Table of Contents
Passive resistance, or general defense, includes all innate protective mechanisms that act against a wide range of potential pathogens without needing prior contact or specific recognition. These defenses are always “on” or can be activated very quickly and form the first and second lines of defense before specific immune reactions (antibodies, T cells) become active.
Physical and Mechanical Barriers
Skin
The intact skin is the most important external barrier:
- Multilayered structure: Several cell layers (epidermis) form a tough, abrasion‑resistant armor.
- Keratinization: Keratin in the outermost layers makes the skin water‑repellent and mechanically robust.
- Desquamation: Constant shedding of the outer skin layers mechanically removes microbes and attached particles.
- Low water availability: The dry surface limits many bacteria and fungi that need moisture.
Wounds, burns, and skin diseases that damage this barrier dramatically increase the risk of infection because pathogens can penetrate deeper tissues.
Mucous Membranes
Mucous membranes line body surfaces that are not covered by skin but open to the outside (respiratory tract, digestive tract, urogenital tract). They provide a combination of mechanical and chemical defenses:
- Mucus production: Mucus traps inhaled or ingested particles and microbes.
- Continuous flow: Movement of mucus (by cilia or peristalsis) transports trapped material away from vulnerable tissues.
- Rapid cell turnover: Epithelial cells are frequently renewed; attached microbes are sloughed off.
Ciliated Epithelium in the Respiratory Tract
- Cilia (“mucociliary escalator”): Tiny motile hairs on airway cells beat in a coordinated manner.
- Function: They push mucus, with trapped dust, pollen, and microorganisms, toward the throat to be swallowed or coughed out.
- Impairment: Smoking, some pollutants, and certain viral infections can paralyze or destroy cilia, increasing susceptibility to respiratory infections.
Mechanical Cleansing Processes
Several simple but effective mechanical processes support general defense:
- Tears and blinking: Regular rinsing of the eye removes particles and microbes.
- Saliva and swallowing: Dilutes and transports microbes to the stomach’s acidic environment.
- Coughing and sneezing: Forcefully expel irritants and microorganisms from the airways.
- Urine flow: Flushes the urinary tract and hinders bacterial colonization.
- Peristalsis and bowel movements: Move contents along the intestine and prevent long‑term colonization by many potential pathogens.
Chemical Barriers
Chemical defenses are substances that directly kill or inhibit microorganisms, or create an environment unfavorable for them.
pH and Enzymes
- Stomach acid (gastric juice):
- Very low pH (about 1–2) kills most swallowed bacteria and viruses.
- Drugs that reduce stomach acid (e.g., proton pump inhibitors) can increase the survival of ingested microbes.
- Skin acidity (“acid mantle”):
- Slightly acidic pH (about 4.5–5.5) due to sweat and sebum.
- Inhibits growth of many bacteria and fungi that prefer neutral pH.
- Lysozyme:
- Enzyme in tears, saliva, nasal secretions, and some other body fluids.
- Attacks the cell wall of many bacteria (especially Gram‑positive), causing them to burst.
Antimicrobial Peptides and Secretions
- Defensins and related peptides:
- Short positively charged molecules produced by skin, mucous membranes, and some white blood cells.
- Insert into microbial membranes and make them leaky, leading to cell death.
- Sebum and fatty acids:
- Oily secretions from sebaceous glands on the skin.
- Contain fatty acids with antimicrobial properties.
- Lactoferrin and other iron‑binding proteins:
- Found in secretions (e.g., milk, saliva, tears) and in neutrophil granules.
- Bind iron, making it less available to bacteria that require it for growth.
The Role of Normal Flora (Microbiota)
The body’s surfaces are colonized by vast communities of mostly harmless or beneficial microorganisms (bacteria, some fungi), especially on the skin and in the gut. They contribute to passive resistance in several ways:
- Space and nutrient competition:
- Occupy binding sites so pathogens cannot easily attach.
- Consume available nutrients, leaving less for invading microbes.
- Production of inhibitory substances:
- Many normal flora produce bacteriocins or acids that inhibit or kill competing bacteria.
- Lactic acid bacteria in the vagina, for example, acidify the environment and suppress pathogens.
- Stimulation of barrier integrity:
- Certain gut microbes promote the tight sealing of the intestinal epithelium and support the production of protective mucus.
Disruption of this normal flora—by broad‑spectrum antibiotics, drastic dietary changes, or illness—can lead to overgrowth of opportunistic pathogens (e.g., Clostridioides difficile in the intestine, Candida species in the mouth or vagina).
Complement System as Immediate Chemical Defense
The complement system is a group of plasma proteins that circulate in the blood in an inactive form and can be rapidly activated as part of nonspecific defense.
Although complement also interacts with specific immune responses, several of its actions belong to general defense:
- Direct killing of bacteria:
- Certain activated complement components form pores in bacterial membranes (membrane attack complex).
- Opsonization:
- Complement fragments bind to pathogen surfaces and “label” them.
