Imm: Exam III Flashcards
Topic 9
What are histocompatibility (transplantation) antigens?
antigens on tissues and cells that determine rejection when grafted between genetically different individuals
Topic 9
What are major histocompatibility antigens?
antigens that cause very strong immune response
most important in rejection; encoded by MHC
Topic 9
What is the major histocompatibility complex (MHC)?
Collection of genes arrayed within long continuous stretch of DNA on chromosome 6 in humans, 17 in mice;
presents peptides
Topic 9
MHC class I is expressed on... MHC class II is expressed on...
I: (glycoproteins) expressed on the surface of nearly all nucleated cells
II: only professional antigen presenting cells
Topic 9
What is the structure of MHC class I? What is the structure of MHC class II?
I: alpha chain ( alpha1, alpha2, alpha3 ) and beta2 microglobulin
II: alpha chain ( alpha1-2 ) and beta chain ( beta1-2 )
Topic 9
MHC class I presents peptide antigens to Tc or Th cells? CD8 or CD4?
MHC class II presents peptide antigens to Tc or Th cells? CD8 or CD4?
I: Tc cell ( cytotoxic T cells ) CD8 cells
II: Th cell ( helper T cells ) CD4 cells
Topic 9
____ sends negative signals to natural killer ( NK ) cells
MHC class I
Protects nucleating cells from being killed by them
Topic 9
What is the MHC property of polygeny?
Multiple MHC genes within one individual for some function
Topic 9
What is the MHC property of polymorphism?
multiple varients of the same allele in a population
Topic 9
What is the MHC property of codominant expression?
All loci are always expressed; opposite of B cells
Quiz 5
Which of the following cell types does NOT express MHC class I?
a) hepatocyte
b) dendritic cell
c) erythrocyte
d) lymphocyte
e) neutrophil
c) erythrocyte
because no nucleus
Quiz 5
MHC class II molecules are made up of two polypeptide chains called _______, whose function is to bind peptides and present them to _______ T cells:
a) alpha (α) and beta (β); CD8+
b) alpha (α) and beta (β); γ:δT cells.
c) alpha (α) and beta2-microglobulin (β2m); CD8+
d) alpha (α) and beta (β); CD4+
e) alpha (α) and beta2-microglobulin (β2m); CD4+
d) alpha (α) and beta (β); CD4+
* Note: C would be correct if asking about MHC class I
Quiz 5
The peptide-binding groove of MHC class I molecule is composed of the following extracellular domains:
a) α2: α3
b) α1: β1
c) α1: α2
d) β1: β2
e) α2: β2
c) α1: α2
* Note: B would be correct if asking about MHC class II
Quiz 5
Which of the following describes the sequence of events involved in processing of protein antigens that will be presented as antigenic peptides with MHC class I?
a) endogenous protein → proteasome → TAP 1/2 → endoplasmic reticulum → MHC class I → plasma membrane
b) TAP 1/2 → proteasome → MHC class I → endoplasmic reticulum → plasma membrane →endogenous protein
c) proteasome → TAP 1/2 → MHC class I → endoplasmic reticulum → endogenous protein → plasma membrane
d) plasma membrane → TAP 1/2 → proteasome → MHC class I → endoplasmic reticulum →endogenous protein
e) endoplasmic reticulum → proteasome → endogenous protein→ MHC class I → TAP 1/2 → plasma membrane
a) endogenous protein → proteasome → TAP1/2 → endoplasmic reticulum → MHC class I → plasma membrane
Quiz 5
Human major histocompatibility complex (MHC) genes are NOT….
