IMMUNOLOGY TEST 2

How long does B-cell maturation from an HSC to a mature B cell take?

1 to 2 weeks

Central tolerance is maintained in a patient when

: the BCR is autoreactive, and it undergoes receptor editing, clonal deletion, or anergy.

Define Plasma cell

A B cell that has matured and differentiated; produces and secretes antibodies

- Define Allelic exclusion

A mechanism that has evolved to make sure that a B cell only transcribes and expresses 1 heavy chain allele and 1 light chain allele

What is the effector molecule of humoral immunity?

Antibodies

Which of the following constitutes the critical survival cytokine for B cells in the secondary lymphoid tissue cortex?

BAFF

Define autoreactive

Binds to self-antigens and results in immunity against self cells

dentify primary lymphoid tissue/organs and the major process that occurs in these sites

Bone marrow: hematopoiesis, maturation of B cells § Thymus: maturation of T cells

Deficiency in RAG1 and/or RAG2 can affect the proper development of which of the following cell types, resulting in decreased numbers of circulating cells of those types?

Both B and T cells

Activated TH cells signal to B cells to initiate their activation program via which of the following?

CD40L on the T cell to CD40 on the B cell

Which cell type is found in both B- and T-cell lineages?

Common lymphoid progenitors

performed on liquid samples

ELISA

y-axis label (ng/ml)

ELISA

uses antibodies to detect specific molecules

ELISA and IHC

Identify the technique that could be used to demonstrate the function of RAG

EMSA would test ability of RAG to bind to RSS segment on the DNA

if an antibody was attached to a virus, this region would be specifically binding to the virus

Fab

this region contains the variable regions of the heavy and light chains

Fab

Heavy chain polypeptides are either called kappa or lambda chains

False

if an opsonizing antibody was attached to a virus, this region could bind to receptors on a phagocytic cells and then signal for the virus/antibody complex to be phagocytosed

Fc

this region contains the constant region of the heavy chain

Fc

this region determines the isotype of the antibody

Fc

this region is always different between IgG and IgE

Fc

Which Fc-receptor is responsible for triggering the release of histamine, proteases, and other inflammatory signals from IgE?

Fcε receptor

Define a follicle and the type of cells located in follicles

Follicle: located in cortex of lymph node and white pulp of spleen; contains B cells and follicular dendritic cells

Define germinal center the type of cells located in germinal centers

Germinal center: site in a follicle where B cells are concentrated to undergo proliferation and differentiation to form a colony of B cells with high affinity for the same antigen.

y-axis label(% stained tissue)

IHC

Hypothesize what would occur in patients that lacked poly Ig receptor

If a patient lacked polyIgR, they would not be able to neutralize pathogens in digestive, respiratory, and reproductive tracts and those tissues would be more susceptible to infection/disease.

• Identify the antibody isotypes that often neutralize pathogens or pathogen toxins during an infection

IgA

If a patient has low levels of IL-4, or an absence of IL-4, what antibody isotype would most likely decrease?

IgE

Which type of antibody is MOST effective against the largest variety of pathogens?

IgG

Which class of antibodies is the FIRST to be produced during the primary immune response?

IgM

Identify the antibody isotypes that lead to activation of complement proteins

IgM and IgG

Why is IgM the class of antibody able to form large polymers?

IgM has low affinity and benefits from having a large number of binding sites

performed on tissue biopsies

Immunohistochemistry (IHC)

BCR in T1

In T1 B cells, the BCR aids in negative selection as it is presented with self-antigens and tested for high affinity for self (negative selection against autoreactivity)

BCR in T2 B cells

In T2 B cells, the BCR provides stimulatory survival signals that promote the up-regulation of BAFF-receptor so that the B cell can bind BAFF, a survival factor. Without BAFF binding to the BAFF-R on the B cell, it will undergo apoptosis.

Identify the location of M cells and their relationship to GALT

M cells are located between the gut lumen and the GALT, and they mediate transcytosis of particles from the lumen to the GALT.

describes the action of antibodies whereby antibodies bind to a pathogen and prevent the pathogen from interacting with cell receptors.

Neutralization

describes the recruitment of phagocytic cells by the Fab portion of an antibody.

Opsonization

Define antigen

Part of a pathogen that is recognized by BCRs/TCRs; specificity of the receptors is for the antigen

V-DJ recombination occurs during which phase of a B cell's development?

Pro-B cell

Which enzyme is required to initiate process of VDJ recombination?

RAG

what would occur in a patient born without functional RAG

RAG allows gene recombination so that a variety of antibodies can be produced with the same DNA. If the patient didn't have RAG, they would not be able to generate different types of antibodies because their B cells would not be able to undergo VDJ recombination, so they would be susceptible to infection without a variety of antibodies.

How does allelic exclusion prevent multiple heavy-chain rearrangements from occurring in pre-B cells?

RAG1 and RAG2 are downregulated, and TdT activity is lost so that no additional heavy-chain rearrangements may take place

How does allelic exclusion prevent multiple heavy-chain rearrangements from occurring in pre-B cells?

RAG1 and RAG2 are downregulated, and TdT activity is lost so that no additional heavy-chain rearrangements may take place.

