NAC consultant Eavan Muldoon introduces herself as our new medic and talks a little about her background, part of which was spent at Tufts Medical Centre, Boston, USA. Then Graham Atherton talks about IgG, what they are and how they work.

1. LED BY GRAHAM ATHERTON
SUPPORTED BY
NAC CENTRE MANAGER CHRIS HARRIS
EAVAN MULDOON
CONSULTANT
THE NATIONAL ASPERGILLOSIS CENTRE
NATIONAL ASPERGILLOSIS CENTRE
UHSM
MANCHESTER
Support Meeting for
Aspergillosis Patients & Carers
Fungal Research Trust

2. Aspergillus meeting – Friday 20th
September 2013
Eavan Muldoon
Consultant in Infectious Diseases

4. Tufts Medical Center

5. Differences between the USA and UK
• Differences in healthcare provision
– Funding
– Structure of medical teams
– Clinics
– Number of doctors
• Differences in Management of Aspergillus
disease

6. Aspergillus outbreak USA 2012

7. Programme
 1.30 Eavan Muldoon– NAC Consultant
 2.00 Graham Atherton – Your subject (IgG)
 2.30 Patients Discussion (Break)
 3.00 Group discussion/Requests for information
 ICAAC : A ‘sniffer’ for Aspergillosis
 Patients survey
 3.20 Q & A from the floor or online

8. Suggest a subject
Can be on any relevant subject you would like to hear
our opinion or get our help with
Send suggestions to admin@aspergillus.org.uk
Pass notes to me at clinic or at the meeting
Phone them in (24 hrs) at 0161 291 5866

9. IgE
Immunoglobulin E (IgE) – an antibody
Also have IgA, IgG, IgM – each plays a different role
IgE main role – defence against parasites!
Normally very low levels
IgE is released as soon as an infection is detected –
the hypersensitivity response. Gets all immune cells
ready for action – allergy!

10. IgE/IgG
All look the same!

11. Role in disease
Secondary Immune response (IgE Is part of the
Primary Immune response)
All happens in our Lymph nodes
The most abundant Ig in our bodies – making up
75% of all Ig molecules circulating
Made by B cells
Controls infection – bacteria, virus, fungus

12. Highly specific
Ends are HIGHLY variable so can recognise millions
of different molecules on the surface of foreign
bodies entering our bodies

13. Recognition & replication
Once attached the other end of the antibody
becomes very attractive to B cells, which will stick to
it.
This stimulates the production of more B cells
producing that specific antibody and each B cell
produces lots more antibody. This quickly produces
vast numbers of specific antibodies
All this activity is one reason why your lymph nodes
swell up when you have an infection!

14. Recognition & replication
Interestingly, the better the ‘fit’ (recognition) of the
antibody to the foreign particle (virus, bacterium,
fungus) the more intense the production of that
antibody, so the best antibodies quickly dominate.
Clever!

15. Vaccines
Once B cells go through this process they can
become ‘memory’ B cells with a long life – this is why
vaccination works.
In vaccined individuals, IgG appears about 24–48
hours after infection.

16. How do antibodies work?
Multiple mechanisms
IgG-mediated binding of pathogens causes their
immobilization and binding together via
agglutination;
IgG coating of pathogen surfaces (known as
opsonization) allows their recognition and ingestion
by phagocytic immune cells;
IgG activates the classical pathway of the
complement system, a cascade of immune protein
production that results in pathogen elimination;
IgG also binds and neutralizes toxins

17. Protection of new born child
IgG is small in size allowing it to easily perfuse tissues.
It is the only isotype that can pass through the human
placenta, thereby providing protection to the fetus in utero.
Along with IgA secreted in the breast milk, residual IgG
absorbed through the placenta provides the neonate with
humoral immunity before its own immune system
develops.
Colostrum contains a high percentage of IgG, especially
bovine colostrum.

18. What do your tests mean?
If you have large amounts of IgG circulating in your
blood, you probably have an ongoing infection (not
allergy!)
If we can identify the specific type of antibody as
being one that attaches to a specific bacteria, virus or
fungus then it tells us which organism is causing the
infection.
Useful!

19. Other uses
Screening blood or other tissue

20. Other uses: Detection
Specific detection

21. Other uses: detection
Can link antibody to colours
This is an image showing where 3 different proteins
are in a single cell.

22. Other uses: detection
Highly convenient, disposal tests (very simple to use)

23. Other uses: detection/purification
Great for detection
Used to try to use this to get purified protein –
limited in scale and purity

24. Other uses: purification
Magnetic beads

25. Any other Immunoglobulins?
IgM – very large, found in spleen. Good indicator of
very recent infection. Good at binding infecting
particles even if no prior immunity! Blood
agglutination is mainly caused by this Ig
IgA – Important in the mucosal lining of our organs,
the main immunoglobulin found in mucous
secretions, including tears, saliva, colostrum and
secretions from the genitourinary tract,
gastrointestinal tract, prostate and respiratory
epithelium. Highly resistant to breakdown in gut.
IgD – found in small amounts in blood.

26. ICAAC 2013: Aspergillosis ‘sniffer’
An Aspergillus fumigatus (AF)-Specific Breath Volatile
Organic Compound (VOC) Profile is Diagnostic of Invasive
Aspergillosis (IA)
Sophia Koo, MD; Brigham & Women’s Hosp., Boston, MA
Poster Session 023, Presentation M-219
The suggestion is that this research will enable us to
diagnose invasive aspergillosis by testing the breath of the
patient. This would be a useful tool (if reliable and
accurate) as diagnosis of IA is currently slow and difficult,
and even more importantly all delay in the diagnosis of
invasive aspergillosis has the effect of increasing mortality
rates. The sooner we are able to start treatment the better!

27. Patients Survey

28. Patients Survey

29. Patients Survey

30. Patients Survey
Of those that answered no,
32% of them do not have a
computer or use the
internet.
Anything we can do to
improve this?

31. Patients Survey

32. Patients Survey
Can we fix this in
any way?

33. Patients Survey
Can we improve this?

34. Has the move to Friday Meetings worked?
8 months prior to move - 32 patients/carers
attended
8 months after move - 42 patients/carers attended
(32% increase)
Total numbers of visits have also risen 15 - 20%
=Success! Any other ideas?
Over the whole history of the meetings (3 years),
over 150 patients/carers have attended.

35. Patients Survey
Can we improve this?

36. Thank You
“The best chance we have of beating this illness is to
work together”
Living with it, Working with it, Treating it
Fungal Research Trust