MHC and AG Presentation to T Cells Flashcards
(105 cards)
1
Q
What is cell-mediated immunity due to?
A
The direct action of T cells
2
Q
Where did the term cell-mediated immunity evolve from?
A
The finding that immunity to intracellular pathogens could be transferred to other animals by immune cells from infection-recovered animals
3
Q
What have T cells evolve to do?
A
Protect us against intracellular microbes (viruses and some bacteria)
4
Q
What cell helps to mount a robust Ab-mediated humoral immune response directed against extracellular pathogens
A
T cells
5
Q
What cant T cell directly recognize?
A
Unprocessed Ags or bind to microbes
6
Q
What are Ags in host cells broken up into?
A
Linear peptides (processed)
7
Q
How are linear peptides displayed?
A
Displayed by major histocompatibility complex (MHC) molecules expressed on their cell surface
8
Q
What does the T cell antigen receptor (TCR) only recognizes?
A
Linear antigens (peptides) bound to MHC molecules
9
Q
What can each T cell only recognize?
A
Only one specific foreign peptide but there is a large TCR repertoire generated in the body
10
Q
When does a large TCR repertoire generate in the body?
A
During normal thymus development where the T cells are “educated”
11
Q
What are T cells “educated” for?
A
Selected for survival or eliminated if self-reactive
12
Q
How many phenotypes of T helper cells exist? how are they different?
A
2; each with different functions in the immune response that are dictated by their cytokines produced
13
Q
What recognizes peptide Ags in the context of MHC class II molecules?
A
CD4 T helper cells
14
Q
What recognizes peptides associated with MHC class I molecules?
A
CD8 cytotoxic T cells
15
Q
What cells express MHC Class II molecules?
A
Dendtritic cells, Mo and B cells
16
Q
What do CD4 and CD8 attach to respectively?
A
The non-polymorphic (non-variant) part of the MHC class II and MHC class I molecules, respectively (the differential requirement for CD4 and CD8 is related to this fact)
17
Q
What needs to happen to T cells in order for them to carry out their functions?
A
Need to be activated
18
Q
What is not sufficient to activate the T cells?
A
Recognition of peptide Ag by TCR alone
19
Q
What are also required in addition to recognition of the peptide Ag by the TCR?
A
Co-stimulatory molecules are also required together with co-receptors involved in signaling events
20
Q
What does T cell activation lead to the production of?
A
IL-2
21
Q
IL-2 produced by activated T cells controls what?
A
The clonal expansion of specific T cells
22
Q
What helps Mo to get rid of intracellular microbes and help the development of cytotoxic T cells to kill virus-infected cells?
A
Th1 cells
23
Q
What is produced by Th1 cells to activate Mo?
A
IFN-γ
24
Q
What are mainly involved in helping B cells to develop into memory cells and plasma cells that produce antibodies?
A
Th2 cells
25
What is produced by Th2 cells that is important for B cell proliferation?
IL-4
26
What is only found on the T cell membrane
TCR for Ag
27
What is TCR composed of?
Two polypeptide chains, α and β, which is made up of constant (C) and variable (V) regions
28
Together the α and β chain variable regions constitute what?
The Ag-binding site
29
Some T cells, whose function is not completely understood, express a TCR consisting of what?
γ and δ chains
30
How are γδ T cells similar and different from αβ T cells?
The γδ T cells have some of the characteristics of the αβ T cells, but have a broader specificity for unconventional Ag such as HSPs and phospholipids
31
The TCR of "conventional" is composed of what? What are the MW?
Conventional = αβ
| Composed of two polypeptide chains, α and β, which have MWs of 50 and 39 kDa, respectively
32
The genes coding for TCR polypeptide chains are members of what family?
The Ig superfamily
33
TCRs are what types of proteins?
glycoproteins
34
Each of the glycoproteins (TCR) are made up of what regions?
constant and variable regions like those of Ig
35
Unlike Abs, TCRs DO NOT RECOGNIZE NATIVE ANTIGEN, but can only bind what?
Bind processed Ag presented in MHC molecules
36
The T cell receptor complex consists of what?
TCR (αβ or γδ dimer) in association with CD3
| In addition, a separate signaling molecule made up of two ζ chains
37
What is CD3?
A signaling complex composed of γ,δ, and ε chains (polypeptides)
38
What do CD4 on T cells bind to ? How does this restrict the T (or Th: T helper) cell?
