21.4 The Adaptive Immune Response: B-lymphocytes and Antibodies

What did early scientists notice about individuals who survived bacterial infections?

they were immune to re-infection with the same pathogen.

What did early microbiologists discover when mixing immune patient serum with bacteria?

The bacteria clumped together in a process called agglutination.

Did agglutination occur when mixing the serum with a different bacterial species?

No, agglutination was specific to the original bacterial species.

What causes the agglutination observed in immune serum?

Antibodies, also known as immunoglobulins.

What is an antibody (immunoglobulin)? (Define it)

An immunoglobulin is a protein secreted by plasma cells that specifically binds to antigens; it is the secreted form of the B cell receptor.

What is another name for the B cell receptor?

Surface immunoglobulin.

How are secreted antibodies and surface immunoglobulins related?

They are encoded by the same genes and have the same antigen-binding site and specificity.

what is the minor difference between a naïve B cell and an antibody-secreting plasma cell?

Naïve B cells have antibodies (immunoglobulins) on their surface, while plasma cells secrete antibodies into the body without displaying them on the surface.

What are the five different classes of antibodies found in humans?

IgM, IgD, IgG, IgA, and IgE.

Why is it important to study different classes of antibodies?

Each class has specific functions critical to different adaptive immune responses.

How do B cells recognize antigen differently from T cells?

B cells recognize native, unprocessed antigen directly without needing MHC molecules or antigen-presenting cells.

Do B cells require antigen processing to recognize an antigen?

No, B cells can recognize antigens in their natural (native) form.

Where do B cells differentiate?

In the bone marrow.

How many different B cell clones are generated during maturation?

Up to 100 trillion different clones.

How does B cell diversity compare to T cell diversity?

It is similarly large and diverse.

What is central tolerance? (Define it)

Central tolerance is the destruction or inactivation of B cells that recognize self-antigens while still in the bone marrow.

Why is central tolerance important?

It prevents the release of B cells that could attack the body’s own tissues.

What is clonal deletion? (Define it)

Clonal deletion is the process where immature B cells that bind strongly to self-antigens are triggered to undergo apoptosis (cell death).

What is clonal anergy? (Define it)

Clonal anergy is when B cells exposed to soluble self-antigen in the bone marrow are not killed but become nonfunctional and unable to respond.

What happens to B cells that experience clonal anergy?

They survive but are permanently "switched off" and cannot mount an immune response.

What is peripheral tolerance? (Define it)

Peripheral tolerance refers to the mechanism where mature B cells that encounter self-antigens but receive no helper T cell signals undergo apoptosis outside the bone marrow.

How is peripheral tolerance connected to T cell tolerance?

B cells need help from helper T cells (especially Th2 cells) to activate; without this help for self-antigens, they are eliminated, reinforcing immune self-tolerance

What do B cells become after activation by antigen binding?

They differentiate into plasma cells.

Where do plasma cells often migrate after activation?

Back to the bone marrow.

Why are plasma cells called terminally differentiated?

Because after secreting antibodies, they die; they use their energy for antibody production instead of cell maintenance.

What is a memory B cell?

A B cell that forms after clonal expansion and survives to initiate a stronger and faster secondary immune response upon re-exposure to an antigen.

What are antibodies made of?

Two types of polypeptide chains with attached carbohydrates: heavy chains and light chains.

What is a heavy chain? (Define it)

A heavy chain is one of the two main polypeptides in an antibody, and differences in the heavy chains define the different antibody classes (IgM, IgD, IgG, IgA, IgE).

What is a light chain? (Define it)

A light chain is the smaller polypeptide in an antibody that helps form part of the antigen-binding site.

Which part of the antibody determines the specific antigen it can bind to?

The combination of the variable regions of the heavy and light chains.

What basic structure do all antibody molecules share?

They have two identical heavy chains and two identical light chains.

What is the Fc region? (Define it)

The Fc region is the part of the antibody formed by the two heavy chains joining together; it interacts with Fc receptors on immune cells to increase pathogen targeting.

Why is the Fc region important?

It allows immune cells like macrophages and mast cells to bind to antibody-coated pathogens, enhancing their effectiveness.

Where are the antigen-binding sites located on an antibody?

At the opposite end from the Fc region — there are two identical antigen-binding sites.

What are the two main functions of antibodies?

