IMUNITATEA = APRARE

Toi ne mbolnvim uneori..., apoi ne

nsntoim

Ce se ntmpl n organism n timpul unei
infecii / afeciuni ?
De ce ne nsntoim ?
SISTEMUL IMUN



Colecie de CELULE i MOLECULE care
protejeaz organismul mpotriva infeciilor,
transformrilor maligne i celulelor proprii
transformate non-self
IMUNITATE IMUNITATE

raspuns independent de antigen raspuns independent de antigen
receptori pt. patogeni: receptori pt. patogeni:
codificati in genom codificati in genom
specificitate joasa specificitate joasa
raspuns imediat raspuns imediat
lipsa memorie lipsa memorie

prezenta la toate organismele prezenta la toate organismele
pluricelulare pluricelulare

raspuns dependent de antigen raspuns dependent de antigen
receptori pt. patogeni: receptori pt. patogeni:
generati (rearanjare genica) generati (rearanjare genica)
specificitate inalta specificitate inalta
raspuns lent raspuns lent
memorie imunologica memorie imunologica
(expansiune clonala Ly) (expansiune clonala Ly)
prezenta doar la vertebrate prezenta doar la vertebrate
SISTEM INTEGRAT SISTEM INTEGRAT
INNASCUTA / nespecifica INNASCUTA / nespecifica
(innate (innate immunity immunity))
DOBINDITA DOBINDITA / specifica / specifica
(adaptive immunity) (adaptive immunity)
Rspunsuri imune
Skin & Mucous membranes
rapidly regenerating surfaces,
peristaltic movement, mucociliary
escalator, vomiting, flow of urine/tears,
coughing
Cellular and humoral defences
lysosyme, sebaceous/mucous secretions,
stomach acid, commensal
organisms,complement proteins,
phagocytosis, NK cells
Invasion
& infection
Barriers




Innate immunity






Adaptive immunity
+
+
Inflammation
Cellular and humoral defences
Antibodies, cytokines, T helper cells,
cytotoxic T cells
Factori fizici / mecanici Factori fizici / mecanici
1. Bariere anatomice 1. Bariere anatomice
-- piele piele
-- mucoase mucoase
Functia de prevenire a intrarii Functia de prevenire a intrarii
microorganismelor patogene microorganismelor patogene
Factori chimici Factori chimici
Factori biologici Factori biologici
motilitate: muco-ciliara, peristaltica
mucus
fluxul fluidelor prin organism
pH
molecule antimicrobiene
limfocite T intraepiteliale ()
celule B-1
Imunitatea Imunitatea
innscut innscut
2. Componente moleculare 2. Componente moleculare
-- receptori receptori
-- molecule secretate molecule secretate

Imunitatea Imunitatea
innscut innscut
Functia de recunoastere Functia de recunoastere
Functii efectorii Functii efectorii

Mol. anorganice: Mol. anorganice: HCl, NO, H
2
O
2
Peptide antibacteriene: Peptide antibacteriene: defensine, cathelicidine, histatine
Proteine antibacteriene: Proteine antibacteriene: lizozim, lactoferina, transferina
Lectine: Lectine: colectine, ficoline, receptori pentru Manoza
Complement Complement
Citokine: Citokine: IFN-/, IL-1, TNF-, CSF
Chemokine: Chemokine: IL-8, MIP, MCP
Receptori Receptori:: TLR TLR

3. Componente celulare 3. Componente celulare
Functia de eliminare a Functia de eliminare a
microorganismelor patogene microorganismelor patogene
celule NK celule NK
Fagocitoza Fagocitoza
Inflamatie Inflamatie
Citotoxicitate Citotoxicitate
neutrofile neutrofile
monocite/macrofage monocite/macrofage
celule dendritice celule dendritice
bazofile bazofile
mastocite mastocite
eozinofile eozinofile
Imunitatea Imunitatea
innscut innscut
Immune responses
Skin & Mucous membranes
rapidly regenerating surfaces,
peristaltic movement, mucociliary
escalator, vomiting, flow of urine/tears,
coughing
Cellular and humoral defences
lysosyme, sebaceous/mucous secretions,
stomach acid, commensal
organisms,complement proteins,
phagocytosis, NK cells
Invasion
& infection
Barriers