a) clustered in one region of chromosome #6
b) allelic excluded
c) polygenic
d) co-dominantly expressed
e) highly polymorphic
b) allelic excluded
* When one allele of a gene is expressed while the other allele is silenced
Topic 10
A T cell receptor ( TCR ) has:
- 2 polypeptide chains, ____ and _____
- a _____ (top) and ______ a region (bottom)
- together, this makes the ____
- also has a cytoplasmic tail that reaches through the ____ region into the _____
Bank: cytoplasm, antigen binding site, alpha, variable region (V), constant region (C), beta, transmembrane
A T cell receptor ( TCR ) has:
- 2 polypeptide chains, alpha and beta
- a variable region (V) (top) and a constant region (C) region (bottom)
- together, this makes the antigen binding site
- also has a cytoplasmic tail that reaches through the transmembrane region into the cytoplasm
Topic 10
Similarities between TCRs and BCRs:
- Both are members of _____
- TCR (T cell receptor) resembles the ___ portion of a BCR (B cell receptor)
- The alpha chain: Ig ___ chain
- The beta chain: Ig ___ chain
- TCR V domain resembles Ig ____ and TCR C domain resembles Ig ______
- Interchain disulfide bond: Ig ___
Bank: C domain, light, Ig superfamily, Fab, hinge, heavy, V domain
Similarities between TCRs and BCRs:
- Both are members of Ig superfamily
- TCR resembles the Fab portion of a BCR
- The a chain: Ig light chain
- The b chain: Ig heavy chain
- TCR V domain resembles Ig V domain and C domain to one of the Ig C domains
- Interchain disulfide bond: Ig hinge
Topic 10
Differences Between TCRs and BCRs; in TCRs:
- V-J joining can occur on __ chain due to unique RSS structure
- _____ less stringent for α chain than β chain
- Multiple ___ chains can appear on the same T cell
- No somatic mutation, No ______
- Always ____
- Bind to ____, instead of antigen alone
- α:β T cell receptor and ____ T cell receptor
Bank: β, membrane bound, antigen/ MHC complex, allelic exclusion, α, isotype switching, γ:δ
Differences Between TCRs and BCRs:
- V-J joining can occur on β chain due to unique RSS structure
- Allelic exclusion less stringent for α chain than β chain
- Multiple α chains can appear on the same T cell
- No somatic mutation, No isotype switching
- Always membrane bound
- Bind to antigen/MHC complex, instead of antigen alone
- α:β T cell receptor and γ:δ T cell receptor
Topic 10
Hyperviable Regions (HV) / CDRs:
- CDRs determine TCR’s ____
- TCR’s antigen/ MHC binding site has ____ CDRs
- TCR repertoire is generated by ______
- Creates a ____
Bank: TCR gene rearrangement, binding specificity, 6, loop
For hyperviable Regions (HV) / CDRs:
- CDRs determine TCR’s binding specificity
- TCR’s antigen/ MHC binding site has 6 CDRs
- TCR repertoire is generated by TCR gene rearrangement
- Creates a loop
Topic 10
TCR Diversity:
- Like B cell receptors, TCRs can bind virtually to any existing ____ associated with MHCs
How is diversity generated?
1) Multiple TCR ______
2) Recombination signal sequences (RSS) and ____ recombinase
3) Gene rearrangement follows the same 12/23 (aka _____) rule
4) ______: P- and N-nucleotide additions (TdT)
Bank: peptide antigens, one turn/two turn, gene segments, junctional flexibility, RAG-1/2
TCR Diversity:
- Like B cell receptors, TCRs can bind virtually to any existing peptide antigens associated with MHCs
How is diversity generated?
