Adaptive Immunity: The Third and Final Line of Defense

Overview of Adaptive Immunity

Adaptive immunity is a specialized defense mechanism acquired only after exposure to an immunizing event, such as infection or vaccination. It involves the activation and selection of B and T lymphocytes, which are prepared to react to specific antigens or immunogens.

• Immunocompetence: The body's ability to react with countless foreign substances.

• Specificity: Adaptive immunity targets specific pathogens; antibodies against one virus (e.g., chickenpox) do not work against another (e.g., measles).

• Memory: Lymphocytes "recall" previous encounters with pathogens, enabling a rapid and robust response upon re-exposure.

Key Terms in Immunology

Antigens, Immunogens, and Epitopes

• Antigen: Any molecule that can be recognized by the immune system.

• Immunogen: An antigen that provokes an immune response.

• Epitope: The specific region of an antigen recognized and bound by an antibody or receptor.

• Most antigens are proteins or polysaccharides found on or inside cells and viruses.

• Self-antigens typically do not elicit a response from the host's immune system.

Stages of Immunologic Development and Interaction

Four Stages of Adaptive Immune Response

1. Lymphocyte development and clonal deletion

2. Presentation of antigen and clonal selection

3. Challenge of B and T lymphocytes by antigens

4. T-lymphocyte response: cell-mediated immunity; B-lymphocyte response: production and activities of antibodies

Lymphocyte Development

Origin and Maturation

• All lymphocytes originate from the same stem cell type.

• B cells mature in the bone marrow.

• T cells mature in the thymus.

• Both cell types migrate to distinct areas of lymphoid organs and recirculate through the body.

Antigen Presentation and Clonal Selection

Process of Antigen Presentation

• Pathogens crossing the first line of defense attract resident phagocytes.

• Macrophages ingest pathogens and initiate inflammation.

• Dendritic cells process antigens and present them to T and B lymphocytes in lymphoid organs.

• B cells often require help from T helper cells for activation.

Cell Markers and Receptors

Role in Immune Response

• Cell surface markers are essential for detection, recognition, and communication.

• Markers activate different components of immunity.

Major Histocompatibility Complex (MHC)

• MHC: A set of genes coding for cell markers/receptors (glycoproteins) on all cells except red blood cells.

• Also known as the human leukocyte antigen (HLA) system.

• Vital for self-recognition and rejection of foreign tissue.

Classes of MHC Genes

CD Molecules (Cluster of Differentiation)

• Over 400 CD molecules identified; many involved in immune response.

• Key examples: CD3, CD4, CD8.

Lymphocyte Receptors

Antigen Recognition

• B cells: Receptors bind directly to antigens.

• T cells: Receptors bind antigens processed and presented with MHC molecules.

• There are millions to billions of unique antigen types recognized.

B and T Cell Responses to Antigen

Activation and Differentiation

• Both B and T cells proliferate and differentiate upon antigen challenge.

• Clones of genetically identical cells are produced; some become memory cells.

• B- and T-cell responses differ in mechanism and outcome.

T Cell Functional Types

• Helper T cells: Activate macrophages, assist B cells, help activate cytotoxic T cells.

• Regulatory T cells: Control T-cell response by secreting anti-inflammatory cytokines or preventing proliferation.

• Cytotoxic T cells: Destroy infected host cells and foreign cells.

• T cells secrete cytokines but do not produce antibodies.

B Cell Response

• Activated B cells divide and become plasma cells.

• Plasma cells release antibodies into tissues and blood.

• Antibodies bind specific antigens, marking them for destruction or neutralization.

Contrasting Properties of B Cells and T Cells

Immunologic Diversity and Antibody Variability

Generation of Diversity

• Gene segment rearrangement creates a vast array of lymphocyte specificities.

• Estimated 10 trillion different antibody specificities per human.

Immunoglobulin Structure

• Antigen binding sites: Highly variable pockets at the ends of the molecule.

• Variable (V) regions: Provide versatility from clone to clone.

• Light and heavy chains, constant (C) regions: Amino acid content is relatively stable.

T-Cell Receptors

• Similar to B-cell receptors: genetically modified, variable/constant regions, membrane-inserted, antigen binding site.

• Differences: smaller, never secreted.

Clonal Selection and Deletion

Clonal Selection

• Preprogrammed lymphocyte specificity; only the correct clone is activated by an antigen.

• Each lymphocyte expresses a single specificity for a chemical epitope.

Clonal Deletion

• Clones reactive to self-antigens are destroyed during development to prevent autoimmunity.

Summary Table: Stages of Adaptive Immune Response

Concept Check Examples

• B cells mature in the bone marrow; T cells mature in the thymus. Both migrate to lymph nodes and spleen.

• Properties: Matures in bone marrow (B cell); High numbers in blood (T cell); Require MHC presentation (T cell); Produce antibodies (B cell); Help/suppress/kill other cells (T cell).