Innate Immunity: Nonspecific Defenses of the Host

Copyright and Overview

  • Copyright: © 2010 Pearson Education, Inc.
  • Title: Microbiology: An Introduction, Fourteenth Edition
  • Chapter: 16 Innate Immunity: Nonspecific Defenses of the Host
  • Copyright Notice: © 2024 Pearson Education, Inc. All Rights Reserved

The Concept of Immunity

  • Susceptibility: Lack of resistance to a disease.
  • Immunity: Ability to ward off disease.
  • Innate Immunity: Defenses against any pathogen.
  • Adaptive Immunity: Immunity, resistance to a specific pathogen.

An Overview of the Body's Defenses

1. Innate Immunity

  • First Line of Defense:
    • Intact skin
    • Mucous membranes and their secretions
    • Normal microbiota
  • Second Line of Defense:
    • Phagocytes (e.g., neutrophils, eosinophils, dendritic cells, macrophages)
    • Inflammation
    • Fever
    • Antimicrobial substances
  • Third Line of Defense (discussed in Chapter 17):
    • Specialized lymphocytes (T cells and B cells)
    • Antibodies

Host Toll-like Receptors (TLRs)

  • TLRs are receptors that attach to:
    • Pathogen-associated molecular patterns (PAMPs)
  • TLRs induce cytokines that regulate the intensity and duration of immune responses.

Physical Factors in Innate Immunity

1. Mucous Membranes

  • Composed of epithelial layer and underlying connective tissue layer.
  • Functions:
    • Mucus traps microbes.
    • Ciliary escalator transports trapped microbes away from the lungs.
    • Saliva dilutes microorganisms and washes surfaces of teeth and mucous membranes.
    • Lacrimal apparatus washes the eye.
    • Urine flows out, helping to eliminate microbes.
    • Vaginal secretions flow out to maintain a healthy environment.

2. Skin

  • Epidermis:
    • Consists of tightly packed cells containing keratin, a protective protein.
    • Breakdown leads to subcutaneous infections.

Chemical Factors in Innate Immunity

1. Products of the Lacrimal Apparatus

  • Components:
    • Antimicrobial enzymes like lysozyme and lactoferrin.
    • Antibodies like secretory IgA.

2. Products of Saliva

  • Components:
    • Antimicrobial enzymes (lysozyme).
    • Antibodies (IgA).
    • Neutralizes harmful acids and strengthens tooth enamel.

3. Products of Urine

  • Properties:
    • Urea has antimicrobial effects and proteins prevent bacteria from adhering.

4. Vaginal Secretions

  • Composition:
    • Lactic acid (from Lactobacillus), antimicrobial polypeptides, and immune factors.

Normal Microbiota & Innate Immunity

  • Microbial Antagonism/Competitive Exclusion:
    • Normal microbiota compete with pathogens or alter the environment to prevent infections.
  • Most microbiota are Commensal: One organism benefits while the other is unharmed.
  • Microbiota may become opportunistic pathogens under certain circumstances.

Formed Elements of the Blood

1. Blood Composition

  • Blood = Plasma + Formed Elements
  • Leukocytes (WBCs):
    • Granulocytes: Neutrophils (highly phagocytic and motile), Basophils (release histamine), Eosinophils (phagocytic, combat parasites).
    • Agranulocytes: Monocytes (phagocytic after exiting blood; mature into macrophages), Dendritic cells (derived from monocytes, initiate adaptive responses), and Lymphocytes (natural killer cells, T cells, B cells).

Lymphocytes

1. Types of Lymphocytes

A. Natural Killer Cells
  • Location: Blood, spleen, lymph nodes, bone marrow.
  • Function: Attack any body cell displaying abnormal plasma membrane proteins.
  • Mechanism of Action:
    • Perforin: Protein inserts and creates channels in the membrane, causing cytolysis.
    • Granzymes: Enzymes released that induce apoptosis.
B. T-Cells and B-Cells
  • Roles in adaptive immunity; not usually phagocytic.

2. Leukocyte Types and Counts

A. Differential White Blood Cell Count
  • Percentage of each type in a sample of 100 white blood cells (healthy patient):
    • Neutrophils: 60–70%
    • Basophils: 0.5–1%
    • Eosinophils: 2–4%
    • Monocytes: 3–8%
    • Lymphocytes: 20–25%

Red Blood Cells and Function of White Blood Cells

1. Red Blood Cells

  • Transport O2 and CO2.

2. Function of White Blood Cells:

  • Neutrophils: Phagocytosis
  • Basophils: Release histamine
  • Eosinophils: Kill parasites
  • Monocytes: Phagocytosis
  • Dendritic Cells: Phagocytosis
  • Natural Killer Cells: Destroy target cells
  • T Cells: Cell-mediated immunity
  • B Cells: Produce antibodies
  • Platelets: Blood clotting

Components of the Lymphatic System

  • Components:
    • Tonsils
    • Thymus
    • Lymphatic vessels
    • Spleen
    • Peyer's patches in the small intestine
    • Lymph nodes

Phagocytosis

  • Definition:
    • "Phago" means "eat" in Greek.
    • "Cyte" means "cell" in Greek.
    • Involves the ingestion of microbes or particles by cells known as phagocytes.