The nonpolymorphic region of MHC class II on APCs; restricting the Th cells to recognizing only peptides presented on MHC class II molecules
39
What do CD8 on cytolytic T cells bind to? What does this restrict the cytolytic T cell to do?
Bind to the nonpolymorphic region of MHC class I, restricting killing to cells presenting peptide in MHC class I
40
The MHC alleles express Co-dominance. What does this mean and what is the significance?
Both parental alleles of each MHC gene are expressed. This increases the number of different MHC molecules that can present peptides to T cells
41
Define how MHC are polymorphic genes. Also what is the significance?
Polymorphic: Many different alleles are present in the population
Ensures that different individuals are able to present and respond to different microbial peptides
42
MHC class II is expressed on what cells?
Dendritic cells, macrophages, and B cells
43
MHC class I is expressed on what cells?
All nucleated cells
44
The two classes of polymorphic MHC genes encode what?
Human leukocyte Ag (HLA) that can bind peptides that are thus critical to Ag presentation
45
What are the MHC class I genes?
HLA -A, -B, -C
46
What do MHC class I genes encode?
A polymorphic heavy chain
47
What combines with the polymorphic heavy chain in MHC class I molecules?
With β2-microglobulin
48
What does the heavy chain of MHC class I molecules have for peptides to be recognized by T cells?
'binding groove'
49
What are the MHC class II genes?
HLA-DP, -DR, and -DQ
50
What do MHC class II genes encode?
Molecules composed of TWO dissimilar polymorphic polypeptide chains (an α and β chain)
51
Which chain of MHC class II molecules contributes to the peptide-binding groove?
Both the α and β chains
52
What are the polymorphic regions of MHC class I and class II molecules?
The peptide binding domains
53
What do peptide binding domains do?
Bind peptides ranging from 8-10 (class I) and 10-20 (class II) amino acid residues
54
What are class I molecules composed of?
A polymorphic α chain non-covalently attached to the non-polymorphic β2-microglobulin (β2m)
55
Which chain is glycosylated on class I molecules?
α chain
56
Which chain in class I molecules is polymorphic?
α chain
57
What are class II molecules composed of?
A polymorphic α chain non-covalently attached to a polymorphic β chain
58
Which chain is glycosylated on class II molecules?
α and β chains
59
On peptides, what binds to residues in the class I and II grooves and vary for different MHC alleles?
Anchor residues
60
What holds the peptide bound to MHC molecule in the pockets in the cleft of the MHC molecule
Anchor residues
61
Where are the polymorphic residues of class I and class II MHC molecules located?
In the peptide-binding clefts and the α helices around the clefts
62
What allows class II molecules to accommodate longer peptides than do class I molecules?
Class I molecule's cleft is closed, whereas that of the class I molecule is open
63
What do professional APCs express?
MHC class II molecues
64
What are the professional APCs?
B cells, dendritic cells and macrophages
65
The expression of MHC class I and/or II molecules is modulated by what?
Cytokines
66
Peptides that bind to class I MHC molecules are derived from what?
Viruses that have infected host cells and move as complexes to the surface (endogenous pathway)
67
Ags and pathogens taken from the environment are primarily presented on what MHC molecules?
Class II molecules to CD4 helper T cells
68
What are the different functions of APCs?
1. (Dendritic) Naive T cell activation: clonal expansion and differentiation into effector T cells
2. (macrophages) Effector T cell response: macrophage activation (cell-mediated immunity)
3. (B lymphocytes) Effector T cell response: B cell activation and antibody production (humoral immunity)
69
Class II MHC expression is increased by what on dendritic cells?
It is continually produced (constitutive); increases with maturation; increased by IFN-γ
70
Class II MHC expression on macrophages is increased by what?
Normally low or negative; inducible by IFN-γ
71
Class II MHC expression on B lymphocytes is increased by what?
Constitutive; increased by IL-4
72
What are the costimulators for dendritic cells induced by?
constitutive; inducible by TLR ligands, IFN-γ and T cells
73
What are the costimulators for macrophages inducible by?
Low; inducible by TLF ligands, IFN-γ, and T cells (CD40-CD40L interactions)
74
What are the constimulators for B lymphocytes induced by?
T cells, antigen receptor cross-linking
75
Where do microbial antigens commonly enter through?
The skin and gastrointestinal and respiratory tracts
76
Microbial antigens that enter through the skin and gastrointestinal and respiratory tracts are captured by what?
