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Chapter 8 T Cell-Mediated Immunity
T Cell-Mediated Immunity ,[object Object],[object Object],[object Object],[object Object],[object Object]
Activation of naïve T cells on encounter with antigen
Process of T-cell activation ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Activation of naïve T cells on encounter with antigen ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Dendritic cells carry antigens from sites of infection  ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Dendritic cells carry antigens from sites of infection ,[object Object],[object Object],[object Object]
Macrophages = function in defense and repair of damaged tissues ,[object Object],[object Object]
Dendritic cells take up antigen, migrate to lymphoid organs, and present foreign antigens to naïve T cells ,[object Object],[object Object],[object Object],[object Object]
Dendritic cells take up antigen, migrate to lymphoid organs, and present foreign antigens to naïve T cells ,[object Object],[object Object],[object Object],[object Object]
[object Object],[object Object],[object Object],[object Object],[object Object]
Dendritic cells are developmentally related to macrophages ,[object Object],[object Object],[object Object],[object Object]
Dendritic Cells Processing and Presentation
Dendritic cells change their functions on taking antigen from infected sites to secondary lymphoid tissues ,[object Object],[object Object],[object Object]
Dendritic cells change their functions on taking antigen from infected sites to secondary lymphoid tissues ,[object Object],[object Object]
Dendritic cells change their functions on taking antigen from infected sites to secondary lymphoid tissues ,[object Object],[object Object],[object Object]
Recirculating, Naïve T cells first encounter antigen on APCs in secondary lymphoid tissues ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Recirculating, Naïve T cells encounter antigen during recirculation through lymphoid organs ,[object Object],[object Object],[object Object],[object Object],[object Object]
Naïve T cells encounter antigen during recirculation through lymphoid organs
Recirculating Naïve T-cells
Once Ag-specific T cells are trapped in the LN by an APC…. ,[object Object],[object Object],[object Object],[object Object]
Homing of naïve T cells to secondary lymphoid tissues is determined by cell adhesion molecules. ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Leukocyte adhesion molecules ,[object Object],[object Object],[object Object],[object Object],[object Object]
Leukocyte adhesion molecules
Binding of L-selectin to vascular addressins directs naïve lymphocytes homing to lymphoid tissues. ,[object Object],[object Object],[object Object],[object Object]
Naïve T and B lymphocytes circulate in the blood and enter lymph nodes by crossing high endothelial venules ,[object Object],[object Object],[object Object],[object Object]
Naïve T and B lymphocytes circulate in the blood and enter lymph nodes by crossing high endothelial venules
Cell-surface molecules of the immunoglobulin superfamily initiate lymphocyte adhesion to APC ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Cell-surface molecules of the immunoglobulin superfamily initiate lymphocyte adhesion to APC
Transient adhesive interactions between T cells & dendritic cells are stabilized by specific Ag recognition ,[object Object],[object Object],[object Object],[object Object]
Transient adhesive interactions between T cells & dendritic cells are stabilized by specific Ag recognition
Activation of naïve T cells requires a co-stimulatory signal delivered by a professional antigen-presenting cell. ,[object Object],[object Object],[object Object],[object Object]
The principal co-stimulatory molecules on professional APC are B7 molecules, which bind CD28 proteins on the T-cell surface ,[object Object],[object Object],[object Object],[object Object],[object Object]
In absence of infection professional APC do not express co-stimulatory molecules ,[object Object],[object Object]
[object Object],[object Object],[object Object]
Professional antigen-presenting cells versus other antigen-presenting cells ,[object Object],[object Object],[object Object]
Three types of professional APCs populate different parts of the lymph node Dendritic cells (or interdigitating cells) are situated in the  cortical T-cell areas  of the lymph node.  Dendritic cells are the most effective antigen-presenting cell.
Three types of professional APCs populate different parts of the lymph node ,[object Object],Macrophages are less effective than dendritic cells but more effective than B cells in presenting antigen.
Three types of professional APCs populate different parts of the lymph node These distributions reflect differences in the functions and importance of the three types of professional antigen-presenting cells. B cells mainly populate the  lymphoid follicles  in the cortex.
 
