adaptive

The Immune System

Adaptive Immunity

  • Introduction to Adaptive Immunity:

    • Emphasis on protection and response.

    • Humorously illustrating a misconception of safety post-vaccination (i.e., drinking contaminated water or excessive contact with wild animals).

Main Features of Adaptive Immunity

  • Characteristics:

    • Later response: Activation occurs upon subsequent exposure.

    • Memory: More vigorous response upon repeated exposure to antigens.

    • Specificity and diversity: Tailored responses to varied antigens.

    • Main components: Lymphocytes (T and B cells) and antibodies (Ab).

    • Recognition but nonreactivity to self: Self-tolerance is critical to prevent autoimmunity.

    • Clonal expansion: B and T cells proliferate following activation.

Antigens (Ag)

  • Definition:

    • Any substance that induces an immune response, typically by producing antibodies.

    • Excludes self-antigens unless in case of autoimmunity.

  • Epitopes: Most antigens have multiple antigenic determinants.

  • Recognition of Self vs Non-Self:

    • Self-antigens recognized by the adaptive immune system do not provoke a reaction.

    • Non-self antigens elicit immune responses.

Receptor Features

  • Comparative Summary of Innate and Adaptive Immunity:

    • Inherited specificity: Innate YES, Adaptive NO.

    • Immediate response: Innate YES, Adaptive NO.

    • Broad class recognition: Innate YES, Adaptive NO.

    • Gene encoding: Innate NO, Adaptive YES (requires rearrangement).

    • Clonal distribution: Innate NO, Adaptive YES.

Receptor Specificity and Diversity

  • Innate Immunity: Recognizes shared patterns.

  • Adaptive Immunity: Detailed structural recognition of antigens leading to a plethora of antibodies.

Clonal Distribution/Selection Process

  1. Each lymphocyte has a unique receptor.

  2. Interaction between receptor and antigen activates the lymphocyte.

  3. Effector cells produced from activated lymphocyte share the same unique receptor.

  4. Self-reacting lymphocytes are deleted during development to avoid autoimmunity.

Initiating Innate Immune Response

  • Triggered via:

    1. Viral infection (intracellular).

    2. Bacterial infection (extracellular, phagocytes involved).

  • Contextual connection to adaptive immune response engagement.

Antigen Presentation

  • Purpose: Initiates the adaptive immune response and informs about self-tolerance.

  • Components required for antigen presentation to a T cell:

    1. Major histocompatibility complex (MHC) loaded with antigen.

    2. Cell receptor (T cell receptor, TCR).

Major Histocompatibility Complex (MHC)

  • Definition: Discovered in the context of transplantation in the 1940s-50s, “histo” meaning tissues.

  • MHC Types:

    • MHC I: Expressed on all nucleated cells and platelets.

    • MHC II: Expressed solely on Antigen Presenting Cells (APCs).

MHC I Details

  • Function: Acts as a signal indicating normal health, recognized primarily by CD8+ T cells and NK cells.

  • Significance: Presenting antigens that are not virally infected or abnormal cells.

MHC II Details

  • Function: Expressed on APCs (macrophages, dendritic cells, and B cells).

  • Antigen Recognition: By CD4+ T helper (Th) cells, enhancing:

    1. Antibody response from B cells (Th2).

    2. Macrophage function (Th1).

    3. Cytotoxic T lymphocyte (CTL) activity (Th1).

Antigen Processing and Presentation

  • MHC II: Antigens are loaded in endosomes and presented on the membrane.

  • MHC I: Antigens are loaded in the endoplasmic reticulum (ER) and presented externally.

MHC I Restriction

  • Interaction: CD8+ T cells exclusively interact with MHC I.

  • Mechanism: Identifies foreign peptides (e.g., viral) or abnormal cells leads to targeted killing by CD8+ T or NK cells.

Natural Killer (NK) Cells

  • Classification: Innate lymphoid cells.

  • Objective: Destroy non-self cells or those that are diseased or missing self-signals.