Innate immunity






Adaptive immunity
+
+
Inflammation
Cellular and humoral defences
Antibodies, cytokines, T helper cells,
cytotoxic T cells
Inflamaia
- Component major a rspunsului imun nespecific/
specific
- Rspuns protectiv la injurie, montat s restabileasc
statusul normal
- Iniiat de lezarea esuturilor:
mecanic/fizic (ex. arsuri)
chimic ( ex. expunere la ageni corozivi)
biologic (ex. microorganisme)
imunologic (ex. hipersenzitivitate)
- Implic fagocite i mediatorii secretai de fagocite,
precum i excretai de celulele secretorii
Inflamatia - Functii
- Distrugerea si indeprtarea substantelor
/ particulelor duntoare / strine
- Izolarea zonei infectate/inflamate
- Stimularea rspunsului imun specific
- Vindecare
Rspunsul inflamator celular (1)

- Neutrofilele si
monocitele circulante
au o mobilitate foarte
mare.

PMN si Mo au capacitatea sa
se strecoare prin spatiile
inguste interendoteliale,
recrutate chemotactic
(chemokine) la locul
infectiei
Daca infectia se
raspandeste, fagocite
noi din torentul
circulator sunt atrase
la locul infectiei

- Fagocitele ingurgiteaza
particulele straine
similar cu amoebele
Leukocyte Adhesion
Phagocytic
neutrophils
respond to an
epithelial
chemokine IL-8

Cells migrate
from the blood
into the tissue
underlying the
infection
Diapedesis
Caracteristicile Inflamaiei
- Edemaierea zonei (tumor)
- Eritem (rubor)
- Creterea temperaturii
(calor)
- Durere (dolor)
- Pierderea funcionalitii
(functio lesa)

- Reacii / interferene
inflamatorii locale:
Activarea coagulrii
Cile formatoare ale
Kininelor
Fibrinoliza



Eliberarea de histamin i prostaglandine determin
vasodilataie local nsoit de:
o increased blood flow redness and warmth
o increased capillary permeability
o edema (swelling) due to fluids seeping from
capillaries
o more WBCs to site
o phagocytes move out of vessels into
extracellular fluid (ECF)
o phagocytes engulf and destroy bacteria
Rspunsul inflamator local
Inflammation
Heat - Swelling - Redness - Pain - Loss of Function
Cells Of The
Immune System
Pluripotent
haemopoietic
stem cell
Common
lymphoid
progenitor
Myeloid
progenitor
Lymphocyte Adaptive
immunity

Macrophage
Monocyte

Neutrophil
PMN

Eosinophil



Basophil



Mast cell
Phagocytosis
Ag presentation


Phagocytic
Anti-bacterial


Anti-parasite
Immunity - Allergy



?Protection of
mucosal surfaces?
- Allergy

Protection of
mucosal surfaces
- Allergy
Fagocite profesionale - PMN, MQ (1)
- Leucocite Polimorfonucleare (PMN)
Granulocite:
o Neutrofile, eozinofile, basofile, mastocite
Sunt fagocite cu via scurt, continnd lizozomi
Produc ap oxigenat i radicali superoxid
Proteine bactericide lactoferina
PMNs joac un rol major in protectia mpotriva infectiilor
Defecte genetice/dobndite infectii cronice sau recurente
- Macrofagele fagocite tisulare derivate din monocitele ciculante,
migreaza din sange in tesuturi se diferentiaza:
o celule Kupffer in ficat
o macrofage alveolare in plaman
o celule mezangiale in rinichi
o macrofage splenice (sinusale) in pulpa alba - Sistemul Reticuloendotelial
(SRE) / Reticulohistiocitar (SRH)
o macrofage peritoneale plutind liber in fluidul peritoneal (seroase)
o celule microgliale in SNC
o celule Langerhans in piele
Inflamatia locala
- In tesutul interstitial
exista o populatie
rezidenta de
leucocite.

