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Cell-Mediated Immunity CMI

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Presentation on theme: "Cell-Mediated Immunity CMI"— Presentation transcript:

1 Cell-Mediated Immunity CMI
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

2 T Cells Helper T Cells (CD4, TH) Cytotoxic T Cells (CD8, TC)
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

3 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

4 Structure of T Cell Receptor
CHO Variable region “V” Constant region “C” Hinge “H” Alpha chain Beta chain Disulfide bridge Transmembrane region Cytoplasmic tail +

5 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

6 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

7 What Does the T Cell Receptor (TCR) Recognize?
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

8 Interactions of TH Cell and APC
T helper lymphocyte TCR LFA-2 LFA-1 CD28 TNF-alpha IL-1 IL-6 IL-12 IL-15 TNF-beta IFN-gamma GM-CSF IL-4 CD4 peptide Antigen- presenting cell LFA-3 ICAM-1 Class II MHC B7-1/B7-2 (CD80/CD86

9 Interactions of Tc Cell and Target Cell
T cytotoxic lymphocyte LFA-1 TCR LFA-2 CD8 peptide Target cell ICAM-1 Class I MHC LFA-3

10 T-independent Antigens
B cell Figure 17.17

11 T-Dependent Antigens Figure 17.16

12 T-dependent and independent antigens

13 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

14 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




18 Dendritic cells present antigens
Figure 17.12




22 Helper T Cells Figure 17.13

23 Cell-mediated Cytotoxicity
Figure 17.14

24 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

25 Self MHC Restriction in the Thymus
4 - 8 low 4 low 8 low Sub-capsular region Productive TCR rearrangement Non-productive TCR rearrangement APOPTOSIS TCR Not recognise self MHC Recognise self MHC macrophage TCR TCR recognises self antigens Cortex TCR does not recognise self antigens Negative selection Cortico-medullary region TCR TCR vessel Medulla

26 Self MHC Restriction in the Thymus
4- 8- 4+/- 8+ 4+ 8+ TCR low Express MHC I MHC II No MHC engagement apoptosis TCR high 4+

27 Self MHC Restriction in the Thymus
No interaction with self antigen Interaction with MHC I and self antigen. Interaction with dendritic cells, macrophages and medullary epithelium Interaction with MHC II 8+ TCR high 4+ TCR induced apoptosis Mature T cell pool

28 Self MHC Restriction in the Thymus

29 T-Cell clonal selection Animation

30 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

31 Conventional Antigen Superantigen αC βC βV αV α2 β2 β1 α1 MHC Class II
CHO βV αV α2 β2 β1 α1 MHC Class II T cell receptor Antigen Super antigen T lymphocyte Antigen presenting cell

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