immunology exam 2

lymphoid progenitor cells give rise to

T lymphocytes and B lymphocytes

B lymphocytes start developing in the

bone marrow

T lymphocytes leave the bone marrow and migrate to the … where they mature

thymus

Phase 1 of Development of B Cells

repertoire assembly, generation of diverse and clonally expressed B cell receptors in the bone marrow

Phase 2 of Development of B Cells

negative selection, alteration or inactivation of B cell receptors that bind to components of the human body

Phase 3 of Development of B Cells

positive selection, promotion of a fraction of immature B cells to become mature B cells in the secondary lymphoid tissue

Phase 4 in Development of B cells

searching for infection, recirculation of mature B cells between lymph, blood, and secondary lymphoid tissues

Phase 5 in Development of B cells

finding infection, activation and clonal expansion of B cells by pathogen derived antigens in secondary lymphoid tissue

Phase 6 in Development of B cells

attacking infection, differentiation to antibody-secreting plasma cells and memory B cells in secondary lymphoid tissue

B cells and T cells are important players in … immunity

adaptive

bone marrow stromal cells

non-lymphoid cells in bone marrow, provide the microenvironment for the various stages of B-cell development

Pro-B cells develop from the

pluripotent hematopoietic stem cell

What chain of immunoglobulin develops from the “mu” germline

heavy chain

What chain of immunoglobulin develops from the “kappa/lambda” germline

light chain

B cells at different stages can be identified by … on their surfaces

protein markers

what is the progression from stem cell to pro-B cell

pluripotent hematopoietic stem cell → common lymphoid progenitor → B-cell precursor → pro-B cell

What protein marker is found on the surface of hematopoietic stem cells

CD34

in development of B cells, what type of chain genes are rearranged first?

heavy-chain genes

stem cell stage of B cell development

germline H-chain and L-chain genes, no Ig status

early pro-B cell stage of B cell development

D-J rearrangement in H-chain genes, germline L-chain genes, no Ig status

late Pro-B cell stage of B cell development

V-DJ rearrangement of H-chain genes, germline L-chain genes, no Ig status

Pro-B cell rearrangement of the heavy chain locus is

inefficient, only 50% of cells are signaled to survive and become pre-B cells

at each rearrangement event, there is only a one in … chance of the correct reading frame being maintained

one in three chance

rearrangements occur at the H-chain genes on both chromosomes, and if neither is successful the cell

dies

large pre-B-cell receptor monitors the quality of immunoglobulin

heavy chains

even if a productive “mu” heavy chain is made, it must get along with the

surrogate light chain

the surrogate light chain is made from …. polypeptides

VpreB and lambda-5 polypeptides

the large pre-B cell receptor does not appear on the cell surface but remains inside the cell in the cytoplasm as part of a vesicle

True or False

True

large pre-B cell receptor causes … at the immunoglobulin heavy-chain locus

allelic exclusion

allelic exclusion by large pre-B cell receptors

prevents B cells from making more than one functional heavy mu chain

as soon as the heavy chain is “ok”, no other heavy chain is made from the second heavy chain locus

Allelic exclusion at the immunoglobulin loci results in B cells with antigen receptors of a … specificity

single, monospecificity

During allelic exclusion, what gene is degraded in order to resist gene rearrangement

RAG gene

allelic exclusion gives …. B-cell receptors with … affinity binding

homogenous, high

no allelic exclusion would give … B-cell receptors with … affinity binding

heterogenous, low

rearrangement of the light chain loci by ….. is relatively efficient

small pre-B cells

Why is the rearrangement of light chain loci relatively efficient?

no “D” diversity segment, so more chances to get a correct light chain (VJ)

there is also two loci, kappa and lambda, so two chances

rearrangement of the immunoglobulin light-chain genes in small Pre-B cells lead to the expression of

cell-surface IgM

what immunoglobulin light-chain loci is rearranged first

kappa loci

nonproductive light chain gene rearrangements cannot be superseded by further gene rearrangement

True of False

False

The immature B cell can only express one light-chain loci (kappa or lambda), and can never express both at the same time

True or False

True

Which of the following is characteristic of a large pre-B cell?

A. VDJ is successfully rearranged and mu heavy chain is made

B. V-J is rearranging at the light chain locus

C. mu heavy chain and lambda or kappy light chain is made

D. V is rearranging to DJ at the heavy chain locus

E. D-J is rearranging at the heavy chain locus

VDJ is successfully rearranged and mu heavy chain is made

V-J is rearranging at the light chain locus is characteristic of what stage of B cell

small pre-B cell

mu heavy chain and lambda or kappy light chain is made is characteristic of what stage of B cell

immature B cell

V is rearranging to DJ at the heavy chain locus is characteristic of what stage of B cell

Late pro-B cell

D-J is rearranging at the heavy chain locus is characteristic of what stage of B cell

early pro-B cell

B cells are generated throughout life from stem cells in the bone marrow.

 

True

 

False

True

There is feedback regulation in the Development of B cells immunoglobulin receptor chains.

 

True

 

False

True

Match the type of B-cell with its order of development.....meaning which come first, second, and third in the stages of development.

Immature B Cell

Pro-B cell

Pre-B cell

Third, First, Second

Rearrangement of the heavy-chain locus occur at which stage of B-cell development?

 

Mature B-cell

 

Pro-B-cell

 

at the stem cell level

 

Immature B-cell

 

Pre-B-cell

Pro-B Cell

The pre-B-cell receptor causes allelic exclusion at the immunoglobulin heavy-chain locus

 

True

 

False

True

An immature B-cell can secrete both IgD and IgM antibodies.

