Adaptive Immunity Response 1

Lecture Overview on Adaptive Immunity

  • Topics Covered:

    • Adaptive Immunity: Cell-mediated

    • Antigens and Immunogenicity

    • MHC molecules

    • Key Principles of Adaptive Immunity

    • Specificity

    • Memory

    • Cell-mediated Immunity

  • Required Videos:

    • How The Immune System ACTUALLY Works

    • The Immune System Explained I by Kurzgesagt

    • Sources:

    • Openstax Microbiology Textbook: Chapter 18, Adaptive Immune Responses

Classification of Immune Responses

  • Immune responses are classified as either:

    • Innate immunity

    • Adaptive immunity

    • Referenced in Figure 26.1 of Brock’s Biology of Microorganisms, 16th ed.

Key Features of Adaptive Immunity

  • Primary Effector Cells:

    • Lymphocytes:

    • T lymphocytes (T cells)

    • B lymphocytes (B cells)

  • Characteristics of Adaptive Immunity:

    • Specificity: Targets distinct antigens.

    • Memory: Produces faster and stronger responses upon re-exposure to pathogens.

    • Self-tolerance: Does not attack host tissues.

Memory in Adaptive Immunity

  • Graph Explanation:

    • Demonstrates the primary and secondary immune responses related to antibody production after initial and secondary exposure to an antigen.

    • The secondary response is faster and yields a higher concentration of antibodies, as illustrated in Figure 18.2 of Microbiology, Openstax.

Major Histocompatibility Complex (MHC) Molecules

  • Definitions:

    • MHC molecules are known as "Self" proteins, unique to each individual.

    • Close relatives may have similar MHC profiles.

    • Also referred to as HLA (human leukocyte antigens).

MHC Molecules Identifying Self

  • Characteristics:

    • Surface proteins that are unique to every individual.

    • Two Classes of MHC:

    • MHC I:

      • Expressed on all nucleated human cells.

      • Binds to and displays antigens originating in the cytoplasm.

      • In absence of infection: MHC I displays self-antigen.

    • MHC II:

      • Expressed only on antigen-presenting cells (APCs): macrophages, dendritic cells, and B cells.

      • Binds to and displays antigens originating outside cells.

      • Serves as a crucial link between innate and adaptive immune responses as seen in Figure 18.11 of Microbiology, Openstax.

Lymphatic System Overview

  • Components:

    • Lymph

    • Lymphatic vessels

    • Lymph nodes

  • Organs Involved:

    • Bone marrow

    • Thymus

    • Spleen

  • Functions:

    • Collects excess fluid from tissues and returns it to the blood.

    • Provides sites for immune activation.

    • Lymphocytes circulate between the blood and lymph as referenced in a visual aid from cancer.gov.

Primary and Secondary Lymphoid Tissues

  • Primary Lymphoid Tissues:

    • Site of lymphocyte maturation:

    • Thymus: T lymphocytes mature here.

    • Bone Marrow: B lymphocytes mature here.

  • Secondary Lymphoid Tissues:

    • Encapsulated:

    • Spleen

    • Lymph nodes

    • Diffuse:

    • Mucosa-associated lymphoid tissue (MALT)

    • Gut-associated lymphoid tissue (GALT)

Blood Components: Serum vs. Plasma

  • When blood is drawn and spun, it separates into:

    • Liquid portion

    • Cell portion

  • If blood clots:

    • Liquid portion = Serum (NO clotting factors present).

  • If blood sample is not allowed to clot (using an anticoagulant):

    • Liquid portion = Plasma.

Understanding Lymph

  • Lymph formation process:

    1. Plasma exits capillaries.

    2. Cells and tissues are bathed in interstitial fluid.

    3. Lymph nodes filter lymph before returning it to the circulatory system.

    • Reiterated: Plasma → interstitial fluid → lymph.

Origin of Blood Cells

  • All blood cells originate in the bone marrow as displayed in Figure 26.5 of Brock’s Biology of Microorganisms, 16th ed.

Specificity of Lymphocytes

  • Each lymphocyte contains antigen-specific receptors that are unique:

    • T cells: Mature in Thymus; have T cell receptors (TCR) for specific epitopes.

    • Function in both humoral and cell-mediated immunity.

    • B cells: Mature in Bone Marrow; have unique B cell receptors (BCR) that recognize specific epitope.

    • When secreted, BCR acts as an antibody.

    • Function primarily in humoral immunity.

Activation of Lymphocytes and Memory Cell Creation

  • Naïve lymphocytes are those prior to exposure to a specific antigen.

  • Primary Response:

    • First exposure to an antigen involves:

    • Antigen recognition by specific lymphocyte.

    • Proliferation of lymphocytes (clonal expansion).

    • Differentiation into:

      • Effector cells.

      • Memory cells.

  • Secondary Response:

    • Involves activation of memory cells leading to:

    • Faster and stronger response.

    • Often few to no disease signs/symptoms.

    • This represents immunological memory as illustrated in Figure 27.1 of Brock’s Biology of Microorganisms, 16th ed.

Pathogens and Adaptive Immune Response

  • Pathogens can replicate in:

    • Extracellularly: Grow outside host cells (in tissues and fluids).

