Bài giảng Sự hình thành một đáp ứng miễn dịch - Phạm Hoàng Phiệt

1SÖÏ HÌNH THAØNH MOÄT 
ÑAÙP ÖÙNG MIEÃN DÒCH
• GS Phaïm Hoaøng Phieät
• BS Huyønh Thanh Bình
2. .
Ñoäng hoïc moät ñaùp öùng mieãn dòch
3So 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 
löôïng
Cao hôn thì 1 nhieàu
Chaát 
löôïng
Lôùp KT IgM IgG
Aùi löïc vôùi 
KN
+ +++
4Teá baøo trình dieän 
khaùng nguyeân
HLA lôùp II –TCD4
(peptid 15-34 aa)
HLA lôùp I –TCD8
(peptid 9 aa)
5Class 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
6Class 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 cell
CD4 helper T cell
7IL2 (IL4)
ÑTB,Tc, (B)
Hoaït hoùa Lympho T
1
2
3
4
8Points Concerning Antigen 
Processing and Presentation
1. 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
9Points Concerning Antigen 
Processing and Presentation
2. 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.
10
Hoaït hoùa Lympho baøo
T B
Tín hieäu 
KN
(1)Ti (TCR) KN
(2) CD4 (T
H
) 
HLA
II
(APC)
sIg (BCR) KN
Tín hieäu 
thöù 2
(1) IFN- (T
H
) 
(2) IL1 (APC)
IL2,IL4, IL5
11
Hoaït hoùa 
Lympho B
12
Söï hôïp taùc giöõa 
Ñaïi thöïc baøo, 
lympho T vaø 
lympho B
13
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
14
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
15
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.
16
Söï hôïp taùc haïn cheá trong nhoùm phuø hôïp moâ
(hieän töôïng Zinkernagel vaø Doherty)
Mouse 
Strain A or B
Immunize
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
17
Tc Cell Self MHC Restriction
Mouse 
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 51Cr
51Cr labeled fibroblast
presents antigen
18
Self MHC Restriction in the Thymus
4 -
8 low
4 low
8 low
4 + 8 +
TCR 
4 + 8 +
TCR 
macrophage
Productive TCR
rearrangement
Non-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
19
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
20
Hieän töôïng ñoäi muõ