🦠Microbiology Unit 18 – Adaptive Specific Host Defenses

Introduction to Adaptive Immunity

• Adaptive immunity provides a highly specific and targeted response to pathogens
• Develops after exposure to a specific antigen and adapts to recognize and eliminate it
• Involves two main types of lymphocytes: T cells and B cells
• T cells mediate cellular immunity while B cells mediate humoral immunity
• Adaptive immunity has the ability to generate immunological memory
• Responds more rapidly and effectively to subsequent encounters with the same pathogen
• Complements the innate immune system's non-specific defense mechanisms

Key Components of Adaptive Immunity

• Major histocompatibility complex (MHC) molecules present antigens to T cells
  • MHC class I molecules are expressed on all nucleated cells and present intracellular antigens
  • MHC class II molecules are expressed on antigen-presenting cells (APCs) and present extracellular antigens
• T cell receptors (TCRs) recognize specific antigens presented by MHC molecules
• B cell receptors (BCRs) or antibodies recognize specific antigens in their native form
• Cytokines are signaling molecules that regulate and coordinate immune responses
• Lymphoid organs (thymus, spleen, lymph nodes) provide sites for lymphocyte development and activation

Antigen Recognition and Processing

• Antigens are substances that trigger an adaptive immune response
• Antigen-presenting cells (APCs) such as dendritic cells, macrophages, and B cells process and present antigens to T cells
• Exogenous antigens are taken up by APCs through phagocytosis or endocytosis
  • Processed and presented on MHC class II molecules to CD4+ T cells
• Endogenous antigens (viral proteins, tumor antigens) are processed within the cell
  • Presented on MHC class I molecules to CD8+ T cells
• Cross-presentation allows APCs to present exogenous antigens on MHC class I molecules to CD8+ T cells

T Cell-Mediated Immunity

• T cells mature in the thymus and express unique T cell receptors (TCRs)
• Two main types of T cells: CD4+ helper T cells and CD8+ cytotoxic T cells
• CD4+ T cells recognize antigens presented on MHC class II molecules
  • Secrete cytokines to activate and regulate other immune cells
  • Differentiate into various subsets (Th1, Th2, Th17, Treg) with specific functions
• CD8+ T cells recognize antigens presented on MHC class I molecules
  • Directly kill infected or malignant cells through the release of cytotoxic granules
• T cell activation requires both antigen recognition and co-stimulatory signals from APCs

B Cell-Mediated Immunity

• B cells mature in the bone marrow and express unique B cell receptors (BCRs) or antibodies
• BCRs recognize specific antigens in their native form
• B cells can be activated by T cell-dependent or T cell-independent mechanisms
• T cell-dependent activation involves interaction with CD4+ T cells and leads to the formation of germinal centers
  • Germinal centers are sites of B cell proliferation, affinity maturation, and class switching
• Activated B cells differentiate into plasma cells that secrete large amounts of antibodies
• Antibodies neutralize pathogens, opsonize them for phagocytosis, and activate complement

Memory Cells and Secondary Responses

• Adaptive immunity generates long-lived memory T and B cells after initial antigen exposure
• Memory cells respond more rapidly and effectively to subsequent encounters with the same antigen
• Memory T cells have a lower activation threshold and can quickly proliferate and differentiate into effector cells
• Memory B cells rapidly differentiate into plasma cells and produce high-affinity antibodies
• Secondary immune responses are faster, stronger, and more specific than primary responses
• Immunological memory forms the basis for vaccination and long-term protection against pathogens

Disorders of the Adaptive Immune System

• Immunodeficiencies are conditions where components of the adaptive immune system are missing or dysfunctional
  • Examples include severe combined immunodeficiency (SCID) and AIDS
• Autoimmune disorders occur when the adaptive immune system mistakenly attacks self-antigens
  • Examples include rheumatoid arthritis, multiple sclerosis, and type 1 diabetes
• Allergies are hypersensitivity reactions mediated by IgE antibodies
  • Triggered by harmless antigens such as pollen, food proteins, or drugs
• Transplant rejection occurs when the adaptive immune system recognizes donor antigens as foreign
  • Immunosuppressive drugs are used to prevent rejection in organ transplant recipients

Clinical Applications and Future Directions

• Vaccines stimulate adaptive immunity to prevent infectious diseases
  • Attenuated, inactivated, or subunit vaccines elicit specific immune responses
• Monoclonal antibodies are used to treat cancer, autoimmune disorders, and infectious diseases
  • Engineered to target specific antigens or modulate immune responses
• Adoptive cell therapy involves the transfer of immune cells (T cells, NK cells) to treat cancer or infections
  • Chimeric antigen receptor (CAR) T cell therapy targets specific tumor antigens
• Immunotherapy harnesses the power of the adaptive immune system to fight cancer
  • Checkpoint inhibitors (anti-CTLA-4, anti-PD-1) enhance T cell responses against tumor cells
• Future research aims to develop more effective vaccines, optimize immunotherapies, and understand the role of the adaptive immune system in various diseases