Lecture 12 Flashcards
(37 cards)
What are the primary lymphoid organs? What happens there?
thymus and bone marrow
generation of adaptive immune cells
What are the secondary lymphoid organs? What happens there?
lymph nodes and spleen, mucosal lymphoid tissues (peyer patches)
activation of adaptive immune cells
What are key similarities between secondary lymphoid organs?
contain distinct T-cell and B-cell zones for antigen presentation, use dendritic cells and macrophages to capture/present antigens
What are key differences between secondary lymphoid organs?
spleen filters blood, lymph nodes filter lymph, Peyer’s patches monitor gut antigens
Lymph nodes and Peyer’s patches have high endothelial venules (HEVs) for lymphocyte entry, spleen does not (entry through blood stream)
Peyers patches use M cells to transport antigens, lymph nodes and spleen rely on dendritic cells
Spleen!
antigens enter via arterioles, reach marginal sinus
marginal zone B cells, macrophages, DCs capture antigens
DCs transport antigens to T-cell zones (PALS) for T cell activation
T and B cells enter spleen through blood and migrate to respective zones
Lymph Node!
antigens arrive via lymphatic vessels (free or via DCs)
subcapsular sinus channels antigen to T-cell zones
T cells recognize antigen on DCs, B cells detect intact antigen at follicular borders
T and B cells enter through HEVs and move to zones
What are HEVs?
high endothelial venules: T cells can move directly from the blood into the lymph node
Peyer’s patches!
intestinal (mucosal immunity)
antigens cross gut barrier via M cells, dendritic cells capture antigen, present to T cells in zone
if antigen not recognized, DCs migrate to mesenteric lymph nodes for further screening
T and B cells enter via HEVs, migrate to zones
What are the fates of naive lymphocytes?
if T/B recognize antigen: activate, initiate immune response
if antigen not recognized: exit via lymph nodes, return to circulation, continue search in other lymphoid organs
Why are naive lymphocyte fates important?
increased efficiency: bring antigens/immune cells together in an organized way
immune surveillance: constant movement of lymphocytes = rapid detection
supports adaptive: proper T/B activation, memory formation
How do T cells enter lymphoid tissues?
across specialized small blood vessels, mediated by sequential actions of adhesion molecules/chemokine receptors
What is the role of LFA-1?
lymphocyte function-associated antigen 1
1. rolling: L-selectin (T-cell) binds to GlyCAM-1 & CD34 (HEV endothelium) –> slows T cell down
2. activation: chemokines (CCL21, CCL19) from HEVs & FRCs activate T cells –> triggers LFA-1 activation, increasing binding strength
3. firm adhesion: LFA-1 (T-cell) binds ICAM-1 (HEV endothelium) –> T cell stops rolling
4. migration into lymph node: diapedesis, enters T-cell zone following a chemokine gradient
What are FRCs?
fibroblast reticular cells, specialized fibroblasts found in T-cell zones of lymphoid organs that form a meshwork (lymphoid conduit system) made of reticulin and collagen
Why are FRCs important?
guide T cells: create a network decorated with chemokines (CCL19 & CCL21) that attract T cells
deliver antigens: act as highways bringing free antigens from lymph to DCs
support DC-T cell interactions: T cells move along network, increasing chances of finding their antigen on DCs
How do FRC highways work?
antigen enters via lymphatics –> travels through FRC conduits –> delivered to DCs in T-cell zones
T cells follow chemokines (CCL19, CCL21) –> interact with DCs –> activate if antigen recognized
How do naive T-cells encounter antigen?
recirculation through secondary lymphoid organs, enter via HEVs, guided by chemokines
in paracortex, interact with mature DCs, if no antigen found –> get survival signal (IL-7, self MHC) and exit via lymphatics
What happens if a T cell recognizes its antigen on a DC?
stays in the lymph node, activates, and proliferates. after several days, activated T cells re-express exit receptors and leave via efferent lymphatics
How do DCs migrate to lymph nodes?
- DCs recognize PAMPs/DAMPs via pattern recognition receptors (PRRs)
- Undergo recognition –> CCR7 upregulated, allowing migration toward lymphoid tissues
- CCR7 –> directs migration via CCL19 and CCL21 gradients to draining lymph nodes or the spleen (critical for T cell priming)
- reduce new synthesis of MHC, start expressing co-stimulatory molecules
Describe immature DCs
antigen capture mode (detect infection, take up antigens)
low MHC and co-stimulatory molecule expression (not ready for T activation)
high expression of PRRs for antigen uptake
transition into mature after sensing infection, migrating to lymph nodes to activate T
Describe mature DCs
T cell activation mode (present antigen, activate naive T cells)
high expression of MHC molecules (for antigen presentation)
express co-stimulatory (CD80/CD86) to fully activate T cells
efficient antigen processing/presentation
What is the Antigen Recognition signal for naive T cells? (Signal 1)
TCR binds to peptide:MHC complex on an APC
CD4 (or CD8) co-receptor enhances the signal
What is the Co-Stimulation signal for naive T cells? (Signal 2)
CD28 (T cell) binds B7 (APC) –> enhances T cell proliferation & survival
w out this signal, T cells may become anergic (unresponsive)
What is the Differentiation Cues signal for naive T cells? (Signal 3)
cytokines from the APC determine T cell fate
different cytokines drive different effector T cell subsets (eg Th1, Th2, Th17, Treg)
Describe early activation of a T cell (minutes to hours)
TCR + CD28 signaling activates transcription factors (NFAT, AP-1, NFκB) –> trigger expression for CD69 (retains T in lymph node) and IL-2 & IL-2Rα (drives T proliferation and differentiation)
Akt-mTOR signalling increases aerobic glycolysis –> rapid cell growth
