MHC Flashcards
T cells need …. to recognize their target antigens
MHC
MHC I presents antigens to …. cells
CD8 T cells
….stabilizes the interaction b/w MHC II and TCR on CD4 T cells
CD4
MHC II presents antigens to ….
CD4 T cells
MHC I and II share …. overall structure and are all encoded w/in the …. locus of our genome
MHC I and II share SIMILAR overall structure and are all encoded w/in the MHC locus of our genome
…..this term applies to the human form of MHC
HLA Human Leukocyte Antigens
For MHC I to present antigens in its pocket, the …..antigens must first be broken down in the……by……and transported to the …….interior via TAP
For MHC I to present antigens in its pocket, the CYTOSOLIC antigens must be broken down in the CYTOSOL by PROTEASOME and transported to the ER’s INTERIOR via TAP
B, C, and A are….
Human MHC I ONE genes
T cells can only see antigens……
INSIDE the MHC pocket
antigen loaded MHC I migrates to the…….
PLASMA MEMBRANE
…..encoded by a single chain (alpha) and is stabilized by ….
MHC I is encoded by a single chain (alpha) and is STABILIZED by B2 MICROGLOBULIN
……encoded by two chains (alpha and beta)
MHC II encoded by TWO CHAINS (alpha and beta)
………..binds to LONGER peptides aa 14-20, and binds to more than just the ends of the peptides
MHC II
……binds to SHORTER peptides 8-10 aa long, and bind to just THE ENDS of the PEPTIDES
MHC I
…….can only see antigens inside MHC POCKET
T cells can only see antigens inside MHC POCKET
MHC class…..peptide production occurs in the……whereas MHC class….antigens areprocessed in……and transported to the….where the MHC class…..resides
MHC II peptide production: PHAGOLYSOSOME
MHC I antigens processed in PROTEASOME and brought to the ER where MHC I RESIDES
encoded by TWO CHAINS (ALPHA and BETA)
MHC II
MHC I genes include
B, C, and A
MHC II genes include
DP, DQ, and DR
MHC II presents…….peptides to CD4 T cell
PHAGOCYTOSED
…..MHC expression inducible by BACTERIA and CYTOKINES
MACROPHAGES
…..MHC expression is CONSTITUTIVE and INCREASES on activation
B Cells
MHC II bound to variant chain resides in the……and travels to the……to meet the phagocytosed antigen
GOLGI travels to ENDOSOME to meet antigen
….uptakes antigens by antigen specific receptor Ig
B cells
….located in LYMPHOID tissue and PERIPHERAL BLOOD
B cells
…..located in lymphoid tissue, CONNECTIVE tissue, BODY cavities
MACROphages
…..located UBIQUITOUS throughout the body
Dendritic Cells
lymphoid follicles have …
B cells
DP, DQ, DR
HLA II
Where can we find B cells in lymph node?
lymphoid follicles
Mainly T cells are found in what part of lympho node?
Mainly T cells are found at the Lymph Node’s PARACORTEX
Mainly T cells are found in what part of lympho node?
Mainly T cells are found at the Lymph Node’s PARACORTEX
CD4+ T cells activate other cells like…
macrophages and B cells
cytosolic pathogens are degraded in the…. and its peptides are expressed in …. and presented to ….T cell., and the presenting cell….
Cytosolic pathogens are degraded in the CYTOSOL and its peptides are expressed on MHC ONE (MHC I) and presented to CD8 T cells and the presenting cell DIES!
Intravesicular pathogens are degraded in…. and its peptides presented on ….. and presented to ……T Cells
Intravesicular pathogens are degraded in ENDOCYTIC VESICELS (low pH) and its peptides presented on MHC TWO (MHC II) and presented to CD4 T cells
effect on presenting cell of INTRAVESICULAR pathogen….
Activation to kill intravesicular bacteria and parasites or
secrete Ig
Extraceullular pathogens and toxins are degraded in….. and peptides presented on….. and presented to ……T cells
EXTRAcelluar pathogens and toxins are degraded in ENDOCYTIC VESICLES (low pH) and its peptides presented MHC II and presented to CD4 T cells which leads to ACTIVATION of B CELLS to SECRETE Ig to eliminate extraceullular bacteria/toxins
…..activation of…..to secrete Ig to eliminate….
