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Innate vs Adaptive Immunity

• Innate immunity is the body's first line of defense against pathogens.
• If the innate response is insufficient, the adaptive immune response is activated.
• Adaptive immunity recognizes specific pathogens and mounts a targeted response.
• This process involves induction of adaptive response, which can clear pathogens, and generates immunological memory.

Immune Cell Origin

• Bone marrow stem cells are the origin for all immune cells, including lymphocytes.
• B and T lymphocytes are part of the adaptive immune system, distinct from innate immune cells.

Antibodies

• Antibodies (immunoglobulins) are proteins produced by B lymphocytes.
• They provide highly specific immunity to antigens, composed of heavy and light chains.
• Different antibodies have distinct antigen-binding sites on their structures.
• Any substance triggering an adaptive immune response is called an antigen.
• Antigens can be proteins, carbohydrates, lipids, and nucleic acids; pathogens contain various antigens.
• Each antigen typically has multiple epitopes, which are specific areas on the antigen recognized by antibodies.

Antibody Diversity

• The adaptive immune system creates a huge number of diverse lymphocytes, each with a unique specificity.
• Mature B cells produce antibodies with different structures not seen in other B cells.
• The immune system has the potential to produce a wide array (10^11) of different antibody specificities.
• Antibody diversity is generated by recombination of immunoglobulin (Ig) gene segments during B cell development in the bone marrow.
• Unique combinations of V,D,J gene segments result in unique antigen-binding sites for each antibody.
• Antibody heavy and light chain genes undergo recombination during B cell development.
• The specific combination of gene segments in each B cell leads to unique antibody binding specificities.

Antibody Action

• Antibodies have diverse mechanisms to provide immunity.
• Neutralization - antibodies block pathogen adherence.
• Opsonization - antibodies enhance phagocytosis.
• Complement activation - antibodies activate complement, enhancing opsonization and lysis.
• Directed cytotoxicity - antibodies trigger NK cell to kill target cells.

B Cell Activation

• B cell proliferation and activation mostly occurs in secondary lymphoid tissues, like lymph nodes.
• Activation depends on antigen recognition and the immunoglobulin receptor on the cell's surface.
• Receptor aggregation signaling leads to B cell activation.
• B cells generally need T-cell help to become fully activated.
• T cells deliver activating signals through cytokines and cell surface receptor interactions.
• B cell activation results in maturation and differentiation, either into antibody-secreting plasma cells or long-lived memory B cells.

Isotype Switching

• B cell activation can cause a switch in antibody class.
• B cells begin producing IgM, then can switch to IgG, IgA, or IgE.
• Isotype switching alters the constant region (Fc) of the antibody, leading to structural and functional differences in the antibody.
• The switch occurs by deletion of DNA sequences and does not change the antigen-binding site.

IgG Function

• IgG is recognized by immune cells, macrophages, and NK cells.
• Macrophages and NK cells use receptor-mediated binding to pathogens coated in IgG.
• This process can cause phagocytosis or NK cell-mediated killing of the pathogen.

IgA Function

• Dimeric IgA is transported across intestinal epithelium (transcytosis).
• In the intestinal lumen, IgA blocks pathogens or toxins.
• Transcytosis of IgA also occurs in salivary glands.

IgM and IgG Complement Activation

• The Fc regions of IgM and IgG antibodies act as binding sites for complement proteins.
• When antibodies bind to pathogen surfaces, complement activation is triggered. (forming pores in pathogen membranes that cause lysis)

IgE Function

• IgE antibodies are bound to mast cells through Fc receptors.
• Binding of antigen (allergen) triggers Mast cells to release mediators (like histamine).
• This response can lead to an allergic reaction.

Memory B Cells

• Memory B cells develop in response to antigen exposure.
• A secondary response to the same antigen occurs quicker and with more antibodies and includes larger fractions of non-IgM antibody classes