1) Multiple TCR gene segments
2) Recombination signal sequences (RSS) and RAG-1/2 recombinase
3) Gene rearrangement follows the same 12/23 (aka one turn/two turn) rule
4) Junctional flexibility: P- and N-nucleotide additions (TdT)
* TCR diversity is generated in a similar way as BCRs
Topic 10
Human TCR Gene Loci
- The human T cell receptor gene has an alpha and beta chain locus
- The alpha chain locus has ___, ___, and ___ segments
- The beta chain has ___, ___, ___, and ___ segments (like the ___ chain)
Bank: D, D, C, C, J, J, V, V, light, heavy
Human TCR Gene Loci
- Has an alpha and beta chain locus
- The alpha chain locus has V, J, and C segments
- The beta chain has V, J, C, and D segments (like the light chain)
Topic 10
TCR Gene Rearrangement
- Order of TCR gene rearrangement: _______, _______, ______, (_____), _____
- Alpha chain locus: In order to make functional, any of the ___ segments can join any of the ___ segments
- Beta chain locus: In order to make functional, a _____ is made
Bank: germline DNA, DJC arrangement, T cell receptor protein, recombination, J, (transcription, splicing, translation), V, rearranged DNA
TCR Gene Rearrangement
- Order of TCR gene rearrangement: germline DNA, recombination, rearranged DNA, (transcription, splicing, translation), T cell receptor protein
- Alpha chain locus: In order to make functional, any of the V segments can join any of the J segments
- Beta chain locus: In order to make functional, a DJC arrangement is made
Topic 10
Comparison of TCR
and BCR Diversities
- In the ___ cell receptor, there is more ____: more palindromic nucleotide addition and more junctional diversity
Bank: rearrangement, T, B,
Comparison of TCR
and BCR Diversities
- In the T cell receptor, there is more rearrangement: more palindromic nucleotide addition and more junctional diversity
Topic 10
RSS:
- V-J Joining Is Allowed in TCR ____-chain Locus
(RSS Difference) - The one turn two turn rule makes ____ joining possible
- In the alpha-bata chain, the one turn two turn rule is applicable because a ___ can attach to a ___ ( ___ VJ binding occurs)
- In the k-H chain, the one turn two turn rule is not applicable because a ___ cannot attach to a ____ ( ___ VJ binding occurs)
Bank:
no, yes
J23, J23, V23, V23, J12, J12, V12, V12
V to J, alpha to beta, D to C
alpha, beta
RSS:
- V-J Joining Is Allowed in TCR beta-chain Locus
(RSS Difference) - The one turn two turn rule makes a V to J joining possible
- In the alpha-bata chain, the one turn two turn rule is applicable because a V23 can attach to a J12 (VJ binding occurs)
- In the k-H chain, the one turn two turn rule is not applicable because a V23 cannot attach to a J23 (no VJ binding occurs)
Topic 10
Beta chain rearrangement:
- ___ possible attempts overall
- ___ attempts can be made to achieve a productive rearrangement of the beta chain locus on each _____
- After a ____ rearrangement to C2, the transcription of functional beta-chain ____ can begin
Bank:
One, two, three, four
productive, unproductive
homologous chromosome, different chromosome
tRNA, mRNA, rRNA
Beta chain rearrangement:
- Four possible attempts overall
- Two attempts can be made to achieve a productive rearrangement of the beta chain locus on each homologous chromosome
- After a productive rearrangement to C2, the transcription of functional beta-chain mRNA can begin
Topic 10
TCR Binding:
- TCR binds the _____
- TCR always binds to the peptide associated with ___
- Binds in a ___ epitope (when the proteins that are bound by the antibody are all in a row)
Bank:
Discontinuous, Linear
MHC molecules
MHC & Peptide Complex
TCR Binding:
- TCR binds the MHC & Peptide Complex
- TCR always binds to the peptide associated with MHC molecules
- Binds in a linear epitope (when the proteins that are bound by the antibody are all in a row)
Topic 10
The two classes of T cell receptors:
αβ (alpha beta) TCR and γδ (gamma delta) TCR
- ____ T cells express αβ TCRs
- ____ T cells express γδ TCRs
- ___ structure, encoded by ___ genes
- ____ have/has a V (top) and C (bottom) region
Bank:
Same, Different
Most, Some