B Cells presenting extracellular pathogens and toxins, after presenting to antigen to CD4 T cells, are activated to secrete Ig to eliminate extraceullar bacteria/toxins
activation of …… to kill….. bacteria and parasites
Presenting Cell: Macrophage
Pathogens: Intravesicular
Activation of MACROPHAGE to kill INTRAVESICULAR bacteria and parasites
leads to presenting cell death… what pathogen is it?
CYTOSOLIC pathogens
Where are INTRAvesicular pathogens degraded and what cells is it associated with?
Intravesicular pathogens are degraded in ENDOCYTIC vesicles (low pH) and are associated with MACROPHAGE presenting cell
Where are Extraceullar pathogens and toxins degraded and what is its presenting cell?
Extraceullar pathogens are degraded in ENDOCYTIC vesicles (low pH) and its presenting cell is B CELL
A, B, C
HLA I
Whats the effect on presenting cells associated with Intravesicular pathogens?
Macrophages presenting cells are ACTIVATED to KILL intravesicular bacteria and parasites
Whats the effect on presenting cells associated with Extraceullar pathogens?
B cells presenting cells are ACTIVATED to SECRETE Ig to eliminate EXTRAceullar bacteria/toxins
MHC class…. presents ‘captured’ peptides
MHC II presents ‘captured’ peptides
MHC class… presents peptides made inside of infected cell
MHC I presents peptides made inside of infected cells
Protein translation machinery of infected cells synthesize…. and …
protein translation machinery of infected cells synthesize BOTH PATHOGEN PROTEINS and SELF PROTEINS
Why can peptides that reach MHC i cell surface be self peptides or pathogen peptides?
because the infected cell’s protein translation machinery makes both PATHOGEN and SELF PROTEINS
MHC class…..is a single chain but needs….to form its final structure, so it is retain in the….by…. until……arrives
MHC I is a single but chain but needs b2 microglobulin to form its final structure so it is retained in the ER by CALNEXIN until b2 microglobulin arrives
When….binds the……chain, MHC Class….dissociates from…….
When b2 MICROGLOBULIN binds the alpha chain, MCH I dissociates from CALNEXIN
MHC I
the …..digest…..proteins into peptide fragments and then transports them to the …….via….
potential MHC I antigens are delievered to the ER’s INTERIOR by PROTEASOME, the PROTEASOME digest CYTOSOLIC proteins into peptide fragments and then transports them to the ER INTERIOR via TAP
Just read this slide
Once MHC I binding cleft has peptide fragment loaded up, the MHC I can now move to the PLASMA membrane and is ready to present antigen to a CD8 T cell
maturation of MHC class….occurs w/in the …..
CLASS ONE, ER
antigen loaded MHC I migrates to the…….
PLASMA MEMBRANE
VIrus try to evade….T cell responses by blocking MHC Class…..
CD8, MHC I
List 4 categories of how viruses block MHC I to evade CD8 T Cell Responses
1) Blocks peptide entry to ER
2) Retention of MHC I in ER
3) Degradation of MHC I (dislocation)
- transport some MHC I proteins to cytosl
- ubiquinate MHC I
4) Binds MHC I at cell surface
List 3 mechanism of how viruses BLOCK PEPTIDE ENTRY TO ER
1) blocks peptide binding to TAP
2) inhibits TAP ATPase activity
3) inhibits TAP peptide transport
List 2 mech of how viruses block RETENTION OF MHC I in ER
1) competitive inhibitor of tapasin
2) blocks tapasin function
List 2 mech of how viruses DEGRADE MHC I (dislocation)
1) tranports some newly synthesized MHC I into cytosol
2) E3 ubiquitin ligase activity
List 1 mech of how viruses BIND MHC I at cells surface
interferes with CD8 cell recognition by unknwon mech
What MHC class is this?