- Mastocitul:
elibereaza amine
biogene (histamina,
serotonina)
secreta
prostaglandine,
leukotriene, citokine
si TNF-a.
- PMN:
fagociteaza
agresorul
Neutrophil
Neutrophil
Neutrophils

Also called polymorphonucelar
leukocytes
4 to 10 million per ml of blood
Infection activates cytokines that
stimulate the bone marrow to produce
up to 20 million neutrophils per ml of
blood.
Main role is to get to site of infection
rapidly and ingest microorganisms.
After taking up microorganisms the
neutrophil will die.
Neutrophil Chemotaxis
Neutrophils chasing yeast
Tissue macrophage
Blood monocyte
Monocytes

0.5 to 1 million monocytes per ml of
blood
Migrate into the tissues and
differentiate into Macrophages
Phagocytose microorganisms
Present antigens to T cells
The name of monocyte-derived cells
depends upon the tissue they reside in:
Liver - Kupffer cells
Lung - Alveolar macrophages
CNS - Microglial cells
Bone - Osteoclasts
Human Macrophage ingesting yeast
Fagocite (2)
- Initial, in spatiul interstitial trec
PMN:
se acumuleaza in 30-60 minute de la
aparitia agentului declansator
fagociteaza intrusul si tesuturile
lezate
elibereaza enzime lizozomale
- Daca inflamatia persista:
dupa 12-18 ore interstitiul este
infiltrat cu mononucleare
(macrofage si limfocite)
Macrofagele
o suplimenteaza activitatea PMN
o prezinta Ag, Ly T
- Daca inflamatia continua, raspunsul
inflamator este suplimentat si
accentuat cu elemente ale
imunitatii dobandite Ac si LyT
(Ac activeaza si sistemul
complementului) Vindecare

Fagocite (3)
- Celulele seriei macrofagice au doua functii majore:
Ingereaza si digera microorganisme si particule
straine
Prezinta Antigene (Ag) - componenta imunogena
o Preia Ag, il proceseaza si il prezinta Ly T

* Alte celule prezentatoare de Ag (APC) (precursori
hematopoietici, fagocite mai putin eficiente)
Celule dendritice in splina si ganglioni
Celule interdigitate in timus
Celule Langerhans in piele
Proces activ, initiat de
legarea fagocitului la
patogen prin
intermediul unor
receptori
Agentul patogen este
inconjurat de
pseudopode
membranare si apoi
internalizat:
- Fagozom
- Fagolizozom
- Vacuola digestiva
- Corp rezidual

Fagocitoza (cont)

- Proces activ, initiat de legarea la patogen prin intermediul unor
receptori
- Agentul patogen este inconjurat de pseudopode membranare si apoi
internalizat
Fagocitoza
General scheme of an immune response
Both humans and pathogens are made of
proteins carbohydrates & lipids
Most microorganisms do not cause disease in humans
How does the human immune system distinguish
pathogens from human tissues and harmless
microorganisms?
Pathogens
Disease - causing organisms
Protozoa, Bacteria, Viruses, Fungi, Worms etc
Fagocitoza
- Caracteristici
Definitie: preluarea unor particule de dimensiune mare (in
principal microorganisme), datorita capacitatii de a distinge
intre tipurile de carbohidrati produsi de mamifere si bacterii
(self - nonself)
o Pathogen-associated molecular patterns (PAMPs): LPS,
peptidoglicani, lipoarabinomanani, dsRNA - substante
prezente relativ constant (fara variabilitate antigenica) la
un grup mare de patogeni
Actin-dependenta, chlatrin-independenta
Rata & eficienta mare de internalizare

- Receptori fagocitari - pattern recognition receptors (PRRs) or
molecules (PRMs)
o Externi
FcR (CD16, CD64), CR3 (CD11b), Scavenger receptor
(CD36), Mannose receptor
o Interni
TLRs - Toll like receptors
Fagocitoza
(cont)


opsonin
dependenta, fiind
mediata de:
Ac sau
C3b

Receptori Receptori (self vs. (self vs. nnon on--self microbian) self microbian)::
PRR PRR PPattern attern RRecognition ecognition RReceptor eceptor
PAMP P PAMP Pathogen athogen AAssociated ssociated MMolecular olecular PPattern attern
(Medzhitov & Janeway, 1997)
Recunoastere imuna Recunoastere imuna
Ipoteze Ipoteze
self self
non non--
self self
origine antigen / context biologic origine antigen / context biologic
a) ENDOCITOZA a) ENDOCITOZA -- Endocytic PRRs Endocytic PRRs
proteina bact. proteina bact.
receptori manoza receptori manoza
((lectina C lectina C))
FAGOCIT
receptori scavenger receptori scavenger
(CD36, CD68, SRB (CD36, CD68, SRB--1) 1)
C3b C3b
glicoproteina glicoproteina
bact. bact.
receptori opsonine receptori opsonine
((CR1 CR1))
Bacterie
LPS, LTA LPS, LTA
man
PAMP PAMP
invariabile
inalt conservate
specifice microbilor
(patogeni + non-patogeni)
comune pentru o clasa de microbi
vitale pentru microorganisme

