Adaptive Immunity and Vaccines

Adaptive Immunity: Specific Defenses of the Host

Introduction

• Lymphocytes attach to cancer cells.
• Adaptive immunity is a specific defense mechanism developed over time with memory component. It contrasts with innate immunity, which is present at birth.

Innate vs. Adaptive Immunity

• Innate Immunity:
  • Present at birth.
  • Non-specific defenses.
  • Rapid response.
  • No memory.
• Adaptive Immunity:
  • Develops over time.
  • Specific defenses.
  • Slow response initially.
  • Has memory.

The Adaptive Immune System

• Adaptive immunity targets specific pathogens after exposure.
• Primary Response: The first encounter with a foreign substance.
• Secondary Response: Subsequent encounters with the same foreign substance, resulting in a faster and more effective response due to immunological memory.

Big Picture: Immunity

• Non-Specific Defenses (Innate Immunity):
  • First Line of Defense:
    • Skin.
    • Mucous membranes.
    • Secretions of skin and mucous membranes.
    • Normal microbiota.
  • Second Line of Defense:
    • Antimicrobial proteins.
    • Formed elements (e.g., phagocytes).
    • Phagocytosis.
    • Inflammation.
    • Fever.
• Specific Defenses (Adaptive Immunity):
  • Third Line of Defense:
    • Lymphocytes.
    • Antibodies.
    • Memory cells.

Dual Nature of the Adaptive Immune System

• Humoral Immunity:
  • Produces antibodies.
  • Involves B cells.
  • Effective against extracellular pathogens and toxins.
• Cellular Immunity (Cell-Mediated Immunity):
  • Involves T lymphocytes.
  • Effective against virus-infected cells and intracellular bacteria.

Cytokines: Chemical Messengers of Immune Cells

• Cytokines are protein messengers produced in response to a stimulus.
  • Interleukins (ILs): Communicate between leukocytes.
  • Chemokines: Induce migration (chemotaxis) of leukocytes.
  • Interferons (IFNs): Interfere with viral infections of host cells.
  • Tumor Necrosis Factor alpha: Involved in the inflammation of autoimmune diseases.
• Overproduction of cytokines leads to a cytokine storm.

Antigens

• Antigens: Substances that cause the production of antibodies.
  • Usually components of invading microbes or foreign substances.
• Haptens: Molecules too small to be antigenic unless attached to carrier molecules, then provoke an immune response.

Humoral Immunity: Antibodies

• Antibodies have four protein chains forming a Y shape.
• Variable (V) Regions: Bind epitopes.
• Constant (Fc) Region: Identical for a particular Ig class.
• Five classes of Ig: IgG, IgM, IgA, IgD, IgE.

Results of the Antigen-Antibody Interaction

• An antigen-antibody complex forms when antibodies bind to antigens.
  • Protects the host by tagging foreign molecules or cells for destruction through:
    • Agglutination: Reduces the number of infectious units to be dealt with.
    • Opsonization: Coating antigen with antibody enhances phagocytosis.
    • Antibody-dependent cell-mediated cytotoxicity: Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells.
    • Neutralization: Blocks adhesion of bacteria and viruses to mucosa; blocks attachment of toxin.
    • Activation of the complement system: Causes inflammation and cell lysis.

Major Histocompatibility Complex (MHC)

• MHC genes encode molecules on the cell surface.
• Two types of MHC:
  • Class I MHC: On the membrane of nucleated cells; identifies a cell as “self”.
  • Class II MHC: On the surface of antigen-presenting cells (APCs).

Humoral Immunity Response Process

• Clonal Selection: B cell is activated when its B-cell receptor (BCR) binds to its antigen.
• Clonal Expansion: The activated B cell proliferates and differentiates into plasmocytes (secrete antibody) and memory B cells.

Activation and Clonal Expansion of Antibody-Producing Cells

• Two ways to activate B cells:
  • T-dependent antigens: Require a T helper cell.
    • These antigens are proteins.
    • Require antigen presentation by a B cell to a T cell.
    • The activated T cell produces cytokines that help activate the B cell.
  • T-independent antigens: Do not need T helper cell assistance.
    • These are non-protein antigens (e.g., polysaccharides).

Antigen-Presenting Cells (APCs)

• Dendritic Cells (DCs): Engulf and degrade microbes and display them to T cells.
• Macrophages: Activated by cytokines or the ingestion of antigenic material.
• B Cells

Classes of T Cells

• Clusters of differentiation (CD) are surface glycoproteins that distinguish T cell populations.
  • $CD4^+$ T helper cells ($T_H$):
    • Cytokines activate B cells.
    • Cytokines help activate other cells.
    • Bind MHC class II molecules on APCs.
  • $CD8^+$ Cytotoxic T lymphocytes (CTL):
    • Bind MHC class I molecules.

