IMUNITATEA = APĂRARE SISTEMUL IMUN

Toţi ne îmbolnăvim uneori..., apoi ne

Colecţie de CELULE şi MOLECULE care
însănătoşim…
protejează organismul împotriva infecţiilor,
transformărilor maligne şi celulelor proprii
● Ce se întâmplă în organism în timpul unei transformate non-self
infecţii / afecţiuni ?
● De ce ne însănătoşim ?

IMUNITATE
INNASCUTA / nespecifica
(innate immunity)
 raspuns independent de antigen
 receptori pt. patogeni:
 codificati in genom
 specificitate joasa
 raspuns imediat
 lipsa memorie
 prezenta la toate organismele
pluricelulare
SISTEM INTEGRAT
DOBINDITA / specifica
(adaptive immunity)
 raspuns dependent de antigen
 receptori pt. patogeni:
 generati (rearanjare genica)
 specificitate inalta
 raspuns lent
 memorie imunologica
(expansiune clonala Ly)
 prezenta doar la vertebrate
Răspunsuri imune
Barriers Skin & Mucous membranes
Invasion rapidly regenerating surfaces,
peristaltic movement, mucociliary
& infection escalator, vomiting, flow of urine/tears,
coughing
Innate immunity Cellular and humoral defences
lysosyme, sebaceous/mucous secretions,
+
stomach acid, commensal
organisms,complement proteins,
phagocytosis, NK cells
+ Inflammation
Cellular and humoral defences
Adaptive immunity Antibodies, cytokines, T helper cells,
cytotoxic T cells

1
 Imunitatea
- piele
Innate immune response innăscută
1. Bariere anatomice - mucoase

Inbuilt immunity to resist infection

Native, natural immunity
• Functia de prevenire a intrarii
• Present from birth
microorganismelor patogene
• Not specific for any particular microbial substance
• Not enhanced by second exposure • motilitate: muco-ciliara, peristaltica
Factori fizici / mecanici • mucus
• Has no memory • fluxul fluidelor prin organism
• Uses cellular and humoral components
• Is poorly effective without adaptive immunity
• pH
Factori chimici • molecule antimicrobiene

Also involved in the triggering and amplification of

adaptive immune responses • limfocite T intraepiteliale ()
Factori biologici • celule B-1

Imunitatea Imunitatea
- receptori
innăscută 2. Componente moleculare innăscută
- molecule secretate 3. Componente celulare

Functia de eliminare a
Functia de recunoastere
microorganismelor patogene
Functii efectorii
neutrofile
Mol. anorganice: HCl, NO, H2O2 monocite/macrofage Fagocitoza
celule dendritice
Peptide antibacteriene: defensine, cathelicidine, histatine
Proteine antibacteriene: lizozim, lactoferina, transferina bazofile
Lectine: colectine, ficoline, receptori pentru Manoza mastocite Inflamatie
eozinofile
Complement
Citokine: IFN-/, IL-1, TNF-, CSF
Chemokine: IL-8, MIP, MCP celule NK Citotoxicitate
Receptori: TLR

2
 First line of defence - Epithelial cells
Immune responses

Barriers Skin & Mucous membranes

Functions within seconds of contacting a rapidly regenerating surfaces,
pathogen Invasion peristaltic movement, mucociliary
A mechanical, selectively permeable & infection escalator, vomiting, flow of urine/tears,
barrier between the „outside‟ and „inside‟: coughing
• Produce natural antibiotics - cationic
antibacterial peptides - defensins and
Outside cathelicidins Innate immunity Cellular and humoral defences
+ lysosyme, sebaceous/mucous secretions,
• May possess motile cilia stomach acid, commensal
• Rapidly renewable organisms,complement proteins,
phagocytosis, NK cells
• Produce cytokines - proteins that alter
the behaviour of other cells
Inside + Inflammation
• Produce chemokines - proteins that
attract other cells Cellular and humoral defences
Primary role is to block • May produce mucins Antibodies, cytokines, T helper cells,
the entry of Adaptive immunity
• Transport antibodies from „inside‟ to cytotoxic T cells
microorganisms „outside‟