Dendritic cells are developmentally related to macrophages ,[object Object],[object Object],[object Object],[object Object]
Dendritic cells are developmentally related to macrophages ,[object Object],[object Object],[object Object],[object Object],[object Object]
Immature DC: DEC205  facilitates  phagocytosis  and  pinocytosis  of antigens. Mature DC:   Increase  expression of B7 co-stimulators, MHC molecules  and  adhesions molecules  like  DC-SIGN
Macrophages in lymph nodes have different functions ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Macrophages in lymph nodes have different functions ,[object Object],[object Object],[object Object],[object Object]
Microbial substances induce co-stimulatory activity in macrophages ,[object Object],[object Object],[object Object]
Third Type of P-APC ,[object Object],[object Object],[object Object],[object Object]
Signals from TCR and co-receptors alter the pattern of gene transcription in activated T cells. ,[object Object],[object Object],[object Object],[object Object],[object Object]
Clustering of the TCR and a co-receptor initiates signaling within the T cell
Signaling pathways initiated by the T-cell receptor complex, its CD4 co-receptor and CD28
Proliferation and differentiation of activated T cells are driven by the cytokine interleukin-2 (IL-2) ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Proliferation and differentiation of activated T cells are driven by the cytokine interleukin-2 (IL-2) ,[object Object],[object Object],[object Object],[object Object],[object Object]
Activated T cells secrete and respond to IL-2 ,[object Object],[object Object],[object Object],[object Object],[object Object]
 
Antigen recognition without co-stimulation leads to a nonresponsive T cell ,[object Object]
Antigen recognition without co-stimulation leads to a nonresponsive T cell ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Studying Ab and T-cell responses in lab animals ,[object Object],[object Object],[object Object],[object Object],[object Object]
 
On activation, CD4 T cells can acquire different helper functions ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
 
Cytokine Environment Plays Large Role in Type of T-cell Produced ,[object Object],[object Object],[object Object]
Stages of activation of CD4 T cells ,[object Object],[object Object]
Cytokines  produced by  TH1  cells can  suppress  the  differentiation  of  TH2 cells  and  Cytokines  produced by  TH2  cells can  suppress  the  differentiation  of  TH1   cells.
Naïve CD8 T cells can be activated in different ways to become cytotoxic cells ,[object Object],[object Object],[object Object],[object Object],[object Object]
 
T Cell-Mediated Immunity
T Cell-Mediated Immunity ,[object Object],[object Object],[object Object],[object Object],[object Object]
The properties and functions of  effector  T- cells
After differentiating (secondary lymphoid organs) effector T cells detach from the APC that nursed their differentiation Effector T cells CD4 TH2 CD4 TH1  Cytotoxic CD8 T cells Sites of infection -CD8 kills infected cells -CD4 secrete cytokines Stays in the secondary lymphoid organs -CD4 secrete cytokines
T-cell effector functions are turned on when TCRs bind to peptide:MHC complexes ,[object Object],T cell Target Cell TCR------ peptide:MHC
Effector T cells can be stimulated by antigen in the absence of co-stimulation ,[object Object],[object Object],[object Object],[object Object]
Example of CD4 T cell Surface Molecules
Effector T cells can be stimulated by antigen in the absence of co-stimulation ,[object Object],[object Object],[object Object],[object Object],[object Object]
 
