Mô tả:
SÖÏ HÌNH THAØNH MOÄT
ÑAÙP ÖÙNG MIEÃN DÒCH
• GS Phaïm Hoaøng Phieät
• BS Huyønh Thanh Bình
1
Ñoäng hoïc moät ñaùp öùng mieãn dòch
.
.
2
So saùnh ñaùp öùng thì 1 vaø thì 2
ÑÖMD
Thì 1
Tính chaát
Tieàm aån
Dieãn Taêng SLKT
tieán Bình oån
Giaûm suùt
Thì 2
1-2 tuaàn
3-5 ngaøy
Taêng nhanh
Taêng raát nhanh
2-3 tuaàn
Nhieàu thaùng- naêm
Nhanh
Töø töø
Soá
löôïng
Cao hôn thì 1 nhieàu
Lôùp KT
Chaát
löôïng Aùi löïc vôùi
KN
IgM
IgG
+
+++
3
Teá baøo trình dieän
khaùng nguyeân
HLA lôùp II –TCD4
(peptid 15-34 aa)
HLA lôùp I –TCD8
(peptid 9 aa)
4
Class I MHC Pathway
Peptide is presented
by MHC-I to CD8
cytotoxic T cell
Plasma membrane
Peptide passes
with MHC from Golgi
body to surface
Viral protein is made
on cytoplasmic
ribosomes
Globular viral
protein - intact
Peptide associates
with MHC-I complex
rER
Proteasome
degrades
protein to
peptides
Peptide transporter
protein
moves
peptide into ER
Golgi body
Peptide with MHC
goes to Golgi body
MHC class I alpha
and beta proteins
are made on the rER
5
Class II MHC Pathway
Peptide MHC-II
complex is presented
to CD4 helper T cell
Endosome fuses with
plasma membrane
Immunodominant
peptide binds
to class II MHC
Golgi
body
Globular
protein
CD4 helper T cell
Endosome
Fusion of endosome
and exocytic vesicle
Endocytosis
Lysosome
Exocytic vesicle fuses
with endosome
releasing Ii from αβ dimer
Protein is processed to
peptides in endosome
or lysosome
Class II MHC
α
Synthesis
3 chains: α,β and
Ii
β Ii
6
Endoplasmic reticulum
Hoaït hoùa Lympho T
ÑTB,Tc, (B)
4
IL2 (IL4)
3
2
1
7
Points 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
8
Points 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.
9
Hoaït hoùa Lympho baøo
T
Tín hieäu
KN
Tín hieäu
thöù 2
B
(1)Ti (TCR) KN
(2) CD4 (TH)
HLAII(APC)
sIg (BCR) KN
(1) IFN- (TH)
(2) IL1 (APC)
IL2,IL4, IL5
10
Hoaït hoùa
Lympho B
11
Söï hôïp taùc giöõa
Ñaïi thöïc baøo,
lympho T vaø
lympho B
12
Cellular Events in 1o Response to
T-dependent Ags
• Lag
– Clonal selection
• Log
1o Ag
– IgM
– Class switching
• Stationary
• Decline
• Memory Cell Pool
IgM
IgG
Memory Cells
13
Cellular Events in 2o Response to
T-dependent Ags
• Lag phase
– Virgin cells
– Memory cells
Virgin B cell
• Log phase
IgG
– Pool size
– IgG, IgA or IgE
• Stationary
• Decline
– Sustained
production
IgM
Memory
Pool
Memory
Cells
IgG
14
Memory
Cells
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.
15
Söï hôïp taùc haïn cheá trong nhoùm phuø hôïp moâ
(hieän töôïng Zinkernagel vaø Doherty)
Mouse
Strain A or B
Mouse
Strain A or B
Immunize
with antigen
Period of 7 days
Peritoneal macrophage
Antigen
T cells isolated
from lymph nodes
T cell primed with
antigen
Macrophages and
T cells are co-cultivated
Macrophage presents antigen
Anti X-induced
Macrophage T-cell proliferation
Assay DNA
synthesis
after 48 hr
Strain A
Strain A
Strain B
Strain B
A
B
B
A
yes
no
yes
16
no
Tc Cell Self MHC Restriction
Mouse
Strain A or B
Mouse
Strain A or B
Immunize
with virus
Purify
Fibroblasts
Period of 7 days
Isolate spleen
Virus-specific
cytotoxic T cells (CTLs)
isolated from spleen
51Cr labeled fibroblast
presents antigen
Spleen
Fibroblast 51Cr release
CTLs
(target cells) from fibroblasts
immunized infected
(lysis)
with
with
Virus-specific
CTLs
CTLs and fibroblasts
are co-cultivated
Infect fibroblasts
with virus and
radiolabel with 51Cr
Assay 51Cr
release
Strain A
Strain A
Strain B
Strain B
A
B
B
A
yes
no
yes 17
no
Self MHC Restriction in the Thymus
4 low
8 low
48 low
Productive TCR
rearrangement
4+ 8 +
TCR
Sub-capsular region
Non-productive TCR
rearrangement
Not recognise self MHC
APOPTOSIS
Recognise self MHC
TCR recognises
4+ 8 +
self antigens
TCR
TCR does not
recognise self antigens
Negative selection
4- 8 -
macrophage
Cortex
Cortico-medullary region
4+ 8 +
TCR
Medulla
vessel
4+ 8 TCR
4- 8 +
TCR
18
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
19
Hieän töôïng ñoäi muõ
20
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