  • Mechanisms:

    1. Formation of pores via Perforin in the target's membrane.

    2. Release of Granzymes, catalyzing apoptosis (programmed cell death).

MHC II Restriction and T Cells

  • CD4+ T cells: Interact strictly with MHC II on APCs, crucial for responding to extracellular pathogens.

  • Antigen Binding: TCR must engage with MHC, relying on specific physiological cues for the differentiation of Th cell subtypes.

Outcomes of MHC-Ag Recognition

  1. Killing of virus-infected or abnormal cells by CD8+ T cells (MHC I dependent).

  2. Enhanced function of macrophages via Th1 cells (MHC II dependent).

  3. Activation of B cells for antibody production via Th2 cells (MHC II dependent).

  4. Promotion of CTL activity (Th1, MHC II dependent).

CTL Activation & Function

  • Requirement: Must be activated by an APC, will not target indiscriminately, nor can bind free antigens.

  1. Naïve CD8+ T cells recognize Ag through APC presentation to TCR.

  2. Clonal proliferation leads to memory and effector cell formation.

  3. Effector CTL targets specific antigens displayed from any MHC I.

Types of T Helper Cells

  • Th Subclasses Specifics:

    • Th1: Involves cell-mediated immunity against intracellular pathogens.

    • Th2: Supports humoral immunity against extracellular pathogens.

    • Th17: Associated with mucosal immunity and certain autoimmune conditions.

    • Treg: Regulates immune responses, maintaining balance in the immune system.

Th Cell Activation & Function

  • Activation resembles that of CTL: must be taught by an APC.

  • Th cell roles include:

    1. Activating B cells for antibody generation (Th2).

    2. Boosting CTL function (Th1).

    3. Enhancing macrophage activity (Th1).

B Cells as Adaptive APCs

  • Naïve B cells can absorb free antigens.

  • The antigen binding to membrane-bound antibodies acts as receptors, and subsequently prepares B cells to further associate with T cells for full activation.

B Cell Activation Processes

  • Origin: Produced in the bone marrow, awaiting activation in secondary lymphoid organs (lymph nodes, spleen).

  • After binding antigens and displaying them using MHC II, B cells become activated through pairing with TCR, leading to clonal expansion and differentiation into plasma and memory B cells.

Sequence of B Cell Activation**

  1. Antigen binding induces signaling pathways regulating activation-associated gene transcription.

  2. Internalization of BCR (B-cell receptor).

  3. MHC II processing and transport to cell surface for TCR recognition.

  4. Activation of Th2 cells facilitating B-cell response and antibody secretion.

Activation Dependence**

  • T Cell Dependent Activation:

    • Involvement of helper T cells leading to long-lived plasma cells.

  • T Cell Independent Activation:

    • Results in short-lived plasma cells producing IgM antibodies.

General Functions of Antibodies

  • Roles Include:

    • Complement activation.

    • Lysis of microbes and enhancement of phagocytosis.

    • Inducing inflammation and opsonization for better microbial clearance.

    • Neutralization of pathogens such as viruses and toxins.

Classes of Immunoglobulins (Ig)

  • The five major subclasses include IgG, IgA, IgM, IgD, and IgE, produced at a rate of 2,000 Abs/sec, involved in serum and tissue responses, and can switch classes post-activation (switching from IgM to others).

Purpose of Class Switching and Affinity Maturation

  1. Class Switching: Change in antibody type (e.g., from IgM to IgG) through somatic recombination.

  2. Affinity Maturation: Greater affinity for particular antigens typically after secondary exposure or vaccination.

Antibody Concentration Dynamics**

  • Primary Exposure: IgM appears followed by IgG peaking around 10-20 days post-initial exposure.

  • Secondary Exposure: Rapid elevation of IgG, demonstrating active immunity derived from prior antigen exposure or vaccination.

Active vs. Passive Immunity

  • Active Immunity:

    • Resulting from exposure to antigens, inducing long-lasting T and B cell memory (e.g., vaccinations).

  • Passive Immunity:

    • Transfer of antibodies through natural means (e.g., maternal transfer of IgG through pregnancy and IgA during nursing) or via medical interventions (e.g., immunoglobulin treatments for infectious diseases or autoimmunity).