PCB 3233 Module 5 Exam Review: B Cell Development, Functions, and Mucosal Immunity

Comprehensive practice question-and-answer flashcards covering Chapter 9 (B cell development, BCR signaling, germinal center reactions, antibody classes, and transport) and Chapter 10 (mucosal immunity, GALT organization, M cells, and immune responses).

What are the four primary mechanisms antibodies use to fight infection?

Neutralization, activating complement, opsonizing, and binding to mast cells and basophils.

What are the 6 phases in the development of B cells?

Phase 1: Repertoire assembly; Phase 2: Negative selection; Phase 3: Positive selection; Phase 4: Searching for infection; Phase 5: Finding infection; Phase 6: Attacking infection.

What immunoglobulin gene rearrangement and expression events define each stage of B-cell development?

Stem cell; Early pro-B cell (D-J rearrangement of heavy chain); Late pro-B cell (V-DJ rearrangement of heavy chain); Large pre-B cell (Testing of heavy chain with surrogate light chain); Small pre-B cell (V-J rearrangement of light chain); Immature B cell (IgM only); Mature B cell (IgM and IgD).

Where do the stages of B-cell development from stem cell to mature B cell take place?

Stages from stem cell through immature B cell occur in the bone marrow, while the mature B cell stage occurs in peripheral circulation.

What clinical condition in infants results in a lack of T cells required to activate Thymus-Dependent (TD) B cells?

DiGeorge's syndrome.

What are the key developmental and immunological characteristics of B-1 cells?

They do not require T cell activation, are produced while a fetus, do not undergo isotype switching, do not have memory, and express CD5 on their surface.

From which three cell types can plasma cells directly differentiate?

Activated B cells, memory B cells, and isotype-switched, somatically-hypermutated centrocytes.

Which signaling molecules are used by BCRs versus TCRs to activate intracellular pathways?

BCRs use $\text{Ig}\alpha$ and $\text{Ig}\beta$, whereas TCRs use the CD3 complex.

What role does Syk play in the intracellular B-cell receptor signaling cascade?

Syk binds to the phosphorylated ITAMs of the $\text{Ig}\beta$ cytoplasmic tail, leading to changes in gene expression in the nucleus.

What are the three B-cell co-receptor proteins and their respective functions?

CR2 binds to complement on the pathogen; CD19 functions in receptor signaling; CD81 (or TAPA-1) binds to CD81 and helps bring it to the B-cell surface.

How does the binding of CR2 to C3d amplify B-cell activation?

CR2 binding to C3d causes clustering and phosphorylation of CD19, which binds intracellular signaling molecules to increase signals by up to 10,000-fold.

Why are subcapsular macrophages and follicular dendritic cells (FDCs) specialized for displaying immune complexes in follicles?

They express CR1 and CR2 on their dendrites, have an extensive dendritic surface area, lack phagocytic ability (so immune complexes are not internalized or degraded), and hold onto non-degraded antigens.

Which chemokines and chemokine receptors guide lymphocytes into the lymph node and then into the primary follicle?

CCL19 and CCL21 bind to CCR7 to direct lymphocytes into the lymph node via high endothelial venules (HEVs), while CXCL13 binds to CXCR5 to direct B cells into the primary follicle.

What molecular interaction between activated T cells and B cells increases adhesion strength via ICAM-1 and LFA-1?

CD40 ligand on the T cell binds to CD40 on the B cell, activating the transcription factor $\text{NF}\kappa\text{B}$, which increases expression of ICAM-1 to strengthen adhesion to LFA-1.

Where are the primary and secondary foci of antigen-activated B-cell expansion located?

The primary focus forms in the medullary cords (with $\text{T}_{\text{FH}}$ cells secreting IL-5 and IL-6), and the secondary focus forms in the primary follicle, creating the germinal center.

How do centroblasts and centrocytes differ in their proportion, zone location, BCR expression, and proliferative activity in the germinal center?

Centroblasts make up $\sim 80\%$ of the germinal center in the dark zone, have no surface BCR, divide rapidly, and undergo somatic hypermutation and isotype switching; centrocytes make up $\sim 20\%$ in the light zone, express surface BCR to test against antigen, and are slowly non-dividing.

Which cytokines are secreted by FDCs to promote the proliferation of B cells in the germinal center?

IL-6, IL-15, and BAFF.

What is the fate of a centrocyte in the light zone that fails to bind antigen and engage CD40 ligand?

It undergoes apoptosis and is engulfed by tingible body macrophages.

Which protein functions to prevent apoptosis in centrocytes that successfully bind antigen?

Bcl-xL.

What is affinity maturation?

The process by which the affinity of antibodies for specific antigens increases over the course of an immune response.

What two key factors are required for B-cell isotype switching?

Cytokines secreted by helper T cells (which stimulate transcription from switch regions $5'$ to heavy chain C genes) and the interaction between B-cell CD40 and T-cell CD40 ligand.