lipopolizaharid lipopolizaharid
peptidoglican peptidoglican
acid lipoteichoic acid lipoteichoic
lipoproteine lipoproteine
manoza manoza
ADN ADN
ARN dc ARN dc
flagelina flagelina
pilina pilina
zimozan zimozan
Gram Gram--negative negative
Gram Gram--positive positive
Receptori fagocitari de suprafata - PRR:
leaga carbohidrati bacterieni
-1. Mannose-binding receptor
Recunoaste reziduuri de manoza cu o orientare
spatiala certa/unica microorganismelor
Se gaseste doar pe MQ (nu i pe Mo sau PMN)
-2. Glucan Receptor
Prezent pe toate fagocitele
Receptori fagocitari de suprafa - PRR:
leag ali compui bacterieni
-3. Scavenger Receptor - CD36
Recunoaste liganzi:
o polianionici (ds-RNA, LPS)
o carbohidrati
o Lp cu densitate mica (LDL) acetilate
Se gasesc pe toate fagocitele
Specific MQ, leaga peretele celulei bacteriene &
LPS
Fagociteaza celule apoptotice
o factor nou MFG-E8 (eliberat din MQ activate se
leaga la celulele apoptotice via fosfatidilserina)
b) TRANSMITERE SEMNAL b) TRANSMITERE SEMNAL -- Signaling PRRs Signaling PRRs
TLR TLR
Toll Toll--like receptors like receptors
NOD NOD
nucleotide nucleotide--binding binding
oligomerization domain oligomerization domain
RIG RIG--11
retinoic acid retinoic acid--inducible gene inducible gene--11
+ TLRs sunt proteine transmembranare
+ Toll - molecula identificata ca fiind esentiala pentru patern-ul
embrionic de Drosophila
+ Conservat pe parcursul evolutiei la insecte & oameni
+ TLRs la mamifere este omolog cu domeniul citoplasmatic al receptorului
IL-1 si IL-18 (Toll-IL1-R sau TIR domain)
+Domeniul extracelular este diferit
+ Au fost raportati 10 TLRs (1-10)
+Exprimati diferentiat pe celulele imune (nivel scazut)
+Expresia este modulata (inductibila) ca raspuns la anumiti
stimuli
+Exprimati si pe alte tipuri celulare (e.g., celule endoteliale)
Receptorii fagocitari interni
Toll-like (TLRs)
Toll Toll--like receptors (TLR) like receptors (TLR)

proteine transmembranare tip I proteine transmembranare tip I
conservate filogenetic ( conservate filogenetic (Drosophila Drosophila om) om)
domeniu extracelular bogat in leucina domeniu extracelular bogat in leucina
domeniu intracelular TIR (similar IL domeniu intracelular TIR (similar IL--1R) 1R)
TLR mamifere (11 TLR mamifere (11--om, 13 om, 13--soarece): soarece):
recunoastere PAMPs recunoastere PAMPs
asociere cu alti TLR sau alte proteine (MD2,CD14) asociere cu alti TLR sau alte proteine (MD2,CD14)
Lipoproteins, lipopeptides Lipoproteins, lipopeptides
Peptidoglycan Peptidoglycan
Zymosan Zymosan
LPS LPS Leptospira interrogans Leptospira interrogans
LPS LPS P.gingivalis P.gingivalis
GPI ( GPI (T.cruzi) T.cruzi)
Lipoarabinomannan Lipoarabinomannan
Phosphatidylinositol dimannoside Phosphatidylinositol dimannoside
((M. tuberculosis) M. tuberculosis)
TLR2 TLR2
+(TLR1/TLR6) +(TLR1/TLR6)
LPS LPS
Taxol Taxol
HSP60 HSP60
Fibronectin Fibronectin
F Protein (RSV) F Protein (RSV)
Flagellin Flagellin CpG DNA CpG DNA
TLR4 TLR4 TLR5 TLR5 TLR9 TLR9
Functiile imunitatii innascute Functiile imunitatii innascute
PAMP
Stimulare PRR Stimulare PRR
stimuleaza fagocitoza stimuleaza fagocitoza
induce activitate microbicida induce activitate microbicida
induce citokine inflamatorii: induce citokine inflamatorii:
IL IL--11, IL , IL--6, TNF 6, TNF-- (NF (NF--kB) kB)
activeaza imunitatea dobindita activeaza imunitatea dobindita
^^ expresia mol expresia molec. ec. ccoo--stim. stim.
(MHC cls.II, CD80/CD86 (MHC cls.II, CD80/CD86)


