42.1 Innate Immune Response

The innate immune system is your body's first line of defense against pathogens. It responds immediately and non-specifically, meaning it doesn't target one particular invader but instead attacks anything recognized as foreign. This system includes physical barriers like skin, cellular defenders like natural killer cells, and protein-based systems like complement. Understanding innate immunity is essential because it sets the stage for the adaptive immune response covered later in this unit.

Physical and Chemical Barriers

Identify key physical and chemical barriers in the innate immune system

Your body's barriers work together to stop pathogens before they ever reach internal tissues.

Skin acts as a physical wall preventing pathogen entry. It also maintains an acidic pH that inhibits microbial growth, and its sebaceous glands secrete oils containing antimicrobial fatty acids and enzymes.

Mucous membranes line the respiratory, digestive, and reproductive tracts. They secrete mucus that physically traps pathogens like dust and bacteria. These membranes also contain antimicrobial enzymes such as lysozyme, which breaks down bacterial cell walls.

Chemical barriers are found throughout the body:

• Saliva, tears, and sweat contain lysozyme, IgA antibodies, and peroxidase
• Gastric acid in the stomach kills ingested bacteria and viruses
• Defensins in the intestines disrupt the cell membranes of bacteria like E. coli and Salmonella

Innate Immune Responses

Immediate vs. induced innate responses

Not all innate responses kick in at the same speed. The distinction between immediate and induced responses matters.

Immediate innate responses are always present and ready to act. These include the physical and chemical barriers described above, the complement system, and phagocytic cells like macrophages and neutrophils. They respond to pathogens right away without needing prior exposure.

Induced innate responses are activated only when the body detects pathogens or tissue damage. These include inflammation, fever, and acute-phase proteins such as C-reactive protein and fibrinogen. They take several hours to days to become fully active.

Both types rely on pattern recognition receptors (PRRs) on immune cells. PRRs detect conserved molecular structures found on pathogens, called pathogen-associated molecular patterns (PAMPs). When a PRR binds a PAMP, it triggers the appropriate innate immune response.

Role of natural killer cells

Natural killer (NK) cells are lymphocytes that patrol the body looking for infected or abnormal cells, such as virus-infected cells or tumor cells. They don't need prior exposure to a specific pathogen to act.

NK cells kill their targets through a two-step mechanism:

1. Perforin is released from granules inside the NK cell and forms pores in the target cell's membrane.
2. Granzymes enter through those pores and trigger apoptosis (programmed cell death) in the target cell.

NK cells also secrete cytokines like interferon-gamma, which activate other immune cells such as macrophages and T cells, amplifying the overall immune response.

Function of MHC I molecules

Major histocompatibility complex class I (MHC I) molecules are found on the surface of all nucleated cells. They display small peptide fragments from proteins made inside the cell, including viral proteins if the cell is infected.

This display system acts like a window into what's happening inside a cell. NK cells and cytotoxic T cells monitor MHC I molecules. If a cell shows abnormal peptides or has reduced MHC I expression (a common trick used by viruses and cancer cells to hide), immune cells recognize it as a threat and destroy it through apoptosis or cell lysis.

Complement System

Complement system for pathogen destruction

The complement system is a group of over 30 plasma proteins that circulate in the blood in inactive forms. When activated, they trigger a cascade of reactions that destroy pathogens in several ways.

Three pathways can activate the complement system:

• Classical pathway: activated by antibody-antigen complexes (IgG or IgM bound to a pathogen)
• Alternative pathway: activated directly by microbial surface components like lipopolysaccharide
• Lectin pathway: activated when mannose-binding lectin recognizes specific carbohydrates (like mannose) on pathogen surfaces

All three pathways converge on the same downstream effects:

1. Opsonization: Complement protein C3b coats the pathogen surface, making it much easier for phagocytes to recognize and engulf it.
2. Chemotaxis: Complement fragment C5a acts as a chemical signal that attracts phagocytic cells to the site of infection.
3. Membrane attack complex (MAC): Complement proteins C5b through C9 assemble into a ring-shaped pore in the pathogen's membrane, causing it to lyse (burst).

The complement system bridges innate and adaptive immunity because the classical pathway depends on antibodies, which are products of the adaptive immune response.

Inflammatory Response

Key components of the inflammatory response

Inflammation is a localized response to infection or tissue damage. Its purpose is to contain the threat, recruit immune cells, and begin tissue repair.

Here's how the process unfolds:

1. Damaged cells and resident immune cells release inflammation mediators such as histamine and prostaglandins.
2. These mediators cause vasodilation (widening of blood vessels) and increased vascular permeability, which allows more blood flow and immune cells to reach the affected area. This produces the classic signs of inflammation: redness, heat, swelling, and pain.
3. Cytokines produced by immune cells coordinate the response by signaling to recruit additional defenders, especially neutrophils and macrophages, to the infection site.
4. Innate lymphoid cells contribute by producing their own cytokines and helping mediate tissue repair once the threat is controlled.