MHC And Ag Presentaiton To T Cells Flashcards
T cells have evolved to protect us against ____ microbes.
Intracellular microbes (viruses and some bacteria)
T cells have evolved to protect us against intracellular microbes. They also help to mount a robust Ab-mediated humoral immune response against ____ pathogens.
Extracellular
True or false: t cells cannot directly recognize unprocessed Ags or bind to microbes.
True
What are Ags in host cells broken up into?
Linear peptides.
They are displayed by MHC molecules expressed on the cell surface.
True or false: each T cell recognizes many specific foreign peptides.
False, each T cell recognizes one specific foreign peptide.
This occurs during normal thymus development.
CD4 T helper cells recognize Ags in the context of what MHC class of molecules?
MHC class II.
These are expressed by DCs, macrophages and B cells.
CD8 cytotoxic T cells recognize peptides associated with what MHC class of molecules?
MHC class I
CD4 and CD8 attach to what part of the MHC class I and II molecules?
The non-polymorphic (non-variant) part.
In order for naive T cells to carry out their functions, what needs to occur?
They need to be activated.
Recognition of the peptide Ag by the TCR is not sufficient to activated the cells.
T cell activation leads to ____ of specific T cells.
Clonal expansion.
What is the function of T helper cells?
They help macrophages to get rid of intracellular microbes and help the development of cytotoxic T cells to kill virus infected cells.
What substance produced by Th1 cells activates macrophages?
IFN-gamma
What is the primary role of Th2 cells?
They are involved in helping B cells to develop into memory cells and plasma cells that produce antibodies.
What substance produced by Th2 cells is important for B cell proliferation?
IL-4
Where is the TCR for an Ag only found?
On the T cell membrane.
What is the TCR composed of?
Two polypeptide chains (alpha and beta), which are made up of constant and variable regions.
What constitutes the Ag binding sites of T cell receptors (TCRs)?
The alpha and beta chain variable regions.
What is the difference between alpha-beta T cells and gamma-delta T cells?
The gamma-delta T cells have some of the characteristics of alpha-beta T cells, but have a broader specificity for unconventional Ag such as HSPs and phospholipids.
The genes coding for TCR polypeptide chains are members of what superfamily?
Ig superfamily
What is a difference between Abs and TCRs?
Unlike Abs, TCRs do not recognize native antigens, but can only bind processed Ag presented in MHC molecules.
What does the T cell receptor complex consist of?
The TCR
Alpha beta or gamma delta dimer in association with CD3
What is CD3?
A signaling complex composed of gamma, delta and sigma chains. It is associated with TCRs
What is the significance of co-dominant expression of the MHC gene?
It increases the number of different MHC molecules that can present peptides to T cells.
What is the significance of polymorphic genes of the MHCs?
They ensure that different individuals are able to present and respond to different microbial peptides.
What do CD4 helper T lymphocytes interact with?
DCs, macrophages and B lymphocytes
What is CD8 capable of?
Killing an virus-infected cell.
What is contained on the heavy chain of MHFC molecules?
A binding groove for peptides to be recognized by T cells. They are derived from class I genes.
What do Class II genes encode?
Molecules composed of two dissimilar polymorphic polypeptide chains, both of which contribute to the peptide-binding groove.
What cells express class I MHC?
All nucleated cells
What cells express class II MHC?
DCs, phagocytes, B lymphocytes, endothelial cells, thymic epithelium
What is the source of protein antigens in the class II MHC pathway?
Endosomal/lysosomal proteins
What is the source of proteins found in the class I MHC pathway?
Cytosoloic proteins
What is the site of peptide loading for the class II MHC pathway?
Specialized vesicles
What is the site of peptide loading of MHC for the class I MHC pathway?
Endoplasmic reticulum
True or false: anchor residues on the peptides bind to residues in the class I and II grooves and vary for different MHC alleles.
True
Where are the polymorphic residues of class I and class II MHC molecules located?
In the peptide-binding clefts and the alpha helices around the clefts.
The cleft of class I MHC molecule is closed, whereas that of the class II molecule is open. As a result, what happens?
Class II molecules accommodate longer peptides than do class I molecules.
Where are MHC class I molecules expressed?
On all nucleated cells.
The expression of class I and/or II molecules is modulated by what?