General scheme of an immune response Cytokines and Chemokines

Pathogen with non-self proteins

damages the epithelium to break
through the epithelial barrier • A diverse collection of soluble proteins and peptides that modulate the
behaviour of cells at nM to pM concentrations

• Conceptually similar to hormones

However cytokines and chemokines are not exclusively produced
Epithelial cells „activated‟ upon by organised cells located in glandular tissue
contact with microorganism
• Act both locally and systemically

• Have highly pleiotropic effects (show many biological activities)

Chemokines and cytokines are made
by activated epithelial cells • Chemokines largely associated with chemoattraction of other cells

• The activities of cytokines and chemokines often overlap with other

cytokines and chemokines

3
 Inflammation Răspunsul inflamator celular (1)
Cytokines - tumour necrosis factor  (TNF)
and interleukin 1 (IL-1) change the morphology,  Neutrofilele si
adhesive properties and permeability of monocitele circulante
endothelial cells 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
Post capillary endothelial circulator sunt atrase
la locul infectiei
cells are impermeable to
 Fagocitele ingurgiteaza
cells and plasma particulele straine
Inflammation similar cu amoebele
Heat - Swelling - Redness - Pain - Loss of Function

Mechanism of Cell Migration

Tethering and rolling Activation dependent adhesion & arrest
Cytokine activated endothelial cells express adhesion molecules
Cytokines from epithelium activate expression of
Intracellular adhesion molecules (ICAMs)

Tethering
Cells normally roll past resting endothelial cells
Rolling
Tethering and rolling are mediated
by SELECTINS Rolling
Selectin is shed Cell activation
Neutrophil changes integrin
INTEGRIN
is activated by to high affinity
(adhesion molecule)
chemokines format
has low affinity for
ICAM

4
 Leukocyte Adhesion Migration and diapedesis

Firm adhesion causes the neutrophil

to flatten and migrate between the
• Phagocytic endothelial cells
neutrophils
respond to an
epithelial Neutrophil migrates towards site of
chemokine IL-8 infection by detecting and following a
gradient of chemokine.
• Cells migrate
from the blood
into the tissue Neutrophils migrate readily to IL-8
underlying the made by epithelilal cells that have
infection encountered microorganisms

Inflammation
Diapedesis Heat - Swelling - Redness - Pain - Loss of Function

5
Fagocite profesionale - PMN, MQ (1) Neutrophils
 Leucocite Polimorfonucleare (PMN)
Also called polymorphonucelar
● Granulocite:
leukocytes
o Neutrofile, eozinofile, basofile, mastocite
● Sunt fagocite cu viaţă scurtă, continând lizozomi 4 to 10 million per ml of blood
● Produc apă oxigenată şi radicali superoxid Infection activates cytokines that
● Proteine bactericide – lactoferina Neutrophil stimulate the bone marrow to produce
● PMNs joacă un rol major in protectia împotriva infectiilor up to 20 million neutrophils per ml of
● Defecte genetice/dobândite – infectii cronice sau recurente blood.
 Macrofagele – fagocite tisulare derivate din monocitele ciculante, Main role is to get to site of infection
migreaza din sange in tesuturi  se diferentiaza: rapidly and ingest microorganisms.
o celule Kupffer in ficat
After taking up microorganisms the
o macrofage alveolare in plaman
neutrophil will die.
o celule mezangiale in rinichi
o macrofage splenice (sinusale) in pulpa alba - Sistemul Reticuloendotelial Neutrophil Chemotaxis
(SRE) / Reticulohistiocitar (SRH)
Neutrophils chasing yeast
o macrofage peritoneale plutind liber in fluidul peritoneal (seroase)
o celule microgliale in SNC
Neutrophil
o celule Langerhans in piele

Monocytes Fagocite (2)

0.5 to 1 million monocytes per ml of
blood
Migrate into the tissues and
differentiate into Macrophages
Blood monocyte
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
Tissue macrophage Human Macrophage ingesting yeast
 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