Fagocitoza Fagocitoza
independent de oxigen independent de oxigen dependent de oxigen dependent de oxigen
Mecanism Mecanism
- defensine defensine
-- cathepsina B cathepsina B
-- lizozim lizozim
-- lactoferina lactoferina
-- enzime proteolitice enzime proteolitice
OO
22

HH
2 2
OO
22
11
OO
22
OCl OCl
OH OH

Rol Rol
eliminare a microorganismelor patogene eliminare a microorganismelor patogene
prelucrare prelucrare AAtg pt. prezentare tg pt. prezentare
Mecanismele uciderii bacteriilor - cont.
-Explozia oxidativa
Activata in urma fagocitozei
Stimulata de PRRs
Consum crescut de O
2

Produce substante care sunt toxice directe pentru
bacterii:
o Produsi derivati ai Oxigenului
o Produsi derivati ai Nitrogenului
NO (monoxidul de azot)
Produs de NO sintetaza inductibila (iNOS)
Enzima este indusa de cytokine, LT, TNF
Explozia oxidativa-speciile reactive ale O
2
Speciile reactive ale oxigenului se formeaza prin
Explozia oxidativa, care presupune:
Cresterea consumului de O
2

Glicogenoliza - cresterea oxidarii glucozei
Formarea anionului superoxid, apei oxigenate si a acidului
percloric:
o 2O
2
+ NADPH 2O
2
-
+ NADP
+
+ H
+

(NADPH oxidaza)
o O
2
-
+ 2H
+
H
2
O
2
HO

(SOD superoxid dismutaza) (Fe
2+
)

o H
2
O
2
+ Cl
2
2HOCl
(MPO mieloperoxidaza - granulele azurofile,
doar in PMN nu si in MQ)
Radicalii derivati de O
2
sunt detoxifiati de ceruloplasmina,
transferina, superoxid dismutaza (SOD), catalaza & glutation
peroxidaza (H
2
O
2
)
Danger hypothesis Danger hypothesis
Danger Danger
signal signal
Naive Naive
T cells T cells
APC APC
Normal Normal
cell cell
Damaged Damaged
cell cell
Signal 1 Signal 1
Signal 2 (co Signal 2 (co--
stimulation) stimulation)
-- infection infection
-- tissue damage tissue damage
-- stress cells stress cells
-- hypoxia hypoxia
-- temperature shifts temperature shifts
-- hsp hsp

Citokine Citokine
Macrofag activat Macrofag activat
IL IL--11
- activeaza
endoteliul vascular
- activeaza Ly
- ^^ acces cel. efect.
- activeaza
endoteliul vascular
- creste
permeab. vasculara
- ^^ acces cel. efect.
- activeaza Ly
- ^^ producere Atc.
- activeaza NK
- induce dif. Th1

TNF TNF--
IL IL--66
IL IL--12 12
EFECTE EFECTE LOCALE LOCALE
EFECTE EFECTE SISTEMICE SISTEMICE
- febra
- producere de IL-6

