Innate and Adaptive Immunity

Innate and Adaptive Immunity Notes

Immune Response

  • Definition: The collective, coordinated response of the cells and molecules of the immune system.
  • Types of Immune Defenses:
    • Innate (Nonspecific) Immunity: Natural resistance present at birth.
    • Adaptive (Specific) Immunity: A second line of defense that responds less rapidly but more effectively than innate immunity.

Principal Cells of the Immune System

  • Lymphocytes: Cells that specifically recognize and respond to foreign antigens.
  • Accessory Cells:
    • Macrophages and dendritic cells.
    • Function as antigen-presenting cells (APCs) by processing complex antigens into epitopes for lymphocyte activation.

Mediators of the Immune System

  • Cytokines: Soluble proteins secreted by cells of both the innate and adaptive immune systems.
  • Chemokines: Cytokines that stimulate the migration and activation of immune and inflammatory cells.
  • Colony-Stimulating Factors: Stimulate the growth and differentiation of bone marrow progenitors of immune cells.

Innate Immunity

  • Components:
    • Epithelial barriers.
    • Phagocytic cells (neutrophils and macrophages).
    • Natural killer (NK) cells.
    • Plasma proteins.
    • Opsonins, cytokines, and acute-phase proteins.
  • Induction: Initiates inflammatory response.

Phagocytosis

  • Phagocytosis involves the engulfment of pathogens or foreign particles by phagocytic cells like neutrophils and macrophages.
  • The process includes:
    • Attachment of the phagocyte to the pathogen.
    • Ingestion of the pathogen into a vesicle called a phagosome.
    • Fusion of the phagosome with a lysosome, forming a phagolysosome.
    • Digestion of the pathogen by lysosomal enzymes.
    • Release of the digested products and residual material.

Natural Killer (NK) Cells

  • NK cells are a type of cytotoxic lymphocyte critical to the innate immune system.
  • They recognize and kill infected or cancerous cells.
  • Mechanism of Action:
    • NK cells differentiate between healthy and unhealthy cells by balancing signals from activating and inhibitory receptors.
    • Activating receptors bind to ligands on target cells, signaling for cell killing.
    • Inhibitory receptors recognize MHC-I molecules (self-recognition). If MHC-I is present (normal cell), the inhibitory signal prevents cell killing.
    • Virus-infected or tumor cells often downregulate MHC-I expression, preventing the inhibitory signal and leading to NK cell activation and cell killing.

Soluble Mediators of Innate Immunity

  • Opsonins: Facilitate phagocytosis.
    • Examples: Acute-phase reactants, lectins, complement proteins.
    • IgG and IgM (adaptive immunity).
  • Cytokines: TNF, interleukins, interferons, and chemokines.
  • Acute-Phase Proteins:
    • Mannose-binding ligand (MBL) and C-reactive protein (CRP).
  • Complement System:
    • Functions: Cytolysis, opsonization, chemotaxis, anaphylaxis.

Innate Recognition Systems

  • Pattern Recognition Receptors (PRRs): Receptors that recognize conserved molecular patterns on pathogens.
  • Pathogen-Associated Molecular Patterns (PAMPs): Molecules associated with pathogens that are recognized by PRRs.
  • Toll-Like Receptors (TLRs): A type of PRR that recognizes various PAMPs.

Characteristics of Innate and Adaptive Immunity

  • Innate Immunity:
    • Recognition: Recognizes molecular patterns common to microbes.
    • Receptors: Limited diversity expressed by germline genes (e.g., Toll-like receptor, mannose receptor).
    • Cellular Expression: Effector cell types express identical receptors (e.g., neutrophils express Toll-like receptors).
    • Self-Nonself Discrimination: Yes, by recognizing molecules unique to pathogens; NK cells recognize MHC-I self-recognizing molecules.
  • Adaptive Immunity:
    • Recognition: Recognizes specific microbial molecules.
    • Receptors: Great diversity expressed through recombination of somatic genes (B-cell receptor and T-cell receptor).
    • Cellular Expression: Each clone of lymphocytes expresses unique receptors.
    • Self-Nonself Discrimination: Yes, lymphocytes use MHC-I and MHC-II and foreign peptides (e.g., microbial peptides in recognition).

The Complement System

  • Found in the blood and essential for the activity of antibodies.
  • Activation increases bacterial aggregation, which renders bacteria more susceptible to phagocytosis.

Adaptive Immunity

  • Able to recognize and react to a large number of microbes and nonmicrobial substances.
  • Distinguishes among different, even closely related, microbes and molecules.
  • “Remembers” the pathogen, producing a heightened immune response upon subsequent encounters.
  • Involves lymphocytes and their products.
  • Relies on antigen identification.

