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Antigen presenting cells and antigen presentation. Contents. Antigen presenting cells Antigen presentation. Antigen presenting cell, APC. A variety of cell types which carry antigen in a form that can stimulate lymphocytes. It is also termed accessory cell. professional APC:M Φ ,DC,B - PowerPoint PPT Presentation
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Antigen presenting cells and
antigen presentation
Antigen presenting cells
Antigen presentation
Contents
A variety of cell types which
carry antigen in a form that can
stimulate lymphocytes. It is also
termed accessory cell.
professional APC:MΦ,DC,B
non-professional APC
Antigen presenting cell, APC
The 3 types of professional APCs
Constitutively express a high level of MHC II and the co-stimulatory protein,B7. the most effective APC
Constitutively express class II MHC but must be activated to produce B7.
must be activated by the process of phagocytosis before expressing class II MHC and B7.
I. Dendritic cells (DC)
Dendritic cells were first described by Paul Langerhans (Langerhans cells) in the late nineteenth century. It wasn't until 1973, however, that the term "dendritic cells" was coined by Ralph M. Steinman and Zanvil A. Cohn. In 2007 Steinman was awarded the Albert Lasker Award for Basic Medical Research for his discovery.
MarksMouse 33D1,NLDC145Rat OX62Human CD1a,CD11c,CD83Other marks:MHCⅡ,CD80,CD86
Sources of DC
单 核细 胞
巨 噬细 胞
中 性粒 细 胞
B细 胞T细 胞NK细 胞
髓 系 DC
BTN K
髓 系 DC
淋 巴系 DC
淋 巴 系 前 体 细 胞
髓 系前 体 细胞
多 能造 血 干细 胞
GM-CSFTNF-IL-4
HSC
Myeloid progenitor
Lymphoid progenitor
DC Mo
macrophageDC
PMN
DC
Dendritic Cell Maturation
LPS
IL-1,TNFα
Menu FB
Functions of DC: antigen presentation, immune activation, immune tolerance
mononuclear phagocyte system, MPS
1.Differentiation and distribution
2. Surface markers
3. function
Antigen presenting cells
Bone marrow Blood tissues
HSC
Myeloid progenitor
Pre-monocyte
monocyte
monocyte macrophage
Differentiation and distribution of MPS
1. Surface markers:
MHC-I/ moleculesⅡ CKR: M-CSFR
CAM: LFA-1,ICAM-1,B7,CD40
FcR, CR1/3/4 2. secretion : -enzymes: lysosome , myeloperoxidase
-cytokines (IL-1,TNF,IL-12)
-complement:C1 ~ C9, Bf
-coagulation factor, PG, LTs, ACTH, etc.
Mononuclear phagocyte system, MPS
Biological functions of MPS Phagocytosis antitumor : indirect or direct killing, ADCC; participating in immune response: -Ag presenting, providing the second signal; -CMI participating in immune regulation:
-positive regulation : secrete IL-1/12 , TNF-α
-negative regulation : PG, TGF-β Mediating inflammation: phagocytosis, secrete
inflammation medium
phagocytosis
Antigen presenting cells
B cells
The properties of various APCs
DefinitionAPCAg presentation -MHC class I molecule pathway -MHC class II molecule pathway
Ag presentation
Antigen capturingPhagocytosisPinocytosisReceptor-mediated endocytosis
Antigen processing
The conversion of an
antigen into a form in which it can
be recognized by lymphocytes.
Antigen presentation
The process by which certain cells in the
body (APC) express antigen peptide-MHC
molecule complex on their cell surface in a
form recognize by lymphocytes.
Recourses of antigens* exogenous antigen
* endogenous antigen
YThe site of pathogen replication or mechanism of antigen uptake determines the antigen processing pathway used
Y
Cytosolic compartmentEndogenous processing
(Viral antigens)
Vesicular CompartmentContiguous with extracellular fluid
Exogenous processing(Streptococcal, Mycobacterial antigens)
Distinct mechanisms of antigen generation are used to raiseT cells suited to the elimination of endogenous or exogenous pathogens
INTRACELLULAR REPLICATION
EXTRACELLULAR ORENDOSOMAL REPLICATION
Pathogens in Cytosol/Vesicles
The pathway of MHC I -associated endogenous Ag presentation
endogenous antigen ( such as virus Ag, tumor Ag)
cytoplasm degraded by proteasome
antigen peptide ( 8-13 AA ) transported to endoplasmic
reticulum by TAP
Peptide/MHC-I molecule complex
to surface of APC
submit to CD8+T
Degradation in the proteasome
The components of the proteasome include MECL-1, LMP2, LMP7These components are induced by IFN- and replace constitutive
components to confer proteolytic properties.
LMP2 & 7 encoded in the MHC
Proteasome cleaves proteins after hydrophobic and basic amino acids and releases peptides into the cytoplasm
Cytoplasmic cellular proteins, including non-self proteinsare degraded continuously by a multicatalytic protease of 28 subunits
ER membrane
Lumen of ER
Cytosol
Transporters associated withantigen processing (TAP1 & 2)
Transporter has preference for >8 amino acid peptideswith hydrophobic C termini.
TAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
Peptide
ER membrane
Lumen of ER
Cytosol
TAP-1 TAP-2
Peptide
ATP-binding cassette(ABC) domain
Hydrophobictransmembranedomain
Peptide antigensfrom proteasome
Endoplasmic reticulum
Calnexin bindsto nascent
class I chainuntil 2-M binds
TAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
TAP-1 TAP-2
PeptideTAP-1 TAP-2
Peptide
B2-M binds and stabilises
floppy MHC
Tapasin, calreticulin, TAP 1 & 2 form a complex with
the floppy MHC
Cytoplasmic peptides are loaded onto the
MHC molecule and the structure becomes
compact
Maturation and loading of MHC class I
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The pathway of MHC II -associated exogenous Ag presentation
Exogenous antigen newly synthesised MHC class II molecule ( in the endoplasmic reticulum )
early endosome li binds in the groove of MHC class II molecule
lysosome protease MIIC
late endosome li degrade
protease
Degrade into 1318AA peptide + MHC class II molecule Ag peptide/MHC class II molecule complex
transport to the surface of APC, recognized by CD4+T
Phagocytosis, pinocytosis,
FcR-phagocytosis
Y Y
Pinocytosis
Phagocytosis
Membrane Igreceptor mediateduptake
Y
Uptake of exogenous antigens
Complement receptormediated phagocytosis Y
Fc receptor mediated phagocytosis
opsonization
Proteases produce ~24 amino acid long peptides from antigensDrugs that raise the pH of endosomes inhibit antigen processing
Endosomes
Exogenous pathway
Increasein acidity
To lysosomes
UptakeProtein antigens
In endosome
Cathepsin B, D and L proteases are activated by the decrease in pH
involve in the assembling and folding of MHC class II molecule; Block the groove of MHC class II molecule; Lead the assembled class II molecule to M C.Ⅱ
The functions of Ii:
CLIP : class II-associated invariant chain peptide
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Cross-presentation
Class I MHC molecules present exogenous Ags to CD8+ T cells
Cross-presentation of Ags by DC plays an important role in anti-viral infection and anti-tumor immunity.
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