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SÖÏ HÌNH THAØNH MOÄT

ÑAÙP ÖÙNG MIEÃN DÒCH

• GS Phaïm Hoaøng Phieät

• BS Huyønh Thanh Bình

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. .

Ñoäng hoïc moät ñaùp öùng mieãn dòch

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So saùnh ñaùp öùng thì 1 vaø thì 2

ÑÖMD

Tính chaát

Thì 1 Thì 2

Dieãn

tieán

Tieàm aån 1-2 tuaàn 3-5 ngaøy

Taêng SLKT Taêng nhanh Taêng raát nhanh

Bình oån 2-3 tuaàn Nhieàu thaùng- naêm

Giaûm suùt Nhanh Töø töø

Soá

löôïngCao hôn thì 1 nhieàu

Chaát

löôïng

Lôùp KT IgM IgG

Aùi löïc vôùi

KN+ +++

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Teá baøo trình dieän

khaùng nguyeân

HLA lôùp II –TCD4

(peptid 15-34 aa)

HLA lôùp I –TCD8

(peptid 9 aa)

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Class I MHC Pathway

Viral protein is made

on cytoplasmic

ribosomes

Plasma membrane

Proteasome

degrades

protein to

peptides

Peptide transporter

protein moves

peptide into ER

MHC class I alpha

and beta proteins

are made on the rER

Peptide associates

with MHC-I complex

Peptide with MHC

goes to Golgi body

Peptide passes

with MHC from Golgi

body to surface

Peptide is presented

by MHC-I to CD8

cytotoxic T cell

Golgi body

rER

Globular viral

protein - intact

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Class II MHC Pathway

Globular

protein

Endocytosis

Protein is processed to

peptides in endosome

or lysosome

Endosome

Lysosome

Fusion of endosome

and exocytic vesicle

Endoplasmic reticulum

Class II MHC

Synthesis

3 chains: α,β and Ii

Golgi

body

Exocytic vesicle fuses

with endosome

releasing Ii from αβ dimer

α

β Ii

Immunodominant

peptide binds

to class II MHC

Endosome fuses with

plasma membrane

Peptide MHC-II

complex is presented

to CD4 helper T cellCD4 helper T cell

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IL2 (IL4)

ÑTB,Tc, (B)

Hoaït hoùa Lympho T

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4

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Points Concerning Antigen

Processing and Presentation1. Location of pathogen

• viruses in cytosol, MHC class I pathway, Tc response

• extracellular bacteria, MHC class II pathway, Th2 response, Ab formation

• intracellular bacteria, MHC class II pathway, Th1 response

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Points Concerning Antigen

Processing and Presentation2. Peptides derived from both self and

non-self proteins can associate with

MHC class I and class II molecules.

3. Chemical nature of MHC groove

determines which peptides it will

bind.

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Hoaït hoùa Lympho baøo

T B

Tín hieäu

KN

(1)Ti (TCR) KN

(2) CD4 (TH)

HLAII(APC)

sIg (BCR) KN

Tín hieäu

thöù 2

(1) IFN- (TH)

(2) IL1 (APC)

IL2,IL4, IL5

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Hoaït hoùa

Lympho B

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Söï hôïp taùc giöõa

Ñaïi thöïc baøo,

lympho T vaø

lympho B

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Cellular Events in 1o Response to

T-dependent Ags

• Lag

– Clonal selection

• Log

– IgM

– Class switching

• Stationary

• Decline

• Memory Cell Pool

IgM

Memory Cells

IgG

1o Ag

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Cellular Events in 2o Response to

T-dependent Ags• Lag phase

– Virgin cells

– Memory cells

• Log phase

– Pool size

– IgG, IgA or IgE

• Stationary

• Decline

– Sustained

production

IgM

Memory

Cells

IgG

IgG

Memory

Cells

Memory

Pool

Virgin B cell

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Hieäu öùng Hapten-taûi

Hapten khoâng coù tính gaây MD

Hapten phaûi gaén vôùi 1 protein taûi =>

phöùc hapten taûi (hapten-carrier

complex)

Th nhaän dieän taûi, B nhaän dieän hapten

Taûi ôû thì 1 vaø thì 2 phaûi gioáng nhau.

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Söï hôïp taùc haïn cheá trong nhoùm phuø hôïp moâ

(hieän töôïng Zinkernagel vaø Doherty)

Mouse

Strain A or BImmunize

with antigen

Period of 7 days

T cells isolated

from lymph nodes

T cell primed with

antigen

Mouse

Strain A or B

Peritoneal macrophage

Antigen

Macrophage presents antigen

Macrophages and

T cells are co-cultivated

Anti X-induced

Macrophage T-cell proliferation

Strain A A yes

Strain A B no

Strain B B yes

Strain B A no

Assay DNA

synthesis

after 48 hr

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Tc Cell Self MHC RestrictionMouse

Strain A or B

Immunize

with virus

Period of 7 days

Virus-specific

cytotoxic T cells (CTLs)

isolated from spleen

Virus-specific

CTLs

Mouse

Strain A or B

Purify

Fibroblasts

CTLs and fibroblasts

are co-cultivated

Spleen Fibroblast 51Cr release

CTLs (target cells) from fibroblasts

immunized infected (lysis)

with with

Strain A A yes

Strain A B no

Strain B B yes

Strain B A no

Assay 51Cr

release

Isolate spleen

Infect fibroblasts

with virus and

radiolabel with 51Cr51Cr labeled fibroblast

presents antigen

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Self MHC Restriction in the Thymus4 -

8 low

4 low

8 low

4 + 8 +

TCR

4 + 8 +

TCR

macrophage

Productive TCR

rearrangementNon-productive TCR

rearrangement

Recognise self MHC

Not recognise self MHC

TCR does not

recognise self antigens

Negative selection

TCR recognises

self antigens

APOPTOSIS

4 + 8 +

TCR 4 - 8 -

Sub-capsular region

Cortex

Cortico-medullary region

4 + 8 -

TCR 4 - 8 +

TCRvessel

Medulla

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KN khoâng leä thuoäc thymus

Caáu truùc: ñaïi phaân töû do truøng phaân caùc ñôn

vò nhoû (lipopolysaccharide, dextran…)

Caùc epitop gioáng nhau treân ñaïi phaân töû lieân

keát vôùi nhieàu sIg taïo thaønh ñaùm (hieän töôïng

ñoäi muõ) => hoaït hoùa Lympho B thaønh töông

baøo => SX KT

KT thuoäc lôùp IgM, khoâng taïo ra trí nhôù MD

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Hieän töôïng ñoäi muõ