CHAPTER 8
T-cell activation/priming occurs in the secondary lymphoid organs with the help of antigen-presenting cells (APCs).
Dendritic cells
Myeloid dendritic cells take up antigens and present them in secondary lymphoid organs.
Blood infections stimulate a T-cell response in the spleen.
The DC can move thanks to its changing morphology:
- Immature dendritic cells in the periphery focus on phagocytosis – they contain many endocytic vesicles.
- Moving dendritic cells in the lymph are focus on digestion of antigen – they contain lysosomal proteins and MHC.
o Activation of the Toll-like receptors on DCs change their expression pattern.
o They start to express CCR7 so they can respond to CCL21 and migrate to the nodes.
- Mature dendritic cells in the lymph nodes focus on antigen-presentation - they have large dendrites.
Ways in which the DC can process and present
antigen:
o Receptor-mediated endocytosis
o Micropinocytosis = small volumes of
ECF.
o Macropinocytosis = non-specific
drinking of
large ECF volumes. For pathogens not
recognized by endocytic receptors.
o Viral infection:
Either the infected cell presents the
antigen
to a T-cell or it gives up its antigen to
other
APCs when it is too sick.
o Cross-presentation = endocytosis of the viral
pathogen (endocytic pathway) and then onto
the exocytic pathway for MHCI-presentation.
Macrophages in lymph nodes
Macrophages in the lymph node have several functions:
1. They filter pathogens in the lymph and prevent systemic infection.
2. They ‘eat’ lymphocytes signaled to die by apoptosis in their development.
T-cell activation in lymph nodes
There are 2 ways to enter a T-cell area where cells are activated by DCs presenting a specific MHC:peptide complex:
- Via the HEV
- Via the afferent lymphatics from an upstream lymph node.
Differentiate into an effector T-cell takes several days = delay between infection and 1 o adaptive immune response.
Homing
= process by which naive T cells enter the lymph
nodes (similar to neutrophil homing).
1. Chemotaxis: CCL21 and CCL19 are secreted
by stromal cells and DCs and bound
to the
endothelial cells of HEV.
CCR7 can bind CCL21 and CCL19.
2. Rolling: interaction between sialyl-Lewis X