Both, αβ, γδ
The two classes of T cell receptors:
αβ (alpha beta) TCR and γδ (gamma delta) TCR
- Most T cells express αβ TCRs
- Some T cells express γδ TCRs
- Same structure, encoded by different genes
- Both have a V (top) and C (bottom) region
Topic 10
Gene Structures of γ (gamma) and δ (delta) Gene Loci
- The number of gene segments of γ and δ genes are much ____
- __ gene locus is located within the __ gene locus
- ___ is sometimes used by α-chain gene rearrangement
- Chromosome __ has an alpha and beta chain locus
- Chromosome __ has a γ chain locus
- γ: like the Ig ___ chain and the _____, there is no ___ segment
Bank:
7, 14
light, heavy, MHC alpha chain
V, J, C, D
Vδ, Vγ
δ, α
smaller, larger
Gene Structures of γ (gamma) and δ (delta) Gene Loci
- The number of gene segments of γ and δ genes are much smaller
- δ gene locus is located within the α gene locus
- Vδ is sometimes used by α-chain gene rearrangement
- Chromosome 14 has an alpha and beta chain locus
- Chromosome 7 has a γ chain locus
- γ – like the Ig light chain and the MHC alpha chain, there is no D segment
Topic 10
The link between alpha chain and δ ( delta ) chain:
- _______ of an alpha chain always _____ the linked δ ( delta ) chain locus
- How does this happen? During rearrangement, the alpha chain completely loops out of the δ ( ___ ) chain locus
- This is the reason why there is far less of the γ ( ___ ) and δ ( delta ) chains compared to the alpha and beta chains
Bank:
Recombination, Transport, Rearrangement
delta, lambda, gamma
Increases, decreases, eliminates
The link between alpha chain and δ ( delta ) chain:
- Rearrangement of an alpha chain always eliminates the linked δ ( delta ) chain locus
- How does this happen? During rearrangement, the alpha chain completely loops out of the δ ( delta ) chain locus
- This is the reason why there is far less of the γ ( gamma ) and δ ( delta ) chains compared to the alpha and beta chains
Topic 10
γδ (gamma delta ) T Cells:
Their function is not fully understood…
- May function as a part of _____, like B-1 cells
- More important in ____ embryonic development
- Can be activated ____ infection
- Involved in ____; function of inflammation
- Due to spectrum of _____ secreted, may serve regulatory role to attract αβ T-cells
Bank:
cytokine mapping, tissue repair, immune response
early, middle, late, post-
with, without
T cells, cytokines, B cells
adaptive immunity, innate immunity
γδ (gamma delta ) T Cells:
Their function is not fully understood…
- May function as a part of innate immunity, like B-1 cells
- More important in early embryonic development
- Can be activated without infection
- Involved in tissue repair; function of inflammation
- Due to spectrum of cytokines secreted, may serve regulatory role to attract αβ T-cells
Topic 10
T Cell Receptor
Complex
- Like BCRs, besides αβ chains, T cell receptors also have other proteins to form a ______
- TCR complex has 6 proteins: ___, ___, ___, __, ___, ____ (order matters here, read left –> right)
- The proteins used in this complex are collectively called ___
- CD3 = unique marker for ____
- Makes signal transduction ___
Bank:
T cells, B cells
alpha, beta, gamma, lambda, omega, epsilon, epsilon, delta
TCR complex, MHC complex
occur, not occur
CD3, CD4, CD8
T Cell Receptor
Complex
- Like BCRs, besides αβ chains, T cell receptors also have other proteins to form a TCR complex
- TCR complex has 6 proteins: epsilon, delta, alpha, beta, gamma, epsilon 2
- The proteins used in this complex are collectively called CD3
- CD3 = unique marker for T cells
- Makes signal transduction occur
Topic 10
CD4 and CD8 co-Receptors
- CD4 has _ external domains, CD8 has _ external domains
- CD4 is expressed on __ cells, CD8 is expressed on __ cells
- CD4 binds to ____, CD8 binds to ____
- Both reach into the _____ and are anchored there
Bank:
MHC I, MHC II
1, 2, 3, 4, 5
cytoplasm, transmembrane region
Tc, Th
CD4 and CD8 co-Receptors
- CD4 has 4 external domains, CD8 has 2
- CD4 is expressed on Th cells, CD8 is expressed on Tc cells
- CD4 binds to MHC II, CD8 binds to MHC I