6
 Fagocite (3) Fagocitoza (cont)
•Proces activ, initiat de
 Celulele seriei macrofagice au doua functii majore: legarea fagocitului la
patogen prin
● Ingereaza si digera microorganisme si particule intermediul unor
straine receptori
•Agentul patogen este
● Prezinta Antigene (Ag) - componenta imunogena inconjurat de
o Preia Ag, il proceseaza si il prezinta Ly T pseudopode
membranare si apoi
internalizat:
* Alte celule prezentatoare de Ag (APC) (precursori
hematopoietici, fagocite mai putin eficiente) - Fagozom
 Celule dendritice in splina si ganglioni - Fagolizozom
 Celule interdigitate in timus - Vacuola digestiva
 Celule Langerhans in piele - Corp rezidual

Fagocitoza Fagocitoza
 Proces activ, initiat de legarea la patogen prin intermediul unor  Caracteristici
receptori ● Definitie: preluarea unor particule de dimensiune mare (in
 Agentul patogen este inconjurat de pseudopode membranare si apoi principal microorganisme), datorita capacitatii de a distinge
internalizat 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

7
 Fagocitoza
Fagocitoza
(cont) Mecanism

dependent de oxigen independent de oxigen

opsonin
dependenta, fiind
mediata de: O2– - defensine

•Ac sau H2 O2 - cathepsina B

1O - lizozim
•C3b 2

 OCl - lactoferina
OH - enzime proteolitice

• eliminare a microorganismelor patogene

Rol
• prelucrare Atg pt. prezentare

Mecanismele uciderii bacteriilor - cont. “Explozia oxidativa”-speciile reactive ale O2

 “Explozia oxidativa” Speciile reactive ale oxigenului se formeaza prin

“Explozia oxidativa”, care presupune:
● Activata in urma fagocitozei ● Cresterea consumului de O2
● Stimulata de PRRs ● Glicogenoliza - cresterea oxidarii glucozei
● Consum crescut de O2 ● Formarea anionului superoxid, apei oxigenate si a acidului
percloric:
● Produce substante care sunt toxice directe pentru
o 2O2 + NADPH  2O2- + NADP+ + H+
bacterii: (NADPH oxidaza)
o Produsi derivati ai Oxigenului o O2- + 2H+  H2O2  HO 
(SOD superoxid dismutaza) (Fe2+ )
o Produsi derivati ai Nitrogenului o H2O2 + Cl2  2HOCl
 NO (monoxidul de azot) (MPO mieloperoxidaza - granulele azurofile,
 Produs de NO sintetaza inductibila (iNOS) doar in PMN nu si in MQ)
 Enzima este indusa de cytokine, LT, TNF ● Radicalii derivati de O2 sunt detoxifiati de ceruloplasmina,
transferina, superoxid dismutaza (SOD), catalaza & glutation
peroxidaza (H2O2 )

8
 General scheme of an immune response
Most microorganisms do not cause disease in humans

Pathogens
Disease - causing organisms
Protozoa, Bacteria, Viruses, Fungi, Worms etc

Both humans and pathogens are made of

How does the human
proteins immune system
carbohydrates distinguish
& lipids
pathogens from human tissues and harmless
microorganisms?

non-
self Pattern Recognition Receptors - PRR
Recunoastere imuna self
• glycosylphosphatidylinositol  LPS
Endocytic PRRs (gpi)-linked receptor

• Scavenger receptors (SR)  oxLDL; microbes

origine antigen / context biologic
• C-type lectin receptors Microbes; microbial
(CLR) moieties

Ipoteze • Toll-like receptors (TLR)  Microbial moieties

Signaling PRRs
• NOD-like receptors (NLR)  Bacterial lipoproteins
Receptori (self vs. non-self microbian):
 Nucleic acids
• RIG1-like helicases (RLH)
PRR Pattern Recognition Receptor
• Collectins  Sugars
PAMP Pathogen Associated Molecular Pattern Bridging molecules
• Ficolins  Glycoproteins

(Medzhitov & Janeway, 1997) • Pentraxins Microbes; microbial

moieties

(adaptat dupa Jeannin et al. “Pattern recognition receptors in the immune response against
dying cells”, Current Opinion in Immunology 2008, 20:1–8)

