Transcript Activation by another means: role of immune system in Graves

Previously on Bio308
Large intracellular
signaling proteins
Types
2nd Messengers
Ca++
Similarities
Nucleotides
Advantages
IP3
DAG
Coordination
How does it all add up in Graves’ Disease?
Causes Treatments
Introduction to paper discussion:
What 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
Possible causes of Graves’ disease?:
Genetic predisposition, appear to need multiple ‘hits’
Gender
hormonal role suggested
Environment exposure to toxins (smoking),
radiation, stress
“Diffusible/Destructible signal”
antibodies
What are antibodies?
Antigen (Ag)
binding domain
Why make Ab?
What do they do?
How are antibodies made?
Fig 3-21
General structure of an antibody (Ab)
How does the body know
when to make Ab?
Antibody production
Poliovirus
Self vs. Non-self
Adenovirus
+Invasion by ‘foreign body’
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
Woman and child case
Sometimes just not feeling like ‘self’
Autoimmune responses
Relatively common
5% exhibit chronic,
debilitating symptoms
Causes– not known in all
cases
Graves’ disease patients
show high titer of TSI (also
called LATS)
www-immuno.path.cam.ac.uk/~immuno/part1/lec12/lec12_97.html
Predicted effect of TSI binding?
Clinical effect of TSI binding
Is activation by TSI
surprising?
Why do TSI get made?
www-immuno.path.cam.ac.uk/~immuno/part1/lec12/lec12_97.html
Yersinia entericolitica and Graves’ disease : ONE hypothesis
REMEMBER DISEASES CAN HAVE MULTIPLE
CAUSATIVE FACTORS
gram negative coccobacillus
Dennis Kunkel
Food borne pathogen
Generally porcine source
Can invade body through
structures in intestine
Can cause dysenteric
diarrhea
Thyroid
Lipoprotein epitope
TSH-Receptor
Ligand binding site
Molecular Mimicry
(Remember this is a hypothesis supported by
evidence in a small % of Graves’ cases. Most
people do not contract Graves’ this way.)
Cures 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
Case 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
Next on Bio308
Discussion of journal article:
Tuesday:
Terms and technique questions
Thursday: The paper-- figure by figure
Paper and study questions are found as links
under Assignments and Quizzes on Blackboard
The questions will take time to complete and the
article will be ‘heavy reading’-- do not put it off.