Host Defenses Overview and Innate Immunity

Learning Outcomes Section 12.1

  • Summarize the three lines of host defenses.
  • Define "marker" and discuss its importance in the second and third lines of defense.
  • Name the body systems that participate in immunity.
  • Describe the structure and function of the lymphatic system and its connection with the circulatory system.
  • Name three kinds of blood cells that function in innate immunity.
  • Connect the mononuclear phagocyte system to innate immunity.
  • Describe how T and B lymphocytes are involved in adaptive immunity.
  • Summarize the importance of cytokines, and list one pro-inflammatory and one anti-inflammatory cytokine.

Defense Mechanisms of the Host

Overview of Host Defenses

  • Host defenses consist of a multilevel network of:
    • Innate, nonspecific protections (first and second lines of defense)
    • Adaptive, specific protections (third line of defense)
First Line of Defense
  • Definition: Any barrier that blocks invasion at the portal of entry, limiting access to internal tissues of the body, and acting very generally.
    • Examples:
    • Skin
    • Mucous membranes
    • Normal microbiota
Second Line of Defense
  • Definition: An internalized system of protective cells and fluids that acts rapidly once the first line of defense is breached.
    • Includes:
    • Inflammation
    • Phagocytosis
    • Antimicrobial substances
Third Line of Defense
  • Definition: Acquired on an individual basis as each unique foreign substance is encountered by lymphocytes.
    • Characteristics:
    • Unique protective substances are produced in response to different microbes.
    • Provides long-term immunity.

Flowchart Summarizing Major Components of Host Defenses

  • First Line of Defense: Surface protection composed of anatomical and physiological barriers.
  • Second Line of Defense: Cellular and chemical systems that engage if infectious agents breach surface defenses.
  • Third Line of Defense: Specific host defenses developed uniquely for each microbe through specialized white blood cells (Gamma-delta T cells, Natural Killer T cells).
Overlapping Functions
  • Most defenses overlap and are redundant in some effects, making survival of invading microbes unlikely.

Overview of Immunology

  • Definition: The study of all features of the body’s second and third lines of defense, including the body's response to infectious agents, allergies, and cancer.
Mandate of the Immune System
  • A healthy immune system is responsible for:
    • Surveillance of the body
    • Recognition of foreign material
    • Destruction of foreign entities

Immune Function

White Blood Cells

  • Role: Constantly move throughout the body, searching for potential pathogens.
  • Functions:
    • Recognize body cells (self)
    • Differentiate them from foreign material (non-self)
  • The ability to evaluate macromolecules as self or non-self is central to immune functioning.
  • Implication: Many autoimmune disorders arise when the immune system mistakenly attacks its own tissues.

Antigens and Markers

  • Definition of Antigens: Molecules on the surface of cells that the immune system recognizes.
  • Importance: Antigens allow immune cells to determine if newly found cells are threats:
    • Common method of destruction: Phagocytosis.
PAMPs and PRRs
  • PAMPs (Pathogen-associated molecular patterns):
    • Markers common to many kinds of microbes.
  • PRRs (Pattern recognition receptors):
    • Used by host cells in the innate immunity of the second line of defense to recognize PAMPs.
  • Nonself proteins that are not harmful are recognized, signaling the immune system to react differently.

The Immune System as a Network

  • Description: A large, complex, diffuse network of cells and fluids, permeating every organ and tissue, promoting surveillance and recognition processes.

Tissues, Organs, and Cells Participating in Immunity

  • Effective immune responsiveness requires communication between compartments:
    • Mononuclear Phagocyte System (MPS):
    • In direct contact with tissue cells and extracellular fluid (ECF).
    • Allows diffusion of cells and chemicals into blood and lymphatics.

The Lymphatic System

Overview

  • Structure: Network of vessels, cells, and specialized accessory organs transporting lymph.
  • Function:
    • Provide a return route for extracellular fluid to the circulatory system.
    • Act as a drain-off system for inflammation.
    • Render surveillance against foreign materials through a system of lymphocytes, phagocytes, and antibodies.
Lymphatic Fluid
  • Definition: Plasmalike liquid carried by the lymphatic circulation, formed when blood components exit vessels into ECF and migrate into lymphatic capillaries.
    • Functions:
    • Transports white blood cells, fats, cellular debris, and infectious agents.
Lymphatic Vessels
  • Similar to thin-walled veins, accompany blood capillaries.
  • Extend into all body areas except parts of the central nervous system and certain organs.
  • Walls are easily permeated by extravasated fluid from the circulatory system.
  • Flow direction is only towards the heart, assisted by skeletal muscle contractions.
Lymphatic Organs
  • Primary Lymphatic Organs (sites of immune cell birth and maturation):
    • Red bone marrow
    • Thymus
  • Secondary Lymphatic Organs (sites of immune cell activation):
    • Lymph nodes
    • Spleen
    • Associated lymphoid tissues
Red Bone Marrow
  • Site of blood cell production, especially B lymphocytes.
Thymus
  • Site of T-cell maturation.
Lymph Nodes
  • Small, encapsulated organs found along lymphatic pathways.
Spleen
  • Filters blood, removes worn-out red blood cells, and filters pathogens for phagocytosis by macrophages.
  • Implication: Adults without spleens can live normally, but children face severe immunocompromise.
Associated Lymphoid Tissues
  • Bundles of lymphocytes near body surfaces.
  • Examples:
    • Skin-associated lymphoid tissues (SALT)
    • Mucosa-associated lymphoid tissues (MALT)
    • Tonsils, GALT (gut-associated lymphoid tissue), Peyer’s patches.

