1Where is the major histocompatibility complex (MHC) found?
found on all nucleated cells (class I) in the body
2What is the role of the MHC?
plays a role in development of both humoral and cellular immunity
3What is the main function of the MHC?
brings antigen to the cell surface for recognition by T cells
4What is necessary of the antigen to trigger T cell activation?
when antigen is combined with MHC molecules
5What is MHC in humans?
Human leukocyte antigen (HLA)
6What is MHC linked to?
MHC linked to genetic capability that allows the body to mount to immune response
7What are MHC molecules involved with?
transfusion reactions, graft rejection, and autoimmune diseases
8How is MHC unique to the individual?
each individual inherits ability to produce certain limited repertoire of MHC (one from each parent)
9How does polymorphism of MHC essential for survival?
MHC triggers the immune response to diverse antigens
10Where are the genes for MHC molecules found?
short arm of chromosome 6, divided into 3 categories
11What are the 3 categories / classes of MHC?
class I, class II, class III
12What is the designation of class I MHC?
HLA-A, HLA-B, HLA-C
13What are the designation of class II MHC?
DR, DQ, and DP
14Where is class III MHC found?
between class I and II
15What are class I and II MHC gene products involved in?
antigen recognition and influence the repertoire of antigens to which T cells can respond
16What are class III MHC?
secreted proteins that have immune fxn but not expressed on cell surfaces
17Each loci of class I, II, and III code for multiple ____
alleles
18What is important about the multiple alleles controlling MHC?
they code for slightly diff forms of the gene (each individual inherits 1 copy from each parent of chromosome 6)
possibility of 2 diff alleles at gene 6
19What are alleles?
alternate forms of a gene that code for a slightly diff variety of the same product
20How are MHC described (alleles)?
codominant
21What does codominant MHC genes mean?
all alleles that have individual alleles inherited code for products expressed on cells
22What is a haplotype?
a gene inherited from each parent
23Why is it good that MHC genes are haplotypes?
haplotypes lead to large diversity and differences between ethnic groups
24What does a full genotype of MHC consist of?
two of each gene at a particular locus
25Where are class I MHC molecules expressed?
on all nucleated cells
26Even though class I MHC are expressed on ALL nucleated cells, how do they differ?
differ in the level of expression
27Where are MHC highest?
on lymphocytes
28Where are MHC present least?
hepatocytes, neural cells, muscle cells, sperm
29What Class I MHC gene antigen is expressed the least?
HLA-C
30What is each Class I antigen made of?
a glycoprotein dimer, made up of 2 noncovalently linked polypeptide chains
31What are class I antigens composed of?
alpha chain (3 domains)
beta 2 microglobulin
32In class I MHC antigens, which chain reacts with cytotoxic T cells?
alpha 3
33Where are class II MHC molecules found?
on antigen-presenting cells (APC), such as B lymphocytes, monocytes, mq, and dendritic cells
34What does class II molecules contain?
2 noncovalently bound polypeptides (that are encoded by separate genes)
2 alpha chains
2 beta chains
35What is the highest expressed genes in class II MHC?
Dr
36What are the highest level of class II MHC proteins?
dendritic cells (best APCs)
37What class of MHC has both ends of peptide binding cleft open?
Class II
38What is the purpose of both ends of the peptide-binding cleft left open?
to allow capture of longer peptides compared to class I
39What is the job of class I and class II MHC molecules?
bind peptides within cells and transport them to plasma membrane?
40Why does class I and class II want to transport peptides to plasma membrane?
so T cells can recognize them in antigen presentation
41When can T cells 'see' and 'respond' to antigens?
only when antigen is combined with MHC molecules
42What molecules do class I MHC present to?
CD3+ CD8+ cytotoxic T cells
43What molecules do class II MHC present to?
CD3+ CD4+ Helper T cells
44What are the 2 types of infectious agents?
