Lecture 5: Antigen Recognition in the Adaptive Immune System

A set of practice flashcards covering antibody and TCR structures, functions, clinical uses of monoclonal antibodies, and lymphocyte maturation.

What are the two types of antigen receptors in the adaptive immune system?

Antibodies and T cell antigen receptors (TCRs).

What abbreviation is used for the three variable antigen-binding loops in antibodies?

CDRs.

In antibodies, what does CDR stand for?

Complementarity-determining regions.

What serve as the B cell receptors for antigens?

Antibodies.

Which antibody isotype has two subtypes labeled 1 and 2?

IgA.

What is the average serum concentration of IgA?

$3.5\,mg/ml$.

What is the serum half-life of IgA?

$6\,\text{days}$.

In what three secreted forms can IgA exist?

Mainly dimer, also monomer and trimer.

Which protein chain connects the multi-unit forms of IgA and IgM?

J chain.

What is the primary function of IgA?

Mucosal immunity.

Which antibody isotype occupies only a trace concentration in serum?

IgD.

What is the serum half-life of IgD?

$3\,\text{days}$.

What is the primary function of IgD?

Naive B cell antigen receptor.

What is the serum concentration of IgE?

$0.05\,mg/ml$.

What is the serum half-life of IgE?

$2\,\text{days}$.

What are the two major functions of IgE?

Defense against helminthic parasites and immediate hypersensitivity.

Which antibody isotype has subtypes 1 through 4?

IgG.

What is the average serum concentration of IgG?

$13.5\,mg/ml$.

Which antibody isotype has the longest half-life, and what is its duration?

IgG, with a half-life of $23\,\text{days}$.

What is the secreted form of IgG?

Monomer.

List four functions of IgG.

Opsonization, complement activation, antibody-dependent cell-mediated cytotoxicity, and neonatal immunity.

Which antibody isotype is involved in feedback inhibition of B cells?

IgG.

What is the average serum concentration of IgM?

$1.5\,mg/ml$.

What is the serum half-life of IgM?

$5\,\text{days}$.

In what form is IgM secreted?

Pentamer.

What are the two primary functions of IgM?

Naive B cell antigen receptor (monomeric form) and complement activation.

What represents the heavy chain for IgA?

$\alpha1$ or $\alpha2$.

What represents the heavy chain for IgD?

$\delta$.

What represents the heavy chain for IgE?

$\epsilon$.

What represents the heavy chain for IgG?

$\gamma1$, $\gamma2$, $\gamma3$, or $\gamma4$.

What represents the heavy chain for IgM?

$\mu$.

Into what type of cells are spleen cells from a mouse fused to create hybridomas?

Mutant immortal myeloma line.

Why is the mutant myeloma line used in hybridoma generation unable to grow in selection medium?

It lacks specific growth properties that are restored by fusion with spleen B cells.

What is the name of the medium used to grow hybridomas?

Selection medium.

What is the result of screening supernatants of hybridoma clones?

Identification of clones producing anti-X antibody.

Which clinical target is associated with the depletion of B cells for treating rheumatoid arthritis and B cell lymphoma?

CD20.

Which clinical target is blocked to treat allergy-related asthma?

IgE.

Blocking the IL-6 receptor is a treatment for which disease?

Rheumatoid arthritis.

What is the effect of monoclonal antibodies targeting TNF (tumor necrosis factor)?

Blocking inflammation.

In which three diseases is TNF targeted clinically?

Rheumatoid arthritis, Crohn's disease, and psoriasis.

Which monoclonal antibody target results in the depletion of lymphocytes?

CD52.

CD52 targeting is used to treat which disease?

Chronic lymphocytic leukemia.

What is the clinical effect of targeting CTLA-4 with monoclonal antibodies?

Activation of T cells.

For which disease is CTLA-4 targeting primarily used?

Melanoma.

What does EGFR stand for in the context of cancer targets?

Epidermal Growth Factor Receptor.

What is the clinical effect of targeting EGFR?

Growth inhibition of epithelial tumors.

List three types of cancer treated by targeting EGFR.

Colorectal, lung, and head and neck cancers.

What is the dual effect of targeting HER2/Neu in breast cancer?

Inhibition of EGF signaling and depletion of tumor cells.

PD-1 and PD-L1 targeting leads to the activation of which cells?

Effector T cells.

List two targets used to activate effector T cells in melanoma and other tumors.

PD-1 and PD-L1.

What does VEGF stand for?

Vascular Endothelial Growth Factor.

What is the clinical effect of blocking VEGF?

Blocking tumor angiogenesis.

Besides breast and colon cancer, what eye-related disease is treated by targeting VEGF?

Age-related macular degeneration.