Dendritic cells and transported to regional lymph nodes
77
Antigens that enter the blood stream are captured by what?
APCs of the spleen
78
Where are langerhans cells located?
They are in the epidermis as tissue resident DC
79
What is the principle function of tissue resident dendritic cells?
Antigen capture
80
What is the principle function of activated dendritic cells?
Antigen presentation to T cells
81
When is the expression of Fc receptors, and mannose receptors present on dendritic cell?
When it is tissue resident dendritic cell ready for antigen capture
82
What is the half-life of Class II MHC molecules as tissue resident dendritic cells?
~10 hr
83
What is the half-life of Class II MHC molecules as activated dendrtic cells?
>100 hr
84
What do NK cells produce during innate immune reactions to microbes or by T cells during adaptive immune reactions?
IFN-γ
85
What stimulates class II MHC expression on APCs and thus enhances the activation of CD4 T cells?
INF-γ
86
What have similar effect on the expression of class I MHC molecules and the activation of CD8 T cells?
IFN-γ and type i interferons
87
Why do αβ T cells recognize only peptides?
Because only peptides bind to MHC molecules
88
Why do αβ T cells recognize linear peptides?
Because conformation is lost during enzymatic processing of protein Ags into peptides
89
Why do αβ T cells recognize cell-associated and not soluble Ags?
Because MHC stably bind peptides, and the complexes are located on the cell surface
90
Why do CD4 T cells recognize extracellular Ags?
Because MHC class II molecules display peptides that are taken up from the extracellular environment of APCs by pinocytosis (DCs and B cells) and phaygocytosis (Mo)
91
Why do CD8 T cells recognize intracellular Ags?
Because MHC class I molecules present peptides from cytosolic proteins including intracellular pathogens
92
How are cytosolic pathogens processed?
Degraded in cytosol
Peptides presented by Class I MHC
Peptides presented to CD8 T cells
Effect on APC: cell death
93
How are intracellular pathogens processed?
Degraded in acidic vesicles
Peptides presented by Class II MHC and presented to CD4 T cells
Effect on APC: activation of macrophages to kill intracellular parasites
94
How are extracellular pathogens processed?
Degraded in acidic vesicles
Peptides presented by Class II MHC and presented to CD4 T cells
Effect on APC: Activation of B cells to secrete Ig, to eliminate extracellular pathogens/toxins
95
What are the steps of Class I MHC pathway?
1. production of proteins in cytosol (ex. viral protein)
2. ubiquinate protein
3. proteolytic degradation of protein
4. Transport of peptides into ER by TAP
5. Assembly of Class I complexes in ER ->golgi
6. Surface expression by exocytic vesicle
96
What are the steps of Class II MHC pathway?
1. Uptake of extracellular proteins into vesicular compartments of APC
2. processing of internalized proteins in endosomal/lysosomal vesicles
3. Class II MHC transported from ER to golgi to the endosome containing peptides
4. Association of processed peptides with class II MHC molecules in vesicles
5. Expression of complex
97
What does the HLA-DM editing mechanism work to ensure?
The presentation of only the protein fragments most relevant for eliciting an immune response
98
What are the 3 major functions of HLS-DM?
1. Causes the dissociation of CLIP from peptide binding groove of MHC II
2. Stabilizes and prevents degradation of the empty MHC II
3. Facilitates the binding of antigen fragments to the open, stabilized binding groove
99
What makes MHC complex stable?
The peptide, if not present HLS-DM keeps MHC II specifically stable until it is stabilized by peptide
100
Where may cytosolic proteins enter cytosol from?
From phagosomes
101
Where is the site of peptide loading of MHC II and MHC I respectively?
MHCII: specialized vesicles
MHCI: ER
102
What molecules are involved in the MHC II pathway and MHC I pathway?
MHCII: Invariant chain, DM
MHCI: TAP
103
How are DCs able to present extracellular Ags by the class I pathway?
```
Fragments of cells infected with intracellular microbes are ingested by DCs
Ags of infectious microbes are transported into the cytosol and processed and presented in association with class I MHC molecules to CD8 T cells
```
104
What are immunodominant peptides?
Peptides that are obtained by proteases available in cells that bind best to the available class I and/or class II MHC molecules
105
What do immunodominant peptides apply to?
Peptides presented by both class I and class II MHC molecules