Cytokines
Peptide Ags that bind to class I MHC molecules are derived from what?
They are derived from viruses that have infected host cells and move as the complexes to the surface.
Peptide Ags that bind to class I MHC are recognized by what?
CD8 cytotoxic T lymphocytes.
Where are MHC class II molecules expressed?
On professional APCs
Where are peptide Ags that bind to class II MHC taken from the environment primarily presented to?
CD4 helper T cells.
What are the functions of DCs?
Native t cell activation
Clonal expansion and differentiation into effector T cells
What are the primary functions of macrophages?
Effector T cell response: macrophage activation (cell mediated immunity).
What is the primary functio of B cells?
Effector T cell response: B cell activation and and antibody production (humoral immunity).
What increases class II MHC of dendritic cells?
IFN-gamma
What induces class II MHC of macrophages?
IFN-gamma
What increases class II MHC of B lymphocytes?
IL-4
Microbial Ags commonly enter through the skin and GI and respiratory tracts, where they are captured by ___ and transported to regional lymph nodes.
Dendritic cells
Ags that enter the blood stream are captured by APCs in the ____.
Spleen
When do NK cells produce IFN-gamma?
During innate immune reactions to microbes or by T cells during adaptive immune responses.
IFN-gamma stimulates the expression of what class of MHCs?
Class II MHC
Alpha beta cells recognize only peptides. Why is this so?
Only peptides bind to MHC molecules.
Alpha beta cells recognize linear peptides. Why is this so?
Conformation is lost during enzymatic processing of protein Ags into peptides.
Alpha beta T cells recognize cell-associated and not soluble Ags. Why is this so?
MHC stably bound peptides stably and complexes are located on the cell surface.
CD4+ T cells recognize extracellular Ags. Why is this so?
MHC class II molecules display peptides that are taken up from the extracellular enviroment of APCs by pinocytes (DCs and B cells) and phagocytosis (macrophages)
CD8 T cells recognize intracellular Ags. Why is this so?
MHC class I molecules present peptides from cytosolic proteins including intracellular pathogens.
What organelle is associated with the class I MHC pathway?
Endoplasmic reticulum
What is the class I MHC pathway?
Production of proteins in the cytosol
Proteolytic degradation of proteins
Transport of peptides from cytosol to ER
Assembly of peptide class I complexes in the ER
Surface expression of peptide class I complexes.
What is the class II MHC pathway?
Uptake of extracellular proteins into vesicular compartments of APC
Processing of internalized proteins in endosomal/lysosomal vesicles
Biosynthesis and transport of class II MHC molecules to endosomes
Association of processed peptides with class II MHC molecules in vesicles
Expression of peptide MHC complexes on cell surface
What is the function of the HLA-DM editing mechanism?
It works to ensure the presentation of only the most relevant Ags for eliciting an immune response.
What ar the three major functions of the HLA-DM editing mechaism?
It causes the dissociation of CLIP from the peptide binding groove of MHC II.
It stabilizes and prevents degradation of the empty MHC II.
It faciliattes the binding of Ag fragments to the open, stabilizes binding groove.
What is the pathway of HLA-DM?
Synthesis of class II MHC in ER
Transport of class II MHC and Ii to vesicle
Binding of processesd peptides to class II MHC
Transport of peptide0class II MHC complex to cell surface
Expression of peptide MHC complex on cell surface.
What do DCs ingest?
Fragments of cells infected with intracellular microbes.
Where are Ags of infectious microbes transported?
Into the cytosol and processed and presented in association with class I MHC molecules to CD8 T cells.
Thus, DCs are able to present extracellular Ags by the class I pathway.
What is the class I MHC pathway?
Production of proteins in the cytosol
Proteolytic degradation of proteins
Transport of peptides from cytosol to ER
Assembly of peptide-class I complexes in ER
Surface expression of peptide class I complexes
Where are immunodominant peptides obtained?
By proteases available in cells.
The peptides bind best to the available class I and class II MHC molecules.
Applies to peptides presented by both class I and class II MHC molecules.
What is the pathway of immunodominant peptides?
Internalization of antigen into APC
Antigen processing
Processing generates multiple peptides, one of which can bind to class II allele
T cells respond to immunodominant peptide epitope.
Cell mediated immunity is due to the direct action of what type of cells?
T cells