 

True

 

False

False

Many B-cell tumors carry chromosomal translocations that join immunoglobulin genes to genes that regulate cell growth.

 

True

 

False

True

Immature B-cells that are self-reactive are allowed to leave the bone marrow 100%v of the time.

 

True

 

False

False

Immature B-cells become mature in the ___________________.

 

bone marrow

 

brain

 

primary lymphoid tissue

 

secondary lymphoid tissue

 

heart

secondary lymphoid tissue

With respect to the complement lab, we will heat inactivate 0.5mL of our sheep plasma.  At what temperature will you heat inactivate the plasma (complement) before placing a drop of it on your bacterial agar plates?

 

0 degrees Celsius

 

56 degrees Celsius

 

25 degrees Celsius

 

46 degrees Celsius

 

100 degrees Celsius

56 degrees Celcius

B cells have to pass # main checkpoints in their development in the ….

2, bone marrow

First checkpoint of B cell development

a test of whether a functional heavy chain has been produced

Second checkpoint of B cell development

a test of whether a functional light chain has been produced

B Cells that fail either of the checkpoint die by

apoptosis

B-cell tumors carry …. that join immunoglobulin genes to genes that regulate cell growth

chromosomal translocations

Burkitt’s lymphoma

parts of chromosome 8 and 14 have been exchanged. The sites of breakage and rejoining are in the proto-oncogene MYC on chromosome 8 and the immunoglobulin heavy-chain gene on chromosome 14

If a nonproductive rearrangement is made on one chromosome of a homologous pair, then rearrangement is attempted on the second chromosome

True or False

True

negative selection/central tolerance of immature B cells

immature B cells with specificity for multivalent self antigens are retained in bone marrow

immature B cells that don’t react with self antigen, graduate and take off for the secondary lymphoid tissue and also express … in addition to the IgM surface receptor

IgD

Autoreactive

react to self tissue

the antigen receptors of autoreactive immature B cells can be modified by

receptor editing

receptor editing

part of negative selection/central tolerance, deletes the existing self-reactive rearrangement and successive rearrangements of the light chain loci occurs until a new non-self reactive rearrangement is made

receptor editing changes immature B cells

antigen specificity

Peripheral tolerance

B-cells leave the bone marrow and react against self-antigen, but they become unresponsive (anergic) and eventually die

maturation and survival of B cells requires access to

lymphoid follicles

Positive selection

immature B cells enter secondary lymphoid tissue where they mature and become mature B cells and produce a bunch more IgD and fewer IgM

Immature B cells must pass through a … in a secondary lymphoid tissue to become mature B cells

primary follicle

Mature B-cells produce a bunch more … and fewer … on their surfaces

IgD, IgM

Encounter with antigen leads to the differentiation of activated B cells into

plasma cells and memory B cells

Mature B cells

also known as naive B cells because they have NOT been stimulated by antigens yet

When naive B cells encounter antigen, they are quickly retained in the … areas of the lymph nodes and become activated by antigen specific … T cells

T-cell areas, CD4 T cells

some activated B-cells turn into plasma cells and secrete … first

IgM

Some activated B cells form … in the lymph nodes

germinal centers

Germinal centers

formed by activated B cells, where B cells relax for a while and try to hypermutate to fine tune their antigen specificity and sometimes isotype switching

what can possibly happen to mature B cells at germinal centers

somatic hypermutation, isotype switching, differentiation into plasma cells or memory B cells

chemokines … and … attract B cells into lymph node

CCL21 and CCL19

chemokine … attracts immature B cell to HEV

CCL21

chemokine … attracts B cells into the primary follicle of secondary lymphoid tissue

CXCL13

interactions with follicular … cells and … drives the maturation of immature B cells

dendritic, cytokines

The proto-oncogene … is associated with Burkitt’s lymphoma

MYC

What is the immediate fate of immature B cell that encounters and has specificity for self-antigen?

a. If further heavy chain and light chain gene rearrangements are possible it undergoes apoptosis

b. somatic hypermutation

c. decrease production of IgD

d. continued rearrangement of heavy chain genes

e. continued rearrangement of light-chain genes

continued rearrangement of light-chain genes

The circulatory route through a lymphoid tissue for both immature B cells and mature B cells that do not encounter specific antigen is

bloodstream→ HEV of lymphoid cortex → primary lymphoid follicle → efferent lymphatic vessel

Hapten

small organic molecule that is not itself antigenic but that may become antigenic when bound to a larger carrier molecule

Antigens stimulate (1) cell activation and the synthesis of (2) to which antigens react (bind) to

1) T-cell and B-cell

2) antibodies

Epitope

the part of the antigen that stimulates immune system activity

T-cell receptor resembles:

membrane-associated Fab fragment of immunoglobulin

T-cell receptor is a membrane bound heterodimer composed of an …. chain and a …. chain

alpha, beta

the T cell receptor chains both span the cell membrane and have very short…

cytoplasmic tails

the extracellular portion of each chain of a T-cell receptor consists to two domains:

Variable region/domain and Constant region/domain

T cell receptors only bind to what type of antigens?

peptide antigens

What activates T-cells?

antigens!

T-cell receptor diversity is generated by

gene rearrangement/somatic recombination

There is NO T cell gene rearrangement after…

antigenic stimulation

T cell germline DNA rearrangement is exactly similar to that of …. before antigen stimulation

B-cells

only the …. chain of T cell receptors contain diversity gene segments

beta chain