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• Specialized lymphocytes, mostly T cells, respond to intracellular Ags
• After differentiating in the thymus, T cells migrate to lymphoid tissue
• T cells differentiate into effector T cells when stimulated by an Ag
• Some effector T cells become memory cells
Cell-Mediated ImmunityCMI
• Helper T Cells (CD4, TH)
– TH1 Activate cells related to cell-mediated immunity
– TH2 Activate B cells to produce eosinophils, IgM, and IgE
• Cytotoxic T Cells (CD8, TC)
– Destroy target cells with perforin
T Cells
• Delayed Hypersensitivity T Cells (TD) (CD4)
– Associated with allergic reaction, transplant rejection, and tuberculin skin test
• Suppressor T cells (TS) (CD8)
– Turn off immune response when Ag no longer present
T Cells
Structure of T Cell Receptor
CHO CHO
CHOCHO
Variable region “V”
Constant region “C”
Hinge “H”
Alphachain
Betachain
Disulfide bridge
Transmembrane region
Cytoplasmic tail
++ +
Structure of T Cell Receptor (TCR)
• Two polypeptide chains, α and β, of roughly equal length
• Both chains consist of a variable (V) and a constant (C) region
• α chain V region has a joining (J) segment
• β chain V region has both a J and diversity (D) segment
Structure of T Cell Receptor(continued)
• Hypervariable regions in V contribute to diversity of TCR
• TCR recognizes portions of MHC molecule and peptide bound in the groove
What Does the T Cell Receptor (TCR) Recognize?
1. Only fragments of proteins (peptides) associated with MHC molecules on surface of cells
• Helper T cells (TH) recognize peptide associated with MHC class II molecules
• Cytotoxic T cells (Tc) recognize peptide associated with MHC class I molecules
Interactions of TH Cell and APC
LFA-3
LFA-2 LFA-1 TCR
CD4
ICAM-1 Class IIMHC
B7-1/B7-2(CD80/CD86
CD28
TNF-alphaIL-1IL-6IL-12IL-15
TNF-betaIFN-gammaGM-CSFIL-4
T helperlymphocyte
Antigen-presenting
cell
peptide
Interactions of Tc Cell and Target Cell
LFA-1 TCR
CD8
ICAM-1 Class IMHC
LFA-3
LFA-2T cytotoxiclymphocyte
Targetcell
peptide
T-independent Antigens
Figure 17.17
B cell
T-Dependent Antigens
Figure 17.16
T-dependent and independent antigens
•
Self MHC Restriction
• T cells recognize foreign antigen associated with self MHC
• No value for individual to have T cells that recognize foreign antigen associated with foreign MHC
• Self MHC restriction occurs in thymus
Process of Self MHC Restriction in Thymus
• T cells with TCR recognizing self MHC molecules are retained – “positive selection”
• Retained T cells with TCR recognizing self peptide associated with self MHC are eliminated – “negative selection”
• Self MHC-restricted T cells are released
Dendritic cells present antigens
Figure 17.12
Helper T Cells
Figure 17.13
Cell-mediated Cytotoxicity
Figure 17.14
Nonspecific Cells• Activated
macrophages: Macrophages stimulated by ingesting Ag or by cytokines
• Natural killer cells: Lymphocytes that destroy virus-infected cells, tumor
Figure 17.15
Self MHC Restriction in the Thymus4 -
8 low4 low8 low
4 + 8 +TCR
4 + 8 +TCR
macrophagemacrophage
Productive TCRrearrangement
Non-productive TCRrearrangement
Recognise self MHC
Not recognise self MHC
TCR does not recognise self antigens
Negative selection
TCR recognisesself antigens
APOPTOSIS
4 + 8 +TCR
4 - 8 -
Sub-capsular region
Cortex
Cortico-medullary region
4 + 8 -TCR 4 - 8 +
TCRvessel
Medulla
Self MHC Restriction in the Thymus
T-Cell clonal selection Animation
Superantigens• Proteins produced by pathogens• Not processed by antigen presenting cells• Intact protein binds to variable region of
β chain on TCR of T cells and to MHC class II on antigen presenting cells (APC)
• Large numbers of activated T cells release cytokines having pathological effects
Conventional Antigen
αC βC
CHO CHO
CHOCHO
βVαV
α2 β2
β1α1CHO CHO
CHO
αC βC
CHO CHO
CHOCHO
βVαV
α2 β2
β1α1CHO CHO
CHO
MHC Class II
T cell receptor
AntigenSuper
antigen
T lymphocyte
Antigen presenting cell
Superantigen