PHAR 504 Lecture 1 Notes: The Immune System and Adaptive Immunity

Lecture 1: The Immune System and Adaptive Immunity

• Instructor: Dr. Hanakahi (“Dr. H”)

• Course context: PHAR 504, 2025; Location: N301; Contact: hanakahi@uic.edu

Introduction to the Immune System

• Review reference: PHAR 410 (pharmacy students should have a solid understanding of immunity).

• Immunity is crucial for defense against pathogens; highly relevant to pharmacology and therapeutics.

Learning Objectives (Overview)

• Identify major organs, tissues, cells, and molecules of the immune system.

• Explain basic concepts of Innate and Adaptive immunity.

• Compare and contrast Adaptive and Innate immunity across:

  • Time to response

  • Antigen specificity

  • Memory

What is the Immune System?

• Function: prevent or limit infection.

• Keeps a record of every antigen encountered to enable rapid response upon re-exposure.

• Involves a network of tissues, cells, proteins, and small molecules.

• Abnormalities can lead to allergic diseases, immunodeficiencies, and autoimmune disorders.

Cells of the Immune System (Overview)

• Lymphoid lineage (lymphocytes) – Adaptive Immunity:

  • T cells, B cells, NK cells

  • Express antigen-specific receptors

• Myeloid lineage – Innate Immunity:

  • Phagocytes: Neutrophils, Basophils, Eosinophils, Mast Cells

  • Monocytes/Macrophages

  • Dendritic cells (APCs)

• Antigen-presenting cells (APCs): phagocytose pathogens and present antigens on their surface; Dendritic cells and Macrophages are key APCs

Primary Lymphoid Organs

• Definition: origin and development of lymphocytes (B cells and T cells); maturation of B cells and maturation of T cells.

• Role: site of lymphocyte development prior to antigen exposure.

Secondary Lymphoid Organs

• Function: where lymphocytes interact with each other and non-lymphoid cells to generate immune responses to antigens.

• Actions: trap and concentrate foreign materials and expose them to lymphocytes.

• Key organs: Spleen and Lymph Nodes.

  • Spleen: processes antigens from the bloodstream.

  • Lymph nodes: filter lymph.

The Lymphatic System

• Network of vessels, tissues, and organs that transport lymph (extracellular fluid).

• Functions:

  • Facilitates immunity: carries antigens and antigen-presenting cells from periphery to secondary lymphatic tissues to interact with lymphocytes.

  • Maintains body fluid balance.

  • Facilitates absorption of dietary fats from the GI tract and transport to the bloodstream.

Adaptive Immunity vs Innate Immunity

• Adaptive Immunity:

  • Memory: different response to novel vs previously encountered antigens.

  • Constant learning and adaptation; can respond to pathogens that change over time (mutations or surface antigen changes).

• Innate Immunity:

  • Rapid response time (minutes to hours).

  • No memory; response is the same regardless of prior exposure.

Cross-talk Between Innate and Adaptive Immune Systems

• Both systems must interact to achieve full immune benefit.

Overview of Adaptive Immunity (Why It Matters)

• Understanding adaptive immunity is crucial for:

  • Immunosuppressants, vaccines, and immunotherapies.

  • Autoimmune diseases and allergies and their treatments.

Learning Objectives for Introduction to Adaptive Immunity

• Describe the main properties of the adaptive immune system.

• Describe antigen-specific receptors.

• Explain immune specificity and memory in terms of clonal selection of B and T cells.

• Describe B cell activation.

• Describe T cell activation.

• Describe the complementary roles of humoral and cellular immunity.

Adaptive Immune Response: Key Characteristics

• Features: specificity, adaptiveness, discrimination of self vs non-self, clonal selection, memory.

• Major cell types: B cells, T cells, and antigen-presenting cells (APCs).

• Immunity includes development of humoral (B cell) and cellular (T cell) responses.

• Clonal expansion: rapid increase of T and B lymphocytes from one or a few cells to millions.

  • Each clone from the original lymphocyte has the same antigen receptor and recognizes the same antigen.

• Basis for immunizations.

• May fail, leading to autoimmune diseases (e.g., lupus, rheumatoid arthritis).

Cells of Adaptive Immunity: Lymphocytes

• T cells (T lymphocytes):

  • Express antigen-specific T-cell receptor (TCR).

  • Helper T cells: CD4+; regulate other immune cells via cytokines (indirectly help kill or control responses).

  • Killer T cells: CD8+; directly kill infected or cancerous host cells.

  • Regulatory/suppressor T cells: CD4+; immunosuppressive control of effector cells.

  • Memory T cells: long-lived (years); provide long-term immunity.

• B cells (B lymphocytes):

  • Express antigen-specific B-cell receptor (BCR) and immunoglobulin (Ig).

  • Plasma cells: secrete large quantities of Ig.

  • Memory B cells: long-lived (years); provide long-term immunity.

Antigen-Specific Receptors: BCR and TCR (Overview)

• B Cell Receptor (BCR):

  • Membrane-bound antibodies on B cells.

  • Each B cell has a unique BCR generated via genetic recombination.