9
PAMP •lipopolizaharid
•peptidoglican a) ENDOCITOZA - Endocytic PRRs
•acid lipoteichoic
•lipoproteine
 invariabile •manoza
 inalt conservate •ADN
 specifice microbilor •ARN dc
(patogeni + non-patogeni) •flagelina Bacterie
 comune pentru o clasa de microbi •pilina
 vitale pentru microorganisme •zimozan glicoproteina proteina bact.
bact. LPS, LTA
man C3b

receptori manoza receptori scavenger receptori opsonine

(lectina C) (CD36, CD68, SRB-1) (CR1)

FAGOCIT

Gram-negative Gram-positive

Receptori fagocitari de suprafaţă - PRR:

leagă alţi compuşi bacterieni b) TRANSMITERE SEMNAL - Signaling PRRs

 3. Scavenger Receptor - CD36

● Recunoaste liganzi: TLR
o polianionici (ds-RNA, LPS) Toll-like receptors

o carbohidrati
o Lp cu densitate mica (LDL) acetilate
NOD
● Se gasesc pe toate fagocitele nucleotide-binding
● Specific MQ, leaga peretele celulei bacteriene & oligomerization domain

LPS
● Fagociteaza celule apoptotice RIG-1
retinoic acid-inducible gene-1
o factor nou MFG-E8 (eliberat din MQ activate se
leaga la celulele apoptotice via fosfatidilserina)

10
 Receptorii fagocitari interni Toll-like receptors (TLR)

Toll-like (TLRs) proteine transmembranare tip I

 conservate filogenetic (Drosophila  om)
 domeniu extracelular bogat in leucina
 domeniu intracelular TIR (similar IL-1R)
 TLRs sunt proteine transmembranare
 TLR mamifere (11-om, 13-soarece):
 “Toll” - molecula identificata ca fiind esentiala pentru patern-ul  recunoastere PAMPs
embrionic de Drosophila  asociere cu alti TLR sau alte proteine (MD2,CD14)
 Conservat pe parcursul evolutiei la insecte & oameni TLR2
 TLRs la mamifere este omolog cu domeniul citoplasmatic al receptorului +(TLR1/TLR6) TLR4 TLR5 TLR9
IL-1 si IL-18 (Toll-IL1-R sau TIR domain)
Lipoproteins, lipopeptides
 Domeniul extracelular este diferit Peptidoglycan
LPS Flagellin CpG DNA
Taxol
 Au fost raportati 10 TLRs (1-10) Zymosan
LPS Leptospira interrogans HSP60
 Exprimati diferentiat pe celulele imune (nivel scazut) LPS P.gingivalis Fibronectin
 Expresia este “modulata” (inductibila) ca raspuns la anumiti GPI (T.cruzi) F Protein (RSV)
stimuli
Lipoarabinomannan
Phosphatidylinositol dimannoside
 Exprimati si pe alte tipuri celulare (e.g., celule endoteliale) (M. tuberculosis)

Danger hypothesis Missing self

MHC
Naive NKR cls I
Celula  Celula
T cells Absenta
Signal 1 NK  tinta citotoxicitatii
Signal 2 (co-
stimulation) NCR Ligand
activator
APC

Danger
signal
- infection
NKR
- tissue damage Celula  Celula
- stress cells
Damaged Normal tinta
Citotoxicitate
- hypoxia NK 
cell cell
- temperature shifts
- hsp NCR Ligand
activator

11
Functiile imunitatii innascute Citokine Macrofag activat

IL-1 TNF- IL-6 IL-12

PAMP
EFECTE LOCALE
- activeaza - activeaza - activeaza Ly - activeaza NK
endoteliul vascular endoteliul vascular -  producere Atc. - induce dif. Th1
- activeaza Ly - creste
Stimulare PRR  stimuleaza fagocitoza -  acces cel. efect. permeab. vasculara
-  acces cel. efect.
 induce activitate microbicida
 induce citokine inflamatorii:
 IL-1, IL-6, TNF- (NF-kB)
 activeaza imunitatea dobindita
EFECTE SISTEMICE
  expresia molec. co-stim. - febra - febra - febra
(MHC cls.II, CD80/CD86) - producere de IL-6 - mobilizare metaboliti - inducere proteine
- soc faza acuta