Cellular Immunity

• $CD4^+$ T cell activation:
  • T cell receptor (TCR) recognizes antigen.
  • CD4 recognizes MHC II.
  • Produces $T_H$ cells and memory cells.
• $CD8^+$ T cell activation:
  • TCR recognizes antigens.
  • CD8 recognizes MHC I.
  • Results in proliferation and memory CTLs.

Lineage of Effector T Helper Cell Classes and Pathogens Targeted

• $T_{H}1$ cells: Important in cellular immunity; cytokines (IFN-γ and IL-2) activate CD8+ T cells and NK cells to control intracellular pathogens.
• $T_{H}2$ cells: Important in allergic responses and activate eosinophils to control extracellular parasites such as helminths.
• $T_{H}17$ cells: Secrete cytokines that promote inflammatory responses and recruit neutrophils for protection against extracellular bacteria and fungi.

T Regulatory Cells

• $CD4^+$ T regulatory cells ($T_{reg}$):
  • Subset of $CD4^+$ cells; carry an additional CD25 molecule.
  • Suppress T cells against self; protect intestinal bacteria required for digestion; protect fetus.

Cellular Immunity Response Process

• Pathogens entering the gastrointestinal tract pass through microfold cells (M cells) located over Peyer’s patches.
• Transfer antigens to lymphocytes and antigen-presenting cells (APCs).

Superantigen Effects

• Simultaneously bind to MHC II and TCRs.
• Leads to cytokine storm if epitope not recognized, T cell not activated.

Cytotoxic T Lymphocytes ($CD8^+$ T Cells)

• Activation of a naïve $CD8^+$ T cell:
  • T cell receptor must interact with class I MHC and antigenic peptide (endogenous antigen) presented on another body cell.
• Activated cytotoxic T lymphocyte (CTL) will recognize other cells expressing the same antigen.
  • Target cells may harbor an intracellular pathogen such as a virus or may be tumor cells or cells in transplanted tissue.
• Activated CTL attacks target cell with perforin (forming a pore) and granzymes (proteases) causing apoptosis.

Cytotoxic T Lymphocytes ($CD8^+$ T Cells) and Apoptosis

• Apoptosis: Programmed cell death.
  • Cells cut their genome into fragments, causing the membranes to bulge outward via blebbing.

Nonspecific Cells and Extracellular Killing by the Adaptive Immune System

• Natural Killer (NK) Cells:
  • Destroy virus-infected cells, tumor cells, and attack large, extracellular parasites.
  • Not stimulated by antigen.
  • Detect target cells based on whether those cells express MHC class I.

Types of Adaptive Immunity

• Naturally Acquired Active Immunity: Resulting from infection.
• Naturally Acquired Passive Immunity: Transplacental or via colostrum.
• Artificially Acquired Active Immunity: Injection of vaccination (immunization).
• Artificially Acquired Passive Immunity: Injection of antibodies.

Vaccines

• Vaccine: Suspension of organisms or fractions of organisms that induce immunity.
  • Provokes a primary immune response.
    • Leads to the formation of antibodies and long-lived memory cells.
  • Produces a rapid, intense secondary response.
• Herd Immunity: Immunity in most of the population.

Types of Vaccines and Their Characteristics

• Attenuated Vaccines:
  • Weakened pathogen, reduced virulence.
  • Closely mimic an actual infection.
  • Confers lifelong immunity (both humoral and cellular).
  • Not given to immunocompromised patients.
• Inactivated Vaccines:
  • Whole microbes are killed or inactivated.
  • Safer than attenuated vaccines.
  • Require repeated booster doses.
  • Induce mostly humoral immunity.
• Subunit Vaccines: Use antigenic fragments to stimulate an immune response.
  • Recombinant Vaccines: Subunit vaccines produced by genetic modification of yeast or insects.
  • Toxoids: Inactivated toxins.
  • Virus-Like Particle (VLP) Vaccines: Resemble intact viruses but do not contain viral genetic material.
• Polysaccharide Vaccines: Made from molecules in pathogen’s capsule; not very immunogenic.
  • Pneumococcal vaccine.
• Conjugated Vaccines: Polysaccharide antigen is attached to a protein.
• DNA Vaccines:
  • Injected naked or encapsulated DNA into muscle.
  • Stimulates humoral and cellular immunity.
• mRNA Vaccines:
  • mRNA enclosed in a lipid nanoparticle is injected into muscle where it directs the synthesis of the encoded antigen.