1) peptide production in phaglysosome
2) peptide binding by MHC Class…
3) MHC class….presents peptide at cell surface
MHC II
prior to transporting to the plasma membrane with its antigen, MHC I resides in the……
ER
MHC I presents peptides made…..of infected cell
INSIDE
MHC II presents ……peptides
CAPTURED
MHC II presents…….peptides to CD4 T cell
PHAGOCYTOSED
1) antigen is endocytosed and delivered to endosome
> while the MHC II with bound variant chain at GOLGI is directed to the endosome by the variant chain to meet the antigen
2) HLA-DM protein catalyzes the release of invariant chain fragment and binding of antigen-derived peptide
3) delivers peptide and MHC complex to plasma membrane for recognition by CD4 Helper T cell
Please read this slide
……catalyzes the release of invariant chain fragment and binding of antigen derived peptide
HLA-DM
MHC II bound to variant chain resides in the……and travels to the……to meet the phagocytosed antigen
GOLGI travels to ENDOSOME to meet antigen
digested peptide fragments are aka
processed antigen
processed antigen are aka
digested peptide
acidification of endosome/vesicles……
ACTIVATES proteases to DEGRADE antigen into peptide fragments
in early endosome the pH is …..the proteases are….
NEUTRAL, INACTIVE
MHC II is loaded with phagocytosed antigen only after MHC II containg vesicles fuse with the…….
LATE endosomes containg the digested peptide fragment
whe MHC II fuse with the late endosome what is the pH of the endosome
ACIDIC
If MHC I is loaded with peptides while it is in the ER, how does MHC II avoid being loaded with peptide antigens when its being SYNTHESIZED in the ER?
invariant chain, actively blocks the binding cleft of MHC II frombeing loaded with NORMAL CELLUAR MOLECULES (the invariant chain is later processed to just the CLIP peptide)
MHC II is made in the…..resides in the…..and transported to the……by invariant chain to meet its antigens
made in ER
resides in GOLGI
traported to ACIDIC, LATE ENDOSOME
1) invariant chain binds in groove of MHC II molecule
2) cleaved initially to leave a fragment bound to both the class ii MHC and TO THE MEMBRANE
3) further cleavage leaves a SHORT peptide fragment CLIP bound to the class II molecule
please read this slide
How and when does the binding cleft of MHC II become available to bind phagocytosed peptides?
happens in the PHAGOLYSOSOME
CLIP is released from binding cleft of MHC II when HLA-DM binding it in the phagolysosome
once CLIP leaves the binding pocket, and 14-20 aa peptide in the phagolysosome can bind MHC II
Whats the purpose of the invariant chain in MHC II cleft?
Block peptides and misfolded proteins from binding to the MHC II cleft
invariant chain is cleaved in an…..leaving…..still bound to the MHC II
ACIDIFIED ENDOSOME
leaving a SHORT PEPTIDE FRAGMENT CLIP bound to MHC II
What needs to bind to MHC II for it to release CLIP and bind to processed antigens?
HLA-DM
All HLA genes are……expressed on a single cell and …….allels are…..expressed on the same cell
all HLA genes are SIMULTANEOUSLY expressed on the SAME CELL
BOTH PATERNAL and MATERNAL allels are SIMULTANEOUSLY expressed on the SAME CELL
Why are MHC alleles are co-dominant?
both MATERNAL and PATERNAL alleles are expressed SIMULTANEOUSLY on the SAME CELL
the alpha and beta chains of MHC II can be derived from…..parents
DIFFERENT PARENTS
MHCs are hetergenous in that….
some parts can come from dad, and other parts come from mom
MHC expressing cells express HLA from….
BOTH MOM and DAD chromosomes AT THE SAME TIME
*what’s the point in having an MHC that is the unique combination of both parents?
to bind to and present peptides that NEITHER MOM NOR DAD MHC COULD
Expression of MHC alleles are……
CO-DOMINANT
human MHC genes are highly polymorphic which means
there are multiple allels from each HLA gene
…..ensures that each person produces a number of different MHCs able to bind a vast number of antigenic peptides
Polygeny
you have 3 genes for MHC class II DP, DQ,DR
you have 3 genes for MHC class I A,B, C genes
Polymorphism
Allelic difference
More than one allele for each gene
Polymorphism, allelic difference of gene, are concetrated in the…..of MHC
binding cleft
……differences lead to increased diversity in the tyhpes of antigens that can fit in MHC cleft and be presented to a T cell
allelic difference, POLYMORPHISM
T cell recognition of target antigens is MHC restricted because
the T cell receptor must simultaneously recognize
1) SELF MHC
2) ANTIGEN in MHC binding cleft
The shape of TCR must fit the shape of the MHC and the Antigen presented T/F
True
in outbred high polymorphic population, each person has greater diversity of MHC allels which means there is a greater number of…..
