Module 4 Flashcards
Which lymphocyte is key to humoral adaptive immunity?
B cells
Which lymphocytes are key to cell mediated adaptive immunity?
T cells
What does TCR stand for?
T-cell receptor
How are Ag’s expressed?
Through the membrane or in a secreted form
How many polypeptides is an Ag made of?
Four
What does it mean that Ag is bivalent?
That there are two identical binding sites on an Ag
How is a TCR expressed?
On the T-cell membrane only
How many polypeptide chains is a TCR made from?
Two
What does APC stand for?
Antigen presenting cell
Which cells are APC?
Macrophages, dendritic cells and B cells
What does it mean that TCR are monovalent?
That TCRs have one antigen binding site
What is made from an alpha and beta chain or a gamma and delta chain?
TCR
Which is the most abundant T cell? Alpha-beta type or gamma-delta type?
Alpha-beta type T cell receptors
Which has a higher portentously for diversity? TCR or Ig?
TCR
Where does VDJ recombination occurs for TCR?
During development in the thymus
Which sections of VDJ recombination are used for the alpha and beta chains of TCR?
V and J for alpha chain
V, D and J for beta chain
Do TCRs particulate in isotype ditching or affinity maturation?
No, only Ig participates
What are the two major functional classes of T cells?
Cytotoxic T cells (CTL)
Helper T cells (Th)
Which co-receptor does CTL express?
CD8
Which co-receptor does Th express?
CD4
What does the CD8 co-receptor recognize?
Antigens of diseased or dying cells
What is the function of CTL?
Induce death in target cells
What is the function of Th?
Modulate responses of innate and adaptive immunity
What does TCR require to recognize an antigen?
Presentation of MHC molecules on APC or target cell surface
What does MHC stand for?
Major histocompatability complex
What are the two types of major histonecompatability complex called?
MHC class 1 and MHC class 2
What is a TCR?
A membrane bound glycoproteins that resembles a single antigen-binding arm of an Ig molecule
What is MHC class 1 made up of?
A single polypeptide (alpha) chain
How many structural domains does MHC class 1 have?
Three, alpha 1, 2 and 3
How is MHC class 2 a heterodimer?
Because it is made up of an alpha and beta chain
How many amino acids make up the peptides bound to MHC class 1?
8-10 amino acids
How many amino acids make up the peptides that bind to MHC class 2?
13-25 amino acids
How are T cell classes distinguished from each other?
By surface expression of CD4 (helper T) and CD8 (CTL)
What are the two co-receptors that function with TCR in MHC binding?
CD4 and CD8
Where does CD8 bind on MHC class 1?
The alpha 3 domain
Where does CD4 bind on MHC class 2?
Beta 2 domain
Which MHC class do nucleated cells bind to?
MHC class 1
Which cells express MHC class 2 molecules?
Antigen presenting cells - macrophages, dendritic cells and B cells
Why are most cells potentially targets?
Because MHC class 1 presents antigens to CTLs
What does a TCR resemble?
The Fab portion of Ig with cytoplasmic tails anchoring it through the transmembrane region
What makes up the ligand for TCR?
A combo of the pathogen peptide and MHC molecule
What is the major cause if tissue incompatibility and transplant rejection?
MHC difference between donor and recipient
What is a T-cell receptor?
A membrane-bound glycoprotein that resembles a single antigen-binding arm of an Ig molecule
What are the three regions of TCR?
The V region, C region and membrane anchoring domain
What are the most variable parts of TCR?
V alpha and V beta domains where antigen-binding occurs
What are the hypervariable regions of TCR referred to as?
Complementarity-determining regions (CDR)
How many CDR loops do the V regions of TCR alpha and beta chains have?
Three - CDR1, CDR2 and CDR3
How many kind of MHC class 1 molecules present antigens to CD8 T cells?
Three - HLA-A, HLA-B and HLA-C
What kinds of cells express MHC class 2 molecules?
“Professional” antigen presenting cells (APC)
How many kinds of MHV class 2 molecules are presented to CD4 T cells?
Three - HLA-DP, HLA-DQ and HLA-DR
What three cells are considered APCs?
Macrophages, dendritic cells and B cells
What is an issue caused by the high level of polymorphism in the HLA molecules of MHC class 1 and 2?
So unique person-to-person that tissue transplantation can be difficult
What is the benefit of polymorphism in the HLA molecules of MHC class 1 and 2?
Variability in Ag binding sites enhances the probability of pathogen recognition
What kinds of cells express MHC class 1 molecules?
Most nucleated cells
Which MHC class is associated with Ag presentation to CD8 cells/CTLs/cytotoxic T cells?
MHC class 1
Which MHC class is derived from intracellular sources and is considered endogenous?
MHC class 1
What are the three subtypes of MHC class 1?
HLA-A, HLA-B and HLA-C
What kinds of cells express MHC class 2 molecules?
Antigen presenting cells (APCs) including macrophages, dendritic cells and B cells
Which MHC class is associated with Ag presentation to CD4 T cells/Th/Helper T cells?
MHC class 2
Which MHC class is derived from extracellular sources and is considered exogenous?
MHC class 2
What are the three subtypes of MHC class 2?
HLA-DR, HLA-DP and HLA-DQ
Which processing pathway is used by endogenous proteins?
The endocytic processing pathway
Where are exogenous proteins presented?
On MHC class 2 to CD4 T cells
Which pathway is used for endogenous proteins?
The cytosolic processing pathway
Where are endogenous proteins presented?
On MHC class 1 to CD8 T cells
What are endogenous antigens?