Mediatorii specifici Interferonii

Proprietati IFN- IFN- IFN-
 Citokinele
● Produsi celulari de natura proteica cu rol de “mesaj” pentru alte NOMENCLATURA Type I, Type I, Type II, Immune
celule, carora “le spun cum sa se comporte” Leukocyte Fibroblast
● IL-1, TNF- si -, IFN- sunt importante in mod special in inflamatii. Inductori MAJORI Virus Virus, LPS Antigens,
● Cresc expresia endoteliala a moleculelor de adeziune, activarea si mitogens, TNF-
agregarea PMNs, etc. + IL-12

 Interferonii Nr de GENE 26 1 1
 Produsi de celulele infectate cu virusuri, actioneaza ca si mesageri de
scurta durata care protejeaza celulele invecinate de infectia virala.
SURSA CELULARA T cells, B cells Fibroblasts, T cells, natural
●  interferon: Macrophages epithelial cells killer cells
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 •Dupa expunere corespunzatoare cele mai multe celule sunt apte sa produca cel putin un tip de IFN I.
●  interferon: •Tipul I de IFN poate fi indus de asemenea de LPS (endotoxina bacteriana), IL-1 si TNF.
o Activeaza macrofagele si induce antigenele MHC-II •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-
o Apararea imuna impotriva infectiilor si proliferarilor maligne.
specifica a gazdei impotriva a numerosi patogeni.

12
 Functii efectorii: Rolul interferonului

Celula infectata viral Celula neinfectata Pathogens Epithelial barrier Activated epithelial cells

IFN receptor
IFN-/

2-5 (A) PKR

Epithelial cytokines Permeabilised endothelium Cell & fluid migration
Sintetaza
degradare mRNA  translatie mRNA
Interaction with
other cells of the
innate and adaptive
Opsonisation
immune systems
Phagocytosis
Inhibare sinteza proteica

Timing of innate immunity after infection Other Cells Involved in Innate Immunity

Barriers - Epithelial activation - Complement - Macrophage Phagocytosis

Seconds Minutes Minutes Cytokines/chemokines -
Monocyte Presentation to
Minutes to days
lymphocytes
Neutrophil Phagocytic
PMN Anti-bacterial

Neutrophils - Eosinophil Anti-parasite

Monocytes/macrophages -
Hours Immunity - Allergy
Hours to days NK cells -
Hours to days

Basophil ?Protection of
mucosal surfaces? - Allergy

Short-
lived Mast cell Protection of
Long-lived & connect with mucosal surfaces - Allergy
adaptive immune system

13
 Eosinophil Eosinophil Basophil

Neutrophil Eosinophil

Neutrophil

Lymphocyt
e
Basophil
Monocyte Eosinophils attacking a schistosome larva in the presence of serum (IgE)
from an infected patient.

Cells Of The
Mast Cells Lymphocyte Adaptive
immunity
Immune System

Macrophage Phagocytosis Common

Monocyte Ag presentation lymphoid
progenitor
Neutrophil Phagocytic
PMN Anti-bacterial
Pluripotent
haemopoietic
Resting Mast cell Degranulated mast cell stem cell
Eosinophil Anti-parasite
Immunity - Allergy
Mediators released include:
Leukotriene C4 & D4, Prostaglandin D2 Platelet Activating Factor,
Myeloid
Chymase, Tryptase, Heparin, Histamine IL-4, IL-5, IL-6, IL-8, TNF- ?Protection of
Basophil progenitor
mucosal surfaces?
Causing: - Allergy
Vasodilation, increased vasopermeability, contraction of smooth muscle,
bronchoconstriction, increase neutrophil chemotaxis, increase eosinophil, Protection of
Mast cell mucosal surfaces
neutrophil and monocyte chemotaxis, anticoagulation, increased
fibroblast proliferation & platelet activation - Allergy

14
 Interactions between phagocytes and other innate
Natural Killer (NK) cells
immune components: Natural Killer cells

IFN
Non-T, non-B cells
No classical antigen receptors
NK
Part of the innate immune system
Cytokines – TNF, IL-12
Recognise and kill abnormal cells such
as tumour cells
Growth factors, angiogenic
Directly induce apoptosis in virus factors, proteinases -
infected cells by pumping proteases REPAIR & REMODELLING
through pores that they make in
target cells Activated macrophage
Interferon 
Similar cytolytic mechanisms to
(IFN) receptor
cytotoxic T lymphocytes (CTL)
Involved in antibody-dependent
cellular cytotoxicity (ADCC)

