21.5 The Immune Response against Pathogens

Development and Function of the Immune System

The immune system defends the body against harmful invaders like bacteria, viruses, fungi, and parasites. It operates on two major levels: innate immunity, which you're born with, and adaptive immunity, which develops over time as you encounter specific pathogens. Understanding how these two systems work together, and how pathogens try to get around them, is central to this unit.

Stages of Immune System Development

Innate immunity is the first line of defense, functional from birth. It provides immediate, non-specific protection through:

• Physical barriers like the skin and mucous membranes
• Phagocytic cells (neutrophils and macrophages) that engulf and destroy pathogens
• The complement system, a group of proteins that promote inflammation and directly destroy pathogens

Passive immunity gives newborns a temporary head start. Maternal antibodies (specifically IgG) cross the placenta during pregnancy, providing the infant with protection against pathogens the mother has already encountered, such as measles and rubella. This protection fades over the first several months of life as the maternal antibodies are degraded.

Adaptive immunity develops after birth through exposure to antigens via infections or vaccines. It has two defining features that innate immunity lacks: specificity and memory.

• T cells mature in the thymus, where they learn to distinguish self from non-self antigens. This process eliminates T cells that would attack the body's own tissues.
• B cells mature in the bone marrow and, once activated, differentiate into antibody-secreting plasma cells.
• Both cell types generate memory cells after an initial encounter with an antigen. These memory B and T cells enable faster, stronger responses upon re-exposure to the same pathogen.

Protection by Mucosal Immunity

Mucous membranes line the digestive, respiratory, and urogenital tracts. These surfaces are major entry points for pathogens, so the body stations significant immune defenses there.

Secretory IgA (sIgA) is the dominant antibody at mucosal surfaces. Plasma cells in the mucosal lamina propria produce it, and it's transported (transcytosed) across epithelial cells into the mucus layer. Once there, sIgA binds and neutralizes pathogens and toxins in the lumen, preventing them from attaching to and invading epithelial cells.

Mucosal-associated lymphoid tissue (MALT) provides organized immune surveillance at these vulnerable surfaces:

• Includes structures like Peyer's patches in the small intestine, the tonsils, and the appendix
• Houses lymphocytes (T and B cells) and antigen-presenting cells (dendritic cells, macrophages)
• Samples antigens from the lumen and mounts localized immune responses without needing to alert the entire systemic immune system

Innate immune cells are also scattered throughout the mucosal epithelium and lamina propria. Dendritic cells capture antigens and present them to T cells, while macrophages and mast cells release inflammatory mediators that recruit additional immune cells to the site.

Key Components of the Immune Response

• Inflammation: The initial response to tissue damage or infection, characterized by the four cardinal signs: redness, swelling, heat, and pain. These result from increased blood flow and vascular permeability, which help deliver immune cells to the affected area.
• Antigens: Molecules (usually proteins or polysaccharides) on the surface of pathogens that trigger an immune response. Each antigen has specific regions called epitopes that immune cells recognize.
• Antibodies: Y-shaped proteins produced by B cells (specifically plasma cells) that bind to specific antigens. They neutralize pathogens, tag them for destruction (opsonization), or activate complement.
• Lymphocytes: White blood cells responsible for adaptive immunity. T cells coordinate immune responses and kill infected cells; B cells produce antibodies.
• Pathogens: Disease-causing microorganisms, including bacteria, viruses, fungi, and parasites.

Immune Responses to Pathogens

The immune system doesn't use a one-size-fits-all approach. Different types of pathogens trigger different combinations of innate and adaptive responses. The table below summarizes the key differences.

Immune Responses by Pathogen Type

• Intracellular pathogens (viruses, some bacteria like Mycobacterium tuberculosis) rely heavily on cell-mediated immunity: cytotoxic T cells and Th1-activated macrophages.
• Extracellular pathogens (most bacteria, fungi, parasites) are more effectively targeted by antibodies and complement.
• Parasites uniquely involve IgE antibodies and Th2 responses, which is why parasitic infections are associated with elevated IgE levels and eosinophilia.

Pathogen Strategies for Immune Evasion

Pathogens are under constant selective pressure to avoid destruction, and many have evolved sophisticated evasion strategies. These are important to understand because they explain why certain infections are so difficult to clear or vaccinate against.

Antigenic variation involves regularly changing surface antigens to escape antibody recognition. The influenza virus does this through mutations in hemagglutinin and neuraminidase (this is why you need a new flu vaccine each year). HIV rapidly mutates its gp120 envelope protein, and trypanosomes periodically switch their variant surface glycoprotein, staying one step ahead of the antibody response.

Immunosuppression means directly inhibiting or dysregulating the host's immune responses. The measles virus suppresses cell-mediated immunity, leaving patients vulnerable to secondary infections. HIV depletes CD4+ T helper cells, progressively crippling the adaptive immune system.

Intracellular survival allows pathogens to hide inside host cells, shielding themselves from antibodies and complement in the extracellular fluid. Mycobacterium tuberculosis survives inside macrophages by preventing phagosome-lysosome fusion. Listeria monocytogenes escapes the phagosome and spreads directly from cell to cell, avoiding extracellular exposure entirely.

Molecular mimicry involves expressing antigens that resemble host molecules, making it harder for the immune system to recognize the pathogen as foreign. Streptococcus pyogenes produces M protein that mimics cardiac myosin, which can trigger autoimmune damage to the heart (rheumatic fever). Staphylococcus aureus produces Protein A, which binds the Fc region of antibodies in the wrong orientation, preventing opsonization and complement activation.

Complement evasion involves secreting proteins that inhibit or degrade complement components. Streptococcus pneumoniae produces pneumolysin, which inhibits C3 convertase. Borrelia burgdorferi (the Lyme disease spirochete) coats itself with host complement regulatory proteins, essentially disguising itself from the complement cascade.