What introduces single-strand break between V(D)J coding sequence and heptamer RSS?

RAG1/2

What does the RAG 1/2 enzyme complex bind to at the start of the V(D)J recombination process?

RSS

o Identify the location of red pulp and white pulp in the body and where B cells are located

Red pulp and white pulp located in spleen § B cells located in white pulp in B cell follicles

identify the two types of B cell activation and molecules involved

T-dependent (TD) B cell activation: requires 1. BCR-antigen interaction, 2. Helper T cell CD40L - CD40 on B cell, 3. Cytokine signal from helper T cell/follicular dendritic cells o T-independent (TI) B cell activation: Either 1. Antigen binds to BCR AND PRR (ex. TLR) or 2. Antigen binds to cross-link BCR

Of the cells listed below, which one represents the MOST developed B cell?

T2 B cells

With regard to the type of B-cell response generated, protein antigens typically provoke which of the following responses?

TD

Two different B cells can have antibodies that have the same variable regions and different constant regions.

TRUE

Which enzyme adds new nucleotides to chromosome that are not present in germline DNA sequence?

TdT

Identify the enzyme that randomly adds nucleotides to the chromosome during VDJ recombination

Tdt

BCR

The BCR has a complete heavy chain (mu chain) expressed on the cell surface with a complete light chain (kappa or lambda).

how BCR expression is tied to B cell development.

The BCR undergoes rearrangement during the early stages of B cell development. Once it is fully expressed, it undergoes negative selection in which auto-reactive BCRs are either deleted or undergo receptor editing. Once a BCR is expressed that is not auto-reactive, the immature B cell leaves the bone marrow to complete maturity in a secondary lymphoid organ.

Fc-receptor molecules tend to have short cytoplasmic tails. How does this influence signaling events within the Fc-receptor cell?

The Fc-receptor is dependent upon a coreceptor (e.g., ITAM or ITIM) that will trigger signaling events within the cell.

Define receptor editing

The light chain is further rearranged when the combination is found to be autoreactive; RAG is turned back on to make another cleavage in the DNA.

pre-bcr

The pre-BCR has a completed heavy chain expressed on the cell surface along with a surrogate light chain (while the light chain is being rearranged).

IgA is typically found as a dimer in high levels of secretions such as milk, tears, and saliva. What is the primary function of IgA in secretions?

To neutralize toxins and pathogens

In heavy chain genes, what are the gene segments?

V, D, J

Central tolerance is lost in a patient when:

an autoreactive B cell is able to leave the bone marrow, so it does not undergo receptor editing, clonal deletion, or anergy

Virally infected host cells are tagged with antigen-antibody complexes. These complexes recruit NK cells that trigger apoptosis in the infected host cell. This is an example of

antibody-dependent cell-mediated cytotoxicity.

BALF would most likely be collected if you were studying:

asthma

Which of the following would NOT be included when examining a person's exposome?

being born with a p53 mutation

Where is the LEAST LIKELY location of a follicle?

bone marrow

B lymphocytes are made in the

bone marrow.

Which of the following processes DOES NOT require DNA recombination?

changing the variable region of activated, mature B cells

Lysis of a pathogen by MAC formation is an example of

complement fixation.

M cells are specialized:

epithelial cells that transport antigens from the lumen of the intestines to leukocytes within the gut lymphoid tissue

Hematopoiesis produces

erythroid, lymphoid, and myeloid lineage cells.

Innate immunity:

first line of defense, happens quickly, many different receptors on one innate cell (non-clonal), low specificity

Adaptive immunity:

induced by innate immunity, takes longer, each adaptive cell has one type of receptor (clonal), high specificity

The research described in the article by Melissa Bates et al., was performed using:

mice that spontaneously develop Lupus-like symptoms over time

benefit of allelic exclusion

o If B cells were to express more than one type of receptor on each cell, there would be a higher likelihood of producing a BCR that would recognize self antigen

RAG:

recombination activating gene

RSS:

recombination signal sequence

Productive:

resulting regions "inside reading frame"; rearrangement occurs successfully and produces a chain that is functional

o Nonproductive:

results in formation of "out of frame" joints

Where do developing B cells complete their maturation through the T1 and T2 stages?

spleen

Which of the following processes is most likely occurring in germinal center B cells?

switching from IgM to IgG

An example of ectopic lymphoid tissue would be follicles located in:

the kidneys

Most people are exposed to DHA when:

they eat fish

Identify the five mechanisms to generate antibody diversity

§ Multiple gene segments (different combinations of V, D, and J) § Heavy chain/light chain combinational diversity (which heavy chains are paired with which light chains) § P-nucleotide addition randomness § Exonuclease trimming, leading to loss of nucleotides § N-nucleotide addition randomness

Identify secondary lymphoid tissue/organs and the major process that occurs in these sites

§ Spleen, lymph nodes, MALT, other diffuse and loosely organized areas (ex tonsils) § In secondary lymphoid organs, adaptive immune cells become activated by interactions with antigen and immune response is initiated.

The first immunoglobulin isotype produced during the course of a primary immune response contains which of the following heavy chains?

μ