- This makes them easier for phagocytes to recognize and ingest.
- Inflammatory signaling:
- Small complement fragments attract immune cells (chemotaxis) and increase blood vessel permeability, supporting rapid recruitment of defense cells.
The complement system can be activated spontaneously on pathogen surfaces (alternative pathway) without antibodies, making it part of passive, innate defense.
Cellular Components of General Defense
Some immune cells act as part of the nonspecific system by reacting quickly and broadly to intruders. They do not require prior “learning” of specific pathogens.
Phagocytes (Eating Cells)
Phagocytes engulf and digest microbes and particles. Important phagocytic cells in general defense include:
- Neutrophil granulocytes:
- Most abundant white blood cells in the blood.
- Rapidly migrate into tissue during infection.
- Ingest bacteria and fungi; release antimicrobial substances and enzymes.
- Short‑lived; large numbers of dead neutrophils form pus.
- Macrophages (and their precursors, monocytes):
- Reside in virtually all tissues.
- Continuously “patrol,” removing dead cells, debris, and microbes.
- Important early defenders; also link to later specific immune responses (antigen presentation, covered elsewhere).
Natural Killer (NK) Cells
NK cells specialize in recognizing and eliminating abnormal body cells, especially virus‑infected cells and some tumor cells, as part of innate defense:
- Recognition: Detect cells with altered or reduced expression of certain surface molecules (e.g., MHC class I).
- Killing: Release perforin and granzymes that induce a form of programmed cell death in target cells.
- Speed: Act much faster than specific cytotoxic T cells, especially during the early phase of viral infections.
Inflammation as a General Defense Reaction
Inflammation is a stereotyped local response to tissue damage or infection and belongs primarily to nonspecific defense. It aims to:
- Remove or neutralize the damaging factor (e.g., microbes, physical injury).
- Eliminate damaged tissue.
- Initiate repair processes.
Typical Signs of Local Inflammation
Classical local signs (using their Latin names) reflect underlying defensive processes:
- Rubor (redness):
- Local blood vessels dilate; more warm, oxygen‑rich blood reaches the affected area.
- Calor (heat):
- Increased blood flow raises temperature; many immune reactions run faster at slightly elevated temperatures.
- Tumor (swelling):
- Vessel walls become more permeable; fluid and proteins leave the bloodstream and enter the tissue.
- Brings antibodies and complement proteins to the site and allows immune cells to exit vessels.
- Dolor (pain):
- Mediators sensitize nerve endings.
- Pain encourages protection of the affected area and signals that something is wrong.
- Functio laesa (loss of function):
- Due to pain and swelling, normal function is restricted, supporting rest and healing.
Key Mediators and Events
Many chemical messengers contribute to the inflammatory response:
- Histamine:
- Released from mast cells and basophils.
- Causes vasodilation and increases vessel permeability.
- Prostaglandins and leukotrienes:
- Derived from membrane lipids; promote vasodilation, pain, and further mediator release.
- Cytokines (e.g., interleukins, interferons):
- Signaling proteins produced by many cell types.
- Attract and activate additional immune cells, coordinate local and systemic responses.
During inflammation:
- Phagocytes (especially neutrophils and macrophages) are attracted by chemotactic signals and eliminate pathogens and debris.
- Blood clotting factors help wall off the infected area and prevent spread of microbes via the bloodstream.
While acute inflammation is protective and essential for healing, dysregulated or chronic inflammation can damage tissues and contribute to many diseases.
Fever as a Systemic General Defense
Fever is a regulated rise in body temperature above normal due to a shifted “set point” in the hypothalamus. It often accompanies systemic infections.
How Fever Arises
- Pyrogens (fever‑inducing substances) can be:
- Exogenous: Components of microbes (e.g., parts of bacterial cell walls).
- Endogenous: Cytokines (e.g., interleukin‑1, TNF‑α) produced by immune cells in response to infection.
- These pyrogens act on the hypothalamus, which regulates body temperature, leading to:
- Reduced heat loss (e.g., vasoconstriction in skin, shivering to generate heat).
- Increased heat production (e.g., increased metabolism).
Defensive Functions of Fever
Within moderate ranges, fever can:
- Slow growth of some pathogens that replicate best at normal body temperature.
- Enhance certain immune responses, such as the activity of phagocytes and production of some immune mediators.
Extremely high or prolonged fever, however, is dangerous, especially for young children, the elderly, and people with pre‑existing health problems.
Summary: Characteristics of Passive General Defense
Passive resistance (general defense) is characterized by:
- Broad action: Effective against many different potential pathogens.
- Immediate or very fast response: No prior exposure necessary.
- Reliance on barriers, mechanical and chemical factors, and innate cells:
- Skin, mucous membranes, secretions, normal flora.
- Complement, antimicrobial molecules.
- Phagocytes, NK cells, inflammation, fever.
These mechanisms act together to prevent pathogens from entering the body, to limit their spread if they do enter, and to buy time until more targeted specific immune responses become active.