Week 4 - Antigen Recognition in the Adaptive Immune System

Flashcards covering introductory concepts of antigen receptors, differences and similarities between B and T cell receptors, antibody structure and classes, lymphocyte maturation processes, gene recombination, and therapeutic uses of monoclonal antibodies.

What is the primary role of antigen receptors?

Antigen receptors serve critical roles in the maturation of lymphocytes, specifically B and T cells.

What types of receptors do B lymphocytes express to recognize antigens?

B lymphocytes express membrane-bound antibodies.

What types of receptors do T lymphocytes express to recognize antigens?

T lymphocytes express T cell receptors (TCR).

How is the diversity of antigen receptors generated?

Diversity of antigen receptors is generated during lymphocyte development.

What is a basic difference in antigen recognition between B cell receptors and T cell receptors?

Membrane-bound B cell receptors can recognize many chemical structures, while T cell receptors only recognize protein antigen bound to MHC molecules.

Do B cells or T cells secrete antibody?

B cells can secrete antibody (immunoglobulin), while T cells never interact with free or soluble antigens and do not secrete antibody.

What are the antigen-recognizing domains of antigen receptors called?

The antigen-recognizing domains are called variable (V) regions, specifically the hypervariable regions within the V domains bind antigen.

What are the conserved portions of antigen receptor molecules called?

The conserved portions are the constant (C) regions, which allow structural integrity and effector functions (for B cells).

What proteins are associated with antigen receptors to deliver intracellular signals upon antigen recognition?

Invariant membrane proteins, forming the B cell receptor (BCR) complex for B cells and the T cell receptor (TCR) complex for T cells.

Can immunoglobulins (Ig) be expressed as membrane receptors or secreted proteins?

Immunoglobulins (Ig) may be expressed as membrane receptors or secreted proteins.

Are T cell receptors ever secreted?

T cell receptors only function as membrane receptors and are never in secreted form.

What molecules form the BCR complex?

The BCR complex consists of Ig⍺ and Igβ associated with an immunoglobulin (antibody).

What molecules form the TCR complex?

The TCR complex consists of CD3 and ζ, which are associated with the T cell receptor.

What is crosslinking in the context of antigen receptor signaling?

Crosslinking occurs when at least 2 antigen molecules (epitopes) bind to adjacent receptors, pulling the receptors together and initiating signal transduction.

What is the typical structure of a T cell antigen receptor (TCR)?

A TCR is a heterodimer composed of one alpha chain and one beta chain, each with one V region and one C region, anchored in the plasma membrane.

What chains are crucial for initiating signaling when the TCR recognizes an antigen?

The CD3 and ζ chains are crucial for the initiation of signaling when the TCR recognizes an antigen.

What additional coreceptors are required for T cell activation?

T cell activation requires engagement of the coreceptor molecules CD4 or CD8.

How do antibodies and TCRs differ in their binding affinity and range of recognized structures?

Antibodies can bind many types of chemical structures, often with high affinities, while TCRs only recognize peptide-MHC complexes and bind with low affinity.

What percentage of T cells do Gamma Delta (ΓΔ) T cells account for, and what are their characteristics?

Gamma Delta (ΓΔ) T cells account for 5-10% of T cells, have γ and δ (vs. ⍺ and β) chains, may recognize non-protein antigens usually displayed by classic MHC molecules, and are abundant in epithelia.

What are NK-T cells, and what type of antigen do they recognize?

NK-T cells express markers for natural killer cells and ⍺β TCRs with limited diversity; they recognize lipid antigens displayed by class I MHC-like molecules.

What characterizes Mucosal Associated Invariant T (MAIT) Cells?

MAIT cells express ⍺β TCRs with limited diversity and are specific for bacterially derived vitamin B metabolites bound to MHC-like proteins, accounting for up to 20-40% of human liver T cells.

What is the first step in the maturation of lymphocytes, driven by transcription factors?

Lineage commitment, where common lymphoid progenitors become B or T cells, and their Ig and TCR genes become accessible for recombination.

What is the purpose of positive selection during lymphocyte maturation?

Positive selection promotes the survival of cells with receptors that can recognize antigens, such as microbial antigens, and ensures that T cells recognize self-MHC.

What is the outcome of negative selection during lymphocyte maturation?

Negative selection eliminates cells that strongly recognize self-antigens (self-reactive B and T cells) to prevent autoimmune responses, or non-functional cells that undergo apoptosis.

What is somatic gene recombination in lymphocyte development?

