Host Defenses II: Specific Immunity

Introduction to Adaptive Immunity

Adaptive (specific) immunity is the third and final line of defense in the human body, acquired only after exposure to an immunizing event such as infection or vaccination. This system involves highly specialized B and T lymphocytes that recognize and respond to specific antigens, providing targeted and long-lasting protection.

• Immunocompetence: The ability of the body to react with countless foreign substances.

• Antigen: Any molecule that can be recognized by the immune system; if it provokes a response, it is called an immunogen.

Characteristics of Specific Immunity

• Specificity: Immune responses are tailored to particular antigens (e.g., antibodies against chickenpox do not affect measles).

• Memory: Lymphocytes "remember" previous encounters, enabling a faster and stronger response upon re-exposure.

Stages of Immunologic Development and Interaction

Lymphocyte Development

• All lymphocytes originate from the same stem cell type.

• B cells mature in the bone marrow; T cells mature in the thymus.

• Both types migrate to lymphoid organs (e.g., lymph nodes, spleen) and recirculate throughout the body.

Antigen Presentation and Clonal Selection

• Pathogens crossing the first line of defense are ingested by phagocytes (e.g., macrophages, dendritic cells).

• Antigen-presenting cells (APCs) process and present antigens to B and T lymphocytes.

• Clonal selection: Activation of the specific lymphocyte clone that recognizes the antigen.

• Clonal expansion: Rapid multiplication of activated lymphocyte clones.

• Clonal deletion: Destruction of self-reactive lymphocyte clones during development to prevent autoimmunity.

Markers and Receptors in Immunity

Major Histocompatibility Complex (MHC)

• MHC (Human Leukocyte Antigen, HLA): Glycoproteins on cell surfaces essential for self-recognition and immune regulation.

CD Molecules (Cluster of Differentiation)

• Surface markers important for immune cell identification and function.

• Key examples: CD3 (T cell receptor complex), CD4 (T helper cells), CD8 (cytotoxic T cells).

Lymphocyte Receptors

• B cell receptors (BCR): Bind directly to antigens.

• T cell receptors (TCR): Bind antigens presented with MHC molecules on APCs.

• Both have variable and constant regions, allowing recognition of a vast array of antigens.

B and T Cell Responses to Antigen

T Cell Responses

• Helper T cells (CD4+): Activate macrophages, assist B cells, and help activate cytotoxic T cells.

• Regulatory T cells: Control immune responses, prevent overactivation.

• Cytotoxic T cells (CD8+): Destroy infected or abnormal host cells.

• T cells secrete cytokines but do not produce antibodies.

B Cell Responses

• Upon activation, B cells differentiate into plasma cells that secrete antibodies.

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

Immunologic Diversity

• Each B and T cell is genetically programmed to recognize a unique antigen.

• Diversity arises from gene segment rearrangement, allowing the production of antibodies with up to 10 trillion specificities.

Immunoglobulins (Antibodies)

Structure of Immunoglobulins

• Y-shaped glycoproteins with two identical heavy chains and two identical light chains.

• Fab (antigen-binding) fragments: Bind specific epitopes.

• Fc (crystallizable) fragment: Binds to cell receptors and mediates effector functions (e.g., opsonization, allergic responses).

• Variable (V) regions: Highly diverse, determine antigen specificity.

• Constant (C) regions: Relatively conserved among antibodies of the same class.

Classes of Immunoglobulins

Antigen Types and Immunogenicity

• Proteins and polypeptides: Enzymes, cell surface structures, exotoxins.

• Lipoproteins, glycoproteins, nucleoproteins, polysaccharides, lipopolysaccharides: Various roles in immune recognition.

• Good antigens: Large, complex, and foreign molecules (e.g., proteins) are more immunogenic than small, repetitive ones.

• Haptens: Small molecules that become immunogenic only when attached to larger carrier molecules (e.g., drugs, metals).

• Alloantigens: Cell markers that differ among individuals of the same species (basis for blood groups, transplant compatibility).

• Superantigens: Potent bacterial toxins that overstimulate T cells, leading to excessive cytokine release (e.g., toxic shock syndrome).

• Allergens: Antigens that provoke allergic reactions.

Antigen Processing and Presentation

• Most antigens must be processed and presented by antigen-presenting cells (APCs) such as macrophages, dendritic cells, and B cells.

• APCs display processed antigen fragments on MHC molecules for recognition by T cells.

• Some antigens (T-cell-independent) can directly activate B cells without T cell help (e.g., certain bacterial polysaccharides).

T Cell Subsets and Functions

Antibody-Antigen Interactions

• Fab region: Binds to specific epitopes on antigens; high specificity due to hypervariable regions.

• Fc region: Binds to immune cell receptors, mediating processes such as opsonization and allergic responses.

• Antibodies can cross-link antigens, neutralize toxins, and facilitate phagocytosis.

Monitoring Antibody Production

• Titer: The concentration of antibodies in serum over time.

• Primary response: First exposure to antigen; slower, lower antibody production.

• Secondary response: Subsequent exposures; rapid, robust antibody production due to memory cells.

Types of Acquired Immunity

Vaccination and Immunization

Principles of Vaccination

• Vaccines stimulate a primary immune response and memory cell formation without causing disease.

• Qualities of an effective vaccine include safety, efficacy, long-lasting protection, and ease of administration.

Types of Vaccines

• Whole-cell/virus vaccines: Live attenuated or killed pathogens.

• Subunit vaccines: Purified antigenic components (proteins, polysaccharides).

• Conjugated vaccines: Subunits linked to proteins to enhance immunogenicity.

• DNA vaccines: Plasmid DNA encoding microbial antigens is introduced into the host, leading to antigen expression and immune response.

Adjuvants

• Substances added to vaccines to enhance immune response (e.g., alum).

• Prolong antigen retention and facilitate interaction with immune cells.

Vaccine Side Effects and Herd Immunity

• Most side effects are mild (local reactions, fever, allergies); serious adverse events are rare.

• No credible evidence links vaccines to autism or most chronic diseases.

• Herd immunity: When a critical portion of the population is immune, the spread of infectious disease is limited, protecting vulnerable individuals.

Key Definitions and Examples

• Antigen-presenting cells (APCs): Macrophages, dendritic cells, and B cells that process and present antigens to T cells.

• Gamma globulin: Concentrated immunoglobulin preparation used for passive immunization.

• Colostrum: Early breast milk rich in IgA, providing passive immunity to infants.

• Superantigen Example: Staphylococcal enterotoxins causing toxic shock syndrome.

Sample Concept Check Answers

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

• Antigen-presenting cells include macrophages, dendritic cells, and B cells (not T helper cells).

• Cytotoxic T cells do not kill bacteria directly.

• Antibody types:

  • IgA: Secreted on mucous membranes

  • IgD: Receptor on B cells

  • IgE: Produced in response to allergies

  • IgG: Most prevalent antibody

  • IgM: First antibody produced

• Active immunity: Recovery from influenza, receipt of influenza vaccination

• Passive immunity: Infusion of gamma globulin, antibodies passed from mother to infant through breastfeeding

Additional info: This summary integrates foundational immunology concepts relevant to the immune system's adaptive branch, as covered in Anatomy & Physiology courses (Ch. 21: The Immune System: Innate and Adaptive Body Defenses).