Effector T cells Respond Without the need for Co-stimulation ,[object Object],[object Object],[object Object]
Effector T cells express more adhesion molecules than naïve T cells ,[object Object],[object Object],[object Object],[object Object]
Example of Resting CD4 T cell ,[object Object],[object Object]
Example of Activated CD4 T cell ,[object Object],[object Object]
Example of CD4 T cell increased sensitivity ,[object Object]
Changes in adhesion molecule expression = changes in migration patterns ,[object Object],[object Object],[object Object]
Integrin VLA-4 enables effector T cells to home to inflamed tissue ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Integrin VLA-4 enables effector T cells to home to inflamed tissue Recruitment of effectors T cells into inflamed or infected tissues T cell migration or antigen presentation
Effector T-cell functions are performed by cytokines and cytotoxins ,[object Object],[object Object],[object Object],[object Object],[object Object]
Secreted  cytokines ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
Many cytokine receptors signal through a pathway in which receptor-associated kinases activate transcript factors directly ,[object Object],[object Object],[object Object],[object Object],[object Object]
Many cytokine receptors signal through a pathway in which receptor-associated kinases activate transcript factors directly
[object Object]
TH1 &TH2 cells make characteristic sets of cytokines that have distinct effects on the immune response
Cytotoxic CD8 T cells are selective and serial killers of target cells at sites of infection ,[object Object],[object Object],[object Object],[object Object]
Effector cytotoxic T cells contain lytic granules ,[object Object],[object Object],[object Object],[object Object]
Delivery of cytotoxins by CD8 T cells is aimed directly at the target cell. LG=  lytic granules (red) MTOC= microtubule organizing center  (microtubules – green) GA = golgi apparatus Initial contact has no effect Cytoskeleton reorganizes TCR:MHC Die
Cytotoxic CD8 T cells kill infected cells selectively ,[object Object],[object Object]
In addition to cytotoxic functions, CD8 cells also contribute to the immune response by secreting cytokines ,[object Object],[object Object],[object Object],[object Object]
Apoptosis Versus Necrosis ,[object Object],[object Object],[object Object],[object Object]
Apoptotic cell  in  early  stages showing  chromatin condensation  (red) but well-defined plasma membrane that is  shedding vesicles .  Apoptotic cell  in  late  stages has very  condensed nucleus ,  no mitochondria , and the  cytoplasm  and  cell membranes  are largely  lost  through  vesicle shedding . Necrotic cell  with plasma membrane poorly defined Healthy cell with normal nucleus Shriveled and shrunken
Time course of programmed cell death ,[object Object],[object Object],[object Object],[object Object],1. 2. 3. 4.
Cytotoxic T cells kill their targets by inducing apoptosis – two pathways ,[object Object],[object Object],[object Object]
Cytotoxic T cells kill their targets by inducing apoptosis – two pathways ,[object Object],[object Object],[object Object],[object Object]
Lymphadenopathy in autoimmune lymphoproliferation syndrome  (ALPS) ,[object Object],[object Object],[object Object]
TH1 CD4 cells induce macrophages to become activated ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]
TH1 CD4 cells induce macrophages to become activated ,[object Object],[object Object],[object Object],[object Object]
TH1 CD4 cells activate macrophages to become highly microbicidal ,[object Object],[object Object],[object Object],[object Object],[object Object]
TH1 CD4 cells activate macrophages to become highly microbicidal ,[object Object],[object Object],[object Object],[object Object]
TH1 cells coordinate the host response to intravesicular pathogens ,[object Object],[object Object],[object Object],[object Object],[object Object]
Immune response to intravesicular bacteria is coordinated by TH1 cells
Granulomas form when an intracellular pathogen resists elimination ,[object Object],[object Object],[object Object],[object Object],[object Object]
TH2 cells stimulate the proliferation and differentiation of naïve B cells ,[object Object],[object Object],For B cell to receive T cell help, both cells must recognize the same antigen –  cognate interactions .
Molecular complexes recognized by both B and T cells make effective vaccines ,[object Object],[object Object],[object Object],[object Object],[object Object]
Molecular complexes recognized by both B and T cells make effective vaccines
Regulatory CD4 T cells limit the activities of effector CD4 and CD8 T cells ,[object Object],[object Object],[object Object],[object Object],[object Object]
Summary: The properties of the P-APC
 
 
Summary: The T-cell response has two distinct stages ,[object Object],[object Object],[object Object],[object Object],[object Object],[object Object]