Types of Adaptive Immune Responses

  • Humoral Immunity:
    • Mediated by molecules in the blood (antibodies).
    • The principal defense against extracellular microbes and toxins.
  • Cell-Mediated (Cellular) Immunity:
    • Mediated by specific T lymphocytes.
    • Defends against intracellular microbes such as viruses.

Types of Immune Cells

  • Regulatory Cells:
    • Assist in orchestrating and controlling the immune response.
  • Effector Cells:
    • Accomplish the final stages of the immune response by eliminating the antigen.
    • Activated T lymphocytes, mononuclear phagocytes, and other leukocytes function as effector cells.

Antigens and Antibodies

  • Antigens: Substances foreign to the host that can stimulate an immune response.
  • Antibodies: Recognize antigens.
    • Serve as receptors on immune cells.
    • Secreted proteins.

Types of Antigens

  • Bacteria
  • Fungi
  • Viruses
  • Protozoa
  • Parasites
  • Nonmicrobial agents

Properties of MHC Molecules

  • HLA Antigens:
    • Class I: HLA-A, HLA-B, HLA-C
    • Class II: HLA-DR, HLA-DP, HLA-DQ
  • Distribution:
    • Class I: Virtually all nucleated cells.
    • Class II: Restricted to immune cells, antigen-presenting cells, B cells, and macrophages.

Functions of MHC Molecules

  • Class I:
    • Presents processed antigen to cytotoxic CD8+ T cells.
    • Restricts cytolysis to virus-infected cells, tumor cells, and transplanted cells.
  • Class II:
    • Presents processed antigenic fragments to CD4+ T cells.
    • Necessary for effective interaction among immune cells.

Antigen Presentation

  • Macrophages and dendritic cells process and present antigen peptides to CD4+ helper T cells.
  • Capture antigens and enable their recognition by T cells.
  • Initiates adaptive immunity.

Lymphocytes

  • B cells:
    • Humoral immunity.
    • Memory.
  • T cells:
    • Cell-mediated immunity.
    • Memory.

Identifying Factors of B Lymphocytes

  • Presence of membrane immunoglobulin that functions as the antigen receptor.
  • Class II MHC proteins.
  • Complement receptors.
  • Specific CD molecules.

Functions of T Lymphocytes

  • Activation of other T cells and B cells.
  • Control of intracellular viral infections.
  • Rejection of foreign tissue grafts.
  • Delayed hypersensitivity reactions.

Classes and Functions of Immunoglobulins

  • IgG:
    • Displays antiviral, antitoxin, and antibacterial properties.
    • Responsible for protection of newborn.
    • Activates complement and binds to macrophages.
  • IgA:
    • Predominant Ig in body secretions.
    • Protects mucous membranes.
  • IgM:
    • Forms natural antibodies.
    • Prominent in early immune responses.
    • Activates complement.
  • IgD:
    • Found on B lymphocytes.
    • Needed for maturation of B cells.
  • IgE:
    • Binds to mast cells and basophils.
    • Involved in parasitic infections, allergic, and hypersensitivity reactions.

Functions of the Lymphoid Organs

  • Central Lymphoid Organs (Bone Marrow and Thymus):
    • Provide the environment for immune cell production and maturation.
  • Peripheral Lymphoid Organs:
    • Function to trap and process antigen.
    • Promote interaction with mature immune cells.

Functional Groups of Cytokines

  • Inflammation Mediators: (e.g., IL-1, IL-6, TNF)
    • Produce fever and the acute-phase response.
    • Attract and activate phagocytes (e.g., IL-8, IFN-γ).
  • Maturation Factors: (e.g., IL-3, GM-CSF)
    • For the hematopoiesis of white or red blood cells.
    • GM-CSF stands for Granulocyte-Macrophage Colony-Stimulating Factor

Immune Response - Active and Passive Immunity

  • Active Immunity:
    • Specific protection induced following exposure to antigens.
  • Passive Immunity:
    • Specific protection induced through the transfer of protective antibodies against an antigen from another source.
    • Examples:
      • Maternal IgG crosses the placenta, protecting the newborn during the first few months of life.
      • IgA in colostrum.

Development of an Immune Response

  • Fetal development at 5 to 6 weeks.
  • Secondary lymphoid organs well developed at birth.
  • IgA and IgM shortly after birth, reaching adult levels by 1 year of age.

The Elderly Immune System

  • Declining ability to adapt to environmental stresses.
    • Decline in immune responsiveness.
    • Decrease in the size of the thymus gland.
    • Biological clock in T cells.
    • Altered responses of the immune cells to antigen stimulation.