• 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