Adaptive Immunity - Humoral Response

No institutional email? Start your 1 week free trial, now!

Adaptive Immunity - Humoral Response

The humoral response is mediated by B cells, which produce antibodies that act combat infectious agents.

Class switching and somatic hypermutation provide diversity in antibody specificity and response, which protects the host from a wide variety of infections.

Passive immunity vs Active immunity Passive immunity occurs when an individual is given antibodies to infectious agents. Active immunity occurs when an individual's immune system produces antibodies in response to infection.

B cell Maturation

Antigen-independent B-cell maturation is antigen-independent (in other words, B cell maturation does not require antigen interactions). Occurs within the bone marrow.

Maturation begins with Pre-B cells, which are characterized by ?-chains.

Upon stimulation by Burton's tyrosine kinase (BTK), the pre-B cell transitions to an immature B cell; it expresses the antibody IgM (immunoglobulin M) as its B cell receptor (aka, BCR).

Immature B cells undergo negative selection, also called clonal deletion, which removes B cells that bind with self-antigen.

The surviving B cells become naïve mature cells, characterized by both IgM and IgD.

These cells exit the bone marrow and travel via the circulation to the secondary lymphoid organs for activation: B cells encounter activating antigens in the splenic nodules and lymphoid germinal centers.

B cell Activation

Thymus-Dependent activation Most antigens require input from Helper T cells to activate naïve B cells; this is referred to as Thymus-Dependent activation. 1. Naïve B cells bind and internalize antigen. 2. Within the B cell, the antigen is complexed with MHC II and displayed on the B cell surface. 3. When a Helper T cell recognizes and interacts with the antigen-MHC II complex, the B cell is activated. 4. The B cell proliferates and differentiates, giving rise to memory cells, which participate in subsequent immune responses, and, plasma cells, which secrete large quantities of antibodies that circulate in the blood to fight infection.

Thymus-independent B cell activation Occurs when antigens, such as polysaccharide bacterial products, directly activate B cells. Thymus-independent B cell activation results in minimal class switching.

Details of B and T cell interactions:

Two key signals are required:

The first signal involves MHC recognition by the T cell, and is necessary for the second signal.

The B cell displays the antigen-MHC II complex, which is recognized by the T-cell receptor (TCR) and CD4 proteins of the Helper T cell.

The second signal involves co-stimulation by B and T cell proteins: Binding of B7-2 with CD-28 triggers cytokine activation. Binding of CD40 with CD40L (L is for ligand) triggers class switching and affinity maturation.

Cytokines released by the Helper T cell influence class switching from IgM/IgD to the other isotypes (IgA, IgG, and IgE).

Antibodies

Key Functions:

Antibodies do not directly kill pathogens.

They neutralize microbes by blocking their extracellular receptors and inhibiting their attachment to host cells; antibody binding can also inhibit viral replication, stopping the spread of infection.

They opsonize microbes, which means they bind to them and make it easier for phagocytes to recognize and engulf them.

They activate the complement cascade, leading to formation of membrane attack complexes (MAC) and, consequently, microbe lysis.

Agglutination occurs when antibodies bind multiple cell-bound antigens simultaneously, causing them to clump; precipitation, which we haven't shown, occurs when antibodies simultaneously bind multiple soluble antigens. In both cases, binding makes antigen capture and phagocytosis easier.

Antibody-dependent cellular cytotoxicity occurs when antibody-coated cells are targeted by natural killer cells.

Primary and secondary humoral immune responses:

First Exposure At the time of first exposure, antibody concentration is low; exposure provokes the primary response, which is characterized by a rise in low-affinity antibody concentration.

When infection is cleared, antibody concentration dips back down (but notice that it is not as low as pre-exposure levels).

Second Exposure Upon subsequent exposure to the same antigen, the secondary response rapidly produces a spike in high-affinity antibodies; thus, the secondary response is "primed" by the first.

Antibody Structure & Isotypes:

Antibodies are also called immunoglobulins.

Because IgG is a the most abundant antibody, we'll use it as an example of representative antibody structure; however, be aware that IgM and IgA look quite different.

Antibodies are glycoproteins that comprise heavy and light chains.

Fragments and regions:

Fab: F = fragment, ab = antigen-binding; notice that IgG has two Fab's.

Paratope binds the eptiope of a specific antigen.

Fc end: c = crystallizable region, but it can also be remembered because the C fragment interacts with Fc Cell surface receptors.

Variable and constant regions; the variable regions differ across antibodies, while the constant region is constant.

Isotypes:

IgM is the first antibody formed during B cell development; it opsonizes antigens and fixes complement.

IgD, the second antibody type formed, can bind bacteria and activate B cells.

IgG, which we drew above, is the predominant antibody type during secondary responses; it opsonizes bacteria, fixes complement, and neutralizes toxins. Importantly, it passes from maternal to fetal blood via the placenta, and is an example of naturally acquired passive immunity.

IgA is the predominant antibody in secretions, including breast milk (another example of passive immunity); it neutralizes antigens and blocks their adhesion to mucosal surfaces.

IgE provides defense against parasites; it is associated with hypersensitivity and allergic reactions.

Adaptive Immunity - Humoral Response

Related Tutorials