Secreted Pattern Recognition

Molecules (sPRM)
Produse mai ales de ficat, dar si de fagocite, cu rol in:
•Activarea Complementului
•Opsonizarea celulelor microbiene

Sistemul proteinelor plasmatice - Proteine de faza acuta

raspunsul imun nespecific umoral

15
Cascada coagularii Complement System

 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)

16
 Activation of C’ System - cont. Imunitatea Innăscută - faze

C4b C3b
+ +
C2b Bb

Inflamaţia Inflamatia - Functii

 Componentă majoră a răspunsului imun nespecific/

specific  Distrugerea si indepărtarea substantelor
 Răspuns protectiv la injurie, montat să restabilească / particulelor dăunătoare / străine
statusul normal
 Izolarea zonei infectate/inflamate
 Iniţiată de lezarea ţesuturilor:
● mecanică/fizică (ex. arsuri)  Stimularea răspunsului imun specific
● chimică ( ex. expunere la agenţi corozivi)  Vindecare
● biologică (ex. microorganisme)
● imunologică (ex. hipersenzitivitate)
 Implică fagocite şi mediatorii secretaţi de fagocite,
precum şi excretaţi de celulele secretorii

17
 Caracteristicile Inflamaţiei
 Edemaţierea zonei (tumor)
 Eritem (rubor)
 Creşterea temperaturii
(calor)
 Durere (dolor)
 Pierderea funcţionalităţii
(functio lesa)
 Reacţii / interferenţe
inflamatorii locale:
● Activarea coagulării
● Căile formatoare ale
Kininelor
● Fibrinoliza
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
Răspunsul inflamator local
Eliberarea de histamină şi prostaglandine determină
vasodilataţie locală însoţită 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
Răspunsul 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
18
Răspunsul inflamator sistemic (2) Răspunsul inflamator sistemic (3)
Febra are efecte pozitive şi negative asupra infecţiei şi
funcţiei organismului
POSITIVE
 indicate a reaction to
infection
 stimulate phagocytosis
 slow bacterial growth
● increases body temperature
beyond the tolerance of some
bacteria
● decreases blood iron levels
Imunitate innascuta Immune responses
Barriers
 Nu este doar un sistem de aparare simplu,
menit sa tina in loc infectia pina la Invasion
interventia imunitatii dobindite & infection
 “Instruieste” sistemul imunitatii dobindite
pentru a raspunde la infectii
Innate immunity
+ lysosyme, sebaceous/mucous secretions,
Decizia majora de a raspunde
sau nu unui antigen este luata de
imunitatea innascuta, prin + Inflammation
receptorii codificati in genom !
Adaptive immunity
NEGATIVE
 extreme heat  enzyme
denaturation and interruption
of normal biochemical
reactions
> 39° C (103°F) is dangerous
> 41°C (105°F) could be fatal and
requires medical attention
Skin & Mucous membranes
rapidly regenerating surfaces,
peristaltic movement, mucociliary
escalator, vomiting, flow of urine/tears,
coughing
Cellular and humoral defences
stomach acid, commensal
organisms,complement proteins,
phagocytosis, NK cells
Cellular and humoral defences
Antibodies, cytokines, T helper cells,
cytotoxic T cells
19
Imunitatea
innăscută INNATE ADAPTIVE IMMUNITY
ROL și FUNCTII IMMUNITY cellular immune response

PAMP

originea si contextul pathogen

Recunoastere Ag
TLR
Endocytic IL-12 Th1
Functii efectoare PRR IFN-

• prevenire intrare microorganisme CD80/86 CD28

• eliminare patogene DC
TCR Naive Th1
MHC-II
Rol “instructiv” asupra imunitatii specifice T cells IFN-

initierea si tipul raspunsului

(adapted after Medzhitov R,
Nature Reviews Immunology, 1,
2001, 135-145)

20