Immunopharmacology Notes

Introduction to Immunopharmacology

• Immunopharmacology is the study of how drugs modify the immune response.
• Focuses on endogenous or synthetic chemicals interacting with the immune system.
• A significant percentage of new drugs target the immune system for autoimmune conditions, inflammatory pathways, or to enhance immune activity.
• Understanding immune system components and their actions is crucial.

Inflammation

• Inflammation is a response to injury or pathogens, aiming for defense and repair.
• Key signs: heat, redness, swelling, pain, and loss of function.
• The goal is to restore tissue structure and function.
• Involves innate (non-adaptive) and adaptive (acquired) immune responses.
• Chronic inflammation results from persistent immune system activation.

Events During Inflammation

• Onset: Triggered by pattern recognition in response to injury or infection; involves increased vascular permeability and vasodilation.
• Resolution: Involves fluid exudates, complement system activation, coagulation, and the kinin system.
• Cellular events: Neutrophil recruitment and apoptosis, followed by monocyte differentiation into macrophages.
• Pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns (PAMPs).

From Acute to Chronic Inflammation

• Prolonged, dysregulated inflammatory response.
• Characterized by tissue destruction, fibrosis, and immune dysregulation.
• Key mediators include cytokines (IL-1, IL-6, TNF-α), chemokines, reactive oxygen species (ROS), matrix metalloproteinases (MMPs), and growth factors (VEGF).

Cytokines

• Cytokines are immune mediators that stimulate or inhibit immune cell differentiation, proliferation, or activity.
• Chemokines guide immune cells to infection sites.

Extravasation

• Cytokines (histamine) promote adhesion molecule expression on the endothelium and vascular permeabilization, facilitating white blood cell extravasation.

Organs of the Immune System

• Thymus: T-cell maturation.
• Tonsils: Trap pathogens.
• Spleen: Filters blood and activates immune cells.
• Lymph nodes: Filter lymph and activate lymphocytes.
• Bone marrow: Produces immune cells.

Types of Immunity

• Innate Immunity: Rapid, generalized response using physical barriers, cytokine production and complement activation; lacks memory.
• Adaptive Immunity: Slower, specific response involving T cells, B cells, and NKT cells; forms long-lasting memory.
• Humoral Immunity: Uses antibodies to target extracellular antigens.
• Cell-Mediated Immunity: T cells, macrophages, or NK cells destroy infected cells.

Monoclonal Antibodies (mAbs)

• mAbs bind antigens with high specificity due to their unique antigen-binding sites.
• Used in cancer therapy, autoimmune diseases, allergic conditions, infectious diseases, and more.
• The global market for monoclonal antibodies is significant and growing.

Treatment of Inflammatory Disorders

• Non-steroidal anti-inflammatory drugs (NSAIDs).
• Glucocorticoids.
• Immunosuppressants.
• Monoclonal antibodies.

Summary

• Inflammation results from tissue injury or infection and involves both innate and adaptive immune responses.
• Intervention is needed when inflammation is unresolved (chronic).
• Conditions are treated with drugs like NSAIDs, steroids, and immunosuppressants.
• Development & use of mAbs is increasing, but cost & toxicity are issues.