Immune Sensing 3: Linking innate and adaptive immunity Flashcards
Macrophages and dendritic cells can both act as immune sentinels. Which of the following statements applies to dendritic cells, macrophages, or both?
-Can act as professional antigen presenting cells (APC) for T cells
-Activates naive T cells
-Which cell activates first (select both for they activate simultaneously)
-Phagocytose microbes
-Sample the environment to present Ag to T cells
-Travel to the lymph node after detecting infection
-Respond to DAMPs and PAMPs via PRRs
quiz
- both
- DC
- Both
- Macrophage
- Both
- DC
- Both
Both macrophages and DC can act as professional APC to activate T cells, and both sample environmental Ag in order to present them to T cells. Both will likely activate simultaneously upon infection as both are present in large numbers at barrier sites and have PRRs to detect PAMPs and DAMPs.
DCs are more specialised at the initial activation of naïve T cells. Once they detect PAMPs and become activated they carry Ag sampled at the infection site to the LN where they present their Ag to naïve T cells to initiate the T cell response. T cell activation is a DCs main function, and they do not tend to act as pathogen killing cells and do not phagocytose microbes.
Macrophages remain at the infection site (do not travel to LN) and so do not tend to come into contact with naïve T cells that only travel to LNs. The macrophage’s role is to produce inflammatory warning cytokines and to try and kill pathogens, usually via phagocytosis. Once a T cell is activated by a DC it migrates to the infection site where macrophages present pathogen Ag to them. This tells the T cell the infection is still ongoing (as pathogen Ag are still present) and stimulates the T cell to produce IFN-γ to further activate the macrophage and help it kill the pathogen. Thus, although macrophages have the potential to activate naïve T cells, they tend to communicate with activated T cells at the infection site.
Which of the following statements apply to MHC Class I, MHC Class II, or both?
-Present intracellular antigen
-Present extracellular antigen
-Expressed on all nucleated cells
-Only expressed by professional APC
-Are co-dominantly expressed
-Presents Ag to CD4+ Th cells
-Presents Ag to CD8+ cytotoxic T cells
quiz
- Class I
- Class II
- Class I
- Class II
- Both
- Class II
- Class I
MHC Class 2 molecules are only expressed by professional APC and present extracellular Ag to CD4+ Th cells. As Th cells control immune responses it is very important that only pathogen-specific Th cells are activated, and that Th cells specific to self-Ag or non-pathogen Ag (E.g. food) are not accidently activated. Thus, Th cells can only be activated by specialised cell types called professional APC.
MHC class 1 molecules are expressed on all nucleated cells and present intracellular Ag to cytotoxic T cells. The role of cytotoxic T cells is to kill infected host cells, and scanning for intracellular Ags presented by MHC class 1 molecules allows cytotoxic T cells to identify infected cells. As any cell in the body can become infected all cells need to express MHC class 1.
Both MHC class 1 and MHC class 2 alleles are codominantly expressed. This increases the number of different MHC alleles your cells express so increasing the number of different Ag you are able to present to T Cells.
How does a DC communicate to a T cell that the Ag it is presenting is from a pathogen?
quiz
Signal 2 (B7 on DC binds CD28 on T cell). The DC upregulates B7 to complete signal 2 only when its PRRs recognise danger signals.
T cells require 2 signals to become activated. Signal 1 is the TCR binding to MHC-Ag on the APC. This tells the T cell that the it recognises the Ag that the DC is presenting, but does not tell the T cell what type of Ag it is recognising (E.g. from a pathogen, self-Ag, harmless food Ag). If a DC detects PAMPs via PRR and becomes activated it upregulates B7 expression which binds to CD28 on the T cell to provide signal 2. Signal 2 tells the T cell that the DC has detected danger signals and that the Ag being presented to it is from a pathogen and so the T cell activates.
IL-2 does stimulate T cells to undergo clonal expansion, but it is produced by T cells not DC and it is only produced after the T cell has received signal 2 and been given permission to activate.
Which of the following statements could be true if a T cell receives signal 1 in the absence of signal 2?
Select all that are correct.
-The antigen presented is a self-antigen
-The antigen presented is from a pathogen.
-The T cell activates and undergoes clonal expansion.
-The T cell deactivates or dies.
-The PRRs on the DC have detected PAMPs.
-The PRRs on the DC have not detected PAMPs.
quiz
-The antigen presented is a self-antigen
-The T cell deactivates or dies.
-The PRRs on the DC have not detected PAMPs
If a T cell receives signal 1 without signal 2 it means that the DC has not detected danger signals (PAMPs) via it’s PRRs and so the Ag being presented is not from a pathogen. In this case it is likely the Ag is either a self-Ag or harmless Ag (e.g. food Ag), which you do not want to mount an immune response against. Hence, the T cell will deactivate or die.
