Immuno Exam 2 Chapter 6 Flashcards
(159 cards)
1
Q
What cells play an important role in adaptive immune system function?
A
T cells
2
Q
What cells activate other immune system cells?
A
effector T cells
3
Q
What other immune system cells are activated by effector T cells?
A
macrophages
neutrophils
B cells
4
Q
What relies on the action of T cells?
A
pathogen clearance that requires an adaptive immune response
5
Q
What does MHC stand for?
A
major histocompatibility complex
6
Q
What presents a specific antigenic peptide?
A
a cell using a MHC protein
7
Q
What on each T cell interacts with a specific antigenic peptide?
A
surface receptor
coreceptor
8
Q
What is MHC diversity due to the presence of?
A
MHC gene families and genetic polymorphism
NOT recombination events
9
Q
What do a wide variety of MHC molecules bind and present?
A
the many antigens that must be displayed to T cells as part of the adaptive immune response
10
Q
What is the major function of the T-cell receptor?
A
recognize a specific MHC-peptide complex
11
Q
What does T-cell recognition occur, in part, through?
A
a coreceptor located on the cell surface (CD4 or CD8)
12
Q
How many types of genes are activated by T-cell receptor:MHC-peptide complex signaling pathways?
A
two
13
Q
What are the genes activated by T-cell receptor:MHC-peptide complex signaling pathways?
A
those required for proper division and differentiation of the T cell
those required to carry out the effector functions of the activated T cell
14
Q
What do activated CD8 T cells become, and what do they do?
A
cytotoxic T cells
target cells infected with intracellular pathogens
15
Q
What do activated CD4 T cells become, and what do they do?
A
helper T cells (TH)
activate cells that combat extracellular pathogens
16
Q
What are coreceptors CD4 and CD8 important in the recognition of?
A
MHC-peptide complex on an antigen-presenting cell
16
Q
What are coreceptors CD4 and CD8 important in the recognition of in a location separate from the peptide-binding groove?
A
the MHC-peptide complex on an antigen-presenting cell
17
Q
What do T-cell receptor proteins lack?
A
a significant cytoplasmic domain
18
Q
What can T-cell receptors not do?
A
initiate intracellular signaling events on their own
19
Q
What must T-cell receptors interact with to initiate signaling?
A
other cell-surface molecules (CD4 or CD8 coreceptor, along with the CD3 complex)
20
Q
What is the CD3 complex composed of?
A
δ, ε and γ chains
two ζ chains
21
Q
What do the polypeptides composing the CD3 complex recruit?
A
signaling molecules that are activating upon TCR engagement
22
Q
What is an essential costimulatory signal for naive T-cell activation?
A
CD28
23
Q
What binds to the same molecule as CD28, down-regulates T-cell activation, and prevents unchecked T-cell activation and effector functions?
A
CTLA4
24
What can exonucleases do?
trim the P nucleotides left in the overhang region of the opened end of the gene segment
25
What can terminal deoxynucleotidyl transferases (TdT) do?
add N nucleotides to the ends of each gene segment (every rearrangement)
26
What is random?
removal of P nucleotides
addition of N nucleotides
27
What are productive rearrangements?
the production of a functional receptor subunit
28
What are unproductive rearrangements?
result in a nonfunctional T-cell receptor subunit
29
What do checkpoints test for?
whether a productive rearrangement has occurred at the α and β loci
30
What do checkpoint mechanisms promote?
further recombination
31
What will exhaustive unproductive rearrangements lead to?
apoptosis
32
What can be produced during rearrangement?
a functional but self-reactive TCR
33
What may T cells with a self-recognizing receptor that escape the thymus lead to?
autoimmune disorders
destruction of healthy tissue
34
How many subunits are in MHC class I molecules?
two
35
What are the subunits in an MHC class I molecule?
α chain
soluble protein β2-microglobulin
36
What does an α chain of an MHC class I molecule do?
anchors the MHC to the plasma membrane
37
What contains a transmembrane segment?
α chain
38
What does not contain a transmembrane segment?
β2-microglobulin
39
What are the three domains of the α subunit of an MHC class I molecule?
α1
α2
α3
40
The peptide-binding groove of an MHC class I molecule binds peptides ______ amino acids long.
