Nonspecific Host Defenses and Bacterial Infections

Bacteria and Nonspecific Host Defenses

Copyright Information

  • Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings.

Overview of Nonspecific Host Defenses

  • Nonspecific host defenses are critical elements in the fight against infectious diseases.

Proteins and Disease Resistance

  • A protein found in sweat may protect people from Lyme disease.   - Function of the Protein: Prevents disease-causing bacteria from growing in lab dishes or infecting mice.   - Population Insights: Approximately 40% of study participants have a mutated version of the protein, which is less effective, potentially increasing their risk of infection.   - Date of Insight: March 2024 regarding microbiology.

Herpesvirus Infections

  • More than half of the population are carriers of chronic herpesvirus infections.   - Infection Risks: Despite the capability of the herpesvirus to infect nerve cells, it leads to serious brain inflammation (herpes encephalitis) in only 1 out of 250,000 cases.   - Protective Mechanism: Brain cells produce a protein that inhibits herpesvirus entry into nerve cells.   - Genetic Insights: Two children who developed herpes encephalitis were found to have a genetic defect disabling the protective gene.   - Date of Insight: July 2024.

Interferonopathies

  • Too Much Interferon: Can lead to severe inflammatory conditions.

  • Too Little Interferon: Results in susceptibility to viral infections.

Learning Objectives

  1. Explain the role of nonspecific defenses in preventing infectious diseases:    - Skin, mucous membranes, normal microbiota, interferon, complement, phagocytosis, N.E.T.s (Neutrophil Extracellular Traps), inflammation, fever.

  2. Describe nonspecific defense mechanisms present at major portals of entry into the body.

  3. Analyze how bacteria survive or bypass nonspecific defenses at different entry points.

  4. Compare the protective roles of complement and natural killer cells against infections.

Vocabulary

  • Innate Resistance: Genetic resistance due to incompatible physiological processes.

  • Nonspecific Defense: General defense mechanisms not tailored to specific pathogens.

  • Normal Microbiota: Collection of microorganisms that inhabit various environments in the human body.

  • Transferrin/Lactoferrin: Proteins that bind iron, preventing access to bacteria.

  • Siderophore: Molecules capable of binding iron, aiding bacteria.

  • Interferon: Proteins that stimulate antiviral responses, not virus-specific.

  • Complement: A series of proteins that enhance immune responses.

  • Membrane Attack Complex (MAC): Structure formed by complement proteins that leads to cell lysis.

  • Opsonization: Process by which pathogens are marked for phagocytosis.

  • Inflammation: Biological response to harmful stimuli.

  • Pathways of Complement Activation: Classical and alternate pathways.

  • Phagocytes: Cells that engulf and digest pathogens.

  • Natural Killer Cells: Lymphocytes that destroy virally infected and tumor cells.

Innate Resistance

  • Definition: Genetic resistance to pathogens due to physiological incompatibilities.   - Mechanisms:     - Correct receptors may be absent on human cells.     - Temperature and pH of human body may be unsuitable for pathogen survival.

Host Defenses

  • Innate Defenses:   - Definition: Nonspecific defenses present from birth that target broad groups of pathogens.

  • Specific Adaptive/Acquired Immunity:   - Definition: Immunity developed after exposure to an agent; specific to a particular pathogen.

Types of Nonspecific Defenses

  • Skin and Mucous Membranes: Primary physical barriers against microbes.   - Skin Characteristics:     - Dry and cool.     - Low pH environment.     - Presence of chemicals (salt, fatty acids, lysozyme).     - Competitive action from normal microbiota.     - Lymphoid cells beneath the surface.     - Antimicrobial peptides (AMPs) such as defensins.     - Example: Metabolites from skin microbiome inhibit Staphylococcus aureus biofilm formation.

  • Mucous Membrane Differences:   - Characteristics:     - Moist and warm.     - Living tissue.   - Defensive Mechanisms:     - Mucus production.     - Sloughing of cells.     - Action of chemicals.     - Peristalsis, ciliary escalator, and urine flow aiding in pathogen expulsion.     - Presence of normal microbiota.     - Immune responses with cells and molecules like defensins and AMPs.

Other Chemical Defenses

  • Lysozyme: Found in tears, saliva, and vaginal secretions, it aids in breaking down bacterial cell walls.

  • Stomach Acid: Destroys many pathogens through low pH.

