Innate Immunity: Nonspecific Lines of Defense in Microbiology

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Chapter 15: Innate Immunity – Nonspecific Lines of Defense

Overview of Defense Mechanisms

The human body employs multiple layers of defense to protect against pathogenic microorganisms. These defenses are categorized as innate (nonspecific) and adaptive (specific) immunity. Innate defenses are present at birth and provide immediate, broad protection, while adaptive defenses are specific and develop after exposure to pathogens.

Innate defenses: Natural resistance to most pathogens, present before exposure.
Nonspecific defenses: First and second lines of defense, acting against a wide range of pathogens.
Specific defenses: Third line, involving lymphocytes and antibodies, targeting specific pathogens (covered in Ch. 16).

Diagram of the three lines of defense: skin/mucous membranes, phagocytosis/inflammation, and lymphocytes/antibodies

First Line of Defense: Physical and Chemical Barriers

Physical Barriers

The first line of defense consists of anatomical structures and secretions that prevent pathogen entry into the body. These barriers are nonspecific and act against a broad range of invaders.

Skin: The epidermis is composed of tightly packed cells that are continually shed, removing attached microbes. Dendritic (Langerhans) cells in the epidermis perform phagocytosis.
Dermis: Contains collagen fibers for strength and sweat glands that secrete antimicrobial substances.
Mucous membranes: Line all body cavities open to the environment (respiratory, digestive, urinary, reproductive systems). Consist of a tightly packed epithelial layer and a supportive connective tissue layer.
Tear ducts (lacrimal apparatus): Wash away foreign material from the eyes using fluid containing lysozyme.
Normal flora (microbial antagonism): Compete with pathogens for nutrients and space, secrete antimicrobial substances, and alter local pH.

Scanning electron micrograph of the skin surface Diagram of skin structure showing epidermis and dermis

Mucous Membranes

Mucous membranes are specialized to trap and remove pathogens. Goblet cells produce mucus, ciliated cells propel mucus, and dendritic cells perform phagocytosis. Lysozyme in mucus degrades bacterial cell walls.

Diagram of the respiratory tract showing mucous membranes Diagram of the digestive tract showing mucous membranes Diagram of ciliated epithelium with goblet cells Micrograph of cilia on epithelial cells Diagram of respiratory epithelium with cilia and mucus

Tear Ducts (Lacrimal Apparatus)

The lacrimal apparatus produces tears that mechanically flush the eye and contain lysozyme, which has antimicrobial properties.

Diagram of the lacrimal apparatus and tear flow

Microbial Antagonism (Normal Flora)

Normal flora protect the body by outcompeting pathogens, secreting antimicrobial substances, consuming nutrients, altering pH, and stimulating the immune system. They also contribute to host health by producing vitamins (e.g., B5 in the intestine).

Diagram showing locations and types of normal flora in the human body

Chemical Barriers

Body organs secrete chemicals and enzymes that inhibit microbial growth:

Perspiration (sweat glands): Contains salt (promotes desiccation of microbes) and lysozyme (destroys bacterial cell walls).
Sebum (sebaceous glands): Keeps skin pliable and lowers pH, inhibiting many bacteria.
Other secretions: Urination, defecation, vomiting, coughing, sneezing, and crying help expel pathogens.
Antimicrobial peptides (defensins): Create holes in microbial membranes and disrupt bacterial signaling (quorum sensing).
Toll-Like Receptors (TLRs): Recognize common microbial molecules and trigger immune responses.

Table of Toll-Like Receptors, their ligands, and sources

Second Line of Defense: Internal Nonspecific Responses

Blood and Immune Cells

When pathogens breach the first line of defense, the second line is activated. This includes cellular and chemical components found in blood, but not physical barriers.

Plasma: Contains water, electrolytes, nutrients, proteins (including complement proteins and antibodies).
Serum: Plasma without clotting factors.
Formed elements: Erythrocytes (gas transport), platelets (clotting), leukocytes (defense).
Leukocytes: Granulocytes (basophils, eosinophils, neutrophils) and agranulocytes (lymphocytes, monocytes).

Diagram of blood cell hematopoiesis

Phagocytosis

Phagocytes (certain leukocytes and derivatives) ingest and destroy pathogens in a tightly regulated process. The five stages are:

Chemotaxis: Movement toward chemical signals (cytokines).
Adherence: Attachment to microbes via receptors (opsonization enhances this step).
Ingestion: Formation of a phagosome (vacuole).
Digestion: Fusion of phagosome with lysosome; enzymes degrade the microbe.
Elimination: Expulsion of digested material.

Diagram of the stages of phagocytosis Micrograph of a phagocyte ingesting a microbe

Phagocytosis – Blocking Mechanisms

Some pathogens evade phagocytosis by various mechanisms, such as preventing chemotaxis, adherence, ingestion, or digestion.

Diagram of phagocytosis and microbial evasion mechanisms

Protection of Self

Body cells are marked with autoantigens (MHC) to prevent phagocytosis. Phagocytes have receptors for microbial components not found on host cells, and signaling molecules (complement, antibodies, interferons, defensins) provide targeted instructions.

Inflammation

Inflammation is a nonspecific response to tissue damage, characterized by redness, heat, swelling, and pain. It can be acute (short-lived, beneficial) or chronic (long-lasting, potentially damaging).

Acute inflammation: Involves vasodilation, increased permeability, migration of phagocytes, and tissue repair.
Chronic inflammation: Prolonged, can damage tissues.

Diagram of vasodilation and increased capillary permeability during inflammation Diagram of the inflammatory response: tissue injury and signaling molecules

Fever

Fever is an elevated body temperature triggered by pyrogens (e.g., bacterial toxins, interleukin-1). It enhances phagocyte activity, tissue repair, and interferon effects, while inhibiting some pathogens.

Nonspecific Chemical Defenses

Chemical responses protect against broad classes of invaders and promote phagocytosis, inflammation, and fever. Major systems include:

Interferon system: Proteins released by virus-infected cells signal neighboring cells to produce antiviral proteins (AVPs), which block viral replication.
Complement system: Serum proteins activated by infection that assist in phagocytosis (opsonization), promote inflammation, and form membrane attack complexes (MAC) to lyse foreign cells.

Diagram of the interferon system and antiviral protein production Diagram of the complement system pathways and outcomes Diagram of the membrane attack complex (MAC) formation

Summary Table: Main Functions of the Complement System

Function	Description
Opsonization	Coating of microbes to enhance phagocytosis
Promotion of Inflammation	Recruitment and activation of immune cells
Membrane Attack Complex (MAC)	Formation of pores in pathogen membranes, leading to lysis

Key Terms and Concepts

Innate immunity: Nonspecific, immediate defense present at birth.
Phagocytosis: Cellular process of engulfing and destroying pathogens.
Inflammation: Localized response to tissue injury or infection.
Fever: Systemic increase in body temperature as a defense mechanism.
Interferons: Proteins that inhibit viral replication.
Complement system: Group of proteins that enhance immune responses.
Normal flora: Beneficial microorganisms that inhabit the body and prevent pathogen colonization.

Equations and Formulas

Fever temperature conversion:

Additional info: This guide covers the main concepts of innate immunity, focusing on the first and second lines of defense as outlined in Chapter 15 of a typical microbiology curriculum. For adaptive (specific) immunity, see Chapter 16.