    • Intracellularly: Grow inside host cells.

  • The adaptive immune response must recognize and respond to both types of pathogens:

    • Cell-mediated immunity:

    • Primary function of T cells to eliminate intracellular pathogens.

    • Antibody-mediated (humoral) immunity:

    • Primary function of B cell antibodies to eliminate extracellular pathogens.

Response Mechanism of B and T Cells

  • B cells respond primarily to extracellular pathogens.

  • T cells respond primarily to intracellular pathogens.

  • Extracellular antigens interact with MHC II-epitope complexes.

  • Intracellular antigens interact with MHC I-epitope complexes.

Cytotoxic T Cells and Cell-Mediated Immunity

  • Cytotoxic T Cells (TC):

    • Also known as T-cytotoxic (Tc) or cytotoxic T lymphocytes (CTLs).

    • Identified as CD8+ T cells.

    • Function:

    • TCR binds to specific MHC I-epitope complexes.

    • CD8 provides co-stimulation needed for activation.

    • Causes death of infected cells through:

      • Release of cytokines attracting NK cells and macrophages.

      • Release of perforins and granzymes leading to apoptosis of the target cell.

    • Further referenced in Norman-McKay's Microbiology textbook.

Interaction of TCR with MHCI

  • All nucleated cells process intracellular antigens through:

    • Proteasome:

    • Loads epitopes onto MHCI in the endoplasmic reticulum (ER).

    • The complex is then exported to the cell surface.

  • In uninfected cells:

    • MHCI-epitope complexes display self epitopes.

  • In infected cells:

    • MHCI-epitope complexes display pathogen-derived epitopes.

  • These complexes are recognized specifically by cytotoxic T cells (CTLs).

Activation of Cytotoxic T Cells (CTLs)

  • Activation process involves:

    • Interaction of naïve CTL with an infected cell displaying a specific antigen on MHCI.

    • Co-stimulation provided by CD8.

  • Following activation, CTLs release perforin and granzymes leading to controlled cell death (apoptosis) as shown in a figure of Microbiology, Openstax.

Outcomes of Lymphocyte Activation

  • Activation of lymphocytes leads to:

    • Proliferation of cells with the same specificity.

    • Creation of memory cells for future immunological responses.

    • Illustrated in Figures 12.14 and 12.19 of Norman-McKay's Microbiology textbook.

Mechanism of Infected Cell Death by CTLs

  • CTLs engage in apoptosis of infected cells, an essential part of the immune response.

  • Additional illustration provided in Figure 12.16 of Norman-McKay's Microbiology textbook.

Overview of Immune Response to Intracellular Pathogen: Cell-Mediated Immunity

  • Innate Immune Responses:

    • Features include:

    • Invasion of host cells.

    • Host cell injury leading to the release of cytokines.

    • Inflammation and involvement of NK cells.

  • Adaptive Immune Responses:

    • Mechanisms include:

    • Infected host cells display foreign antigens in complex with MHCI.

    • Activation of specific CTLs.

    • Proliferation and differentiation into effector and memory cells.

    • Ultimately results in the death of the infected host cells.

    • Memory cells persist to enable quick reactions in future infections.

Comparison: NK Cells vs. Cytotoxic T Cells (CTLs)

Feature

NK Cells

Cytotoxic T Cells (CTLs)

Type of Immunity

Innate

Adaptive

Timing

Rapid

Requires activation by antigen presentation (MHC I + specific antigen)

Target

Detect cells lacking “self” MHC I

Recognize specific antigen peptides on MHC I

Receptors

Non-specific

Antigen-specific (TCR)

Effector Molecule

Perforins and granzymes

Perforins and granzymes

Memory

No

Yes; forms long-lived memory T cells

Main Targets

Virus-infected and tumor cells

Primarily virus-infected and tumor cells

Co-stimulation

None

Requires CD8

Importance of MHC Class I

  • Functions:

    • Found on all nucleated cells (absent from RBCs).

    • Presents endogenous antigens, including:

    • Normal self-antigens.

    • Intracellular foreign antigens or altered self-antigens (such as tumors).

    • These antigens are displayed on the cell surface bound to MHC I and recognized by CD8+ CTLs.

  • When a foreign antigen is detected:

    • CTLs release perforin and granzymes, resulting in apoptosis of the infected cell.

  • Importance:

    • Facilitates monitoring of the health of all body cells by the immune system.

    • Loss of MHC I in infected or tumor cells can trigger attack by NK cells through “missing-self” recognition.

Learning Objectives from Lecture

  • Post-lecture, students should be able to:

    • Describe concepts of adaptive immune specificity, memory, and tolerance.

    • Differentiate between serum and plasma.

    • Describe lymph including its collection and filtration processes.

    • Identify primary and secondary lymphoid tissues and their basic roles.

    • Compare and contrast MHC I and MHC II relative to expression patterns.

    • Outline the sequence of events for processing and presenting intracellular antigens for both normal and infected cells.

    • Explain immunological memory in terms of primary and secondary immune response.

    • Present details on T cytotoxic cells regarding activation signals, differentiation, functions, and antigen elimination processes.

    • Differentiate between effector lymphocytes and memory lymphocytes.

    • Distinguish between CTLs and NK cells.