Lecture 11: Integration: Role of Antigen Presenting Cells Flashcards
What is an antigen presenting cell?
a cell that presents antigens
Which cells present antigens?
those that express MHC because MHC molecules can only be expressed on the plasma membrane if they are bound to peptide, so “expressing MHC” and “presenting antigen” is the same thing
What happens when there are no foreign proteins?
cells are continually presenting their MHC I peptides derived from their own proteins; they are all APC of self but in normal conditions there are no CD8 T cells that can recognise self and nothing happens
What happens when foreign proteins are present e.g. virus? (MHC I)
infected cells start presenting viral peptides along with self peptides and some CD8 T cells will be able to recognise MHC molecules bound to the foreign peptides
What does an infected cell act as?
acts as “the APC” of the viral antigen and the CD8 T cell kills it
What is a non-professional APC?
do not express MHC II and can only “communicate” with CD8 T cells
What is a professional APC?
express MHC II (and also MHC I) so they can “communicate” with CD4 T cells
they can capture material from the extracellular medium
What are examples of APCs?
macrophages, B cells and dendritic cells
Which professional APCs undergo macropinocytosis?
only dendritic cells
macrophages are inducible
Which professional APCs undergo phagocytosis?
dendritic cells and macrophages
Which professional APCs undergo receptor-mediated endocytosis?
dendritic cells (mannose, Fc, etc), macrophages (mannose, Fc, etc) and B cells (surface Ig only)
What do macrophages use MHC II antigen presentation for?
to “ask for permission” from CD4 T cells to kill phagocytosed material and to promote inflammation in tissues
What happens when there is no infection and macrophages use MHC II antigen presentation?
material in endosomes (self, whether endogenous or exogenous) is presented but since there are no CD4 T cells that can recognise it, nothing happens
What happens when there is infection and macrophages use MHC II antigen presentation?
some CD4 T cells recognise the foreign peptides and deliver signals to the macrophage to kill the phagocytosed material
(e.g. bacterium) by increasing formation of toxic compounds in the phagosome and release pro-inflammatory compounds
What do B cells use MHC II antigen presentation for?
to “ask for permission” from CD4 T cells to secrete Ab
What happens when there is no infection and B cells use MHC II antigen presentation?
the sIg has nothing to bind to
material in endosomes (self, whether endogenous or exogenous) is presented, but since there are no CD4 T cells that can recognise it, nothing happens
What happens when there is infection and B cells use MHC II antigen presentation?
the pathogen is bound by the sIg, internalised and presented
a CD4 T cell recognises the antigen and signals the B cell to secrete Ab
What must happen in order for CD8 T cells to kill targets or for CD4 T cells to “give permission” to macrophages or B cells?
they must be “given permission” by dendritic cells
Why do we have dendritic cells?
each T cell cannot contact every other cell of the body
immune responses are dangerous and there have to be several layers of control so that a full-blown response only happens after passing several checks
DCs are in charge of the initial and most important check: activation of naive CD4 and CD8 T lymphocytes
How do T lymphocytes search for pathogens?
they cannot scan the whole body and instead recirculate between the blood and the secondary lymphoid organs (spleen and lymph nodes)
What do DCs provide a “communication link” between? How do they do this?
the periphery and the lymph nodes
they capture pathogens, cells etc in tissues, migrate to secondary lymphoid organs and present the captured material on their MHC molecules
What happens in DCs when there is no infection?
present self antigens
nothing happens
What happens in DCs when there is infection?
DCs present pathogen antigens
Immature DCs that have not seen pathogen are dedicated to…
sample their environment by endocytosis and detect pathogens or tissue damage
Activated dendritic cells that have detected pathogens are dedicated to provide information to T cells by…
presenting antigens and informing about type and location of pathogen
How do DCs detect pathogens?
express pathogen associated molecular pattern (PAMP) receptors
What is cross-presentation?
the ability of dendritic cells to take up, process and present extracellular antigens with MHC class I molecules to CD8 T cells (cytotoxic T cells)
How do dendritic cells present endocytosed antigens via MHC class I?
they can transfer antigens from endosomes to the cytosol to access the processing machinery normally used for presentation of endogenous proteins i.e. cross-presentation