8 to 10
41
How many subunits are in MHC class II molecules?
two
42
What are the subunits in an MHC class II molecule?
α and β
43
What type of peptides are MHC class II subunits?
transmembrane polypeptides
44
What does each of the subunits of an MHC class II molecule fold to form?
a peptide-binding groove
45
What length peptide can the peptide-binding groove of an MHC class II molecule bind?
13 to 25 amino acids
46
What do other portions of each subunit of an MHC class II molecule fold to contain?
immunoglobulin-like domains that support the structure of the peptide-binding groove
47
What does the peptide-binding groove of a T-cell receptor:MHC-peptide complex allow the peptide to do?
protrude between the two α-helices
48
What does the TCR and MHC-peptide complex interaction involve?
the bound peptide
a larger surface area composed of the MHC molecule and the bound peptide
the variable regions of both TCR subunits
49
What are extracellular pathogens cleared by?
activation of phagocytes
B cells
antibody production
50
What recognizes the structural domains on both subunits of MHC class II when peptide is presented?
CD4 coreceptor
51
When are intracellular pathogens cleared?
CD8 recognizes the structural domain of the α-subunit of MHC class I on an infected cell
52
What has CD8 been shown to interact with?
β-microglobulin
53
What is required for clonal selection?
T-cell receptor/MHC-peptide/coreceptor complex
co-stimulation
54
What T-cell receptor signaling molecules are required to link the receptor-peptide interaction to signaling events that lead to activation of that cell?
CD3 complex
CD28
CD45
55
What do T-cell signaling molecules do?
activate gene transcription that produces cytokines required for activation and differentiation
56
What is vital to the successful activation of T cells?
peptide loading onto MHC molecules
57
Where are MHC class I molecules loaded with peptides from intracellular proteins?
in the endoplasmic reticulum (ER)
58
After MHC class I molecules are loaded, where do they move to present peptide to CD8 T cells?
plasma membrane
59
What molecules cannot bind to peptides in the ER?
MHC II molecules
60
Where do MHC II molecules move to, and what does it fuse with?
a vesicle
phagolysosome
61
Where are MHC II molecules loaded with peptides from extracellular proteins?
phagolysosome
62
Where do MHC class II molecules move to after they are loaded and present extracellular peptides to CD4 T cells?
plasma membrane
63
Nearly all ______ cells of the body express MHC class I.
nucleated
64
How many steps does intracellular peptide loading in the ER take?
five
65
What is step one of intracellular peptide loading?
formation of the peptide-loading complex
66
Upon entry, what does the α chain bind to during step one of intracellular peptide loading?
ER chaperone calnexin
67
Once properly folded, what does the α chain and β2-microglobulin associate with during step one of intracellular peptide loading?
peptide-loading complex
68
What is a major player in step one of intracellular peptide loading?
tapasin
69
What does the major player of step one of intracellular peptide loading do?
allows efficient peptide loading on MHC class I molecules
promotes the association of a peptide that can bind tightly with MHC class I molecules
70
What is another important player in step one of intracellular peptide loading?
ER chaperone calreticulin
71
What does the second important player in step one of intracellular peptide loading do?
promote proper assembly of MHC class I molecules with the tightly bound peptide
72
What is step two of intracellular peptide loading?
digestion of proteins by the proteasome
73
What does the proteasome do?
cleaves intracellular proteins into small peptides of varying lengths
74
What produces the immunoproteasome?
cytokines secreted during an inflammatory response
75
What do the subunits of the immunoproteasome do during step two of intracellular peptide loading?
promote MHC class I presentation at the surface of cells
76
What immunoproteasome subunit aids in processing MHC class I molecules during step two of intracellular peptide loading?
11S
77
What immunoproteasome subunits generate peptides 8 to 10 amino acids long during step two of intracellular peptide loading?
