Ανοσοθεραπεία 100 χρόνια
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Transcript of Ανοσοθεραπεία 100 χρόνια
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1911-2011
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LEONARD NOON
E St. Marys London UK.
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Noon L. Prophylactic inoculation against hay fever. Lancet. 1911;1:1572.
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Noons original hand-drawn chart.The numbers at the sides denote the resistance of the patient, given in terms of the strength of pollen extract, one drop of which was sufficient to excite a conjunctival reaction. The arrows indicate subcutaneous inoculations of pollen extract, quantities given in units described in the text. Figs.1 and 2 refer to a patient at different periods of treatment; Fig.3 shows the response obtained after about a months treatment in another case; and Fig. 4 the early stages of treatment. The subcutaneous injection was begun with small doses every 3 to 4 days and the dose was increased as the intervals between doses too.It was found out in the early stages of immunization that an overdose could induce a severe attack of hay fever, lasting nearly 24 hours, which was not observed in the later stages. After the inoculations there was an increase in tolerance (Fig.1).
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ROBERT A. COOKE- .- .- shock .
-1910: -1911: .- ALBERT VANDER VEER : , I.D. tests, >> >> >> test & SCIT, hay fever, >> , >> ,
.-1922: 1 SCIT (Journal of Immunology). COOKE: , , SCIT (- ). COCA: . BROWN: SPT vs ID tests.
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-1912: o SCHLOSS .-1917: o WODEHOUSE .-1917: o WALKER .-1926: PHILIP LEVINE & ARTHUR COCA (IgE) SCIT .-1927: o VANDER VEER, COOKE & SPAIN hay fever SCIT.
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1930: FREEMANrush immunotherapy 1,5-2 h 14 h.1932: R. COOKE- ,- - . SCIT.1933: A.STULL & R.COOKE- PNU (Protein Nitrogen Units)- standardization .1934: HARRISON- (alum precipitated extracts).1935: COOKEs team- RooseveltN.Y. USA.- blocking SCIT.
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-1940: A.STULL, R.COOKE & W.SHERMAN depot -1949: SCIT.-1950: & .
-1935: MARY LOVELESS Cooke. blocking , .-1937: LOUIS TUFT .
MARY LOVELESS
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1951 - 1970Scit Scit
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1951:LOWELL & FRANKLIN SCIT (DB Ragweed-SCIT).
1954: MARY LOVELESS - SCIT . -Rush SCIT ( 6 1 ).
1955: (1 ). , . 2000 FDA & .
1957: MARY LOVELESS (adjuvants) .
1957: .
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-1962: POTTER & BOYCE - .
-1950 1970: : - BURNET: clonal selection theory - - - - .
1967: ISHIZAKA & ISHIZAKA IgE .
& .
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SCIT
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SCIT- - (Metzger et al, 1987)- SCIT FEV1>)- / = 4% (Reid , Nelson)
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- ( IgG -) . (Sobotka, Valentine, Ishizaka, Lichtenstein, Hunt, 1970).
-M , . (Lockley et al, 1982)
- SCIT .
- SCIT
- SCIT
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1991 - 2010
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SCIT : 1991 - 2010
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- SCIT . (Des Roches et al, 1997), (Pajno et al, 2001).
- N SCIT . . (PAT-Study : Moller et al, 2002).
- ~73% & ~57% SCIT. (M.A. Calderon-Cochrane Database Syst Rev, 2007).
- SCIT ( 9,5-14) (Johnstone & Dutton, 1968), (Cools et al, 2000)
1991 - 2010
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SCIT1991 2010
TH2 TH1 , mRNA INF- & IL-10.(Durham et al, 1996), ( 2001-2004).
- IL-10 (2-4 w) & . , IgG4 (6-12 w).(Francis et al, 2008)
- - , Foxp31CD25+CD3+ - SCIT & & .(Radulovic et al, 2008)
- IgG4 blocking , SCIT.(Frew, 2010).
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( 100 ?)
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: - - - &
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- SCIT plus OMALIZUMAB
- TOLL-like Receptors
- Allergoids
- Recombinant Allergens
- Peptides
- Other Routes of Administration
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SCIT plus OMALIZUMAB
OMALIZUMAB(anti-IgE ) SCIT.
-plan: Omalizumab IgE & FcR1 receptors , . SCIT .
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SCIT plus OMALIZUMAB
( ): 9 w Omalizumab placebo, 1-day rush placebo . 12 w Omalizumab placebo + maintenance .Omalizumab group: 5 SCIT, & .(T.B.Casale et al.,JACI 117, 2006). ( ): Omalizumab + SCIT(maintenance) - vs- SCIT () Omalizumab group.(J. Kuehr et al, JACI 109, 2002).- : 12w Omalizumab placebo, SCIT ()Omalizumab group: SCIT, , .(M.Massanari et al, JACI 125, 2010).
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: SCIT plus omalizumab - scit - . :- Omalizumab, SCIT 3-5 ?- ?
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TOLL-like Receptors (TLR)
= , TH1 regulatory T-cell . .. TLR-4 (.LPSs), TLR-9 - CpGs DNA.
Plan: TLR- SCIT.
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TOLL-like Receptors (TLR)
POLLINEX QUATTRO (Allergy Therapeutics, West Sussex, U.K.)= glutaraldehyde L-tyrosine TLR-4 monophosphoryl lipid A. - & . . , , . , 3 w.: - SPT. - >> >> IgE. - >> IgG. - ~ 93,5% . - ~ 80% >> - ~ 6,3% . - ( ) ~ 0,5%.
CpG (ISSs) (.. Ragweed). (phase II).
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ALLERGOIDS
glutaraldehyde formaldehyde , IgE-epitopes T-cell epitopes. , FDA (). - POLLINEX QUATTRO - ALLERGOVIT (Allergopharma KG Reinbek, Germany) - DEPOGOID (Leti Pharma GmbH, Witten, Germany)
( ): - & - IgG1 & IgG4 - (conjunctival provocation testing)
: - ? ( ).
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RECOMBINANT ALLERGENS ( )
= , , & .
: , , .
/ .
( ): - IgG1 & IgG4, - SPT, - oral allergy syndrome.
( ): - (trimer- recombinant allergens). - (fragments-recombinant allergens).
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PEPTIDES () T-cell , & .
, 3 .
Allervax Cat Immunologic, Waltham, Mass) , 2 , 230 . . .
Bee Venom Peptide Immunotherapy (5). . .
.
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& : .
: .
PATCH : .
(ORAL IMMUN.)M : , & .
(ORAL + SUBLINGUAL IMMUNOTHERAPY)K , , , .
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SLIT ( )
- .- . FDA. (WAO Position Paper 2009).
: - - - - - - - .
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75 . 25 : , , .
100!
.. ,
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