Antigen Presentation and the MHC Flashcards
List the different types of Ag presenting cells
Macrophages
Dendritic cells
B lymphocytes
What are the signals required to activate T lymphocytes?
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What is special about Ag presenting cells in regard to MHC?
Cells that present Ag in context of an MHC class II molecule are called Ag presenting cells, even though all cells express and can present Ag via MHC class I molecules
Where are macrophages found? Are they phagocytic?
Blood, liver, spleen
they are phagocytic
Where are dendritic cells found? Are they phagocytic?
Skin, lymphoid tissue
They are phagocytic
Where are B cells found? Are they phagocytic?
Lymphoid tissues, sites of immune reactions
They are not phagocytic
What are mononuclear phagocytic cells localized in tissue called? What are some tissue specific names of these?
Macrophages
Macrophages in the brain are microglial cells
Macrophages in the liver are Kupffer cells
What is the function of macrophages?
phagocytosis and activation of bactericidal mechanisms
Ag presentation
What are the different sub-types of tissue specific dendritic cells?
Skin: Langerhans’ cells, present to T lymphocytes
T-lymphocyte area of lymph node: interdigitating dendritic cells
B-lymphocyte area of lymph node: follicular dendritic cells
What is the function of Dendritic cells, and where/to whom do they present Ag?
Ag uptake in peripheral sites, Ag presentation in lymph nodes
Found in B lymphocyte areas of the lymph node and spleen - present to B lymphocytes
What are the two lineages of dendritic cells?
conventional: undergo maturation
plasmocytoid: release IF in response to viral infections
during which response is B cell presentation most important?
The secondary response
What compartments does Ag and MHC processing take place in for class I and II?
Cytoplasmic processing is associated with MHC class I
Endosomal processing is associated with MHC class II
From what are Ag peptides that bind to MHC class I typically derived?
From viruses that take over cellular machinery and produce viral protein
Can also be from defective proteins (DRiPs - defective ribosomal products)
How are viral proteins/DRiPs degraded by the cell?
via proteosomes (LMP2 and LMP7)
What occurs after degradation of protein into peptides?
The viral peptides are transported into the ER via TAP1 and TAP2, where they are further trimmed by ERAAP
What are the chaperone proteins that help assemble the MHC class I molecule in the ER?
Calnexin: binds alpha chain until beta2 microglobulin binds
Erp57, Calreticulin
What does the MHC-I/Erp57/Calreticulin complex do next?
It binds to TAP via Tapasin, and accepts peptide
From what are Ag peptides that bind to MHC class II typically derived?
From Ag captured and internalized by specialized APCs
Where are peptides that bind to MHC class II generated?
in acidified endosomes that fuse with vesicles containing MHC class II
How are MHC Class II molecules transported from the ER?
MHC-II molecules are synthesized in the ER and are transported with a chaperone moleule, Ii (invariant chain) that blocks binding of peptide in the active site
How is Ii degraded?
Acidification of the vesicle degrades the invariant chain, but leaves a small portion (CLIP) in the binding site
How is CLIP released?
After fusion of the vesicle carrying the MHCII molecule with an endosome carrying peptide, the protein loader/unloader HLA-DM removes CLIP
How does MHCII sample peptide?
HLA-DM will repeatedly place different peptides into the MHCII binding groove until one fits with high affinity
What do MHCI and MHCII bind under normal (non-pathogenic conditions?)
MHCI binds self-peptide, MHCII binds CLIP
What do CD4+ T lymphocytes recognize?
They do not recognize free/soluble Ag!
They recognize Ag presented by APCs in the context of MHCII
How does an APC determine the fate of a T cell?
The T cell is restricted by the MHCII molecule on which the Ag was recognized: Antigenic restriction
What is the response of CD4+ T cells?
Can either mediate phagocyte activation or act as helper cells by releasing cytokine
What are the subtypes of CD4+ cells, and what are their main functions?
Th1: Produce cytokines that activate macrophages
Th2: produce IL that results in the proliferation of B cells to induce Ab synthesis
Activation of a naive T cell by Ag requires what two signals?
Ag presentation via MHCII
Interaction between B7 on the APC and CD28 on the T cell
APCs that have taken up Ag that is not a microorganism, do not always express B7. In this case, how do they activate T cells?
T cells that recognize Ag in context of MHCII on an APC will express CD40L, which engages CD40 on the APC. This stimulates the APC to produce B7, which can activate the T cell via CD28 on the T cell
B cells that have taken up Ag often require both B cells and T cells. How does this interaction lead to the production of Ab?
B cells take up Ag and present it via MHCII, which also stimulates the B cell to produce B7.
MHCII interaction with a TCR and B7 interaction with CD28 will co-stimulate the T cell to produce CD40L.
CD40L engages CD40 on the B cell, which stimulates the B cell to produce cytokine receptors, and stimulates the T cell to release cytokines necessary for the proliferation of the B cell.
The B cell binds the cytokines, resulting in proliferation into an Ab secreting plasma cell.
Define the mature immunological synapse
a specific pattern of receptor segregation, with a central cluster of TCRs/CD4/CD28 that are important in signaling surrounded by a ring of adhesion molecules, such as LFA-1 (aka CD11a, T cells) interacting with I-CAM1 (on the APC)
What is the co-stimulatory molecule expressed on CD4+ T lymphocytes?
CD28
What type of Ag do B cells present?
Only the Ag to which the B cell receptor is specific
How is B cell recognition of Ag different from other APCs?
MHCI: Viral (cytoplasmic protein)
MHCII: endocytosis of foreign material
B cells: bind Ag on BCR, endocytose (they are NOT phagocytic), load into MHCII
What is the inhibiter of DM?
DO
What are the different genes and their products that are included in the HLA Class II gene?
DP, DQ, DR - MHCII molecule
LMP (2 and 7) - proteasome
TAP - TAP
TAPBP - Tapasin
DO(A/B) - inhibitor of DM
DM - peptide loader
