Innate Immunity: The Human Immune Response

Overview of Human Immunity

The human immune system is divided into two main branches: innate immunity (non-specific, present from birth) and adaptive immunity (specific, acquired after exposure). Innate immunity provides the first and immediate line of defense against pathogens, while adaptive immunity develops more slowly and provides long-lasting protection.

Innate Immunity

Definition and General Features

Innate immunity refers to the non-specific defense mechanisms that come into play immediately or within hours of an antigen's appearance in the body. These defenses include physical barriers, chemical factors, and cellular responses that do not require prior exposure to the pathogen.

• Non-specific: Responds to a broad range of pathogens.

• Immediate response: Acts as the first line of defense.

• No memory: Does not improve with repeated exposure to the same pathogen.

Physical Factors (First Line of Defense)

Skin

The skin acts as a physical barrier to prevent the entry of pathogens. The epidermis consists of tightly packed cells containing keratin, a protective protein that prevents desiccation and forms a shield between the environment and underlying sterile tissues. The outer layers are constantly shed and replaced, removing attached microbes.

Mucous Membranes

Mucous membranes line body cavities open to the exterior (e.g., respiratory, digestive, urogenital tracts). They secrete mucus, a viscous substance containing inorganic salts and antimicrobial molecules (e.g., lactoferrin, lysozyme). Mucus traps microbes and keeps the epithelium moist and intact. The ciliary escalator in the respiratory tract transports trapped microbes away from the lungs.

Washing/Flushing Mechanisms

Several body fluids help wash away microbes and prevent their colonization:

• Lacrimal apparatus: Produces tears that wash the eyes.

• Saliva: Washes microbes from teeth and oral mucosa.

• Urine: Flushes microbes from the urinary tract.

• Vaginal secretions: Remove microbes from the vaginal tract.

Chemical Factors (First Line of Defense)

Chemical barriers enhance the effectiveness of physical barriers:

• Sebum: Oily substance from skin glands; fatty acids lower skin pH (3–5), inhibiting microbial growth.

• Lysozyme: Enzyme present in perspiration, tears, saliva, and urine; breaks down bacterial cell walls.

• Gastric fluid: Contains hydrochloric acid (HCl), creating a very low pH (1.2–3.0) that destroys most microbes.

• Vaginal secretions: Maintain a low pH (3–5), inhibiting pathogens.

Human Microbiome (First Line of Defense)

The human microbiome consists of trillions of prokaryotes, fungi, and other microbes that inhabit the skin, mucous membranes, and associated cavities. These native microbes compete with pathogens for nutrients and attachment sites, a phenomenon known as microbial antagonism or competitive exclusion, thereby preventing colonization by harmful organisms.

Innate Second Line Defenses

Overview

If pathogens breach the first line of defense, the body employs cellular and molecular mechanisms such as phagocytosis, the inflammatory response, and the complement system. These are facilitated by non-specific immune cells, primarily leukocytes (white blood cells) produced in the bone marrow.

Phagocytosis

Phagocytosis is the process by which certain leukocytes (e.g., neutrophils, macrophages, dendritic cells) engulf and destroy microbes and foreign particles. These cells constantly survey body tissues and fluids for invaders.

• Neutrophils (PMNs): Rapid responders, abundant in blood, form extracellular traps to immobilize pathogens.

• Macrophages/Monocytes: Engulf larger particles and present antigens to adaptive immune cells.

• Dendritic cells: Bridge innate and adaptive immunity by presenting antigens.

Recognition of Pathogens

Phagocytes distinguish 'self' from 'non-self' using Pattern Recognition Receptors (PRRs) that bind to Pathogen-Associated Molecular Patterns (PAMPs) found on microbes but not on host cells.

• TLRs (Toll-Like Receptors): Recognize bacterial proteins, lipopolysaccharides (LPS), and carbohydrates.

• CLRs (C-type Lectin Receptors): Bind microbial carbohydrates.

• NODs: Detect bacterial peptidoglycan fragments.

Inflammatory Response

The inflammatory response is an acute reaction to tissue damage or infection, characterized by redness, pain, swelling, heat, and loss of function. It is mediated by macrophages, mast cells, and other immune cells that release signaling molecules upon detecting PAMPs or Damage-Associated Molecular Patterns (DAMPs) from injured host cells.

• Inflammatory mediators (e.g., leukotrienes, bradykinins, histamines) attract neutrophils, increase blood vessel permeability (causing edema and redness), and sensitize nerves to pain.

• Neutrophils migrate to the site, phagocytose microbes, and amplify the response.

Secreted Antimicrobial Molecules

The body produces several molecules that directly inhibit or destroy microbes:

• Interferons: Proteins induced by viral infection that inhibit viral replication.

• Antimicrobial peptides (AMPs): Small proteins (e.g., dermcidin, defensins, cathelicidins, thrombocidin) that disrupt microbial membranes.

Complement System

The complement system is a group of about nine serum proteins produced by the liver. When activated, these proteins trigger a cascade of reactions that enhance phagocytosis, recruit immune cells, and directly kill bacteria by forming Membrane Attack Complexes (MACs) that create pores in microbial membranes.

• Opsonization: Complement proteins (e.g., C3b) coat microbes, making them easier for phagocytes to recognize and ingest.

• Chemotaxis: Fragments like C3a and C5a attract phagocytes to the site of infection.

• Cytolysis: MACs cause lysis of bacterial cells by forming transmembrane channels.

Complement Activation Pathways

There are three main pathways for complement activation:

• Classical pathway: Triggered by antibodies bound to pathogens.

• Alternative pathway: Triggered spontaneously on microbial surfaces.

• Lectin pathway: Triggered by mannose-binding lectin or ficolins binding to microbial carbohydrates.

Summary Table: Key Components of Innate Immunity

Additional info: The innate immune system is essential for immediate defense and also plays a critical role in activating and shaping the adaptive immune response, which provides long-term and specific protection against pathogens.