Essential Concepts in Immune System Function

Immune Responses and Definitions

Innate Immune Response

Natural Barriers: Antimicrobial skin, mucous secretions, pH, iron sequestration (not free), normal microbiota.

Inflammatory Innate Immunity Cells: Eosinophils, basophils, mast cells.

Phagocytes: Dendritic cells, macrophages, neutrophils.

Cytotoxic Cells: NK cells, NKT lymphocytes, Tγ/δ lymphocytes, B1 lymphocytes.

Adaptive Immune Response

Involves humoral immunity and T cells. Key cells include B lymphocytes (B2) and T lymphocytes (CD4/CD8).

Immunity

A response aggressively directed against foreign substances.

Tolerance

A lack of active immune mechanism against a substance (tolerogen), which can be self or foreign, acquired over time.

Hypersensitivity

An exaggerated, nonspecific response leading to collateral secondary damage, often triggered by an allergen.

Lymphoid Structures and Molecular Recognition

Primary Lymphoid Organs

Where immune cells form and mature:

• Bone Marrow: Contains stromal cells (macrophages, reticular cells, adipocytes) and hematopoietic cells.
• Thymus: Site where T lymphocytes (thymocytes) mature and differentiate.

Secondary Lymphoid Organs

Sites where activated B and T lymphocytes interact with antigens:

• Lymph nodes/ganglia
• Spleen
• Mucosa-Associated Lymphoid Tissue (MALT)

Diapedesis

The exit of lymphocytes from the bloodstream into the lymph stream.

Immunogenicity

The ability of a substance to provoke an immune response. Factors include: foreignness, size, route of inoculation (e.g., parenteral), dose, complexity, chemical nature (protein/heteropolymer), and adjuvants (e.g., Freund's).

Epitope

The specific site on an antigen recognized by an antibody (typically 5-6 amino acids or carbohydrate units). Often involved in polyvalent antigen responses.

Hapten

A small substance that does not induce antibody formation on its own. It must unite with a carrier protein to produce an immune response against the hapten.

Pattern Recognition Receptors (PRR)

Receptors found on innate immunity cells (e.g., macrophages), determined genetically, enabling immediate response activation. Includes Toll-Like Receptors (TLR).

Pathogen-Associated Molecular Patterns (PAMPs)

Molecular structures found only in pathogens. Their recognition induces phagocytosis and inflammation. Examples include LPS (lipopolysaccharide), PGN (peptidoglycan cell wall), and double-stranded RNA.

Humoral Immunity and Immunoglobulins

Humoral Immunity

Part of the adaptive immune response mediated by B lymphocytes and their B Cell Receptors (BCR).

Immunoglobulin (Antibody)

A glycoprotein composed of heavy and light chains linked by disulfide bonds. It exists as a monomer (e.g., IgG, IgD, IgE, part of the BCR) or a dimer (IgA in secretions).

Immunoglobulin Isotypes (Classes)

The five main classes are IgG, IgA, IgM, IgE, and IgD:

• IgM: Synthesized early (fetus, B1 and activated B2 cells). Pentameric structure.
• IgG: Crosses the placenta (via Fc receptor). Predominant in serum.
• IgA: Monomer or dimer. Crucial for mucosal immunity and secretions.
• IgD: Found on naive B lymphocytes, recognizing antigen as part of the BCR.
• IgE: Associated with allergic phenomena, recognized by inflammatory cells.

Idiotype

Defined by the unique antigen-binding site, formed by the Variable (V), Diversity (D), and Joining (J) segments of the heavy chain, specifically the Complementarity Determining Regions (CDR).

Allelic Exclusion and Gene Rearrangement

The process of generating diversity:

• Heavy Chain: VDJ rearrangement (50% success rate).
• Light Chain: VJ rearrangement (Kappa/Lambda).
• If successful, only one allele is expressed (allelic exclusion).
• IgM is expressed early in immature B lymphocytes.

V(D)J Recombinase

Enzyme complex that recognizes recombination signal sequences (12/23 rule) and mediates the rearrangement of V, D, and J segments in immunoglobulin genes (heavy chain) and T cell receptor genes.

Isotype Switching (Class Switch Recombination)

After activation, memory B lymphocytes change the constant region of the antibody produced (e.g., switching from IgM/IgD to IgG, IgA, or IgE). The specificity (VDJ region) of the B lymphocyte does not change, but the affinity may change (due to hypermutation).

Somatic Hypermutation

Occurs after B lymphocyte activation (especially in memory cells), leading to increased antibody affinity for the antigen. The antibody recognizes the same antigen but binds better.

Clinical Immunology Concepts

Serum vs. Plasma

• Serum: Plasma without coagulation factors (used for serological testing).
• Plasma: Contains coagulation factors (used for transfusions).

Vaccines

Preparations containing antigens designed to induce protective immunity. Types include:

• Classical Vaccines (Whole Organism/Component):
  • Attenuated (weakened live viruses or bacteria)
  • Killed (inactivated viruses or bacteria)
  • Toxoids (chemically modified toxins)
  • Subunit (antigenic fragments)
• Recombinant Vaccines: Produced at the genetic level (e.g., amplified proteins).