Documente Academic
Documente Profesional
Documente Cultură
Imunitate Imunitate
innascuta dobindita
(prima linie de aparare) (a II-a linie de aparare)
adaptat dupa
“Microbiology and Immunology on-line”, University of South California, School of Medicine
http://pathmicro.med.sc.edu/book/immunol-sta.htm
Celulele sistemului imun
preluat din
“Microbiology and Immunology on-line”, University of South California, School of Medicine
http://pathmicro.med.sc.edu/book/immunol-sta.htm
preluat din
“Microbiology and Immunology on-line”, University of South California, School of Medicine
http://pathmicro.med.sc.edu/book/immunol-sta.htm
Tesutul limfoid
Distributia organelor limfoide
preluat din
“Microbiology and Immunology on-line”, University of South California, School of Medicine
http://pathmicro.med.sc.edu/book/immunol-sta.htm
Circulatia limfocitelor in organele limfoide periferice
preluat din
“Microbiology and Immunology on-line”, University of South California, School of Medicine
http://pathmicro.med.sc.edu/book/immunol-sta.htm
preluat din
“Microbiology and Immunology on-line”, University of South California, School of Medicine
http://pathmicro.med.sc.edu/book/immunol-sta.htm
Raspunsul imun fata de patogeni
Raspunsul imun fata de patogeni
IMUNITATE INNASCUTA
preluat din Janeway, CA, Travers, P, Walport M, Shlomchik M “Immunobiology“, New York and
London: Garland Science; c20
http://www.ncbi.nlm.nih.gov/sites/entrez?db=books
IMUNITATE
INNASCUTA / nespecifica DOBINDITA / specifica
(innate immunity) (adaptive immunity)
SISTEM INTEGRAT
Specificitatea raspunsului imun adaptativ
Teoria selectiei clonale
ROL SI FUNCTII
originea si contextul atg
Recunoastere
Functii efectoare
microorganisme
• prevenire intrare patogene
• eliminare
ELEMENTE CONSTITUTIVE
1. Bariere anatomice
2. Componente moleculare
3. Componente celulare
Innate immunity
1. Bariere anatomice
- piele
- mucoase
• pH
Factori chimici • molecule antimicrobiene
3. Componente celulare
• Functia de eliminare a
microorganismelor patogene
neutrofile
monocite/macrofage Fagocitoza
celule dendritice
bazofile
mastocite Inflamatie
eozinofile
celule NK Citotoxicitate
Recunoastere imuna non-
self self
Ipoteze
Receptori (self vs. nonself microbian)
PRR Pattern Recognition Receptor
INNASCUTA DOBINDITA
(innate immunity) (adaptive immunity)
codificati in genom generati prin rearanjare
genica
Gram-negative Gram-positive
Pattern Recognition Receptors - PRR
• glycosylphosphatidylinositol
LPS
(gpi)-linked receptor
• Scavenger receptors (SR)
Endocytic PRRs oxLDL; microbes
• C-type lectin receptors (CLR)
Microbes; microbial moieties
Sugars
• Collectins
Bridging Glycoproteins
• Ficolins
molecules
(adaptat dupa Jeannin et al. “Pattern recognition receptors in the immune response against
Microbes; microbial moieties
dying cells”, Current Opinion• Pentraxins
in Immunology 2008, 20:1–8)
Pattern Recognition Receptors - PRR
Bacterie
FAGOCIT
Pattern Recognition Receptors - PRR
TLR
Toll-like receptors
NOD
nucleotide-binding
oligomerization domain
RIG-1
retinoic acid-inducible gene-1
Toll-like receptors (TLR)
proteine transmembranare tip I
conservate filogenetic (Drosophila om)
domeniu extracelular bogat in leucina
domeniu intracelular TIR (similar IL-1R)
TLR mamifere (11-om, 13-soarece):
recunoastere PAMPs
asociere cu alti TLR sau alte proteine (MD2,CD14)
Celule CD14+
(mo/M, PMN)
Celule CD14-
(endoteliu, epiteliu)
Celule CD14-
(ly B)
(adaptat dupa Donata Vercelli: Innate Immunity in Diseases of Lung, Heart and Blood)
TLR Infectie
PAMP
Spatzle PAMP
Toll Toll
Insecte Mamifere
dorsal NFkB
TINTE FARMACOLOGICE
Purpose
TLR agonists are novel agents for cancer therapy which
modify the immune response.