β
78
What is step three of intracellular peptide loading?
peptide transport into the ER
79
Where are peptides generated by the proteasome or immunoproteasome first released into in step three of intracellular peptide loading?
cytosol
80
Why must peptides be transported into the ER during step three of intracellular peptide loading?
to be loaded on MHC class I molecules
81
What is a transporter associated with antigen processing (TAP)?
peptide transporter in the ER membrane
82
What does a TAP do during step three of intracellular peptide loading?
carries proteasome-derived peptides into the ER where they can interact with MHC class one molecules
83
What is step four of intracellular peptide loading?
peptide trimming
84
What does tapasin do in step four of intracellular peptide loading?
functions in the peptide-loading complex to ensure that a tightly bound peptide is engaged in the peptide-binding groove of an MHC class I molecule
85
What happens to some peptides that are produced too long to fit the peptide-binding groove during step four of intracellular peptide loading?
ERAP, another protease in the ER, trims the N-terminal end of the overhanging peptide to the length needed
86
What does ERAP stand for?
endoplasmic reticulum aminopeptidase
87
How many amino acids are needed for tight binding to the peptide-binding groove?
8 to 10
88
What is step five of intracellular peptide loading?
transport to the plasma membrane
89
How is an MHC class I molecule loaded with peptide transported during step five of intracellular peptide loading?
via vesicles through the secretory pathway through the Golgi apparatus before its cargo vesicle fuses with the plasma membrane
90
Where is the loaded MHC class I molecule expressed on?
plasma membrane
91
What does the loaded MHC class I molecule wait for during step five of intracellular peptide loading?
a CD8 T cell bearing a TCR that can recognize the MHC-peptide complex
92
What do MHC class II molecules present?
peptides from extracellular proteins on the surface of APCs
macrophages, dendritic cells, and B cells
93
Where do MHC class II molecules begin in?
the secretory pathway
94
When are MHC class II molecules loaded?
not until they are part of the vesicle capable of fusing with a phagosome
95
How many steps does MHC class II peptide loading take?
four
96
What is step one of MHC class II peptide loading?
MHC class II molecule assembly in the ER
97
Despite being in the ER, what are class II molecules not loaded with?
intracellular peptides
98
What is an invariant chain in regards to step one of MHC class II peptide loading?
a protein that assembles with MHC class II in the ER and blocks the peptide-binding groove
prevents binging binding of proteasomal peptides
99
What is step two of MHC class II peptide loading?
clip production
100
Where are MHC class II molecules transported during step two of MHC class II peptide loading?
the MHC compartment
101
What cleaves the invariant chain during step two of MHC class II peptide loading?
protease cathepsin S
102
What does the protease that cleaves the invariant chain leave bound to the peptide-binding groove?
a peptide called the class II-associated invariant chain peptide (CLIP)
103
Where does the endosome CLIP remain until fusion with a phagolysosome?
in an intracellular pool
104
What is step three of MHC class II peptide loading?
phagocytosis and fusion with the MHC compartment
105
What happens during step three of MHC class II peptide loading?
phagocytes engulf pathogens and internalize them in phagosomes
106
What does each phagosome in step three of MHC class II peptide loading do?
fuses with a lysosome, acidifies, and becomes a phagolysosome
107
What does protease activity within the phagolysosome generate?
peptides from ingested material (extracellular material)
108
What does the phagolysosome fuse with during step three of MHC class II peptide loading?
MHC compartment
109
What is step four of MHC class II peptide loading?
peptide loading
110
What are MHC class II molecules in the fused vesicle still bound do in step four of MHC class II peptide loading?
CLIP
111
What promotes the exchange of CLIP for lysosomal peptides during step four of MHC class II peptide loading?
HLA-DM (human leukocyte antigen DM)
112
Where do the vesicle and MHC class II molecule and peptide travel to during step four of MHC class II peptide loading?
plasma membrane
113
What does the loaded MHC class II molecule wait for in step four of MHC class II peptide loading?
a CD4 T cell bearing a TCR capable of recognizing the MHC-peptide complex
114
What cells express the costimulatory receptor and can stimulate naive CD4 and CD8 T cells at any time?
dendritic cells
115
Most cells only express which molecule during an inflammatory response?
costimulatory
116
What drive expression of costimulatory molecules on a potential APC?
cytokines
117
If an intracellular pathogen is phagocytosed, how are the peptides from the intracellular pathogen presented by MHC class I molecules?
phagocytic cells can use cross-presentation to present phagocytosed material via MHC class I molecules
118
Where is phagocytosed material typically presented via?
