Germline-encoded receptors
Gene rearranged receptors: TCR/BCR
Ags………. Innate immunity
Adaptive immunity
B/T cells
Pattern recognition
Epitope recognition
?Ags……….
Foreign AgSelf Ag
Ag recognition
Self tolerance
自我耐受性
BCR/TCR:Ag recognition
Fig. 5.1
MHC-restriction
Extracellular Ag
Intracellular Ag
Structure
Gene rearranged receptors
Heavy chain (H)
Light chain (L)
Variable region
Hematopoiesis
Central lymphoid organs
Microenvironment
Cell survival & death
Commitment
Productive rearrangement?
2
Clonal selection Immune diversity
Antigenspecificity Diversity
Memory
Gene rearrangement
of TCR/BCR
Adaptive immunity
Bone marrow 骨髓
Note: low frequency of Ag-specific cellsClone
Peripheral tolerance
Central tolerance
Thymus 胸腺
Adaptive immunity
1. Antigen specificity
2. Diversity
3. Immunological memory
4. Self tolerance
Four characteristics
AIRE expression on thymic medulary cells(Autoimmune regulator)
Medulary epithelial marker MTS10
AIRE regulates the expression of ubiquitous self antigens & a wide variety of tissue-restricted self Ag (e.g. pancreas, brain) at low levels in the thymus
Negative selection : Self Ag presentation
T cell development
AIRE medulary cells
The presence of autoreactive lymphocytes
in periphery
Natural Treg
Induction of adaptive immunity
Differentiation of Th
Cytokines
Cell-mediated immunity
Humoral immunity
Immunological memory
Adaptive immunity
Ag Innate Adaptive
Extracellular Phagocytes B cells
Intracellular NK CD8 Tc cells(Altered self)
Immunity & Ag location
Cytotoxicity
CD4 Th
Humoral response
Cell-mediated immunity (CMI)
Th1
Th2
Phagocytes
Antigen-Presenting Cells (APC)
B/T cells
Lymphocyte activationClonal selectionHumoral Imm/CMIMemory
Inflammatory site
Inflammation
Inflammatorysite
Lymph node
Induction of adaptive immunity
Dendritic cells (DC)
Induction of adaptive immunity
Differentiation of CD4 Th
Cytokines
Cell-mediated immunity
Humoral immunity
Immunological memory
Immune effector
function
Three signals in naïve T cell activation
PrimingThe activation and differentiation of naïve T cells
Costimulation
TH17
Recruitment of neutrophils
Activation of macrophages
Antimicrobial peptides
Ubiquitous expression of IL17R on tissue cells: fibroblasts, epithelial cells, keratinocytes, etc.
Cytokines: G-CSF, GM-CSF
Chemokines: CXCL8, CXCL2
Proinflammatory cytokine
Antimicrobial peptides PhagocytosisInflammed site
Signal 1+2
Cytokines made in the later stages of infection
Differentiation of Th1 or Th2(polarization)
IL12 – Th1 IL4 – Th2
Intracellular infection Extracellular infection
Adaptive Treg
TH17
Rapid response to
infectionPreventing anti-selfresponse
Inhibition of proliferation & differentiation
TH17
Limiting immunopathology
Peripheral tolerance
Regulation among CD4 T subsets
Cytokine pattern of the dominant response
Inhibition of early Th17 response
Induction of adaptive immunity
Differentiation of Th
Cytokines
Cell-mediated immunity
Humoral immunity
Immunological memory
Immune effector
function
Effector response
Induction of adaptive immunity
Differentiation of Th
Cytokines
Cell-mediated immunity
Humoral immunity
Immunological memory
Immune effector
function
Effector response
Induction of adaptive immunity
Differentiation of Th
Cytokines
Cell-mediated immunity
Humoral immunity
Immunological memory
Immune effector
function
Ab:Affinitymaturation
AgHighly sensitive to
small amount of Ag
CD4 Th2 in B cell differentiation
54
Variable region
Ab: class switching