Phagocyte Types

  • Neutrophils: Dominant in initial infections.
  • Macrophages:
    • Fixed (immotile, located in tissues like lymph nodes) and wandering (migrate to infected areas).
  • Mononuclear Phagocytic System: Includes monocytes, macrophages, and neutrophils.
  • As infections progress, macrophages become dominant.

Phases of Phagocytosis

  1. Chemotaxis: Chemical attraction of phagocytes to microorganisms.
  2. Adherence: Attachment of phagocyte plasma membrane to surface of microorganisms or foreign materials.
  3. Ingestion: Pseudopods engulf microorganisms into a phagosome.
  4. Digestion: Phagosome fuses with lysosomes to form a phagolysosome for microbial breakdown.
  5. Discharge: Release of indigestible materials.

Microbial Evasion of Phagocytosis

  • Strategies utilized by pathogens to avoid phagocytosis include:
    • Inhibit adherence: M proteins and capsules (e.g., Streptococcus pyogenes, S. pneumoniae).
    • Kill phagocytes: Leukocidins (e.g., Staphylococcus aureus).
    • Lyse phagocytes: Membrane attack complex (e.g., Listeria monocytogenes).
    • Escape phagosome: (e.g., Shigella, Rickettsia).
    • Prevent phagosome-lysosome fusion: (e.g., HIV, Mycobacterium tuberculosis).
    • Survive in phagolysosome: (e.g., Coxiella burnetii).

Inflammation

  • Definition: Response to microbial, physical, or chemical injury.
  • Types:
    • Acute Inflammation: Example: Staphylococcus boil.
    • Chronic Inflammation: Example: Tuberculosis (TB).

Purpose of Inflammation

  • To destroy injurious agents, limit their effects on the body, and repair or replace damaged tissues.
  • Acute-phase proteins: Activated proteins include complement, cytokines, and kinins.

Symptoms of Inflammation

  • Vasodilation caused by histamine and other mediators leading to:
    • Redness
    • Swelling (edema)
    • Pain
    • Heat

Chemicals Released by Damaged Cells

  • Histamine: Causes vasodilation and increases vascular permeability.
  • Kinins: Contributes to vasodilation and increased permeability.
  • Prostaglandins: Intensifies the effect of histamines and kinins.
  • Leukotrienes: Increase vascular permeability and aid phagocyte attachment.

Phagocyte Migration and Phagocytosis Process

  • Step 1: Chemicals released by damaged cells trigger inflammation.
  • Step 2: Blood clot forms and abscess starts to develop.
  • Step 3: Phagocytes migrate toward the site of inflammation through margination and diapedesis.
  • Step 4: Phagocytosis of invading bacteria occurs.

Tissue Repair

  • Process:
    • Formation of a scab, blood clot, and regeneration of epidermis and dermis.

Fever

  • Definition: Abnormally high body temperature.
  • Normal Set Point: Hypothalamus typically set at 37°C.
  • Induction: Gram-negative endotoxins provoke phagocytes to release interleukin-1 (IL-1), prompting the hypothalamus to release prostaglandins that raise body temperature.

Physiological Responses during Fever

  • Increase in metabolic rate and shivering associated with raising temperature.
  • Following crisis, vasodilation and sweating lead to a decrease in temperature.

Advantages of Fever

  • Increases transferrins and IL-1 activity.
  • Produces Interferon to combat infection.

Disadvantages of Fever

  • Can lead to tachycardia, acidosis, dehydration, and can be fatal at temperatures between 44–46°C.

The Complement System

  • Definition: A group of serum proteins activated in a cascade.
  • Components of the Cascade: Complement proteins C1 through C9.

Results of the Complement Cascade

  1. C3b causes opsonization of pathogens.
  2. C3a and C5a promote inflammation.
  3. C5b-9 (the membrane attack complex) leads to cell lysis.

Activation of the Complement Cascade

  • Pathways for Activation:
    • Classical Pathway: Triggered by antigen-antibody reactions.
    • Alternative Pathway: Initiated by factors B, D, and P combining with C3 on the pathogen surface.
    • Lectin Pathway: Involves lectin binding to microbial carbohydrates.

Cascade Steps Explained

  1. Inactivated C3 splits into activated C3a and C3b.
  2. C3b binds to microbes for opsonization.
  3. C5 is activated which results in cell lysis through formation of a membrane attack complex.

Evasion of the Complement System by Bacteria

  • Mechanisms:
    • Capsules preventing C activation.
    • Surface lipid-carbohydrates inhibit membrane attack complex formation.
    • Enzymatic digestion of C5a to hinder immune signaling.

Interferons (IFNs)

  • Types:
    • IFN-alpha and IFN-beta: Cause uninfected neighboring cells to produce antiviral proteins inhibiting viral replication.
    • Host-cell specific: Not specific to the virus type.
    • Gamma Interferon: Induces phagocytosis by neutrophils and macrophages.

Antiviral Actions of Interferons (IFNs)

  • Process:
    1. Virus infects the cell, inducing the production of interferon mRNA.
    2. Interferons are released and bind to uninfected neighboring cells, triggering the synthesis of antiviral proteins (AVPs).
    3. AVPs degrade viral mRNA and inhibit new viral protein synthesis, thus protecting the neighboring cells from infection.