MHC class II molecules
119
What are examples of phagocytic cells?
especially dendritic cells
macrophages
B cells
120
What does cross-presentation activate?
CD8 T cells responsible for combating the intracellular infection
121
What is cytosolic diversion?
endocytosed material in a cross-presenting cell is transported to a specialized endosome and ends up in the cytosol
122
How can diverted material in the cytosol be processed and presented?
using the normal MHC class I machinery
123
What is cross-presentation believed to play an important role in?
activating naive CD8 T cells required to mount an adaptive immune response to an intracellular pathogen such as virus
124
Why must a dendritic cell be licensed?
to properly cross-present antigen
125
What is licensing of cross-presentation in dendritic cells postulated to require?
CD4 T cells
126
What is the mechanism required for the licensing of cross-presentation in dendritic cells?
dendritic cells present phagocytosed extracellular antigens on MHC class II and activate a naive CD4 T cell
activated CD4 T cells release cytokines, signaling the dendritic cell to begin cross-presentation, potentially activating naive CD8 T cells
127
What is mice H-2 (histocompatibility 2) analogous with in humans?
HLA (human leukocyte antigen)
128
What parallel the diversity seen in TCRs?
MHC molecules
129
What is MHC diversity driven by?
genes and the presence of different alleles for each gene and their expression
130
The proteins expressed by the gene familiar for each MHC class are known as ______.
isotypes
131
How are MHC alleles expressed?
codominantly
132
The proteins expressed by MHC alleles are ______.
allotypes
133
What do all the alleles of every MHC class I and class II gene make up?
a person's haplotype
134
What provides a person's overall MHC diversity?
haplotype
135
How many MHC class I isotypes are there in humans?
six
136
What are the MHC class I isotypes in humans?
HLA-A
HLA-B
HLA-C
HLA-E
HLA-F
HLA-G
137
What do all human MHC class I isotypes have?
immune function, but a different focus
138
If considering the alleles of the first three human MHC class I isotypes, how many different haplotypes are there for MHC class I?
5.1x10^11
139
How many MHC class II isotypes are there in humans?
five
140
What are the MHC class II isotypes in humans?
HLA-DM
HLA-DO
HLA-DP
HLA-DQ
HLA-DR
141
What play different roles within the immune system?
class II isotypes
142
If considering the alleles of MHC class II, how many haplotypes are there?
1.6x10^23
143
What is the total number of possible haplotypes in the human genome (since class I and class II are both present)?
8.2x10^34
144
What make the alleles associated with MHC isotypes highly polymorphic?
changes within the peptide-binding groove
not due to random muations
145
What does the peptide-binding motif allow for?
flexibility regarding most amino acids within the bound peptide
146
What do anchor residues do?
support peptide binding to a specific isotype and limit flexibility
key amino acid requirements in a peptide
147
What may infectious disease act as a selective pressure on the maintenance of within an individual and in a population?
MHC heterozygosity (variation of alleles)
148
What does a diverse array of heterozygosity limits?
the presence of a susceptible MHC allele
149
What does a diverse array of heterozygosity confer?
genetic herd immunity
150
What is the advantage of heterozygosity?
more peptides from the pathogen can be displayed, providing a higher potential for T cells to be activated during infection
151
Because heterozygosity is advantageous in the body's defense against any given pathogen, it is selected for through ______.
balancing selection
152
What is a drawback of heterozygosity?
increased variety of MHC molecules can lead to complications during infectious disease outbreaks and in organ and tissue transplantation
153
What will the new SARS-CoV-2 virus drive selection of?
MHC alleles that are most capable of presenting viral peptides
comes at the expense of heterozygosity
154
What is the shift in selective pressure referred to as?
directional selection
155
What is a danger of heterozygosity?
introduction of allogeneic MHC molecules can elicit an adaptive immune response which results in rejection of transplanted tissues and organs
156
What does allogeneic mean?
from the same species but genetically different
157
What can MHC heterozygosity severely complicate?
medical conditions that require tissue or organ transplantation
158
What minimizes the risk of tissue rejection and slows rejection but still requires immunosuppressive drugs?
allotype matching
