Lecture 10 + 11 (Linking I & II) Flashcards
Once DC cells are activated, where do they go?
Once DC cells are activated, they will travel via lymphatic vessel to the closest lymph node. (there are many lymph nodes)
Activated DCs (mature) express receptors that target them to lymphoid tissue.
DCs are leaving the site of infection.
What do dendritic cells (DCs) do once they are in lymph nodes?
DCs activate T cells.
They present antigens to T cells, activating both CD4 (Th) and CD8 (Tc) T cells.
What are the 3 crucial signals needed for T cell activation by antigen-presenting cells (APCs)?
(1) Activation: pMHC and TCR interaction
(2) Survival: B7 and co-stimulatory molecules (CD28)
(3) Differentiation: Cytokines
What does PAMPs-induced PRR signaling do in dendritic cells (DCs)?
- Increases expression of receptors and adhesion molecules
–> Targets DCs to lymphatics and lymphoid tissues (migration).
How does PAMPs-induced PRR signaling affect DCs?
- Increases antigen processing.
- Induces expression of co-stimulatory molecules (immature DCs don’t express these).
- Increases MHC molecule expression.
How does increased expression of MHC molecules affect DCs?
- Increases the number of MHC:peptide combinations.
- Results in an activated DC capable of priming naïve T cells.
What is T cell priming?
Priming is the first contact that a T cell has with its antigen (Ag), facilitated by activated DCs.
What are the many changes that DCs go through?
1) Unactivated (immature) DC
- many dendrites
- can phagocytose
2) Activated DC in lymphatic vessel
- no longer phagocytic
3) Activated DC in lymphoid tissue
- Express peptide:MHC and co-stimulatory molecules
- Interacts with T cell
What are the two different types of DCs? What are the differences between them?
(1) cDc (conventional dendritic cell)
- travel to lymphoid tissue once activated.
- activate T cells in lymphoid tissue.
- classic APC.
(2) pDC (plasmacytoid dendritic cell)
- very high levels of PRRs
- capable of producing large amounts of type I IFN
- stay at site of infection
- secrete cytokines and can amplify local response
What happens when DCs are activated and migrate to the lymph node?
1) PRR signaling in DCs leads to phagocytosis and activation.
2) Activated DCs migrate to secondary lymphoid organs (e.g., lymph nodes).
3) Mature DCs try to activate a specific naïve T cell by presenting antigens and initiating priming.
What are the types of lymphoid tissues in the body?
1) Lymph nodes
2) Spleen
3) Peyer’s patch
How do DCs and lymphocytes enter the lymph node?
- DCs enter the lymph node via afferent lymphatics.
- T & B cells enter through High Endothelial Venules (HEV), which are post-capillary venules found in lymph nodes, from the blood circulation.
How do activated DCs transfer antigens in the lymph node?
- Activated DCs loaded with antigen (Ag) enter the lymph node and can transfer the antigen to resident DCs.
- This transfer can happen if antigens from viruses rapidly kill the dendritic cells.
- If cDCs (conventional DCs) are absent, tissue-resident macrophages with DC morphology (e.g., Langerhans cells) take over the initial antigen uptake and transport and can transfer the antigen.
- Both DCs and macrophages can stimulate naïve T cells.
How do T cells travel to and within the lymph node?
- Naïve lymphocytes constantly travel through secondary lymphoid organs, scanning for their specific antigen (Ag).
- They spend hours in the lymph nodes, searching for a match.
- If no match is found, they exit the lymph node and return to the blood to restart the search.
How do T cells enter and exit the lymph node?
- T cells enter the lymph node via High Endothelial Venules (HEV) from the blood.
- If the T cell doesn’t encounter its specific antigen (Ag), it exits the lymph node via efferent lymphatics.
What happens when T cells encounter their specific antigen in the lymph node?
- T cells that encounter their specific antigen (Ag) presented by DCs stay in the lymph node.
- The T cell is activated, proliferates, and differentiates (takes time and is trapped in the lymph node until proliferation is complete).
- Once matured, effector T cells exit the lymph node via efferent lymphatics and home to the infected tissue, guided by chemokine receptors and adhesion molecules.
Can dendritic cells (DCs) present multiple antigens at once?
Yes, DCs can present multiple antigens at once.
Where are pattern recognition receptors (PRRs) activated in dendritic cells?
PRRs are activated in peripheral tissues, not in the lymph node.
What happens after PRRs are activated in dendritic cells?
The DC becomes activated, then migrates to the lymph node to present antigens to T cells.
What is the flaw in the figure regarding DC activation and antigen presentation?
The figure incorrectly suggests that PRR activation, DC activation, and antigen presentation occur in the same place and time, but in reality, these steps happen sequentially in different locations.
How are T cells recruited to the lymph node?