- Both reach into the cytoplasm
Topic 10
T cell co-receptors:
- The T cell co-receptors are the ___ T cell and the ___ T cell
- They _____ the
TCR/ MHC/ Peptide Complex - They do this by binding Ig-like domains of ____ molecules
Bank:
neutralize, destroy, stabilize
alpha, beta, delta, gamma, CD8, CD4
MHC, TCR, BCR
T cell co-receptors:
- The T cell co-receptors are the CD8 T cell and the CD4 T cell
- They stabilize the
TCR/ MHC/ Peptide Complex - They do this by binding Ig-like domains of MHC molecules
Topic 10
T cell development
- T cell ____ travel from the _____ to develop in the ____
- Then, ____ T cells leave the ___ and travel to _____ lymphoid tissues
Bank:
bone marrow, thymus, thymus, primary, secondary, precursors, mature
T cell development
- T cell precursors travel from the bone marrow to develop in the thymus
- Then, mature T cells leave the thymus and travel to secondary lymphoid tissues
Topic 10
T Cell Development, Activation and Differentiation
- 4 main phases: _______, ______, _____/ _____, _____ (in order)
- _____ T cells go to the infection site
Bank:
activation, early development, differentiation, effectors, maturation
mature, effector, young, old
T Cell Development, Activation and Differentiation
- 4 main phases: early development, maturation, activation/ differentiation, effectors
- Effector T cells go to the infection site
Topic 10
T cell development:
- The T cell develops in the ____
- Thymus is on top of the ____ and has two regions: ____ and ______
- In the thymus, T cells are called _____
- Lack of T cells can develop ______
- _______: cannot make B cells so T cells can’t be made either ( immune system effected = no hair )
Bank:
naked rat, nude mice, immunocompromised organism
phagocytes, erythrocytes, thymocytes
HIV, DiGeorge syndrome, cancer
stomach, heart, liver
bone marrow, thymus, secondary lymphoid tissues
origin, V domain, medulla, C domain, cortico
T cell development:
- The T cell develops in the thymus
- Thymus is on top of the heart and has two regions: cortico and medulla
- In the thymus, T cells are called thymocytes
- Lack of T cells can develop DiGeorge Syndrome
- Nude mice – cannot make B cells so T cells can’t be made either ( immune system effected ) ( no hair = nude mouse )
Topic 10
Early T cell development
- _____ stem cells arrive in
thymus through HEV from
blood and enter the ______ - Cortical epithelial cells provide key signals that trigger stem cells to proliferate and differentiate to T cell precursors (_______)
- IL- _
- Ligand for Notch- _
Bank:
phagocytes, erythrocytes, thymocytes
CD4, CD8, CD34+
cortex, nucleus, epithelium
5, 6, 7, 8
1, 2, 3, 4,
Early T cell development
- CD34+ stem cells arrive in
thymus through HEV from
blood and enter cortex - Cortical epithelial cells provide key signals that trigger stem cells to proliferate and differentiate to T cell precursors (thymocytes)
- IL-7
- Ligand for Notch-1
Topic 10
Early T cell development pt 2
- Thymocytes stop proliferating and TCR
___ -chain genes rearrange (so do __ & __ genes) - β-chain (or γ/δ chains) are ______.
- New β-chains combine with a 33-KD
______: pre-Ta chain and form pre-T-cell receptor (pre-TCR) - Both α:β T cells and γ:δ T Cells are from
common _____
Bank:
glycoprotein, phagocyte, erythrocyte
hosts, cells, progenitors
repressed, killed, expressed
omega, beta, alpha, epsilon, gamma, delta
Early T cell development pt 2
- Thymocytes stop proliferating and TCR
beta-chain genes rearrange (also γ&δ genes) - β-chain (or γ/δ chains) is expressed.
- New β-chains combine with a 33-KD
glycoprotein: pre-Ta chain and form pre-T-cell
receptor (pre-TCR) - Both α:β T cells and γ:δ T Cells are from
common progenitors
Topic 10
Early T cell development pt 3
- Double ______ thymocytes
______ βγδ gene loci. - Although it seems random to
go to αβ T cells or γδ T cells,
___ T cells are preferred.
Bank:
positive, negative
repress, rearrange, kill, express
αβ, γδ
Early T cell development pt 3
- Double negative thymocytes
rearrange βγδ gene loci. - Although it seems random to
go to αβ T cells or γδ T cells,
αβ T cells are preferred.