peptide antigens that can be presented to their T cell
in outbred population, the population as a whole has a greater combination of MHC allels, so pathogens can’t eveolve to escape detention from the immune system fo the majority of the population limiting the….
potential spread of a pthogen thru a population
Pathogen can avoid immune responses by evolving peptides that are
NOT CAPABLE of binding to the MHC ALLELS
HLA I Genes
A, B, C
If more is better why do we only have 3 genes for HLA II and 3 genes for HLA 1?
further increases in MHC, will increase the range of molecules that T cells could detect, INCREASING the LIKELIHOOD of AUTOIMMUNE DISEASE
HLA II genes
DR, DQ, DP
example of nonclassical MHC that map outside of the MHC locus
CD1 on DENDRITIC CELLS
CD1
1) nonclassical MHC found on DC
2) target to VESISICLES and not ER
3) extracellular pathogen proteins are brokendown in an ACIDIFIED endosomal comparments
4) can bind and present GLYCOLIPIDS, particularly membrane components of MYCOBACTERIAL
Mycobacterium are colored…..in an…….stain
MYCOBACTERIUM become RED in an ACID FAST STAIN…..
…..binds and present glycolipids, esp mycobacterial membrane components
CD1
haplotype
group of alleles in an organism that are inherited together from a single parent.
For MHC class II, which beta chain loci is the most polymorphic
DR-Beta
For MHC class II, which alpha chain loci is the least polymorphic
DR alpha
For MHC class I, which alpha chain loci is the least polymorphic?
HLA-C
For MHC class I, which alpha chain loci is the most polymorphic?
HLA-B
Of the following HLA α-chain loci, which one exhibits the highest degree of polymorphism?
a. HLA-A
b. HLA-B
c. HLA-C
d. HLA-DP
e. HLA-DR
HLA-B
Of HLA α-chain loci, which one exhibits the smallest degree of polymorphism?
HLA-DR α
Which of the following are not encoded on chromosome 6 in the HLA complex? (Select all that apply.)
a. β2-microglobulin
b. HLA-G α chain
c. TAP-1
d. invariant chain
e. tapasin
f. HLA-DR α chain
B2 microglobulin
INVARIANT chain
The _____ refers to the complete set of HLA alleles that a person possesses on a particular chromosome 6
HAPLOTYPE
The function of CD8 T cells is to make contact with……..and………….
CD8 make contact with VIRUS INFECTED CELLS, and KILL VIRUS INFECTED CELLS
The function of CD4 T cells is to make contact with…………… and…………….
1) CD4 make contact with MACROPHAGES and ENHANCE macrophages’s microbicidal powers
2) CD4 make contact with B CELLS and stimulate B cells to DIFFERENTIATE INTO PLASMA CELLS
CD8 T-cell subpopulations are specialized to combat _______ pathogens, whereas CD4 T-cell subpopulations are specialized to combat _______ pathogens
CD8 INTRACELLUAR
CD4 EXTRACELLUAR
Which of the following describes the sequence of events involved in processing of peptides that will be presented as antigen with MHC class I?
a. plasma membrane →TAP1/2 →proteasome →MHC class I →endoplasmic reticulum
b. TAP1/2 →proteasome →MHC class I →endoplasmic reticulum→plasma membrane
c. proteasome →TAP1/2 →MHC class I →endoplasmic reticulum →plasma membrane
d. proteasome →TAP1/2 →endoplasmic reticulum →MHC class I →plasma membrane
e. endoplasmic reticulum →proteasome →MHC class I →TAP1/2 →plasma membrane
c. proteasome →TAP1/2 →MHC class I →endoplasmic reticulum →plasma membrane
One type of bare lymphocyte syndrome is caused by a genetic defect in MHC class II transactivator (CIITA), which results in the inability to synthesize MHC class II and display it on the cell surface. The consequence of this would be that
a. B cells are unable to develop
b. CD8 T cells cannot function
c. CD4 T cells cannot function
d. intracellular infections cannot be eradicated
e. peptides cannot be loaded onto MHC molecules in the lumen of the endoplasmic reticulum.