CONCLUSIONS:
This Phase II safety study suggests that the
administration of the novel lipid A antagonist, eritoran, is
not associated with overt toxicity in cardiac surgical
patients.
IPOTEZE
Naive
T cells
Signal 1 Signal 2
(costimulation)
APC
Danger
signal
- Receptori
(Medzhitov & Janeway, 1997)
- Semnale de pericol (“danger hypothesis”)
(Polly Matzinger, 1994)
MHC
NKR cls I
Celula Celula Absenta
NK tinta citotoxicitatii
NCR Ligand
activator
NKR
Celula Celula Citotoxicitate
NK tinta
NCR Ligand
activator
Innate immunity
ROL SI FUNCTII
Recunoastere
Functii efectoare
•prevenire intrare
microorganisme
•eliminare patogene
Functiile imunitatii innascute
PAMP
Stimulare PRR
stimuleaza fagocitoza
induce activitate microbicida
induce citokine inflamatorii:
IL-1, IL-6, TNF- (NF-kB)
activeaza imunitatea dobindita
expresia mol. costim.
(MHC cls.II, CD80/CD86)
Functii efectorii: Fagocitoza
Ingerarea
Distrugerea
Fagocitoza
Mecanism
dependent de oxigen independent de oxigen
O2 – - defensine
H 2 O2 - cathepsina B
1O - lizozim
2
OCl - lactoferina
OH - enzime proteolitice
- citokine pro-
inflamatorii (TNF-,
IL-1) PAMP / PRR
- vasodilatatoare
- complement
- bradikinine
permeabilitate
capilara
expresia mol.
adeziune cel.
endoteliale
diapedeza
Citokine Macrofag activat
EFECTE LOCALE
- activeaza - activeaza - activeaza ly - activeaza NK
endoteliul vascular endoteliul vascular - producere atc. - induce dif. Th1
- activeaza ly - creste
- acces cel. efect. permeab. vasculara
- acces cel. efect.
EFECTE SISTEMICE
- febra - febra - febra
- producere de IL-6 - mobilizare metaboliti - inducere proteine
- soc faza acuta
Chemokine
proteine masa moleculara mica (8-12 kDa)
rol: inflamatie, reglare raspuns imun, angiogeneza, hematopoieza,
interactie cu SNC
4 Cys pozitie conservata (punti disulfidice)
structura tertiara caracteristica (1- 3, )
redundanta (receptori si celule)
CXC CC C CXXXC
IL-8 MCP-1
-mo/m
-fibroblaste MIP-1, LIMFOTAKTINA FRAKTALKINA
-cel.endoteliale RANTES
NAP-2
-plachete MDC
IP-10 - mo/m
-fibroblaste - fibroblaste
- cel.endoteliale
-endoteliu - cel.epiteliale etc
SDF-1
-celule stromale
Functii efectorii: Rolul interferon
ROL SI FUNCTII
Recunoastere
Functii efectoare
• prevenire intrare
• eliminare
PAMP
Infectie
TLR
APC
costimulator
MHC / peptide
CD28
TCR
T cell Activare
PAMP
ADAPTIVE IMMUNITY
pathogen cellular immune response
TLR
Endocytic IL-12
PRR
Th1
IFN-
CD80/86 CD28
DC
TCR Naive Th1
MHC-II
T cells IFN-
INNATE IMMUNITY
IFN-/
Immature DC Mature DC
Imunitate innascuta
http://microvet.arizona.edu/Courses/MIC419/tutorials.html
http://pathmicro.med.sc.edu/book/immunol-sta.htm
http://immunology.ucsf.edu/immuno/courses/micro204/index
1.html