Immunology Exam 2 Review

What is the basic structure of a B-cell receptor (BCR)?

A membrane-bound immunoglobulin made of 2 identical heavy chains and 2 identical light chains.

What forms the antigen-binding site of a BCR?

The variable regions of one heavy chain and one light chain.

What are the signaling proteins associated with the BCR?

Igα (CD79a) and Igβ (CD79b), which contain ITAMs for signaling.

What is the purpose of V(D)J recombination in B cells?

It creates diverse BCRs by rearranging immunoglobulin gene segments.

What enzymes are required for V(D)J recombination?

RAG1 and RAG2.

What happens during heavy-chain rearrangement?

V, D, and J gene segments are rearranged to create the immunoglobulin heavy chain.

What happens during light-chain rearrangement?

V and J gene segments are rearranged to create the immunoglobulin light chain.

What are the six B-cell developmental phases in the PowerPoint?

Repertoire assembly, negative selection, positive selection, searching for infection, finding infection, and attacking infection.

Where do B cells develop and mature?

B cells develop and mature primarily in the bone marrow before entering the periphery.

What is the first major B-cell checkpoint?

A productive heavy chain forms and pairs with a surrogate light chain to make the pre-BCR.

What is the second major B-cell checkpoint?

A complete IgM BCR is produced and tested for self-reactivity.

What is negative selection of B cells?

Removal or silencing of B cells that strongly recognize self-antigens.

What are three mechanisms of B-cell central tolerance?

Receptor editing, deletion by apoptosis, and anergy.

What is B-cell receptor editing?

A developing self-reactive B cell rearranges its light-chain genes to try to produce a non-self-reactive BCR.

What is B-cell anergy?

A state in which a self-reactive B cell becomes functionally unresponsive.

How long do anergic B cells typically survive according to the PowerPoint?

About 1–5 days.

How long do mature naïve B cells typically survive according to the PowerPoint?

About 40 days.

What is an epitope?

The specific antigenic determinant recognized by a BCR or antibody.

What happens when BCRs are cross-linked by antigen?

Igα/Igβ ITAM signaling is triggered, leading to downstream signaling and gene expression.

What is the CD19/CD21/CD81 B-cell coreceptor complex?

A coreceptor complex that amplifies BCR signaling.

What is T-independent B-cell activation?

B-cell activation caused by extensive BCR cross-linking that can occur without T-cell help.

What is a major feature of T-independent B-cell responses?

They are rapid and generally produce a more limited response with little or no memory according to the PowerPoint.

What is T-dependent B-cell activation?

B-cell activation requiring T-cell help, especially from T follicular helper (TFH) cells.

Where does T-dependent B-cell activation mainly occur?

In secondary lymphoid tissues such as lymph nodes and other lymphoid organs.

What happens after a B cell recognizes antigen and receives TFH help?

It proliferates and can enter a germinal center where affinity maturation and class switching occur.

What does CD40-CD40L interaction do in T-dependent B-cell activation?

Provides an important signal that supports B-cell activation and differentiation.

What cytokine from TFH cells is especially important for B-cell responses?

IL-21.

What is somatic hypermutation?

Mutation of immunoglobulin variable-region genes that allows selection of B cells with higher-affinity antibodies.

What is affinity maturation?

Selection of B cells that produce antibodies with increasingly higher affinity for antigen.

What is class-switch recombination?

Changing the antibody heavy-chain constant region while keeping the same antigen-binding specificity.

What immunoglobulins are normally expressed by naïve B cells?

IgM and IgD.

What are the five antibody classes?

IgM, IgD, IgG, IgA, and IgE.

What is the main role of IgM?

It is the first major antibody produced and is especially effective at activating complement.

What is the structure of secreted IgM?

A pentamer with 10 potential antigen-binding sites.

What is the main role of IgD?

It is primarily expressed as a membrane BCR on naïve B cells and is present at low levels in serum.

What is the main role of IgG?

