IS

Adaptive- Humoral1

Adaptive Defenses

  • Adaptive Immune (Specific Defense) System

    • Functions:

    1. Protects against infectious agents and abnormal body cells

    2. Amplifies inflammatory response

    3. Activates complement system

    4. Must be primed by initial exposure to specific foreign substances (priming takes time)

    • Characteristics:

    • Specific: Recognizes and targets specific antigens

    • Systemic: Not restricted to original site of infection

    • Memory: Produces stronger attacks to previously encountered antigens

    • Two separate, overlapping arms:

    • Humoral Immunity: Antibody mediated

    • Cellular Immunity: Cell mediated

Adaptive Immunity – Two Overlapping Arms

  • Humoral Immunity (Antibody-Mediated):

    • Involves:

    • B lymphocytes (B cells) producing antibodies

    • Antibodies circulate freely in bodily fluids

    • Functions:

    • Bind temporarily to target cells to inactivate them

    • Mark target cells for destruction by phagocytes or complement

    • Focus: Extracellular targets

  • Cell-Mediated Immunity:

    • Involves:

    • T lymphocytes (T cells) acting against target cells

    • Functions:

    • Directly kill infected cells

    • Indirectly enhance the inflammatory response via chemical release

    • Focus: Cellular targets including virus-infected cells, cancer cells, foreign grafts

“Non-Self” Antigens

  • Definition:

    • Non-self antigens are substances that mobilize adaptive defenses and provoke an immune response.

    • Characteristics:

    • Generally large, complex molecules not normally found in the body (non-self)

    • Examples: Foreign proteins, polysaccharides, lipids, nucleic acids

    • Immunogenicity:

    • Ability to stimulate proliferation of specific lymphocytes

    • Reactivity:

    • Ability to react with activated lymphocytes and antibodies released during immunogenic reactions

Antigenic Determinants

  • Definition:

    • Only certain parts of an entire antigen, known as antigenic determinants, are immunogenic.

  • Functions:

    • Antibodies and lymphocyte receptors bind to these determinants.

    • Most naturally occurring antigens have numerous antigenic determinants, which:

    • Mobilize several different lymphocyte populations

    • Form various kinds of antibodies against them

Self-Antigens: MHC Proteins

  • Definition:

    • Proteins on the surface of cells that are not antigenic to self but can provoke an immune response in others, especially in transfusions or grafts.

    • Example: MHC Glycoproteins

    • Functions:

    • Coded by genes in the Major Histocompatibility Complex (MHC), unique to each individual

    • Include a groove that holds self- or foreign antigens

    • T lymphocytes can only recognize antigens presented on MHC proteins

Cells of the Adaptive Immune System

  • Types of Cells:

    • B Lymphocytes (B cells):

    • Responsible for humoral immunity

    • T Lymphocytes (T cells):

    • Responsible for cellular immunity

    • Antigen-Presenting Cells (APCs):

    • Do not respond to specific antigens but play essential auxiliary roles in immunity

Lymphocyte Development, Maturation, and Activation

  • Five General Steps:

    1. Origin: All lymphocytes originate in red bone marrow

    2. Maturation:

    • B cells mature in the bone marrow

    • T cells mature in the thymus

    1. Seeding Secondary Lymphoid Organs and Circulation:

    • Immunocompetent but naive lymphocytes leave primary organs to seed secondary organs (e.g., lymph nodes, spleen)

    1. Antigen Encounter and Activation:

    • Activation occurs when antigen receptors bind to antigens

    1. Proliferation and Differentiation:

    • Activated lymphocytes proliferate and differentiate into effector and memory cells

Maturation of B and T Cells

  • Education Process:

    • B cells mature in the bone marrow; T cells in the thymus

    • Immunocompetence:

    • Lymphocytes recognize one specific non-self antigen by binding to it

    • Unique Antigen Receptors:

    • B or T cells display only one unique type of antigen receptor at maturity

    • Self-Tolerance:

    • Lymphocytes are unresponsive to self-antigens and should not bind to them

T Cell Education in the Thymus: Positive and Negative Selection

  • Positive Selection:

    • T cells must recognize self-major histocompatibility proteins (self-MHC)

    • T cells failing to recognize self-MHC undergo apoptosis

  • Negative Selection:

    • T cells must not recognize and bind to self-antigens

    • Self-antigen recognition leads to apoptosis, eliminating self-reactive T cells to prevent autoimmune diseases

Seeding Secondary Lymphoid Organs, Antigen Encounter & Proliferation

  • Definition of “Naive” Cells:

    • Immunocompetent B and T cells that have not yet been exposed to foreign antigens

    • These cells are exported from primary lymphoid organs to increase chances of encountering antigens in secondary lymphoid organs

  • Clonal Selection:

    • The first encounter of a naive lymphocyte with its specific antigen selects it for further development

  • Proliferation:

    • Activated lymphocytes multiply, forming effector cells that fight infections

    • A few remain as memory cells, ready for future responses

Overview of B and T Lymphocytes

B Lymphocytes

  • Type of Immune Response: Humoral

  • Antibody Secretion: Yes

  • Primary Targets: Extracellular pathogens (e.g., bacteria, fungi, parasites, some viruses in extracellular fluid)