What causes Hyper-IgM syndrome and what are its immunological hallmarks?

It is an X-linked immunodeficiency caused by a lack of CD40 ligand on T cells, resulting in inability of B cells to undergo isotype switching and leading to abnormally high levels of IgM.

Which three immunoglobulin classes protect the blood and extracellular fluids?

IgG, IgA, and IgM.

What are the structural and functional characteristics of IgM?

It is the first antibody produced, has a pentameric structure with 10 antigen-binding sites, exhibits high avidity and low affinity, efficiently activates complement, and has Fc receptors that cannot directly recruit phagocytic cells or leukocytes.

How is IgG transported across vascular endothelium into extracellular spaces?

It is actively transported by the Brambell receptor (FcRB or FcRn), where 2 receptor molecules bind to 1 Fc region of IgG.

At what age are IgG levels at their lowest in infants?

Between 3 and 12 months.

What are the functional differences and locations of monomeric versus dimeric IgA?

Monomeric IgA enters extracellular spaces to protect against bacteria and virus particles; dimeric IgA is made in secondary lymphoid tissue underlying mucosal surfaces and protects epithelial linings (such as the GI tract, eyes, nose, and throat).

How is dimeric IgA transported across mucosal epithelial barriers?

It is bound by a J chain and a poly-Ig receptor on the basolateral surface, undergoes receptor-mediated endocytosis to the apical face, and the receptor is cleaved, leaving a secretory component that binds the IgA to mucus.

How does IgE mediate inflammation against parasites and allergens?

IgE binds to high-affinity $\text{Fc}\epsilon\text{RI}$ receptors on mast cells, basophils, and activated eosinophils; antigen crosslinking of these receptors causes the release of histamine.

What is the primary function of IgD?

It helps signal that a B cell is mature.

Which maternal antibodies are transferred to the baby before and after birth?

IgG is transported across the placenta into the fetus via the Brambell receptor, and IgA is secreted in breast milk and received after birth.

What is antibody-dependent cell-mediated cytotoxicity (ADCC)?

A mechanism in which Fc receptors on NK cells bind antibody-coated human cells (such as anti-CD20 bound to CD20 on a cancerous B cell) and activate the NK cell to destroy the target cell.

What is the distinction between active and passive immunization, and which is used to treat venom exposure?

In active immunization, the body makes its own antibodies, whereas in passive immunization, antibodies are administered to the individual; passive immunization is used for venoms.

What proportion of secondary lymphoid tissue lymphocytes and secreted antibodies are associated with mucosal surfaces?

$75\%$ of lymphocytes in secondary lymphoid tissue serve mucosal surfaces, and $75\%$ of all antibodies secreted is secretory IgA.

What are mucins, what cell type secretes them, and what is their immunological role?

Mucins are glycoproteins secreted by goblet cells that make mucus viscous to impede microbial movement and allow binding to defensins, antimicrobial peptides, and IgA antibodies.

What are the two distinct compartments of the Gut-Associated Lymphoid Tissue (GALT)?

The inductive compartment (includes Peyer's patches and mesenteric lymph nodes) and the effector compartment (includes the lamina propria).

What are the largest lymph nodes in the human body?

Mesenteric lymph nodes.

What are the structural features and functions of microfold (M) cells in Peyer's patches?

M cells transport antigens and microbes from the gut lumen to the GALT, lack a glycocalyx, and do not secrete digestive enzymes or mucus.

Which cytokine is secreted by T regulatory cells in the gut to suppress inflammation?

IL-10; lack of its receptor leads to chronic gut inflammation resembling Crohn's disease.

Why do monocytes that mature into macrophages in intestinal lymphoid tissue fail to perform a respiratory burst?

They become inflammation-anergic.

What is oral tolerance?

A state of immunological tolerance in which food antigens taken up by M-cells and dendritic cells induce the differentiation of CD4 T cells into T regulatory cells.

Which adhesion molecule and vascular addressin pairing directs effector lymphocytes specifically to the gut lamina propria?

Lymphocyte integrin $\alpha_4:\beta_7$ binds to vascular addressin MAdCAM-1 on gut endothelial cells, followed by chemotactic guidance by CCL25.

Why is a lack of IgA not typically fatal or debilitating in IgA-deficient individuals?

Levels of IgM and IgG in mucosal secretions are increased to compensate.

How do TH1 and TH2 immune responses differ in their outcome during a helminth infection?

A $\text{T}_{\text{H}}1$ response causes tissue damage and chronic infection via $\text{IFN}-\gamma$ macrophage activation and IgG production; a $\text{T}_{\text{H}}2$ response results in parasite killing or expulsion via IL-13 (increasing goblet cell turnover and mucus), IL-5 (recruiting eosinophils), IgE production, and IL-3/IL-9 (recruiting mast cells).