PCB 3233 Module 3 Exam Review: T-Cell and B-Cell Biology, MHC, and Lymphocyte Development

Comprehensive question-and-answer study flashcards covering T-cell and B-cell receptor structures, MHC processing and presentation pathways, genetics, tolerance mechanisms, and lymphocyte developmental checkpoints.

How do B lymphocytes and T lymphocytes differ regarding the types of antigens they recognize and their physical form upon maturation?

T lymphocytes recognize only one type of antigen (short peptides presented by MHC molecules) and remain membrane-bound. In contrast, B lymphocytes recognize a diverse range of antigens including carbohydrates, proteins, and lipids, and they can produce a secreted form of their receptor (antibodies).

Where do B lymphocytes and T lymphocytes undergo maturation?

B lymphocytes mature in the bone marrow, whereas T lymphocytes mature in the thymus.

What are the structural chain compositions of MHC Class I and MHC Class II molecules?

MHC Class I is composed of an $\alpha$-chain and $\beta_2\text{-microglobulin}$. MHC Class II is composed of an $\alpha$ chain and a $\beta$ chain.

How do MHC Class I and MHC Class II differ in the length of peptides they bind and the source of pathogens they present?

MHC Class I binds peptides of $8-10$ amino acids derived from intracellular pathogens. MHC Class II binds peptides of $10-25$ amino acids derived from extracellular pathogens.

Which cell types express MHC Class I versus MHC Class II, and which T-cell coreceptors recognize them?

MHC Class I is expressed on all nucleated cells and presents to $\text{CD8}^+$ T cells. MHC Class II is expressed on professional antigen-presenting cells (PAPCs) and presents to $\text{CD4}^+$ T cells.

The binding site of an antibody has what type of chain , and the binding site of a TCR antibody has what type of chain

antibody binding site chain is light and heavy chain while TCR binding site is Alpha and beta chain

Immunoglobulin can be used for ______ (fab) or _______(fc).The TCR is only used for _____.

Recognition , effector , antigen recognition

How many antigen-binding sites and complementarity-determining regions (CDRs) are present on a single TCR compared to a BCR?

A TCR has $1$ antigen-binding site containing $6$ CDRs ($3$ on the $\alpha$ chain and $3$ on the $\beta$ chain). A BCR (monomeric immunoglobulin) has $2$ antigen-binding sites.

True or False: The effector functions of T cells are dependent on secreted TCRs.

False. TCRs are never secreted; they remain membrane-bound on the T-cell surface.

On which chromosomes are the TCR $\alpha$ and $\beta$ chain loci located, and which immunoglobulin chains do they resemble?

The TCR $\alpha$ chain is on chromosome $14$, contains V and J segments, and is similar to the light (L) chain. The TCR $\beta$ chain is on chromosome $7$, contains V, D, and J segments, and is similar to the heavy (H) chain.

What is allelic exclusion

Only 1 heavy and only 1 light chain being made

What is junctional diversity ?

P & N nucleotide , through TDT

What is the 12/23 rule

1 turn 2 turn

Define RSS

Recombination signal sequence rag 1 and 2 which decides which landing sequence tell where to cut

During which developmental window are RAG-1, RAG-2, and TdT expressed?

RAG-1, RAG-2, and TdT are only produced during the development of T and B lymphocytes in primary lymphoid organs.

How many times can recombination occur in the heavy chain per cell ?

Two times

How many times can rearrangement occur in the TCR $\beta$ chain per cell, and what structural feature allows this?

4 times and because 2D and 2J segement

Which membrane protein complex associates with the TCR to mediate intracellular signal transduction?

The CD3 complex (along with the $\zeta$ chain).

Where are s gamma gene segments located ?

Alpha chain and chromosomes 14

Can a cell express both classes of TCR’s ?

No , because of the locus is mechanically destroyed

The ___ gene segments are situated within the a-chain locus on chromosomes ______ .

TCR $\delta$ (delta) , chromosome 14

the ____ TCR structure is similar to the a:B TCR .This is only a small subset of all T cells .

$\delta$ gamma :delta

On which chromosome are both the TCR $\gamma$ and TCR $\beta$ chain loci located?

Chromosome $7$.

What is the primary biological purpose of MHC molecules?

To present the peptide to the TCR

What type of antigen do T cells mostly recognize

Short peptide antigens

What does CD4 T-cells do ?

Can activate B cells , bind to MHC II

What are the primary immune functions of $\text{Th1}$ and $\text{Th2}$ subclasses of $\text{CD4}^+$ helper T cells?

$\text{Th2}$ cells secrete cytokines such as $\text{IL-4}$ and $\text{IL-5}$ to activate plasma cells to produce antibodies. $\text{Th1}$ cells secrete cytokines (such as $\text{IFN}-\gamma$) that activate macrophages to engage in phagocytosis.

Which specific protein domains form the peptide-binding grooves of MHC Class I and MHC Class II molecules?