Topic 10
Pre-T cell receptor
- Heterodimers form a ______
- The superdimer + __ Cell Receptor
Complex forms a ______ pre-T cell receptor - This is done by _______
- Autosignaling is when no extra ____ is bound to the receptor
Bank:
ligand, protein, dimer
T, B, alpha, beta
autosignaling, dimerization, recombination
double dimer, superdimer
functional, nonfunctional
Pre-T cell receptor
- Heterodimers form a superdimer
- The superdimer + T Cell Receptor
Complex forms a functional pre-T cell receptor - This is done by autosiganling
- Autosignaling is when no extra ligand is bound to the receptor
Topic 10
The Assembly of Pre-TCR
- The assembly of Pre-TCR sends _____ signals
- The signals can:
* make the cell become _____ for TCR alpha-chain locus arearrangements* \_\_\_\_\_\_ expression of CD4 and CD8 co-receptors * \_\_\_\_ additional TCR beta-chain locus arearrangements (\_\_\_\_\_\_\_) * Stimulate \_\_\_\_\_\_
Bank:
permissive, nonpermissive
stimulate, stop, start
1, 2, 3, 4, multi-
allelic exclusion, isotope switching
proliferation, signaling
The Assembly of Pre-TCR
- The assembly of Pre-TCR sends multi- signals
- The signals can:
* make the cell become permissive for TCR alpha-chain locus arearrangements
* stimulate expression of CD4 and CD8 co-receptors
* Stop additional TCR beta-chain locus arearrangements (allelic exclusion)
* Stimulate proliferation
Topic 10
Pre-T Cells Rearrange α, γ, and δ Gene Loci
- If α gene is selected, the cell will become ______ double + αβ T cells
- If __ and __ genes are selected, the cell will become __ T cells
- Again, __ T cells are preferred.
Bank:
αβ, γδ
alpha, beta, gamma, delta
CD4/CD8, CD34+/CD38+
Pre-T Cells Rearrange α, γ, and δ Gene Loci
- If α gene is selected, the cell will become CD4/CD8 double + αβ T cells
- If γ and δ genes are selected, the cell will become γδ T cells
- Again, αβ T cells are preferred.
Topic 10
Immature T cells
- The successful assembly of TCR ends the _______ development
- _______ are CD4 and CD8 double positive
Bank:
early T cells, late T cells, immature T cells, mature T cells
Immature T cells
- The successful assembly of TCR ends the
early T cells development - Immature T cells are CD4 and CD8 double
positive
Topic 10
T Cells Prefer __-Receptor to __-Receptor
Why?
1) γ:δ receptors require __ independent productive gene rearrangements, while Pre-T receptors only need __
2) β chain gene structure allows __ rearrangements
3) A successful α-chain gene rearrangement completely _____ δ-gene segments
Bank:
γδ, αβ
1,2,3,4
eliminates, adds
T Cells Prefer αβ-Receptor to γδ-Receptor
Why?
1) γ:δ receptors require two independent productive gene rearrangements, while Pre-T receptors only need one
2) β chain gene structure allows four rearrangements
3) A successful α-chain gene rearrangement completely eliminate δ-gene segments
Topic 10
Why does the B chain rearrange 4 times?
Due to the _____ joining structure
Bank: VDJC, alpha beta
Why does the B chain rearrange 4 times?
Due to the VDJC joining structure
Topic 10
The _____ chain locus can sustain many attempts at a functional rearrangement. This makes it more successful
Bank: alpha, beta, gamma, delta
The alpha chain locus can sustain many attempts at a functional rearrangement
Topic 10
Rearrangement of ___ genes always eliminates ___ genes
Bank: alpha, beta, gamma, delta
Rearrangement of α Gene Always Eliminate δ Gene
Topic 10
Early development of T cells
- T cells are developed in the _____
- At the end, immature double ____ T cells are made
Bank:
lymphnode, thymus, heart
positive, negative, alpha
Early development of T cells
- T cells are developed in the thymus
- At the end, immature double positive T cells are made