It is a major antibody in secondary responses and is important for neutralization and immune-complex formation.

What is the main role of IgA?

Protection at mucosal surfaces.

What is the main role of IgE?

Responses involving parasites and allergic reactions.

What are the three major fates of germinal-center B cells?

Apoptosis, plasma-cell differentiation, or memory-B-cell differentiation.

Where do T-cell precursors originate?

They originate in the bone marrow and migrate to the thymus for maturation.

What cells are important in thymic T-cell development?

Thymic epithelial cells, dendritic cells, macrophages, and developing thymocytes.

What is the role of cortical thymic epithelial cells?

They provide signals for positive selection of developing T cells.

What is the role of medullary thymic epithelial cells and dendritic cells?

They participate in negative selection of strongly self-reactive T cells.

What is the role of macrophages in the thymus?

They remove developing thymocytes that die during selection.

What is Notch1's role in T-cell development?

Notch1 signaling promotes T-cell lineage commitment in developing thymocytes.

What ligand activates Notch1 during T-cell development?

Dll4 on thymic epithelial cells.

What happens to the thymus with aging?

The thymus undergoes involution, with declining thymocyte production and increasing replacement by fatty tissue.

What is the consequence of thymic involution?

Reduced production of naïve T cells and contribution to immunosenescence.

What happens during the double-negative (DN) stage of T-cell development?

T cells begin TCR gene rearrangement before expressing both CD4 and CD8.

What two TCR lineages compete during early development?

γδ T cells and αβ T cells.

What happens if productive γδ rearrangement occurs first?

The cell can become a γδ T cell.

What happens if productive β-chain rearrangement occurs first?

The β chain pairs with pre-Tα to form the pre-TCR, promoting proliferation and progression to the double-positive stage.

What happens at the double-positive (DP) stage?

Developing thymocytes express both CD4 and CD8 and rearrange the TCR α chain.

What is positive selection of T cells?

Selection of T cells whose TCRs can recognize self-MHC molecules.

What is negative selection of T cells?

Removal of T cells whose TCRs strongly recognize self-antigens.

How are B-cell and T-cell development similar?

Both use somatic receptor gene rearrangement and undergo positive/negative selection and tolerance mechanisms.

How do B-cell and T-cell development differ?

B cells mature in the bone marrow, while T-cell precursors mature in the thymus.

What happens when an immature dendritic cell encounters pathogen in peripheral tissue?

It takes up antigen, becomes activated, increases CCR7 expression, and migrates toward a draining lymph node.

What chemokines guide activated dendritic cells toward lymph nodes?

CCL19 and CCL21.

What is the main function of mature dendritic cells in lymph nodes?

Present antigen to T cells and activate naïve T cells.

How do macrophages differ from mature dendritic cells in lymph nodes?

Macrophages help filter lymph and remove pathogens/antigens, while mature dendritic cells specialize in activating naïve T cells.

What do CCL19 and CCL21 do in lymph nodes?

They create chemokine signals that guide naïve T cells into T-cell zones.

What is the immunological synapse?

A stabilized contact between a T cell and antigen-presenting cell that concentrates signaling and adhesion molecules.

What happens when a naïve T cell recognizes its peptide-MHC on a dendritic cell?

The T-cell/APC interaction becomes stabilized and signaling molecules concentrate at the contact site.

What are the two major signals required for naïve T-cell activation?

Signal 1: TCR recognition of peptide-MHC; Signal 2: CD28 binding to B7.

What does Lck do during T-cell activation?

It phosphorylates signaling components associated with the TCR complex.

What does ZAP70 do during T-cell activation?

It binds phosphorylated ITAMs on TCR-associated ζ chains and becomes activated to transmit downstream signals.

What is the role of CTLA-4?

It competes with CD28 for B7 and helps limit/terminate T-cell activation.

What is the role of IL-2 in T-cell activation?

IL-2 promotes T-cell proliferation and clonal expansion.