- febra
- mobilizare metaboliti
- soc

- febra
- inducere proteine
faza acuta

Mediatorii specifici
- Citokinele
Produsi celulari de natura proteica cu rol de mesaj pentru alte
celule, carora le spun cum sa se comporte
IL-1, TNF- si -, IFN- sunt importante in mod special in inflamatii.
Cresc expresia endoteliala a moleculelor de adeziune, activarea si
agregarea PMNs, etc.
- Interferonii
- Produsi de celulele infectate cu virusuri, actioneaza ca si mesageri de
scurta durata care protejeaza celulele invecinate de infectia virala.
interferon:
o Inhiba replicarea virala, creste numarul NK si induce antigenele MHC-I
interferon:
o Inhiba replicarea virala, creste numarul NK si induce antigenele MHC-I
interferon:
o Activeaza macrofagele si induce antigenele MHC-II
o Apararea imuna impotriva infectiilor si proliferarilor maligne.
Interferonii
Proprietati IFN- IFN- IFN-
NOMENCLATURA Type I,
Leukocyte
Type I,
Fibroblast
Type II, Immune
Inductori MAJORI Virus Virus, LPS Antigens,
mitogens, TNF-
+ IL-12
Nr de GENE 26 1 1
SURSA CELULARA T cells, B cells
Macrophages
Fibroblasts,
epithelial cells
T cells, natural
killer cells
Dupa expunere corespunzatoare cele mai multe celule sunt apte sa produca cel putin un tip de IFN I.
Tipul I de IFN poate fi indus de asemenea de LPS (endotoxina bacteriana), IL-1 si TNF.
Sinteza IFN- este inalt reglata numai in anumite tipuri de celule si este indusa de stimuli specifici
IFN- factorul major de activare macrofagica; rol crucial intre mecanismele de aparare ne-
specifica a gazdei impotriva a numerosi patogeni.

Functii efectorii Functii efectorii: Rolul interferon : Rolul interferonului ului
IFN IFN--//
Celula infectata viral Celula infectata viral Celula neinfectata Celula neinfectata
IFN receptor IFN receptor
22--5 (A) 5 (A)
Sintetaza Sintetaza
PKR PKR
Inhibare sinteza proteica Inhibare sinteza proteica
degradare mRNA degradare mRNA
++ translatie mRNA translatie mRNA
Pathogens Epithelial barrier Activated epithelial cells
Epithelial cytokines Permeabilised endothelium Cell & fluid migration
Opsonisation
Phagocytosis
Interaction with
other cells of the
innate and adaptive
immune systems
Barriers -
Seconds
Epithelial activation -
Minutes
Cytokines/chemokines -
Minutes to days
Neutrophils -
Hours
Monocytes/macrophages -
Hours to days NK cells -
Hours to days
Timing of innate immunity after infection
Short-
lived
Long-lived & connect with
adaptive immune system
Complement -
Minutes
Eosinophil Basophil
Neutrophil
Monocyte
Lymphocyt
e
Neutrophil
Basophil
Eosinophil
Eosinophil
Eosinophils attacking a schistosome larva in the presence of serum (IgE)
from an infected patient.
Degranulated mast cell
Resting Mast cell
Mast Cells
Mediators released include:
Leukotriene C
4
& D
4
, Prostaglandin D
2
Platelet Activating Factor,
Chymase, Tryptase, Heparin, Histamine IL-4, IL-5, IL-6, IL-8, TNF-

Causing:
Vasodilation, increased vasopermeability, contraction of smooth muscle,
bronchoconstriction, increase neutrophil chemotaxis, increase eosinophil,
neutrophil and monocyte chemotaxis, anticoagulation, increased
fibroblast proliferation & platelet activation
Non-T, non-B cells
No classical antigen receptors
Part of the innate immune system
Recognise and kill abnormal cells such
as tumour cells
Directly induce apoptosis in virus
infected cells by pumping proteases
through pores that they make in
target cells
Similar cytolytic mechanisms to
cytotoxic T lymphocytes (CTL)
Involved in antibody-dependent
cellular cytotoxicity (ADCC)
Natural Killer (NK) cells
Celula Celula
NK NK
Celula Celula
tinta tinta
Celula Celula
NK NK
Celula Celula
tinta tinta
Absenta
citotoxicitatii
Citotoxicitate
NKR NKR
NCR NCR
Ligand Ligand
activator activator
MHC MHC
cls I cls I
NKR NKR
NCR NCR
Ligand Ligand
activator activator




Missing self Missing self
Interferon
(IFN) receptor
Activated macrophage
Growth factors, angiogenic
factors, proteinases -
REPAIR & REMODELLING
NK
Cytokines TNF, IL-12
IFN
Interactions between phagocytes and other innate
immune components: Natural Killer cells
Sistemul proteinelor plasmatice -
raspunsul imun nespecific umoral
Secreted Pattern Recognition
Molecules (sPRM)
Proteine de faza acuta
Produse mai ales de ficat, dar si de fagocite, cu rol in:
Activarea Complementului
Opsonizarea celulelor microbiene
Cascada coagularii

- Nonspecific defense system
The combination of antibodies with antigens does not cause destruction of
the antigens or pathogen.