They act as B cell antigen receptors and as secreted proteins that bind to pathogens to mark them for immune attack.

Which two antibody classes serve as antigen receptors for naïve B cells?

IgM and IgD.

What is IgD? (Define it)

IgD is an antibody class that acts as a B cell receptor on naïve B cells, but its secreted form has no known major function.

What is IgM? (Define it)

IgM is a large, pentameric antibody (five four-chain units) that is the first antibody made during a primary immune response and is excellent at activating complement.

How does the structure of IgM help its function?

Its 10 identical antigen-binding sites make it highly effective at binding bacterial surfaces and activating immune processes early in infection.

What is class switching? (Define it)

Class switching is the process where a B cell changes the class (type) of antibody it produces (e.g., from IgM to IgG, IgA, or IgE) without changing the antigen specificity.

Does class switching affect the antigen-binding site?

No, only the antibody’s constant region (class) changes; the antigen-binding site remains the same.

What is IgG? (Define it)

IgG is the major antibody class of late primary and secondary immune responses, highly effective in blood and capable of crossing the placenta to protect the fetus.

What are the key functions of IgG?

Clearing pathogens from the blood, activating complement proteins (less effectively than IgM), and moving into tissues to fight infections.

What is IgA? (Define it)

IgA is an antibody found as a monomer in blood and as a dimer in mucosal secretions (like saliva, mucus, and tears) to protect body surfaces.

Why is IgA important for newborns?

It is present in breast milk (colostrum) and helps protect infants from infections early in life.

What is IgE? (Define it)

IgE is an antibody class involved in allergic responses and anaphylaxis; it binds strongly to mast cells via its Fc region.

How does IgE cause allergic reactions?

Allergens (like peanuts) trigger allergen-specific IgE bound on mast cells to cause degranulation, releasing chemicals that lead to allergic symptoms or even anaphylaxis.

Why is IgE usually found in low concentrations in the blood?

Because most IgE is tightly bound to mast cells through its Fc region.

How does clonal selection in B cells compare to T cells?

It works similarly: only B cells with specific antigen receptors are selected for expansion.

What two cell types are generated during a primary B cell response?

Plasma cells (which secrete antibodies) and memory B cells.

What happens during a secondary B cell response?

Memory B cells rapidly differentiate into plasma cells and memory cells, producing a much faster and stronger antibody response.

How does the primary antibody response differ from the secondary response?

The primary response is delayed and produces low antibody levels, while the secondary response is rapid and produces much higher antibody levels.

What happens if a person encounters a new, different antigen?

A new primary response must occur, with a time delay and lower antibody levels.

What is active immunity?

Active immunity is resistance to pathogens that develops through an individual's own adaptive immune response.

How is active immunity naturally acquired?

By getting an infection and developing an immune response.

How is active immunity artificially acquired?

Through vaccines that safely stimulate immunological memory without causing full-blown disease.

What is passive immunity? (Define it)

Passive immunity is the temporary resistance to pathogens provided by transferring antibodies from an immune individual to a nonimmune one, without requiring the recipient’s immune system to respond.

Give examples of naturally acquired passive immunity.

IgG transferred from mother to fetus through the placenta and IgA from breast milk to the newborn.

Give examples of artificially acquired passive immunity.

Injections of preformed antibodies (immunoglobulins) from immune animals to humans (e.g., for snakebites or after exposure to certain viruses).

What is the downside of passive immunity?

It does not lead to immunological memory and protection fades as the transferred antibodies degrade.

What is a T cell-independent antigen? (Define it)

A T cell-independent antigen is a repeating structure (like bacterial carbohydrates) that can directly activate B cells by crosslinking multiple surface antibodies without T cell help.

How do T cell-independent antigens activate B cells?

By crosslinking many B cell receptors at once, providing enough stimulation for activation.

What is a T cell-dependent antigen? (Define it)

A T cell-dependent antigen is usually a protein antigen that cannot crosslink B cell receptors efficiently and requires helper T cell (Th2) cytokines to fully activate the B cell.

What two signals must a B cell receive to be fully activated by a T cell-dependent antigen?

(1) Binding of its surface immunoglobulin to native antigen, and (2) cytokine signals from a nearby helper T cell.

How does a B cell act as a professional antigen-presenting cell during T cell-dependent activation?

It internalizes the antigen, processes it, and presents it on a class II MHC molecule to helper T cells.