This preview has intentionally blurred sections. Sign up to view the full version.View Full Document
Unformatted text preview: • DC and MPHG are present in all the body’s tissues • Mac – wide range of functions; DC – only antigen presentation for TC • Why? Because they are migratory cells which carry and present antigen to secondary lymphoid tissue which is organized to meet naïve TC • Macrophages are resident cells, and reside in infected tissue heavily exposed to pathogen, and have no opportunity to interact with naïve TC • Therefore, macrophages can only really contribute to TC stimulation in the 2 nd LT • For infections in the skin/peripheral tissues, the antigens go to draining lymph node and for blood infections, antigens enter the spleen • Respiratory mucosa; BALT, tonsils GI infections; appendix, GALT, Peyer’s patches • Immature DC are those in peripheral circulation that have the ability to capture, process, present antigen • Mature/Activated DC are those that have bound antigen, move into LN, and have a change in surface molecules, functions, morphology, and now have the ability to activate TC • Remember, antigens/pathogens enter the 2 nd LT by afferent lymph vessel whereas Naïve T cells enter thru blood vessels and then pass thru the HEV Homing is defined as the movement of naïve TC into 2 nd LT • The HEV is made of endothelial cells; there are cell adhesion molecules on the TC surface which bind to complementary adhesion molecules on the surfaces of other cells. These adhesion molecules are proteins, selectins, vascular addressins, and integrins • So, homing is determined by interactions between L-selectin on the naïve TC and CD34 and GlyCAM-1 on the HEV • This contact is then strengthened by additional interactions between LFA-1 on the TC and ICAM-1/2 on the HEV • After this interaction, LFA-1 is induced to undergo activation to strengthen its hold and this is done by a protein called CCL21 (chemokine) made by HEV that binds to CCR7 receptor on naïve TC, and this will activate the TC’s LFA-1 (integrin) • CCL21 is ALSO made by stromal cells and DC amd sets up a chemokine gradient along which naïve TC moves and squeezes between the endothelial cells to enter the lymph-node cortex • The interactions that occur when a TC binds an an APC: Both TC and P-APC have LFA-1; the LFA-1 on TC binds to APC thru ICAM-1/2 and the LFA-1 on the APC binds to ICAM-3 on the TC • This adhesion is strengthened by CD2 on TC and LFA-3 on APC and ICAM-3 on the TC and lectin DC-SIGN which is only uniquely on the DC • These are TRANSITORY interactions that allow the TCR to screen the peptide:MHC complex on the surface of the APC for ones that engage the TCR and activate TC • When a naïve TC encounters a specific peptide::MHC complex, a signal is delivered though the TCR and it induces a change in the TC’s LFA-1 which increases its affinity for ICAMS • The TC proliferates and differentiates all while in contact with the APC • The INC signal generated by ligation of the TCR with a certain peptide:MHC complex is necessary to activate a naïve TC but is insufficient and thus a co-...
View Full Document
- Spring '08
- tc, naïve tc