Antibodies in Host Defense: B Cell Repertoire, Classes, and Monoclonal Therapies

What is the B cell receptor's role in the immune response?

It is involved in the recognition of antigens and activation of B cells.

What is the importance of the J chain in IgA?

The J chain facilitates the transport of IgA across mucosal surfaces.

What is the effect of monoclonal antibodies on tumor-associated antigens?

They can specifically target and neutralize tumor-associated antigens for therapeutic benefit.

What is the significance of the hybridoma technique?

It allows for the production of monoclonal antibodies with a specific target.

What is the primary defense mechanism of IgA?

IgA acts as a non-inflammatory defense at mucosal surfaces.

What is the main function of IgM in the immune response?

IgM is primarily involved in the initial stages of the immune response and complement activation.

What is the clinical relevance of Rituximab?

Rituximab is a monoclonal antibody used for immunotherapy in B cell lymphoma.

What are the potential issues with non-human antibodies in therapy?

They can lead to the development of human anti-mouse antibodies, reducing efficacy.

What is the role of B cells in the immune response?

B cells need to listen and respond to cues to be activated.

What is the B cell repertoire?

The B cell repertoire is vast and consists of different B cell receptors (BCRs) that can adapt to various threats.

What are the two types of B cell responses?

Monoclonal and polyclonal B cell responses.

What is the significance of VDJ recombination?

VDJ recombination creates a diversified heavy chain that is transcribed and translated into a heavy chain protein.

On which chromosome is the heavy chain located?

The heavy chain is located on Chromosome 14.

What is the role of the light chain in B cell receptors?

The light chain pairs with the heavy chain to generate further diversity in the antibody structure.

Where are the kappa and lambda light chains located?

The kappa light chain is on chromosome 2 and the lambda light chain is on chromosome 22.

What is the structure of an antibody?

An antibody is composed of 2 identical heavy chains and 2 identical light chains.

What are complementarity determining regions (CDRs)?

CDRs are hotspots of protein variability in the V domains that form the antigen binding surface of the protein.

What is the Clonal Selection Hypothesis?

The Clonal Selection Hypothesis posits that a population of receptor-bearing lymphocytes is selected and expanded in response to an antigen.

How do T cells assist B cells?

T cells provide help to B cells in an antigen-specific manner through cytokines and CD40 ligand.

What happens to a B cell after receiving T cell help?

The B cell can become either a plasma cell or a memory cell.

What is the function of plasma B cells?

Plasma B cells secrete antibodies at a high rate and can persist for the lifetime of the host.

What is the role of memory B cells?

Memory B cells recirculate through blood and secondary lymphoid tissues and require T cell help for reactivation.

What is the estimated antibody synthesis rate?

The synthesis rate of antibodies is significant, with high levels produced during an immune response.

What induces an activated B cell to become a plasma cell or memory cell?

T cell help

Where do plasma B cells take up residence?

Bone marrow, spleen, lymph nodes, and other secondary lymphoid tissue sites

What is the primary function of plasma B cells?

To secrete antibodies at a high rate into blood and tissues

How long can plasma B cells persist?

For the lifetime of the host

What are the major functions of antibodies?

Neutralization, activation of complement, opsonization, triggering target cell killing by NK cells, and degranulation of mast cells

What does the F(ab) region of an antibody do?

Responsible for antigen recognition

What does the Fc region of an antibody do?

Responsible for effector functions

What are the different antibody classes or isotypes?

IgM, IgD, IgG, IgE, and IgA

What determines the type of antibody produced by a plasma cell?

Which of several C exons is involved in production of the antibody heavy chain

What is class switching in B cells?

The process where a B cell switches from producing IgM to another class while retaining the same antigen specificity

What is the primary antibody response characterized by?

IgM being the first antibody class produced

Which antibody classes dominate the secondary antibody response?

IgG, IgA, and IgE

What is the basic unit of an antibody?

One H2L2 unit, known as a monomer

Where is IgM primarily found?

In blood and can enter tissues at sites of inflammation

Where is IgG found?

In blood and tissues

What is the role of IgA?

Found in body secretions such as mucus, tears, saliva, and breast milk; resistant to stomach acid

Where is IgE located?

In tissues and bound to mast cells

What type of immunity is provided by maternal antibodies?

IgG in utero and IgA in breast milk

What is the role of IgD?

Present on the B cell surface, plays a role in maturation, but secreted IgD is uncommon

What activates complement in relation to antibodies?

Fc of IgM and IgG can engage C1q component of complement

What is opsonization?

Enhanced phagocytosis of antigen facilitated by IgG

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

A mechanism where NK cells kill target cells that are coated with antibodies

What is the role of mast cells in allergic reactions?

Mediators of allergic reactions, full of granules containing histamines and prostaglandins

What differentiates allergic from non-allergic individuals regarding mast cells?

Allergic individuals have allergen-specific IgE preloaded on mast cells

What is the initial response of serum IgE to allergen exposure?

Rapid binding of serum IgE to allergen.

What type of cells are coated with IgE during allergen exposure?

Mast cells.

What is the primary function of IgA antibodies?

Major defense at mucosal surfaces; non-inflammatory with no cell damage.

Which antibody class is primarily responsible for complement activation?

IgM (primary) and IgG (secondary).

What does opsonization by IgG provide defense against?

Viruses, bacteria, toxins, and environmental antigens.

What is the role of IgE in the immune response?

Defense against large parasitic worms and induction of mast cell degranulation.

What is the difference between polyclonal and monoclonal antibody responses?

Polyclonal responses involve many B cell clones responding to multiple epitopes, while monoclonal responses involve a single B cell clone producing antibodies of unique specificity.

How are polyclonal antibodies obtained?

By collecting serum from the blood of immunized people or animals.

What is a characteristic of monoclonal antibodies (mAb)?

They are produced in the lab and have the same specificity, class, and affinity.

What is the process for producing monoclonal antibodies?

Cell fusion of activated B cells with myeloma cells to create hybridomas.

What was the Nobel Prize in Medicine awarded for in 1984?

The development of monoclonal antibodies by Georges Köhler and César Milstein.

What is the primary use of monoclonal antibodies in medicine?

For detection, targeting, and therapy of diseases.

What is an example of a monoclonal antibody used for B cell lymphoma?

Rituximab, which targets CD20 on B cell lymphoma cells.

What challenge did patients face with the mouse monoclonal antibody 3F8?

They developed human anti-mouse antibodies, leading to rapid clearance of the therapeutic mAb.

What is the advantage of 'humanized' monoclonal antibodies?

They are less likely to trigger an immune response and can remain effective in therapy.

What was the outcome of using humanized 3F8 in Grace's case?

It did not induce an immune response and was effective in killing tumor cells.

What percentage of children with high-risk neuroblastoma achieve remission with humanized 3F8?

80% of children.