The Blood

Composition of Blood

  • Whole blood comprises:
    • Blood cells: formed elements suspended in plasma.
    • Plasma: clear, yellowish fluid.
  • Serum: Clotted plasma, used in tests and therapies.
  • Hematopoiesis: Production of blood cells from stem cells in the bone marrow.
Types of Blood Cells
  • Leukocytes (White Blood Cells):
    • Divided into two groups: Granulocytes and Agranulocytes.
    • Granulocytes: Neutrophils, basophils, eosinophils.
    • Agranulocytes: Monocytes, lymphocytes (B and T cells).
  • Functionality: Vital for both nonspecific and specific immunity.

Key Cytokines for Cell Communication

  • Cytokines: Small active molecules involved in regulating and controlling cell responses.
    • Source: Monocytes, macrophages, lymphocytes, mast cells, etc.
Cytokines Examples
  • Pro-inflammatory Cytokines:
    • Interleukin-1 (IL-1): Involved in activating B and T cells.
    • Tumor necrosis factor-β (TNF-β): Involved in immune responses.
  • Anti-inflammatory Cytokines:
    • Interleukin-10 (IL-10): Suppresses immune responses.

Mononuclear Phagocyte System (MPS)

  • Description: A network formed by phagocytic cells connected within the tissues that respond to foreign intruders.
  • Location: Found in thymus, lymph nodes, tonsils, spleen, and lymphoid tissue in mucosal areas.

First Line of Defense

General Overview

  • Nonspecific protection via physical and chemical barriers against entry of microbes.
  • Components:
    • Physical barriers (skin, mucous membranes)
    • Chemical factors (secretions, enzymes)
Built-In Defenses of the Skin
  • Stratum Corneum: Tough outer, waterproof layer that prevents entry.
  • Flushing Effect of Sweat: Helps remove microbes.
Built-In Defenses of the Mucous Membranes
  • Mucous in various tracts (digestive, urinary, respiratory) impedes microbe entry and attachment.
  • Examples of Defenses:
    • Eye: Tear production flushes surface.
    • Saliva: Carries microbes to stomach for acidic exposure.
    • Respiratory: Cilia convey trapped debris towards throat.
Chemical Defenses
  • Antimicrobial secretions include:
    • Sebaceous gland secretions
    • Lysozyme in saliva and tears
    • Hydrochloric acid in stomach
    • Acidic pH of the skin and vagina.

Effect of Barrier Loss

  • Loss of barriers raises infection risk:
    • Example: Severe burns increase susceptibility.

Summary of Immune Response

Second Line of Defense

  • Defined as generalized and nonspecific defenses supporting specific immune responses:
    • Includes:
    • Phagocytosis
    • Inflammation
    • Fever
    • Antimicrobial proteins
Phagocytosis as a Defensive Mechanism
  • Definition: The process of engulfing and destroying pathogens.
  • Types of Phagocytes:
    • Neutrophils
    • Monocytes, leading to macrophages
Phagocytosis Process Steps
  • Stages:
    1. Chemotaxis
    2. Ingestion (engulfment)
    3. Phagosome formation
    4. Phagolysosome formation
    5. Destruction of bacteria
    6. Excretion of debris

Inflammatory Response

  • Definitions:
    • Identified by redness (rubor), heat (calor), swelling (tumor), pain (dolor).
  • Response Characteristics:
    • Mobilize immune components to injury site and clear debris.
    • Triggered by trauma, immune reactions, and microbial activation.
Key Functions of Inflammation
  • Actions:
    • Mobilization and attraction of immune components.
    • Local tissue repair.
    • Destruction of invading microbes.

Fever and its Benefits

  • Definition: An elevated body temperature due to re-setting of the hypothalamic thermostat.
  • Effects:
    • Inhibits bacterial growth.
    • Interferes with microbial nutrient access.
    • Stimulates immune responses and healing processes.
Treatment of Fever
  • Slight to moderate fever may be beneficial; however, high or prolonged fever may require treatment, especially in vulnerable individuals.

Antimicrobial Products

Interferons
  • Definition: Proteins that defend against viral infections and regulate immune responses.
    • Secreted in response to viral infection and can induce protective responses in neighboring cells.
Complement System
  • Definition: A group of over 30 proteins activating sequences to destroy pathogens through a cascade effect.
  • Methods of Action:
    • Classical pathway: By antibody binding.
    • Alternative pathway: Activated by pathogen antigens directly, faster than the classical method.
Antimicrobial Peptides
  • Small proteins that can disrupt bacterial membranes.
  • Investigated for therapeutic potential against infections.

Concept Checks and Summaries

  • Various concept checks are provided within the content to reinforce understanding of:
    • Lymphatic function, immune cell types, reactions of inflammation, and mechanisms of fever.
  • Summaries aid in synthesizing the information provided across chapters and link back to learning outcomes.