- Antibodies serve to identify the targets for immunological attack. Antibody-
induced activation of the complement.

- The complement proteins are designated C-1 to C-9.
These proteins are in an inactive state. Become activated by the
attachment of antibodies to antigens.

- Complement proteins can be subdivided into 3 components:
C1q, r, s: recognization.
C4, C2, C3: activation.
C5-C9: attack (complement fixation).

- Activated via classic (C1) or alternative (C3) pathways to generate MAC (C5
C9) that punch holes in microbe membranes
- In acute inflammation
o Vasodilation, vascular permeability, mast cell degranulation (C3a, C5a)
o Leukocyte chemotaxin, increases integrin avidity (C5a)
o As an opsonin, increases phagocytosis (C3b, C3bi)
Complement System

b
C4b
+
C2b
C3b
+
Bb
Activation of C System - cont.
Imunitatea Innscut - faze
Rspunsul inflamator sistemic (1)
- Induction of fever
Caused by many bacterial products (endotoxins
from G(-) bacteria)
Endogenous pyrogens from monocytes and
macrophages (IL-1 and certain interferons)

- Increased WBC production / releasing

- Increased synthesis of hydrocortisone and
adrenocorticotropic hormone (ACTH)

- Production of acute phase proteins C-reactive
protein binds to membranes of certain
microorganisms to activate the complement
system
Rspunsul inflamator sistemic (2)
POSITIVE
- indicate a reaction to
infection
- stimulate phagocytosis
- slow bacterial growth
increases body temperature
beyond the tolerance of some
bacteria
decreases blood iron levels
NEGATIVE
- extreme heat enzyme
denaturation and interruption
of normal biochemical
reactions
> 39 C (103F) is dangerous
> 41C (105F) could be fatal and
requires medical attention


Febra are efecte pozitive i negative asupra infeciei i
funciei organismului
Rspunsul inflamator sistemic (3)
Nu este doar un sistem de aparare simplu, Nu este doar un sistem de aparare simplu,
menit sa tina in loc infectia pina la menit sa tina in loc infectia pina la
interventia imunitatii dobindite interventia imunitatii dobindite
Instruieste sistemul imunitatii dobindite Instruieste sistemul imunitatii dobindite
pentru a raspunde la infectii pentru a raspunde la infectii
Decizia majora de a raspunde Decizia majora de a raspunde
sau nu unui antigen este luata de sau nu unui antigen este luata de
imunitatea innascuta, prin imunitatea innascuta, prin
receptorii codificati in genom ! receptorii codificati in genom !
Imunitate innascuta Imunitate innascuta
Immune responses
Skin & Mucous membranes
rapidly regenerating surfaces,
peristaltic movement, mucociliary
escalator, vomiting, flow of urine/tears,
coughing
Cellular and humoral defences
lysosyme, sebaceous/mucous secretions,
stomach acid, commensal
organisms,complement proteins,
phagocytosis, NK cells
Invasion
& infection
Barriers




Innate immunity






Adaptive immunity
+
+
Inflammation
Cellular and humoral defences
Antibodies, cytokines, T helper cells,
cytotoxic T cells
ROL ROL i i FUNCTII FUNCTII
Recunoastere Recunoastere
Functii efectoare Functii efectoare
prevenire intrare prevenire intrare
eliminare eliminare
Rol instructiv asupra imunitatii specifice Rol instructiv asupra imunitatii specifice



microorganisme
patogene
initierea si tipul raspunsului initierea si tipul raspunsului
originea originea si contextul si contextul
AAgg
Imunitatea Imunitatea
innscut innscut
PAMP PAMP
TLR TLR
pathogen
Endocytic
PRR
Naive Naive
T cells T cells
CD80/86
Th1 Th1
IFN-
CD28
MHC-II
TCR
IL-12
DC DC
(adapted after Medzhitov R, (adapted after Medzhitov R,
Nature Reviews Immunology Nature Reviews Immunology, 1, , 1,
2001, 135 2001, 135--145) 145)
Th1 Th1
IFN-
INNATE INNATE
IMMUNITY IMMUNITY
ADAPTIVE IMMUNITY ADAPTIVE IMMUNITY
cellular immune response cellular immune response