In MHC Class I, the groove is formed by the folding of the $\alpha_1$ and $\alpha_2$ domains. In MHC Class II, the groove is formed between the $\alpha_1$ and $\beta_1$ domains.

because MHC molecules can bind to many different amino acids sequences, they are considered?

promiscuous and degenerate

True or false :MHC I can have a hydrophobic residue on its C-terminus

True

Which enzymatic complex generates cytosolic peptide fragments for MHC Class I presentation, and which inducible subunits are involved?

The proteasome (specifically the immunoproteasome), which incorporates the inducible catalytic subunits $\text{LMP2}$ ($\beta 1i$) and $\text{LMP7}$ ($\beta 5i$).

What is the function of the TAP transporter in the MHC Class I antigen processing pathway?

TAP (Transporter associated with antigen processing) transports processed peptide fragments from the cytosol across the membrane and into the endoplasmic reticulum (ER) lumen.

After the antigen peptides are prepared, they are transported from the cytosol to the ER and TAP which then the MHC I components are put together with what ?

a-chain and B2-microglobulin

Once the MHC I components a-chain and B2-microglobulin are put together the peptide is then bound to the MHC molecule to complete the folding this is done through a ?

Chaperone

What is the sequential assembly pathway and chaperone requirement for folding the MHC Class I molecule in the ER?

Calnexin , calrecticulm , tapasin

____retains the partly folded a-chain

Calnexin

_____binds the tap -1 subunit of the peptide transporter

Calrecticulm and tapasin

____ holds open the binding groove of MHC molecule for peptide loading

Tapasin

If the MHC molecule is loaded with the peptide that is too long , it is cut by

ERAP (endoplasmic reticulum aminopeptides

Which molecular component is non-functional in patients with Bare Lymphocyte Syndrome Type I?

The TAP complex (peptide transporter).

In MHC 2 extracellular bacteria and viruses particles are processed by a different intercellular pathway, this causing the antigen being taken up into a _____ which becomes acidified

Intracellular vesicles

What leads to the fusing of lysosomes to form _____ which contain proteases and hydrolases activated at low pH ( when it is acidified ). This degrades the proteins into peptides

Phagolysomes

How is MHC Class II prevented from binding peptides inside the endoplasmic reticulum? Thus allowing all peptides in the ER bind MHC 2 molecules only

The invariant chain ($\text{Ii}$) .

____ is a vesicle that contains proteases that selectively cleave the invariant chain and leaves a small fragment called _____ to cover the MHC peptide -binding groove .

MYC and clip

How is the invariant chain processed in endosomes, and what is the role of HLA-DM?

Proteases in acidified endosomes cleave the invariant chain, leaving a small peptide called CLIP in the groove. HLA-DM binds to MHC Class II to catalyze the release of CLIP, allowing foreign peptides to be loaded.

What is immunological cross-presentation?

when MHC 1 issued for extracellular stuff by DC’s

How many CDR’s ( or HV’s) are present in a TCR $\alpha$ or $\beta$ chain ?

3

Will the peptide or the MHC molecule provide more variability?

Peptide

Which regions of the TCR interact with the bound peptide versus the host MHC molecule?

The CDR3 loops interact primarily with the peptide (providing the greatest sequence variability), whereas CDR1 and CDR2 loops primarily make contact with the $\alpha$-helices of the host MHC molecule.

True or False: Like Ig and TCR , MHC genes are able to undergo rearrangement and somatic structural change

False. MHC genes do not rearrange or undergo somatic structural changes; their diversity is entirely due to gene families and polygenic polymorphism in the human population.

True or false : differences in MHC molecules responsible for graft rejection in organ transplantation

True

The MHC has a ____ , which means that are a large number of variants in the human population

High polymorphism

What are the polymorphic classical MHC Class I and MHC Class II human genes?

Classical MHC Class I genes are HLA-A, HLA-B, and HLA-C. Classical MHC Class II genes are HLA-DP, HLA-DQ, and HLA-DR.

How many classical HLA variations will an individual express if they are completely heterozygous versus completely homozygous?

A completely heterozygous individual expresses $18$ classical HLA variations ($6$ Class I and $6$ Class II). A completely homozygous individual expresses $6$ classical HLA variations ($3$ Class I and $3$ Class II).

Is it better to have MHC heterozygosity or homozygosity

Better to have heterozygosity

You have ___ sets of genes , ___ from each parent (haplotype)

2 and 1

What is the function of HLA-E

Inhibits NK cells

HLA stands for ?

Human leukocyte antigen

What is the function of HLA-A,B,C

Present’s intracellular antigens to CD8 T cells

What is the function of HLA-DM

Remove the clip from MHC regulate peptide loading

What is the function of HLA-DP, DQ,DR

Presents extracellular antigens to CD4+ helper T-cells

True or false: genes that encodes MHC I heavy chain and MHC class II $\alpha$ and B chains are closely linked

true

True or false :The class I genes for presentation are all contained in the class I region

True

Where are the genes for tapasin, TAP-1, TAP-2, LMP2, and LMP7 located within the HLA complex?

Inside MHC class 2 region

What is the definition of MHC restriction?

