Immunology: Antibody Structure and Function

Immune Response

• Primary and secondary immune responses involve antigens, immunogens, adjuvants, and haptens.
• Immunoglobulins have structure, classes, subclasses, hypervariable regions, isotypes, allotypes, and idiotypic variations.
• Subsets of T cells (T-helper, T-killer, suppressor cells) and B cells exist.
• T and B cell receptors process and present antigens.
• T and B cell interactions involve cytokines and co-stimulatory molecules like lymphokines and interleukins.
• The complement system is also involved.

Primary and Secondary Humoral Immune Responses

• Primary response is characterized by a smaller magnitude and usually IgM > IgG antibodies after the first infection.
• Secondary response involves a greater magnitude, relative increase in IgG (often IgA and sometimes IgE), higher average affinity antibodies (affinity maturation) after repeat infection.
• Primary responses involve all antigens, while secondary responses mainly to protein antigens.
• A primary response involves activation and differentiation of naive B cells into antibody-secreting cells.
• A secondary response involves memory B cells leading to production of specific antibodies than the primary response.

Antigens

• Antigens are substances that bind specifically to an antibody or T-cell receptor and are often used as a synonym for immunogens.
• Antigen processing involves degrading antigens into antigenic peptides displayed on MHC molecules on antigen-presenting cells (APCs).
• Professional APCs include macrophages, dendritic cells, and B cells.
• Nonprofessional APCs include thymic epithelial cells and vascular endothelial cells.

Adjuvants

• Adjuvants are bacterial components or substances, often in an oil medium, that increase the effectiveness of vaccinations.
• They cause mild inflammation and attract phagocytes, accelerating activation and antigen presentation to T cells.
• Some vaccine components act as their own adjuvant.
• Alum and BCG are examples of adjuvants.

Haptens

• Haptens are small chemical groups that can bind to antibodies but cannot stimulate an adaptive immune response alone.
• They require attachment to a larger macromolecule (carrier) for an immune response.
• Examples include dinitrophenol (DNP).

Tolerogens

• Tolerogens induce adaptive immune unresponsiveness.
• Exposure to a tolerogen leads to a diminished response rather than an enhanced one, unlike immunogens.
• Tolerance to self-molecules develops during immune repertoire development.
• Non-self antigens are recognized as foreign.

Immunoglobulins

• Immunoglobulins are synthesized and secreted by plasma cells, which are terminally differentiated B cells.
• The term antibody is used for an immunoglobulin with specificity for an epitope of antigens.
• Antibodies bind to antigens, neutralize them, or tag them for destruction.
• Antibodies are important components of the humoral immune system.

Immunoglobulin Monomer Structure

• Immunoglobulin monomers contain two identical heavy chains and two identical light chains, connected by disulfide bonds.
• Each chain has a variable domain and one or more constant domains.
• Light chains are κ (kappa) or λ (lambda) and heavy chains are μ, delta, gamma, epsilon, and alpha (for example).
• Variable regions are highly variable between different immunoglobulins.

MHC Molecules

• Class I MHC molecules display peptides derived from proteins in the cytosol for recognition by CD8+ T cells.
• Class II MHC molecules display peptides derived from extracellular proteins for recognition by CD4+ T cells.

T Cell Receptor (TCR)

• TCRs, including a and β chains, are involved in antigen binding.
• TCRs have variable and constant regions similar to antibodies.

Immunoglobulin Isotypes, Allotypes, and Idiotypes

• Isotypes are based on differences in heavy chain constant regions.
• Allotypes are based on variations in constant regions due to genetic variation of the same gene.
• Idiotypes are the unique variable region sequences of an immunoglobulin, which are involved in antigen-binding sites.

Complement System

• The complement system involves plasma and cell surface proteins that interact to opsonize microbes, recruit phagocytes to infection sites, and directly kill microbes in some cases.
• The classical, alternative, and lectin pathways lead to inflammation and opsonization, and formation of a membrane attack complex(MAC) to lyse microbes.
• Key components include C1q, C3, C3a and C3b, C5, C6, C7, C8, C9.
• Proteins like MBL & ficalins are part of the lectin pathway.

Cytokines

• Cytokines are low-molecular-weight protein messengers that regulate and coordinate immune responses.
• They influence growth, differentiation, inflammation, and repair.

T Cell Subsets

• CD4+ T cells are helper T cells that secrete cytokines impacting other immune cells.
• CD8+ T cells (CTLs) recognize and kill virus/bacteria-infected cells and cancer cells.
• Other T cells exist (NKT cells, MAIT cells, γδ T cells)
• Cytokines regulate the development of Th1, Th2, and Th17 cells.

B Cell Subsets

• Follicular B cells, marginal zone B cells and B-1 cells contribute to humoral immunity through various interactions and antibody production, depending on T cell dependency.
• T cell independent development occurs in the spleen, peritoneal cavity and mucosal sites.

Interactions between B and T Cells

• Direct interaction between B and T cells often requires co-stimulatory molecules.
• These interactions lead to B cell proliferation and differentiation into plasma cells.
• Antigen processing and presentation are essential for these interactions.

Receptors

• There are many types of receptors involved: complement receptors, cytokine receptors, BCRs, TCRs.

• They are each specific in their function and activation

• Specific receptors are located on the surface of different immune cells.

B cells and T cells

• B cells and T cells cooperate and work together to produce a high-quality, specific, adaptive immune response
• Cell surface molecules regulate the interaction between B and T cells.

Antigen-Presenting Cells (APCs):

• APCs process and present antigens.
• APCs also express costimulatory molecules to activate T lymphocytes (CD28).