular basis of this disease
How does it all add up?
Causes
Treatments
Introduction to paper discussion Bowling et al.
4What could this case suggest about the cause of
Graves disease?
Case outline 31 year old Caucasian
female Smoker (before pregnancy) Previously
diagnosed with Graves disease 4 weeks post
partum Symptoms lessened during pregnancy
but now have rebounded 4 week old Caucasian
male Exhibiting symptoms of Graves disease
Return visit 5 weeks later Female smoking again
(but never around baby) Graves symptoms have
increased Infant no longer exhibiting symptoms
5Possible causes of Graves disease?
Genetic
predisposition, appear to need multiple hits
hormonal role suggested
Gender
Environment
exposure to toxins (smoking), radiation, stress
Diffusible/Destructible signal
antibodies
6What are antibodies?
Why make Ab? What do they do?
How are antibodies made?
How does the body know when to make Ab?
7Antibody production
Self vs. Non-self
What is foreign?
Immune response mounted
How?
Peptides presented to B cells, Designer Ag
binding domain created
End result
B cells and plasma cells produce specific Ab
T cells, macrophages attack Ab-Ag complex (attack
invader)
Invader forcibly removed
8Woman and child case
Sometimes just not feeling like self
Autoimmune responses
Relatively common
5 exhibit chronic, debilitating symptoms
Causes not known in all cases
www-immuno.path.cam.ac.uk/immuno/part1/lec12/lec1
2_97.html
9Predicted effect of TSI binding?
Clinical effect of TSI binding
Is activation by TSI surprising?
Why do TSI get made?
10Yersinia entericolitica and Graves disease ONE
hypothesis
Food borne pathogen
Generally porcine source
Can invade body through structures in
intestine
Can cause dysenteric diarrhea
An Invader
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12Molecular Mimicry
(remember this is a hypothesis)
13Cures for Graves Disease
Treatments
Radioactive Iodine
Drugs regulate thyroid or alleviate symptoms
Surgery
All require lifetime drug therapy
Graves disease does not appear to have one
causative factor but results from a combination
of genetic predispositions and environmental
factors
14Case study 1 Graves disease
Extracellular signaling
Role of biological membranes
Protein structure (and its importance for protein
function)
Signal transduction
3-D protein structure (and its importance for
binding)
Signaling cascades
Protein modifications and their importance for
activity
Antibodies specificity, role, and the importance
of binding specificity
15Next on Bio308
Discussion of journal article Bowling et al.
Tuesday 2/8 NO CLASS
Thursday2/10 Terms and techniques Tuesday
2/15 The paper-- figure by figure
Paper and study questions are found as links
under Assignments and Quizzes on Blackboard