CD4 T cells cannot function
Which of the following describes the sequence of events involved in the processing of peptides that will be presented as antigen with MHC class II?
a. protease activity →removal of CLIP from MHC class II →binding of peptide to MHC class II →endocytosis →plasma membrane
b. endocytosis →protease activity →removal of CLIP from MHC class II →binding of peptide to MHC class II →plasma membrane
c. removal of CLIP from MHC class II →binding of peptide to MHC class II →protease activity →endocytosis →plasma membrane
d. binding of peptide to MHC class II →endocytosis →removal of CLIP from MHC class II→protease activity →plasma membrane
e. plasma membrane →endocytosis →protease activity →removal of CLIP from MHC class II →binding of peptide to MHC class II
b. endocytosis →protease activity →removal of CLIP from MHC class II →binding of peptide to MHC class II →plasma membrane
Which of the following cell types does not express MHC class I?
a. erythrocyte
b. hepatocyte
c. lymphocyte
d. dendritic cell
e. neutrophil
a. erythrocyte
Which of the following cell types is not considered a professional antigen-presenting cell?
a. macrophage
b. neutrophil
c. B cell
d. dendritic cell
e. all of the above are professional antigen-presenting cells
b. neutrophil
Which is the most likely reason that HIV-infected people with heterozygous HLA loci have a delayed progression to AIDS compared with patients who are homozygous at one or more HLA loci?
a. The greater number of HLA alleles provides a wider variety of HLA molecules for presenting HIV-derived peptides to CD8 T cells even if HIV mutates during the course of infection.
b. Heterozygotes have more opportunity for interallelic conversion and can therefore express larger numbers of MHC alleles.
c. Directional selection mechanisms favor heterozygotes and provide selective advantage to pathogen exposure.
d. As heterozygosity increases, so does the concentration of alloantibodies in the serum, some of which cross-react with and neutralize HIV
a. The greater number of HLA alleles provides a wider variety of HLA molecules for presenting HIV-derived peptides to CD8 T cells even if HIV mutates during the course of infection.
The function of negative selection of thymocytes in the thymus is to eliminate
a. single-positive thymocytes
b. double-positive thymocytes
c. alloreactive thymocytes
d. autoreactive thymocytes
e. apoptotic thymocytes.
d. autoreactive thymocytes
Which of the following statements is correct?
a. In adults the mature T-cell repertoire is self-renewing and long-lived and does not require a thymus for the provision of new T cells.
b. T cells and B cells are both short-lived cells and require continual replenishment from primary lymphoid organs.
c. The human thymus is not fully functional until age 30, at which time it begins to shrink and atrophy.
d. In DiGeorge syndrome the bone marrow takes over the function of the thymus and produces mature peripheral T cells.
a. In adults the mature T-cell repertoire is self-renewing and long-lived and does not require a thymus for the provision of new T cells.
The human thymus begins to degenerate as early as one year after birth. This process is called______ and is marked by the accumulation of ___ once occupied by thymocytes.
a. thymectomy; dendritic cells
b. involution; fat
c. differentiation; γ:δ T cells
d. negative selection; γ:δ T cells
e. involution; thymic stroma.
b. involution; fat
reducing its ability to produce new naive T cells.
Immature B cells develop into B cells in the
a. subendosteum
b. bone marrow
c. thymus
d. blood
e. secondary lymphoid organs.
e. secondary lymphoid organs.
In which location would plasma cells not be present?
a. bone marrow
b. afferent lymphatic vessels
c. medullary cords of lymph nodes
d. lamina propria of gut-associated lymphoid tissues
e. red pulp of spleen
f. efferent lymphatic vessels.
b. afferent lymphatic vessels
afferent lymphatic vessels flow…..a lymph node and carry……lymph fluid
INTO, UNFILTERED
efferent lymphatic vessels flow……a lymph node carry….lymph fluid
OUT OF, FILTERED
_______ of thymocytes is necessary to produce a T-cell repertoire capable of interacting with self-MHC molecules.
a. positive selection
b. negative selection
c. apoptosis
d. receptor editing
e. isotype switching
a. positive selection
MHC restriction…
see only antigens presented by MHC `
some non-classical MHCs map outside the MHC locus T/F
True
Where are cytosolic pathogens degraded and whose its presenting cell?
Cytostolic pathogens are degraded in the CYTOSOL and its presenting cell can be ANY CELL
paracortex are made of mainly…
PARACORTEX are made of MAINLY T cells
Macrophages are found throughout the spleen
True
Dendritic Cells primary function is to
alert the immune system