What happens to the IL-2 receptor after T-cell activation?

An additional receptor chain is expressed, creating a high-affinity IL-2 receptor.

What do CD8+ cytotoxic T lymphocytes recognize?

Peptide presented on MHC class I.

How do CD8+ cytotoxic T cells kill target cells?

They form a synapse with the target and release cytotoxic granules that induce apoptosis.

What are the five major CD4+ T-cell subsets in the PowerPoint?

TH1, TH2, TH17, TFH, and Treg.

What is the main function of TH1 cells?

Promote macrophage-mediated and cell-mediated immunity, especially against intracellular pathogens.

What is the main function of TH2 cells?

Promote eosinophil/IgE-associated responses, especially against parasites and in allergy.

What is the main function of TH17 cells?

Promote inflammatory responses important for extracellular microbes and barrier tissues.

What is the main function of TFH cells?

Help B cells in germinal centers with antibody class switching and affinity maturation.

What is the main function of Treg cells?

Suppress immune responses and help prevent autoimmunity.

What happens during a primary immune response?

Naïve lymphocytes are activated and produce effector and memory cells; the response is slower.

What happens during a secondary immune response?

Memory cells respond more rapidly and strongly to the same antigen.

How do naïve, activated, and memory B cells differ in BCR/antibody expression?

Naïve B cells express IgM/IgD; activated cells can produce secreted antibodies; memory cells generally have higher-affinity, class-switched BCRs such as IgG according to the PowerPoint.

What is FcγRIIB1?

An inhibitory Fc receptor expressed on naïve B cells that helps limit unnecessary B-cell activation.

What is the RhD problem addressed by RhoGAM?

An RhD-negative mother can become sensitized to RhD-positive fetal red blood cells.

Why can RhD sensitization be dangerous in a later pregnancy?

Maternal memory responses can produce IgG antibodies that cross the placenta and attack RhD-positive fetal red blood cells.

How does RhoGAM work?

Rho(D) immune globulin coats fetal RhD-positive red blood cells in the mother's circulation and prevents effective maternal sensitization.

When is RhoGAM given according to the PowerPoint?

Around 26–28 weeks of pregnancy and within 72 hours after delivery.

Where are long-lived plasma cells found?

Primarily in the bone marrow.

What is the function of long-lived plasma cells?

They continuously secrete low levels of high-affinity antibodies to maintain circulating antibody levels.

What is the metabolic state of naïve T cells?

They are metabolically quiet and rely heavily on oxidative phosphorylation, fatty-acid oxidation, and autophagy.

What metabolic change occurs after T-cell activation?

Activated T cells shift toward glycolysis and anabolic growth.

What is mTORC1's role in T-cell differentiation?

mTORC1 regulates metabolism, growth, and differentiation; higher mTORC1 activity favors effector fate while lower activity favors memory fate.

What is asymmetric T-cell division?

Early activated T-cell divisions can distribute factors unevenly between daughter cells, contributing to different effector and memory fates.

What are the three major memory T-cell types?

Central memory (TCM), effector memory (TEM), and tissue-resident memory (TRM).

What is the main feature of TCM cells?

They circulate through secondary lymphoid tissues, express CCR7/CD62L, and have strong proliferative capacity.

What is the main feature of TEM cells?

They are found in peripheral tissues/circulation and can provide rapid effector responses.

What is the main feature of TRM cells?

They remain in tissues such as skin, lung, gut, and other barrier sites for rapid local protection.

Why can memory T cells respond faster than naïve T cells?

They are functionally primed and, according to the PowerPoint, do not require CD28 co-stimulation for activation.

What surface marker distinguishes memory from naïve T cells in the PowerPoint?

Memory T cells express CD45R0, while naïve T cells express CD45RA.

What is active immunity?

Immunity produced by the person's own immune response, resulting in immune memory.

What is passive immunity?

Protection provided by receiving antibodies rather than making the response yourself; it is immediate but temporary.