Innate/Adaptive Links Flashcards
Describe how dendritic cells are critical in activating Th cells
- antigen taken up by Langerhans cells in the skin
- Langerhans cells leave the skin and enter the lymphatic system
- mature dendritic cells enter the lymph node from infected tissues and can transfer some antigens to resident dendritic cells
- B7-positive dendritic cells stimulate naïve T cells
Describe naïve adaptive immune responses initiated by dendritic cells
- Langerhans cells in the skin
- most powerful activator of T cells - powerful co-stimulatory signal
- macrophages and B cells more important during active responses
What is the maturation and up-regulation of co-stimulatory molecules of dendritic cells caused by?
- activation of dendritic cell PRRs by PAMPs
- cytokines
- other signals - damage related
Describe the Lamb et al 2005 study
- strong IFN-ү production in lymph node near site of major infection
- strong IL-4 production in lymph node near site of thoracic cavity
- irrespective of co-infection
What is cell recruitment to site of infection driven by?
- initial recruitment: reliant on innate cell cytokines
- later recruitment driven by lymphocyte cytokines
- cytokines released by immune cells at the site of infection
What are the 4 steps of Leukocyte Extravasation?
- capture
- rolling
- firm adhesion
- transendothelial migration
Describe capture in Leukocyte Extravasation
- TNF-α induces upregulation of adhesion molecules on the endothelium
- important adhesion molecule on endothelial cell upregulated is VCAM-1 (pre-stored)
- main leukocyte ligand binding to VCAM-1 is VLA-4
Describe rolling in Leukocyte Extravasation
- P-selectin and E-selectin thought to be responsible for slow rolling and the initiation of firm adhesion
- main leukocyte ligand binding to P-selectin is PSGL-1
Describe firm adhesion in Leukocyte Extravasation
- ICAM-1: important adhesion molecule on endothelial cell
- main leukocyte ligand binding to ICAM-1 is LFA-1
Describe transendothelial migration in Leukocyte Extravasation
- main receptor involved is PECAM-1 for both cells
How are chemokines important in Leukocyte Extravasation
chemokines activate changes in conformation of adhesion molecules
Describe cell movement in swelling
memory lymphocytes recruit leukocytes to site of infection causing swelling
Describe Cytotoxic T Lymphocyte (CTL)
- major effector cell of adaptive immune system
- requires activation first in lymphoid tissues via MHC class I / TCR interaction
- migrates to infection site
- recognise infected cells via MHC class I
Describe Natural Killer (NK) cells
- innate cell
- lymphoid lineage
- recognise infected host cells
- not as effective as CD8 T Cells
- distinguish infected from uninfected by MHC class I interaction
Describe how NK cells distinguish infected/uninfected cells
- MHC class I on normal cells is recognised by inhibitory receptors that inhibit signals from activating receptors
- NK does not kill normal cell
- no MHC class I triggers activating receptors that activates NK cell
- activated NK cell releases granule contents, inducing apoptosis in target cell