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12 Basic Concepts of Immunity and Inflammation

Chapter 12: Basic Concepts of Immunity and Inflammation

Introduction to the Immune System

  • The immune system is a network of different types of leukocytes (white blood cells) and proteins that work together to defend the host from invasions.
    • Necessity for Survival: It is vital for the survival of the organism.
    • Divisions:
    • Innate Immunity: The first line of defense present at birth.
    • Adaptive (Acquired) Immunity: Developed throughout life following exposure to specific antigens.

Innate Versus Adaptive Immunity

Innate Immunity

  • Characteristics:
    • Present at birth.
    • Not antigen-specific; exposure does not lead to immunologic memory.
    • Always present and provides an immediate response to infections. Innate immune cells are preprogrammed to respond to a broad range of pathogens.
    • Does not improve with repeated exposure to an infectious agent.
  • Cells of Innate Immunity:
    • Neutrophils
    • Monocytes
    • Macrophages
    • Eosinophils
    • Basophils
    • Mast cells
    • NKT-lymphocytes
    • Physical Barriers: Skin and mucosal membranes are critical components creating natural barriers against pathogens.

Adaptive Immunity

  • Characteristics:
    • Develops throughout life following initial exposure to antigens.
    • Antigen-specific; repeated exposure leads to immunologic memory.
    • There is a lag time between infection and response as the immune system learns to counterattack specific pathogens.
  • Cells of Adaptive Immunity:
    • T-lymphocytes
    • B-lymphocytes

Self Versus Non-Self

  • The immune system distinguishes between:
    • Self: Cells or molecules that are part of the body.
    • Non-Self: Foreign substances that may pose a threat.

Primary Purpose of the Immune System

  • The primary purpose is to defend the life of the individual (host) by:
    1. Identifying foreign substances in the body.
    2. Deploying immune cells targeting invaders.
    3. Producing biochemical substances that amplify immune responses and counteract foreign substances.
    • This reaction to an infection is known as the host response.

The Immune Defense System

  • Infectious Organisms:
    • Infectious organisms invade and reproduce in the human body.
    • Examples:
    • Toxic substances are released by organisms or from environmental sources.
    • Parasitic infections.
  • Self:
    • Cancer: Transformation of normal body cells into tumor cells.
    • Transplanted tissues from non-identical donors can provoke immune responses due to recognition of non-self.

Consequences of Dysfunctional Immune Function

  • Dysfunctional immune responses can be deadly.
    • Example: HIV, which infects and replicates in CD4+ T cells, leading to increased susceptibility to other infections.
    • Infected cells produce new HIV viruses, infecting more CD4+ T cells, perpetuating the cycle.

Consequences of an Overactive Immune Response

  • An overactive immune response can lead to unintended harmful effects.
    • Example: Rheumatic heart disease, which occurs due to an immune response against Streptococcus pyogenes.
    • Immune system releases cytokines to combat the bacteria, mistakenly attacking similar peptides in heart tissue as well.

Components of the Immune System

  • The immune system comprises various components crucial for immune responses.

Leukocytes (White Blood Cells)

  • Colorless, nucleated cells originating from hemopoietic stem cells in bone marrow.
  • Categorized based on the presence or absence of cytoplasmic granules:
    • Granulocytes: Include neutrophils, eosinophils, basophils, and mast cells.
      • Neutrophils: First immune cells deployed and most abundant, primarily involved in phagocytosing pathogens.
    • Agranulocytes: Lacking granules, include lymphocytes and monocytes/macrophages.

Neutrophils

  • Functions:
    • Phagocytose invading pathogens.
    • Can migrate through capillary walls (chemotaxis).
    • Contain bactericidal digestive enzymes.
    • Short-lived cells (die during phagocytosis).
    • Normal range: 3,000 to 6,000 per milliliter of blood; deviations can indicate conditions like neutropenia (low) and neutrophilia (high).

Monocytes

  • Characteristics:
    • Large phagocytes with a single irregular, kidney-shaped nucleus.
    • Two to three times larger than red blood cells.
    • Classified as agranulocytes due to lacking granules.

Macrophages

  • Characteristics:
    • The largest leukocytes and highly phagocytic.
    • Agranulocytes that arrive slower than neutrophils.
    • Function primarily as antigen-presenting cells.

Lymphocytes

  • Small mononuclear agranulocytes playing a critical role in recognizing and neutralizing foreign invaders.
  • Types of lymphocytes:
    • B-lymphocytes (B-cells):
    • Smaller than neutrophils and monocytes/macrophages. Originate from hematopoietic cells in bone marrow.
    • Two subclasses:
      • Plasma B-cells: Produce antibodies.
      • Memory B-cells: Remember previous exposures, generate a quicker and more robust response on reinfection.
    • T-lymphocytes (T-cells):
    • Types include T-helper, T-cytotoxic, T-memory, and NKT-lympocytes.
      • Role varies in mediating immune responses.
    • Natural Killer (NK) Lymphocytes:
    • Larger than B- and T-lymphocytes; exhibit features of both innate and adaptive immunity.
    • Preprogrammed to kill virus-infected and tumor cells.

Antibodies

  • Antibodies are Y-shaped proteins composed of two main regions:
    • Fab (Fragment Antigen Binding): The antigen-binding region.
    • Fc (Fragment Constant): Region at the tail end that binds to immune cells and proteins of the complement system.

Immunoglobulins

  • Collective term for all antibodies, classified into major types:
    • IgG: Most abundant antibody; plays a significant role in the activation of the complement system; can cross the placental barrier.
    • IgM: The largest antibody, first to respond to antigen exposure; has a pentamer structure.
    • IgA: Principal defense at mucosal barriers; most prevalent form is secretory dimeric IgA, which can pass to neonates through breast milk.
    • IgE: Mediator of allergic responses.
    • IgD: Least abundant and least understood antibody.

Actions of Antibodies

  • Antibodies eliminate offending agents by:
    1. Coating targets to enhance phagocytosis.
    2. Activating the complement system.
    3. Triggering hypersensitivity immune reactions in certain individuals (allergic responses).

The Complement System

  • Composed of inactive proteins that patrol the body for invaders, neutralizing them upon exposure.
  • Works synergistically with antibodies and phagocytes for an efficient immune response.

Activities of the Complement System

  1. Lysis: Breakdown of pathogen membranes.
  2. Opsonization: Marking pathogens for phagocytosis.
  3. Activation of Inflammatory Response: Promoting inflammation.
  4. Clearance of Immune Complexes: Removing antibody-pathogen complexes from circulation.

Leukocyte Migration

  • Transendothelial Migration: Tissue-resident leukocytes release cytokines and chemokines into connective tissue to recruit more leukocytes from the bloodstream.

Chemotaxis

  • The process where leukocytes migrate toward an infection site in response to bioactive compounds released by other leukocytes.
    • Neutrophils exhibit swarm-like migration patterns surrounding and neutralizing pathogens, known as neutrophilic swarming.

Phagocytosis

  • The mechanism by which neutrophils and monocytes/macrophages engulf and digest pathogens or non-self molecules.

Local Tissue Destruction from Phagocytosis

  • Occurs via lysosomal