Somatic gene recombination initiates the formation of functional genes that encode B and T lymphocyte antigen receptors by bringing together gene segments (V, D, J, C).

Which gene segments are involved in generating receptor diversity and are located between V and C segments?

Diversity (D) and joining (J) gene segments.

What is combinatorial diversity in antigen receptor generation?

Combinatorial diversity occurs due to different combinations of V, D, and J gene segments in different clones of lymphocytes.

What is junctional diversity and how is it generated?

Junctional diversity involves changes in nucleotide sequences introduced at the junctions of recombining V, D, and J segments, generated by exonuclease removal, TdT enzyme addition of random nucleotides, and additional DNA modification.

What are pro-T cells or double-negative T cells?

They are the least developed progenitors in the thymus that do not express CD4 or CD8.

In T cell maturation, what happens after TCR β gene recombination?

The pre-TCR complex is formed, which delivers signals to promote survival and proliferation, followed by TCR ⍺ gene recombination.

What happens to T cells whose TCRs recognize class I MHC-peptide complexes during positive selection?

They preserve the expression of CD8 and lose the expression of CD4.

What happens to T cells whose TCRs recognize class II MHC-peptide complexes during positive selection?

They preserve the expression of CD4 and lose the expression of CD8.

Describe the basic structure of an antibody.

An antibody is a Y-shaped molecule composed of two identical heavy (H) chains and two identical light (L) chains, held together by disulfide bonds.

What regions form the antigen-binding site of an antibody?

The antigen-binding site is composed of the variable (V) regions of both the heavy and light chains, particularly the Complementary Determining Regions (CDR).

What are the two functional regions of an antibody molecule?

The Fab region is the antigen binding domain, and the Fc region is involved in membrane attachment (for membrane-bound Ig) or effector functions like complement binding (for secreted Ig).

What are the five major classes (isotypes) of antibodies?

IgM, IgD, IgG, IgE, IgA.

Which two antibody isotypes are typically found as membrane-bound receptors on naive B lymphocytes?

Membrane-bound IgM and IgD.

What are epitopes?

Epitopes are the specific parts of an antigen that are recognized and bound by antibodies.

What is affinity in antigen-antibody binding?

Affinity is the strength with which one antigen-binding site of an antibody binds to one epitope of an antigen.

What is avidity in antigen-antibody binding?

Avidity is the total strength of binding between a multivalent antibody and multiple epitopes on an antigen, which is much greater than the affinity of a single bond.

What are the major effector functions of IgG?

Opsonization, complement activation, neonatal (passive) immunity via the placenta, and neutralization of viruses and toxins. It is the major antibody of the secondary response.

What is the primary role of IgA?

IgA is vital in mucosal immunity, providing primary defense against local infections in the GI and respiratory tracts, and neonatal passive immunity via breast milk.

What is the secreted form of IgM and what are its main functions?

The secreted form of IgM is a pentamer with 10 antigen binding sites. It is a major player in complement activation and is the major antibody of the primary response.

Which antibody isotype is mainly responsible for allergic reactions and protection against helminths?

IgE.

When naive B cells differentiate into plasma cells, how can they change the type of antibody they produce?

They can undergo class switching (isotype switching) to express other isotypes like IgA, IgG, or IgE, a process often 'helped' by T helper cells and requiring B cell gene recombination.

What happens to the V regions during class switching?

The V regions remain the same, allowing the antibody to maintain the same specificity for the antigen, while the C regions change.

How are monoclonal antibodies generated?

By fusing antigen-specific B cells with immortal myeloma cells to create hybridomas, which are then selected, screened, and cultured to produce large quantities of a single specific antibody.

What is the first checkpoint in B lymphocyte maturation?

It selects pre-B cells that express functional μ heavy chains (part of the pre-BCR), promoting their survival and proliferation.

What is receptor editing during B cell maturation?

If an immature B cell binds a self-antigen with high affinity in the bone marrow, it may undergo additional light chain recombination (receptor editing) to generate a different light chain and change the antigen receptor's specificity.

What is the target and effect of the drug Rituximab in immunological diseases like rheumatoid arthritis?

Rituximab targets CD20, leading to the depletion of B cells.

What is a common therapeutic target for blocking inflammation in rheumatoid arthritis and Crohn's disease?

TNF (Tumor Necrosis Factor).

What is the target of Cetuximab and how does it treat cancers like colorectal cancer?

Cetuximab targets EGFR (Epidermal Growth Factor Receptor), inhibiting EGF signaling and causing depletion of tumor cells.