  • Transferrin/Lactoferrin: These bind iron, making it less available for bacteria due to their use of iron as a nutrient.

  • Normal Microbiota: Produce metabolic products that can inhibit pathogenic organisms.

  • Interferon: Stimulates the production of antiviral proteins but is not specific to any particular virus.

Mechanisms that SARS-CoV-2 Uses to Evade the Immune Response

  • Interaction with Host Factors:   - Involves splicing of pre-mRNA in the nucleus and results in disrupted protein production.   - Pathway also involves various non-structural proteins (NSP) that inhibit the interferon response.

Blood Components and Complement System

  • Blood Composition:   - Plasma: Fluid containing proteins like complement and antibodies.   - Cells:     - Erythrocytes (RBCs): Red blood cells responsible for oxygen transportation.     - Platelets: Involved in clotting mechanisms.     - Leukocytes (WBCs): White blood cells involved in immune responses.

  • Function of Complement Proteins:   - Proteolytic cascade results in:     - Formation of the membrane attack complex (MAC) leading to cell lysis.     - Opsonization of bacteria increasing phagocytosis.     - Recruitment of phagocytes during inflammatory responses.

Activation Pathways of Complement

  • Classical Pathway: Involves antibody-antigen complex formation.

  • Alternative Pathway: Direct binding of complement proteins to pathogen surfaces.

How Bacteria Evade Complement

  • Capsules: Prevent complement activation.

  • Surface Lipid-Carbohydrates: Inhibit MAC formation.

  • Enzymatic Digestion: Some bacteria can enzymatically degrade complement components like C5a.

Virus Interaction with the Complement System

  • Savvy Hijacking: Some viruses, such as SARS-CoV-2, can neutralize the activity of complement proteins, inhibiting the immune response.

Immune Cells: Leukocytes

  • Major Types of Leukocytes:   - Basophils: Involved in allergic reactions.   - Lymphocytes: Major players in specific adaptive immunity.   - Neutrophils and Eosinophils: Capable of phagocytosing pathogens and initiating diapedesis.   - Monocytes: Mature into macrophages and dendritic cells that function in pathogen clearance.

  • Phagocytic Capability of Macrophages:   - Reside in various tissues (e.g., alveolar macrophages in lungs, microglia in CNS).   - Dendritic cells act as initial responders, capable of conveying antigens to lymph nodes for adaptive responses.

Mechanism of Phagocytosis and Destruction

  • Phagocytosis: Involves several steps and mechanisms for pathogen degradation:   - Oxidative Burst: Produces reactive oxygen species (ROS) such as superoxide and hydrogen peroxide.   - N.E.T.s: Neutrophils can form extracellular traps to capture pathogens during infection.

N.E.T.s (Neutrophil Extracellular Traps)

  • Function: Trap pathogens using decondensed chromatin and release granular enzymes for degradation.

Phagocytosis Enhancement by Opsonization

  • Opsonins: Such as complement and antibody provide signals to phagocytes to enhance phagocytosis.

  • Mechanisms of Opsonization:   1. Attachment by nonspecific receptors.   2. Antibody binding to Fc receptors.   3. C3b binding to its receptor.

Strategies Bacteria Employ to Survive Phagocytosis

  • Inhibit Adherence: Through M proteins, capsules, and biofilms (e.g., Streptococcus pyogenes).

  • Kill Phagocytes: Some bacteria produce leukocidins (e.g., Staphylococcus aureus).

  • Escape from Phagosomes: By preventing fusion with lysosomes (e.g., Mycobacterium tuberculosis).

Natural Killer (NK) Cells

  • Function: Kill virally infected cells and tumor cells by releasing perforin and granzymes to induce apoptosis.

  • Activation/Inhibition Mechanism: Depend on balance between activating and inhibitory signals received via receptors:   - Normal cells present MHC class I molecules, providing strong inhibitory signals to NK cells, preventing attacks.   - Tumor or infected cells often downregulate MHC class I, leaving them vulnerable to NK cell initiation of apoptosis.

Inflammation

  • Role: Localizes infections, preventing their spread.

  • Manifestations: Redness, swelling (edema), pain, and heat result from vascular permeability, facilitating phagocytic chemotaxis.

Potential Problems with Chronic Inflammation

  • Concerns: Continuous inflammation can lead to tissue damage and various pathological conditions.