Chapter 5: Antigen Recognition By T Lymphocytes Flashcards
1
Q
What are antigens?
A
- chemical substances capable of mobilizing the immune system and provoking an immune response
- microbes or microbial parts
- stimulate T- and B- cells
- antibodies produced by B-cells react against antigens
- one T-cell, B cell, antibody is recognized by one kind of antigen
2
Q
Hapten
A
- small organic molecule that is not itself antigenic but that may become antigenic when bound to a larger carrier molecule
3
Q
Antigenic Determinant or Epitope
A
- part of the antigen that stimulates immune system activity
4
Q
T-Cell Receptor Diversity
A
- is generated by gene rearrangement (SOMATIC RECOMBINATION)
- resembles a membrane-associates Fab fragment of immunoglobulin
- membrane-bound heterodimer composed of an alpha chain of 40-50 kDa and a beta chain of 35-46 kDa
- extracellular portion contains a C-domain and a V-domain
5
Q
Short cytoplasmic Tails
A
- are expressed on alpha and beta chains
6
Q
T-Cell Germline DNA Gene Rearrangement is…
A
- exactly similar to that of B-cells before antigen stimulations
7
Q
After Antigen Stimulations?
A
- there is NO T-cell gene rearrangement
- THIS IS THE DIFFERENCE between T and B cells
8
Q
RAG Genes
A
- key elements in the origin of adaptive immunity
- important in B cell and T cell diversity
- components of transposon could have evolved to become the RAG genes and the recombination signal sequences of immunoglobulin and T-cell receptor genes
- NO RAG NO ADAPTIVE IMMUNE SYSTEM=== SCIDs disease
9
Q
CD3 Complex
A
- expression of the T-cell receptor on the cell surface requires association with additional proteins (CD3) to anchor it down
10
Q
The functional antigen receptor on the surface of T cells is composed of ________ polypeptides and is called the ______________________ complex.
A
- 8
- T-cell receptor complex
11
Q
The alpha and beta chains bind antigen and form the core T-cell receptor (TCR) which associate with one copy of each of…
A
- CD3y and CD3__ and two copies of each CD3e and the ___ chain
12
Q
There are two more distinct populations of T cells expressed through the receptors
A
- gamma and delta chains
- only compromise 5% of T cells
- aren’t restricted to MHC molecules/presentation
13
Q
Before T cell encounter w/ antigen…
A
- T-cell receptor repertoire exceeds Ig of B cell diversity
- T cells have a single binding site for antigens
- B cells have multiple
- T cells do not change their receptors after encounter with antigen
- B cells do change their receptors after encounter with antigen
- No isotype switching or somatic hypermutation in T cells, B-cells do
14
Q
T-cell receptors must recognize antigens bound to…
A
- cell surface-molecules
15
Q
TCRs and coreceptors allow T cells to recognize and bind to…
A
- the major histocompatibility complex (MHC)
- which are unique for nearly all individuals
16
Q
Class 1 MHC proteins are found…
A
- on the surface of nearly all the body’s cells
17
Q
Class 2 MHC proteins are found…
A
- on the surface of immune cells present (present antigen fragments to naive T cells or APCs)
18
Q
Human Leukocyte Antigen (HLA)
A
- human MHC
- HLA 1 and HLA 2 = MHC 1 and MHC 2 respectively
19
Q
Multigene Families and Genetic Polymorphism
A
- diversity of MHC molecules in the human population is due to this
- immunoglobulin and T cell receptor genes, MHC 1/2 genes have a conventional organization and do not rearrange or undergo somatic mutation
20
Q
____ MHC Class1 isotypes and ____ MHC Class2 isotypes in humans…
A
- 6
- 5
21
Q
MHC molecules have highly promiscuous binding sites for peptides
A
- an MHC molecule is therefore usually able to present a diversity of peptide antigens to a large number of T cell receptors with highly specific binding sites
22
Q
MHC Polymorphism
A
- affects the binding and presentation of peptide antigens to T cells
- triggers T-cell reactions that can reject transplanted organs
- the polymorphism of the MHC of organs/tissues transplanted between individuals of different MHC provoke a strong T-cell response directed against the foreign MHC molecules
23
Q
Of the human MHC Class 1 isotypes, which are highly polymorphic?
A
- HLA-A, HLA-B, HLA-C
- they present peptide antigens to CD8 T cells and interact w/ NK cell receptors
- HLA-E and HLA-G are oligomorphic and interact w/ NK cell receptors
- HLA-F is intracellular and of unknown function, occurs as a single isotype
24
Q
Of the human MHC Class 2 isotypes, which are polymorphic and present peptide antigens to CD4T cells?
A
- HLA-DP, HLA-DQ, HLA-DR
- HLA-DM and HLA-DO occur in a few isotypes, are intracellular, and regulate the loading of peptides onto HLA-DP, HLA-DQ, HLA-DR
25
Most human cells express MHC Class 1
- only selected cell types express MHC class 2
| - expressed on almost all nucleated cells, although they are more abundant on hematopoietic cells
26
MHC Class 2 molecules are normally expressed by only a subset of Hematpoietic cells
- by stromal epithelial cells in the thymus, although they can be produced by other cell types on the exposure to the cytokine interferon-gamma
27
Activated T-cells express MHC class _____ molecules whereas resting T cells do not.
- 2
28
Most cell types in the brain are MHC class 2-____________, but microglial cells (which are closely related to macrophages), are MHC class 2-____________.
- negative
| - positive
29
The two classes of MHC molecules have....
- similar 3-D structures
30
MHC Class 1 Molecules
- composed of one membrane-bound heavy chain and noncovalently bonded beta2-microglobulin
- heavy chain has 4 extracellular domains (alpha 1, 2, and 3) which the amino-terminal alpha1 and alpha2 domains resemble each other in structure and form the peptide binding site
31
MHC Class 2 Molecule
- composed of 2 membrane-bound chains, an alpha chain and a beta chain
- these have two extracellular domains each, the aminoterminal 2 (alpha 1, beta 1) resembling each other in structure and forming the peptide-binding site
32
MHC Class 1 Molecules bind to CD8
- the co-receptor binds to the alpha 3 domain of the MHC class 1 heavy chain
33
MHC Class 2 Molecules Bind to CD4
- the co-receptor binds to the beta2 domain of the MHC class 2 molecules
34
T cell Receptor specifically recognizes...
- both peptide antigen and MHC molecule
35
Peptides generated in the cytosol are transported into the endoplasmic reticulum where...
- they bind to MHC Class 1 molecules
36
Peptides presented by MHC Class 2 molecules are generated...
- in acidified intracellular vesicles
37
MHC Class 1 Processing for Antigen Presentation...
- proteins of the peptide-loading complex aid the assembly and peptide loading of MHC Class 1 molecules in the endoplasmic reticulum
- amino-peptidase in the ER can trim peptides bound to MHC class 1 to improve their binding affinity
38
MHC Class 2 processing for antigen Presentation...
- the invariant chain prevents peptides from binding to an MHC class 2 molecule until it reaches the site of extracellular protein breakdown