Proteins translated by cellular ribosomes and delivered directly to the cytoplasm
What is the barrel shaped protein complex of proteolytic enzymes called?
The proteasome
What does the proteasome do?
Breaks down cellular proteins
What do Tap1 and Tap2 do?
They are transport protein complexes that bring peptide fragments from the proteasome to the ER
What does MHC class 1 and 2 need to leave the ER for the membrane surface?
A peptide, in the absence of infection, the cell displays “self”
Pathogen material is captured in the phagosome and merged with the digestive enzymes in the lysosome forming what?
Phagolysosome
What blocks peptide antigen bind from interacting with other proteins in the ER during the process of antigen presentation?
The invariant chain
During antigen processing and presentation, MHC class 2 and the invariant chain transport through the Golgi apparatus and are cleaved leaving behind what?
The CLIP fragment
What is exchanged for the antigen peptide during the processing and presentation of antigens?
The CLIP fragment
Endogenous Ags present to?
CTLs
Exogenous Ags present to?
Th cells
What is the goal of presenting endogenous Ags to CTLs?
The elimination of infected cells
What is the goal of presenting exogenous Ags to Th cells?
To stimulate B cells to make Abs so that Abs can activate phagocytes
What does MHC class 1 do?
Place red flags on cells indivisible health/disease
What does MHC class 2 do?
Alert helper T cells of tissue infection
What is the first step involved in the processing of peptides that will be presented by MHC class 2?
Endocytosis, or uptake of the pathogen
Which Ig sensitizes mast cells?
IgE
What would happen to someone with a non-functioning TAP protein?
They would have a poor CTL response to viruses
What are four antibody effector functions?
- Neutralization of toxins
- ADCC
- Opsonization
- Complement activation
If gene rearrangement during B cell development results in what?
Assembly of a complete antibody with diverse specificity that is suitable for expression
Which class of MHC molecule do HLA-DR, -DP, and -DQ apply to?
MHC class 2
Which class of MHC molecule do HLA-A, -B, and -C belong to?
MHC class 1
The pairing of light and heavy chain at the V region of Ig results in?
The antigen binding site
What protein enables the stable expression of TCR on the T cell surface?
CD3edgz
Which Ig is expressed along with IgD on the surface of naive B cells?
IgM
What is the most abundant Ig produced in the primary response?
IgM
Which Ig is secreted as a pentamer?
IgM
What does CDR stand for?
Complementarity determining regions
What are the three types of complementarity determining regions?
CD1, CDR2 and CDR3
Where does the complementarity determining region (CDR) reside?
The hypervariable region
What does MHC polymorphism in reference to?
The many alleles of MHC
Which diversity mechanisms do B cells and T cells have in common?
VDJ recombination and P and N additions
What do BCRs undergo that contributes to their diversity, but T cells do not?
Somatic hypermutation of V regions
What is an epitope?
The part of an antigen that can kick off an immune response by binding to a lymphocyte
What are the two types of epitopes?
Linear and discontinuous
Which Ig dominate in the primary and secondary immune response?
IgM in primary
IgG in secondary
How do antibodies produces in secondary response differ from those in the primary?
Somatic mutation/affinity maturation cause Ab in secondary response to have higher affinity for Ag
Which make antibodies, B cells or T cells?
B cells
What is a T Cell receptor?
TCR is a membrane-bound glycoprotein that resembles a single antigen-binding arm of an Ig molecule
Which increase their diversity through somatic hypermutation and isotype switching? TCR or BCR? I
BCR/Ig only
In what way do RAG genes differ from other eukaryotic genes?
They do not have introns
Which has more diversity, alpha:beta T cells or gamma:delta T cells?
Alpha beta TCR
How long are the peptides recognized by TCR?
8-25 amino acids long
What kind of pathogens does MHC class 1 present?
Intracellular
What kinds of antigens do MHC class 2 present?
Extracellular
What kinds of T cells recognize the intracellular peptides presented by MHC class 1?
Effector T cells/Cytotoxic T cells
What kinds of T cells recognize the extracellular peptides presented by MHC class 2?
Helper T cells
T cell co-receptor CD8 and CD4 bind with which MHC class?
CD4 with MHC class 2 and CD8 with MHC Class 1
What is the function of a CD8 T cell?
Kill infected cells
What is the function of a CD4 T cell?
Facilitate macrophages, improve phagocytosis and secrete cytokines
Which MHC class can bind to longer peptides?
MHC class 1 binds 8-10 aa long peptides and MHC class 2 binds 13-25 aa long peptides
What are three physical features shared by all peptides?
Amino terminus
Carboxy terminus
Peptide backbone
What is the proteasome?
A large, barrel-shaped protein complex that degraded poorly folded/obsolete proteins in the cytosol
What does TAP stand for?
Transporter associated with antigen processing
What is TAP?
Membrane embedded protein that transports peptides across the ER
What is the peptide loading complex?
A short lived, multisubunit membrane protein complex located in the ER that orchestrates peptide translocation and selection by MHC class 1
What is the central component of the peptide-loading complex?
Tapasin, a bridging protein that brings beta 2-microglobulin herterodimer and class 1 heavy chain close to TAP
What does Calreculin do as part of the peptide loading complex?
It is a soluble chaperone related to calnexin that binds to MHC class 1 heavy chain to stabilize it and recycle empty MHC class 1 molecules
What kind of chain is identical in all individuals?
Invariant chain that prevents MHC class 2 from binding with the wrong peptide in the ER
Which cells express MHC class 1?
Most cells in the body, except erythrocytes (RBC)
Which cells express MHC class 2?
Professional antigen presenting cells; B cells, macrophages and dendritic cells