  • Site of Origin: Red bone marrow

  • Site of Maturation: Red bone marrow

  • Effector Cells: Plasma cells

  • Memory Cell Formation: Yes

T Lymphocytes

  • Type of Immune Response: Cellular

  • Antibody Secretion: No

  • Primary Targets: Intracellular pathogens (e.g., virus-infected cells) and cancer cells

  • Site of Origin: Red bone marrow

  • Site of Maturation: Thymus

  • Effector Cells: Cytotoxic T cells, Helper T cells, Regulatory T cells

  • Memory Cell Formation: Yes

Antigen-Presenting Cells (APCs)

  • Function:

    • Engulf antigens and present fragments of antigens to T cells for recognition

  • Major Types:

    1. Dendritic Cells:

    • Phagocytize pathogens and present antigens to T cells

    • Most effective antigen presenter known, key link between innate and adaptive immunity

    1. Macrophages:

    • Widespread in lymphoid organs and connective tissues

    • Present antigens to activate themselves into phagocytes that secrete bactericidal chemicals

    1. B Lymphocytes:

    • Present antigens to helper T cells to aid in their activation

Activation and Differentiation of B Cells

  • Activation:

    • B cells become activated when antigens bind to their surface receptors, leading to cross-linking

  • Clonal Selection:

    • Receptor-mediated endocytosis of the cross-linked antigen-receptor complexes occurs.

  • Proliferation and Differentiation:

    • Most effector cells become plasma cells, secreting specific antibodies quickly over four to five days before dying

  • Memory Cells:

    • Clone cells that do not become plasma cells become memory cells providing immunological memory

Immunological Memory

  1. Primary Immune Response:

    • Cell proliferation and differentiation upon first exposure to foreign antigen

    • Lag period: three to six days

    • Peak levels of plasma antibodies reached in around 10 days before declining

  2. Secondary Immune Response:

    • Re-exposure to the same antigen leads to faster, more prolonged, and more effective response

    • Sensitized memory cells respond within hours

    • Antibody levels reach peak in two to three days, remaining high for weeks to months

Active Humoral Immunity

  • Definition:

    • Occurs when B cells encounter antigens and produce specific antibodies against them

  • Types of Active Humoral Immunity:

    1. Naturally Acquired:

    • Response to bacterial or viral infection

    1. Artificially Acquired:

    • Response to vaccination with dead or attenuated pathogens

  • Vaccines:

    • Most consist of dead/attenuated pathogens providing antigenic determinants that are immunogenic and reactive

    • Examples include smallpox, whooping cough, polio, measles.

Passive Humoral Immunity

  • Definition:

    • Immunity gained due to ready-made antibodies introduced into the body

    • B cells are not challenged by antigens, leading to no immunological memory

    • Protection ends when antibodies degrade

  • Types of Passive Humoral Immunity:

    1. Naturally Acquired:

    • Antibodies delivered from mother to fetus via the placenta or to infant through breastmilk

    1. Artificially Acquired:

    • Injection of serum, such as gamma globulin

      • Provides immediate protection that ends as the body degrades the antibodies

      • Treatments include antivenom for snake bites and tetanus antitoxin.

Antibodies

  • Definition:

    • Immunoglobulins (Ig) are gamma globulin proteins in blood produced by plasma cells

    • Capable of binding specifically with antigens detected by B cells

  • Classes of Antibodies:

    • Basic Structure:

    • T- or Y-shaped monomers composed of four looping polypeptide chains linked by disulfide bonds

    • Composed of two identical heavy (H) chains and two identical light (L) chains

    • Have variable (V) regions forming identical antigen-binding sites

    • Constant (C) regions of the stem determine antibody class (IgM, IgA, IgD, IgG, IgE)

Immunoglobulin Classes Overview

Class

Structure

Function

IgM (pentamer)

First secreted during primary response; indicates current infection

Activates complement; clumping of pathogens

IgA (dimer)

Found in body secretions

Prevents pathogen attachment to epithelial cells

IgD (monomer)

Found on B cells surface

Serves as B cell antigen receptor

IgG (monomer)

Most abundant; primary in secondary responses

Protects against circulatory pathogens; crosses placenta

IgE (monomer)

Levels rise during allergic reactions

Binds to mast cells and basophils, triggering histamine release

Antibody Targets and Functions

  • Functions of Antibodies:

    • Antibodies inactivate and tag antigens; do not directly destroy them

    • Immune Complex Formation:

    • Form antigen-antibody complexes

    • Defensive Mechanisms Used by Antibodies:

    1. Neutralization:

      • Antibodies block specific sites on viruses or toxins, preventing binding to cells

      • Promotes phagocytosis of complexes

    2. Agglutination:

      • Antibodies cross-link with multiple antigens on cells, clumping them (e.g., mismatched blood cells)

    3. Precipitation:

      • Cross-linking soluble antigens leads to precipitation for phagocytosis

    4. Complement Fixation:

      • Several antibodies binding to a cellular antigen triggers complement activation, leading to cell lysis and enhanced inflammatory response

Mechanisms of Antibody Action

  • Diagrammatic representation includes:

    1. Neutralization: Antibodies mask dangerous parts of toxins and viruses

    2. Agglutination: Antibodies bind to cell-bound antigens

    3. Precipitation: Specialization of soluble antigens lead to immune response

    4. Complement Activation: Antibodies trigger significant inflammatory responses, enhancing phagocytosis