1. those that attack cells from outside (bacteria)
2. those that attack cells from inside (viruses and intracellular bacteria)
45What do class I MHC present to?
CD3+ CD8+ cytotoxic T cells
(endogenous)
ex. Viral, tumor, and parasitic antigens
46What do class II MHC present to?
exogenous proteins taken into the cell from outside and degraded
presented to CD3+ CD4+ T helper cells
47What surface membrane contains class II MHC?
only on APC
B cells, mq, dendritic cells
48What T cell binds to class I MHC?
CD3+ CD8+ cytotoxic T cells
49What T cell binds to class II MHC?
CD3+ CD4+ helper T cells
50What proteins are used in the endogenous proteins (class I)?
TAP1 and TAP2, tapasin
51How much foreign peptides is necessary to induce response in endogenous pathway (class I)?
small number of peptides can induce response;
self peptides are ignored by T cells
52What is the purpose of TAP proteins?
responsible for transport of peptides suitable for binding to class I molecules from the cytoplasm to the lumen of ER
53What are TAP proteins dependent on?
ATP
54What Is needed for T cell response to be triggered?
1. peptides must be available in adequate supply for MHC molecules to bind
2. must be able to be bound effectively
3. must be recognized by a T cell receptor
55(repeated question) what do class I MHC molecules respond to?
intracellular peptides (viral, tumor, or intracellular bacteria); endogenous antigen
56What is the length of peptides of class I MHC peptide interactions?
8-11 amino acids in length
57What transports are associated with antigen processing in Class I MHC?
TAP1 and TAP2
58Why do class I molecules have slightly different binding affinities?
small differences determine which particular antigen one individual will respond
59What is the purpose of hundreds of class I molecules?
allows CD3+ CD8+ cytotoxic T cells to continuously check cell surfaces for presence of non-self antigens
60What happens after CD3+ CD8+ cytotoxic T cell recognizes foreign antigen?
Cytokines are produced and apoptosis occurs
61What pathway is involved in class II molecules?
exogenous pathway
62What happens in the exogenous pathway (class II)?
antigen is taken form outside by phagocytosis
63Where does class II molecule synthesis occur?
in ER
64What needs to be done to class II molecules before they can bind peptides?
must be transported to endosomal compartment before they can bind peptides
65What are the most potent activators of T cells?
dendritic cells (best APCs)
66What is the job of dendritic cells?
capture and digesting exogenous antigens (like bacteria)
67What protein is associated with class II MHC?
invariant chain (li) cleaved to form CLIP
68What is the purpose of CLIP?
place holder (exchanged) for antigenic peptide
69Where is the MHC II peptide complex transported to?
transported to cell surface
70What degrades invariant chain?
protease
71What happens after invariant chain is degraded by protease?
leaves CLIP fragment attached to peptide-binding cleft, which is then exchanged for exogenous peptides
72What happens when T helper cell recognizes peptide (class II)?
T helper will induce B cells to make antibodies
73What is the clinical significance of MHC?
1. tissue transplant
2. graft rejection
3. development of autoimmune disease
74What disease is B27 strongly associated with?
ankylosing spondylitis (inflammation of vertebrae)
75What is the genetic capacity of MHC?
to mount an immune response by bringing antigen to cell surface for T cell recognition
76What is the only way for T cell activation to occur?
when antigen is brought by MHC molecules up to cell surface
77What is the purpose of a large number of alleles of MHC?
variety prevents population extinction
78What are antigen specific T cells activated by?
peptide / MHC complex
79Why is there a strong selective pressure for pathogen to mutate genes encoding antigens?
so they can evade formation of peptide / MHC complexes
80Can some MHC alleles be better at protection against diseases?
yes!
81What does MHC polymorphism mean?
variation of MHC due to inheritance of different MHC molecules
82In addition to MHC polymorphism, what are other ways the body effectively fights disease?
1. vast number of different T cell antigen that is able to recognize several peptide antigens
2. combination of MHC alleles and TCR are endless