T cell recruitment to the lymph node involves the following stages:
(1) Selectin binding: Selectins bind to adhesion molecules, causing the T cell to roll along the blood vessel.
(2) Chemokine binding: Chemokines (CCL19 & CCL21) bind to the CCR7 receptor on lymphocytes, activating integrins.
(3) Integrin binding: Integrins bind tightly, allowing the T cell to migrate into the lymph node.
How do selectins contribute to leukocyte homing?
Selectins play a key role in leukocyte homing by:
(1) Rolling: Light attachment of selectins on T cells to high endothelial venules (HEVs) causes T cells to roll along the endothelial surface, targeting them to lymphoid tissues.
(2) Tissue specificity: Different tissues express different molecules, such as HEVs in lymph nodes and mucosal epithelium in Peyer’s patches, to guide leukocytes to specific locations.
What are the stages of T cell migration to the lymph node and the molecules involved?
The stages of T cell migration are:
(1) Rolling: Mediated by selectins.
(2) Activation: Triggered by chemokines.
(3) Arrest & Tight Binding (Adhesion): Mediated by integrin interaction.
(4) Diapedesis: Transendothelial migration, where the T cell moves through the endothelial layer.
How do T cells sample antigens in the lymph node?
T cells scan for antigens in the lymph node, and dendritic cells (DCs) can secrete chemokines to attract T cells to them.
What role do fibroblastic reticular cells play in T cell migration in the lymph node?
Fibroblastic reticular cells provide roadways for naïve T cells and secrete CCL19 & CCL21 chemokines, which help attract T cells and DCs to the lymph nodes.
What happens when a T cell encounters an antigen in the lymph node?
Upon encountering an antigen, the T cell engages with the DC, and naïve T cells arrest their movements after binding to Ag:MHC. This interaction slows down the T cell’s movement.
What factors affect the kinetics of T cell and DC encounters?
The kinetics depend on the quality, quantity, availability of the antigen, and the activation state of the DC.
What happens during a long-term T cell/DC interaction?
T cells become involved in long-term (8 hours or more) interactions with DCs, forming an immunological synapse.
How many T cells can survey a dendritic cell (DC) per hour?
More than 5000 T cells can survey a DC per hour.
How long do T cells circulate while searching for their antigen?
T cells can spend between 1 to 24 hours circulating and looking for their antigen.
How long does it take for T cells to experience proliferation and differentiation after encountering their antigen?
T cells can experience proliferation and differentiation over the next ~4 days after encountering their antigen.
What makes the immune system dynamic?
- Balances cell generation in primary lymphoid organs with activation, proliferation, and differentiation in secondary lymphoid organs.
- Constantly deals with microinjury, tissue repair, and the microbiota.
- Involves many events happening in parallel, not in a linear sequence.
- Includes processes that overlap over time, can change locations, and influence each other.
What are the key characteristics of T cells?
- Are a type of lymphocyte.
- Arise in the thymus from bone-marrow progenitors.
- Most adaptive immune responses require activation of T cells.
- Can only recognize peptide fragments of the antigen (Ag) bound to self molecules of the
- Major Histocompatibility Complex (MHC).
- These peptide-MHC complexes are expressed on the plasma membrane of Antigen-Presenting Cells (APCs).
What is the difference between CD8+ and CD4+ T cells?
CD8+ and CD4+ T cells appear very similar but carry different sets of differentiation (CD) co-receptors on their surface.
What is the role of CD8+ T cells?
CD8+ T cells become effector Cytotoxic T Lymphocytes (CTLs).
What are the subsets of CD4+ Helper T cells?
CD4+ Helper T cells can be divided into at least five distinct subsets:
TH1
TH2
TH17
TREG
TFH
How do the subsets of CD4+ Helper T cells differ?
Each subset produces a distinct cytokine profile and regulates distinct activities within the body.
How are CD8+ T cells activated?
CD8+ T cells recognize antigen on MHC I. The activation involves:
1) TCR (T Cell Receptor) binding to the antigen.
2) CD8 binding to MHC I.
3) CD28 on the T cell binding to CD80/86 on the APC.
4) Cytokines also play a role in activation, leading to the differentiation into effector Cytotoxic T cells.
How are CD4+ T cells activated?
CD4+ T cells recognize antigen on MHC II. The activation involves:
1) TCR binding to the antigen.
2) CD4 binding to MHC II.
3) CD28 on the T cell binding to CD80/86 on the APC.
4) Cytokines help activate the T cells and lead to differentiation into subsets:
Th1
Th2
Th17
Tfh
Treg
How does the type of PAMP influence the type of effector T cell that arises?
The activation signals sent to T cells depend on the PAMP (Pathogen-Associated Molecular Pattern) that the dendritic cell has been exposed to. This affects:
- The type of cytokines produced by the dendritic cell.
- The effector T cell that will arise as a result of cytokine signaling.