They have to match

Where are B cells mostly developed

Bone marrow

What are the six recognized phases of B-cell development?

Phase 1: Repertoire Assembly (Generation of diverse receptors);

Phase 2: Negative Selection (Elimination of self-reactive cells);

Phase 3: positive selection/ Positive Selection (Migration and maturation);

Phase 4: Searching for Infection (Recirculation through lymphoid tissues);

Phase 5: Finding Infection (Activation and clonal expansion)

Phase 6: Attacking Infection (Differentiation into effector cells).

What is the major primary lymphoid tissue for B cells ?

Bone marrow

What are some secondary lymphoid tissue for B cells ?

Spleen , lymph nodes , MALT

In B cell development, it proceeds in stages defined by the rearrangement and expression of immunoglobulin genes :

Rerangment by IgG genes

Which immunoglobulin gene rearrangement events define the stem cell , Early Pro-B, Late Pro-B, and large pre-b cell , Small Pre-B cell stages , immature B cell and mature B cell ?

Stem cell- heavy and light chain

Early Pro-B: $D-J$ rearrangement begins on the heavy-chain locus.

Late Pro-B: $V-DJ$ rearrangement occurs on the heavy-chain locus.

Large pre-B cell- Heavy chain is productively rearranged (VDJ)

Small Pre-B: heavy-chain rearrangement ceases and $V-J$ rearrangement begins on the light-chain locus.

Immature B cell-expressed only IgM

Mature B cell - express IgM and IgD

what is the role of VpreB? What is the role for Lambda 5?

heavy rearrangement and constant rearrangement

True or false : Ig$\alpha$ and Ig$\beta$ is only present on IgM and IgD

False

The Pre-B cell receptor molecules lead to allelic exclusion, which stops transcription of ____ and ____ is tagged for destruction.

Rag 1,2 and Rag -2

If we don’t have allelic exclusion, we lose ____?

Infinity

Negative selection in primary lymphoid tissues is _____ tolerance, If it is anywhere else ,it is ____ tolerance

central and peripheral

alternative ____ splicing of Ig heavy -chain gene transcripts produces IgD

MRNA

True or false : IL-7 is a growth factor used in the development of B cells in bone marrow stromal cells

True

IL-7 receptor is found on the _____ ,while IL-7 is secreted by ____\

B cell and bone marrow

SCF is found on the ____ , while Kit is found on the ____

Bone marrow / stromal cells and B-cell

What is the difference between a productive and an unproductive gene rearrangement?

A productive rearrangement can translate . An unproductive rearrangement not going to translate into a protein

Which isotope of the light chain is tested first ? And what is the minimum number of test you can do on the light chain ?

Kappa (k) and 1

True or false : Rag-1 and Rag-2 can be activated outside of the bone marrow after B cell maturation

True

What is the minimum number of test you can do on the light chain ?

4

The pre-BCR is the first checkpoint .We test the ____ chain . In the second checkpoint, we test the ____ chain

Heavy and light

Which invariant signaling molecules are turned on during early B-cell development and remain active on mature B cells?

$\text{Ig}\alpha$ and $\text{Ig}\beta$ (CD79a and CD79b).

What are two proto-oncogenes that prof .Weigel wants you to know ?

MYC AND BCL2

Which proto-oncogene leads to Burkitt's Lymphoma ? In which chromosomes will this translocation occur ?

MYC and resulting in the translocation $t(8;14)$.

What are the defining characteristics of B-1 cells regarding their origin, surface markers, memory, and somatic hypermutation?

B-1 cells develop during fetal development, express surface CD5, are self-renewing, do not require T-cell activation, do not form memory cells, and do not undergo somatic hypermutation, are in a low population.

What is another term for receptor editing ?when does it occur

Clonal editing and bone marrow

if a B-cell is anergic, what does this mean ? How does this occur ?

unresponsive and bind to the monovalent

If receptor editing cannot occur , what happens to the B cell ?

Apoptosis

What is the specialized function of Follicular Dendritic Cells (FDCs) in secondary lymphoid tissues?

hold and display intact unprocessed antigen

What is the function of effector B cells ?

Secrete antibodies

Which chemokines and receptors guide circulating naive B cells across High Endothelial Venules (HEVs) and into the primary follicles?

CCL19 and CCL21 bind to CCR7 to direct naive B cells across HEVs into the lymph node. CXCL13 binds to CXCR5 to attract B cells from the T-cell zone into the primary follicle.

What survival cytokine provides the final maturation signal to circulating transitional B cells?

BAFF (B-cell activating factor).

What distinct cellular events occur in the Dark Zone versus the Light Zone of a germinal center?

In the dark zone, large proliferating B cells (centroblasts) undergo clonal expansion, somatic hypermutation, and isotype switching. In the light zone, non-dividing centrocytes are tested by encountering intact antigens on FDCs and interacting with helper T cells.

True or false : large masses of helper T cells are in the T cell zone and light zone

True

Are all lymphocytes leukocytes? And are all cytokines chemokines

Yes and yes