A cut in your skin leads to a bacterial infection. Put the events below in the correct order.
- PRR on DC detect PAMPs.
- Pathogen specific T cells migrate to infection site.
- T cells produce IFN-γ to activate macrophages.
- Naïve T cells in LN interrogate DC via MHC-Ag-TCR interactions.
- DC activates and increases its ability to take up environmental Ag, but remains poor at Ag presentation.
- DC migrates to LN.
- DC up-regulate MHC class 2 molecules and 2nd signal molecules (B7).
- Mp present pathogen Ag to T cells via MHC class 2.
- Pathogen enters wound.
- T cells that recognise their Ag and receive 2nd signal clonally expand.
- DC activates further to increase environmental sampling, but after a short period then stops taking up environmental molecules.
- DC resting in skin, low-level sampling of environmental Ag and poor at Ag presentation.
- PRR on DC detects DAMPs.
quiz
- DC resting in skin, low-level sampling of environmental Ag and poor at Ag presentation.
- PRR on DC detects DAMPs.
- DC activates and increases its ability to take up environmental Ag, but remains poor at Ag presentation.
- Pathogen enters wound.
- DC activates further to increase environmental sampling, but after a short period then stops taking up environmental molecules.
- DC migrates to LN.
- DC up-regulate MHC class 2 molecules and 2nd signal molecules (B7).
- Naïve T cells in LN interrogate DC via MHC-Ag-TCR interactions.
- T cells that recognise their Ag and receive 2nd signal clonally expand.
- Pathogen specific T cells migrate to infection site.
- Mp present pathogen Ag to T cells via MHC class 2.
- T cells produce IFN-γ to activate macrophages.
Resting DC are present in the skin in the steady state. They perform low-level sampling of environmental Ag, but are unable to present Ag to T cells. The cut would cause tissue damage releasing DAMPs that would partially activate the DC causing it to increase its environmental sampling. However, as the DC has not yet detected an infection (meaning the Ag it is displaying are still likely self-Ag or non-harmful) it remains unable to present Ag and activate T cells. If a pathogen enters the wound then the DC will detect PAMPs that tell it there is an infection. The DC will briefly take up more environmental Ag before stopping its uptake. It then migrates from the infection site to the LN carrying a snap shot of the Ags present at the infection site (if it carried on sampling the environment whilst travelling then it could pick up self-Ag from the areas away from infection). Once in the LN the DC increases its expression of MHC class 2 and 2nd signal molecule and becomes very good at presenting Ag to naïve T cells. Naïve T cells interrogate DC looking for an Ag they recognise. If they detect their antigen (signal 1) and also receive signal 2 then they become activated and clonally expand. They then migrate to the infection site where macrophages will present Ag to them if the infection is still ongoing. This will cause the Th cell to produce IFN-γ to further activate the macrophage
True or False
T cells cannot recognize an antigen unless its presented by a professional APC
True
This cell-cell contact between adaptive cell (T) and innate (APC) ensures correct T cell is activated
What are the three professional APCs?
- DC
- Macrophages
- B cell
Whats the difference between MHC I and II?
MHC I= intracellular (present intracellular Ag); on all nucleated cells
MHC II= extracellular; only on professional APC
What role do MHCs play in antigen presentation?
T cells can only recognize an antigen when its combined with MHC
What’s the difference between extracellular and intracellular Ag recognition
Extracellular
- presented by MHC II
- recognized by Th that express CD4
- coordinate immune response
Intracellular
- presented by MHC I
- recognized by CTL that express CD8
- Kills infected cells
What’s the two signal activation T-cells need?
Signal 1: communicates Ag specificity
- MHC II on APC binds antigen and TCR on Th recognizes it
Signal 2: Danger signal
- PAMPs lead to APC expressing B7 on the surface, which is recognized by CD28 on Th
- signals that the Ag is from a pathogen
w/o signal 2, signal 1 is useless and means that the Ag is self or innocuous
What would be the consequence of incorrectly activating naive T cells?
Would lead to auto immune disease.
How do macrophages and Th interact?
- Tells Th infection still present
- Activated macrophage presents MHC II and B7 which is recognized by Th, and responds by secreting IFN-y
Whats the relationship between Th and B cells?
- B cells need permission from activated Th cells to gain full effector potential
- This is a T-dependent Ab response
- If Th recognizes the Ag presented by the B cell, then this tells the B cell that its pathogenic and it has permission to respond
What are the properties of T-dependent Ab response
Full effector functions ie can switch isotope; affinity maturation
