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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
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• 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
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• 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
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Structure of T Cell Receptor
CHO CHO
CHOCHO
Variable region “V”
Constant region “C”
Hinge “H”
Alphachain
Betachain
Disulfide bridge
Transmembrane region
Cytoplasmic tail
++ +
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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
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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
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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
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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
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Interactions of Tc Cell and Target Cell
LFA-1 TCR
CD8
ICAM-1 Class IMHC
LFA-3
LFA-2T cytotoxiclymphocyte
Targetcell
peptide
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T-independent Antigens
Figure 17.17
B cell
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T-Dependent Antigens
Figure 17.16
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T-dependent and independent antigens
•
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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
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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
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Dendritic cells present antigens
Figure 17.12
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Helper T Cells
Figure 17.13
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Cell-mediated Cytotoxicity
Figure 17.14
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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
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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
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Self MHC Restriction in the Thymus
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T-Cell clonal selection Animation
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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
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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