  • BCRs can recognize intact antigens without antigen presentation.

  • Upon activation, B cells differentiate into plasma cells that secrete antibodies with the same specificity as their BCR.

• T Cell Receptor (TCR):

  • Recognize peptide antigens presented by MHC molecules on APCs.

  • Each T cell has a unique TCR generated via genetic recombination.

  • When a TCR binds its peptide-MHC complex, it triggers signaling that leads to T cell activation, proliferation, and effector functions.

• Shared features:

  • Both BCRs and TCRs are membrane-bound proteins with variable and constant regions.

  • They are heterodimers made of two polypeptide chains and associate with accessory proteins for signal transduction.

  • Antigen binding initiates signaling cascades that lead to effector functions.

  • Each B or T cell expresses a single, unique receptor specificity, enabling clonal selection and expansion.

Clonal Selection

• Concept: lymphocytes express antigen receptors on their surface.

  • B cells carry Ig (BCR); T cells carry TCR.

  • Each lymphocyte expresses multiple identical copies of its unique receptor.

  • Antigens bind to these receptors and stimulate the cells to divide, producing clones with the same specificity.

• Outcome: clonal expansion increases the population of lymphocytes capable of recognizing a dominant antigen.

• Example (illustrative): Ag will stimulate clones and produce populations of identical clones with the same specificity (as shown in the example with B cell clones).

B Cell Activation and Antibodies (Igs)

• Activated B cells differentiate into plasma cells that secrete antibodies with the same specificity as the BCR.

• Antibodies (Ig) functions include:

  • Preventing pathogen binding to host cells.

  • Promoting phagocytosis (opsonization).

  • Activating the complement system, which enhances opsonization and can lyse some bacteria.

Cell-Mediated Immunity (Cellular Immunity)

• Involves activation of effector cells, primarily phagocytes and antigen-specific cytotoxic T-lymphocytes (CTLs).

• Key components:

  • CTLs: directly kill infected or cancerous host cells by inducing apoptosis.

  • Helper T cells: secrete a variety of cytokines that influence the function of other immune cells, especially phagocytes.

T Cell Activation

• TCRs recognize peptide antigens presented by MHC molecules on antigen-presenting cells (APCs).

• Activation requires two signals:

  • Signal 1: TCR recognition of peptide-MHC complex.

  • Signal 2: Costimulatory signals from co-stimulators.

• Post-activation regulation:

  • Costimulatory and coinhibitory molecules modulate growth, differentiation, and function of responding T cells.

• Key players:

  • APCs present antigen via MHC.

  • TCR engages with peptide-MHC.

  • CD4+ or CD8+ T cells (co-receptors) recognize MHC class II or I, respectively.

  • Signals are labeled as Signal 1 and Signal 2.

T Cell Activation: Complex Regulation

• Numerous stimulatory and inhibitory ligand-receptor interactions are integrated to produce the T cell response.

• APCs (e.g., dendritic cells) also produce cytokines that contribute to T cell regulation.

Overview of Acquired Immunity (Summary)

• Abbreviations: Th = T helper; CTL = cytotoxic T lymphocyte.

• Key processes include clonal expansion and diversification of effector functions.

Notes on Real-World Relevance and Implications

• Immunosuppressants, vaccines, and immunotherapies target adaptive immunity pathways (e.g., T cell activation signals, B cell antibody production).

• Understanding clonal selection and memory is essential for vaccine design and predicting immune responses.

• Dysregulation can lead to autoimmune diseases (e.g., lupus, rheumatoid arthritis); therapeutic strategies often aim to modulate T cell activation and B cell antibody production.

Summary of Key Terminology

• Immune system, innate immunity, adaptive immunity, memory, clonal selection, APCs, BCR, TCR, B cells, T cells, helper T cells (CD4+), cytotoxic T cells (CD8+), regulatory T cells, memory B cells, plasma cells, antibodies (Ig), phagocytes, dendritic cells, macrophages, spleen, lymph nodes, MHC molecules, antigen-presenting cells, opsonization, complement.

Practical Takeaways for Exam Preparation

• Be able to distinguish innate vs adaptive immunity by:

  • Response time, memory, receptor specificity, and clonal expansion.

• Recognize the roles of primary vs secondary lymphoid organs in development vs activation.

• Explain how BCRs and TCRs recognize antigens differently and how this leads to humoral vs cellular immunity.

• Describe the two-signal model of T cell activation (Signal 1: TCR-MHC; Signal 2: costimulation) and how this regulates T cell responses.

• Understand clonal selection as the mechanism by which lymphocytes expand particular antigen-specific populations.

• Connect these concepts to real-world applications like vaccines, immunotherapies, and autoimmune disease mechanisms.

Appendix: Quick Reference to Antigen-Specific Receptors

• BCR: membrane-bound antibodies on B cells; recognition of intact antigen; activation leads to antibody production by plasma cells.

• TCR: recognizes peptide antigens presented by MHC on APCs; activation leads to T cell proliferation and effector function.

• Both receptor types enable clonal selection and immunological memory through long-lived B and T cell populations.