What is the clinical target for inhibiting platelet aggregation?

Glycoprotein IIb/IIIa.

Which disease category uses Glycoprotein IIb/IIIa as a clinical target?

Cardiovascular disease.

What are the two chains that make up the T cell antigen receptor (TCR)?

$\alpha$ chain and $\beta$ chain.

How are the $\alpha$ and $\beta$ chains of the TCR linked?

By a disulfide bond.

What region of the TCR anchors the receptor into the cell membrane?

The transmembrane region.

Regarding the TCR structure, what does 'V' and 'C' stand for in regions?

'V' stands for Variable and 'C' stands for Constant.

Is the TCR antigen receptor secreted?

No, it exists as a membrane protein.

Which molecule assembles with a peptide to be recognized by a TCR?

MHC (Major Histocompatibility Complex).

What is the specific complex recognized by a T cell antigen receptor?

The peptide-MHC complex.

What is the component of MHC Class I that is non-covalently attached to the $\alpha$ chain?

$\beta_2m$ (Beta-2 microglobulin).

How many CDRs make up the antigen-binding site of an Immunoglobulin (Ig)?

Three CDRs in $V_H$ and three CDRs in $V_L$.

How many CDRs make up the antigen-binding site of a T cell receptor (TCR)?

Three CDRs in $V_{\alpha}$ and three CDRs in $V_{\beta}$.

What changes occur in the constant regions of Immunoglobulins during an immune response?

Heavy-chain class switching and change from membrane to secretory Ig.

Do T cell receptors undergo changes in their constant regions during immune responses?

No.

What is the affinity range ($K_d$) of antigen binding for Immunoglobulins?

$K_d: 10^{-7} - 10^{-11}\,M$.

What happens to the average affinity of Igs during immune responses to protein antigens?

Average affinity increases.

What is the affinity range ($K_d$) of antigen binding for T cell receptors (TCR)?

$K_d: 10^{-5} - 10^{-7}\,M$.

Does the affinity of TCRs change during immune responses?

No.

Describe the on-rate and off-rate of Immunoglobulin antigen binding.

Rapid on-rate and variable off-rate.

Describe the on-rate and off-rate of T cell receptor antigen binding.

Slow on-rate and slow off-rate.

What is the common progenitor cell for both B and T cells?

Common lymphoid progenitor.

What is the first staged name for developing B or T cells before they express receptors?

Pro-B/T cells.

What is expressed in a Pre-B/T cell?

One chain of the antigen receptor.

What occurs if a cell fails to express a pre-antigen receptor?

Cell death.

What is expressed in an Immature B/T cell?

The complete antigen receptor.

What selection process occurs in the thymus/bone marrow to ensure functional receptors?

Positive selection.

What does 'Weak antigen recognition' lead to during lymphocyte selection?

Positive selection.

What does 'Strong antigen recognition' of self-antigens lead to during lymphocyte maturation?

Negative selection.

On which chromosome is the Ig Heavy (H) chain locus located?

Chromosome 14.

On which chromosome is the Ig $\kappa$ chain locus located?

Chromosome 2.

On which chromosome is the Ig $\lambda$ chain locus located?

Chromosome 22.

On which chromosome is the TCR $\beta$ chain locus located?

Chromosome 7.

On which chromosome is the TCR $\alpha$ chain locus located?

Chromosome 14.

What are the three main types of gene segments that undergo somatic recombination in the Ig H locus?

V (Variable), D (Diversity), and J (Joining).

What gene segments are present in the Ig $\kappa$ chain locus?

V (Variable) and J (Joining).

Approximately how many V gene segments are in the Ig H chain locus?

$\sim 45$.

Approximately how many D gene segments are in the Ig H chain locus?

$23$.

Which enzyme mediates the recombination of antigen receptor genes?

Lymphoid-specific recombinase.

What is the first step of somatic recombination in a B cell at the Ig H locus?

D-J joining.

What is the second step of somatic recombination in a B cell at the Ig H locus?

V-DJ joining.

During Ig H locus recombination, what is the processed product after transcription and splicing?

Messenger RNA (mRNA).

What is the third hypervariable region in both the Ig H chain and L chain?

CDR3.

What allows for the simultaneous expression of IgM and IgD on the surface of a mature B cell?

Alternative splicing of the primary RNA transcript.

What is the first chain to undergo recombination during T cell maturation?

The $\beta$ chain.

What is the name of the receptor formed once the TCR $\beta$ chain is expressed with a surrogate alpha chain?

Pre-TCR.

Where does peptide recognition by T cells occur?

On the surface of antigen-presenting cells.

What are anchor residues?

Residues that attach peptides to pockets in the MHC molecules.