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Immunology chapter 8

  • 1. Chapter 8 T Cell-Mediated Immunity
  • 2.
  • 3. Activation of naïve T cells on encounter with antigen
  • 4.
  • 5.
  • 6.
  • 7.
  • 8.
  • 9.
  • 10.
  • 11.
  • 12.
  • 13. Dendritic Cells Processing and Presentation
  • 14.
  • 15.
  • 16.
  • 17.
  • 18.
  • 19. Naïve T cells encounter antigen during recirculation through lymphoid organs
  • 21.
  • 22.
  • 23.
  • 25.
  • 26.
  • 27. Naïve T and B lymphocytes circulate in the blood and enter lymph nodes by crossing high endothelial venules
  • 28.
  • 29. Cell-surface molecules of the immunoglobulin superfamily initiate lymphocyte adhesion to APC
  • 30.
  • 31. Transient adhesive interactions between T cells & dendritic cells are stabilized by specific Ag recognition
  • 32.
  • 33.
  • 34.
  • 35.
  • 36.
  • 37. Three types of professional APCs populate different parts of the lymph node Dendritic cells (or interdigitating cells) are situated in the cortical T-cell areas of the lymph node. Dendritic cells are the most effective antigen-presenting cell.
  • 38.
  • 39. Three types of professional APCs populate different parts of the lymph node These distributions reflect differences in the functions and importance of the three types of professional antigen-presenting cells. B cells mainly populate the lymphoid follicles in the cortex.
  • 40.  
  • 41.
  • 42.
  • 43. Immature DC: DEC205 facilitates phagocytosis and pinocytosis of antigens. Mature DC: Increase expression of B7 co-stimulators, MHC molecules and adhesions molecules like DC-SIGN
  • 44.
  • 45.
  • 46.
  • 47.
  • 48.
  • 49. Clustering of the TCR and a co-receptor initiates signaling within the T cell
  • 50. Signaling pathways initiated by the T-cell receptor complex, its CD4 co-receptor and CD28
  • 51.
  • 52.
  • 53.
  • 54.  
  • 55.
  • 56.
  • 57.
  • 58.  
  • 59.
  • 60.  
  • 61.
  • 62.
  • 63. Cytokines produced by TH1 cells can suppress the differentiation of TH2 cells and Cytokines produced by TH2 cells can suppress the differentiation of TH1 cells.
  • 64.
  • 65.  
  • 67.
  • 68. The properties and functions of effector T- cells
  • 69. After differentiating (secondary lymphoid organs) effector T cells detach from the APC that nursed their differentiation Effector T cells CD4 TH2 CD4 TH1 Cytotoxic CD8 T cells Sites of infection -CD8 kills infected cells -CD4 secrete cytokines Stays in the secondary lymphoid organs -CD4 secrete cytokines
  • 70.
  • 71.
  • 72. Example of CD4 T cell Surface Molecules
  • 73.
  • 74.  
  • 75.
  • 76.
  • 77.
  • 78.
  • 79.
  • 80.
  • 81.
  • 82. Integrin VLA-4 enables effector T cells to home to inflamed tissue Recruitment of effectors T cells into inflamed or infected tissues T cell migration or antigen presentation
  • 83.
  • 84.
  • 85.
  • 86. Many cytokine receptors signal through a pathway in which receptor-associated kinases activate transcript factors directly
  • 87.
  • 88. TH1 &TH2 cells make characteristic sets of cytokines that have distinct effects on the immune response
  • 89.
  • 90.
  • 91. Delivery of cytotoxins by CD8 T cells is aimed directly at the target cell. LG= lytic granules (red) MTOC= microtubule organizing center (microtubules – green) GA = golgi apparatus Initial contact has no effect Cytoskeleton reorganizes TCR:MHC Die
  • 92.
  • 93.
  • 94.
  • 95. Apoptotic cell in early stages showing chromatin condensation (red) but well-defined plasma membrane that is shedding vesicles . Apoptotic cell in late stages has very condensed nucleus , no mitochondria , and the cytoplasm and cell membranes are largely lost through vesicle shedding . Necrotic cell with plasma membrane poorly defined Healthy cell with normal nucleus Shriveled and shrunken
  • 96.
  • 97.
  • 98.
  • 99.
  • 100.
  • 101.
  • 102.
  • 103.
  • 104.
  • 105. Immune response to intravesicular bacteria is coordinated by TH1 cells
  • 106.
  • 107.
  • 108.
  • 109. Molecular complexes recognized by both B and T cells make effective vaccines
  • 110.
  • 111. Summary: The properties of the P-APC
  • 112.  
  • 113.  
  • 114.