Innate Immunity: Nonspecific Defenses of the Host

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Innate Immune Response

Overview of Innate Defenses

The innate immune system provides the body's first and immediate line of defense against invading pathogens. It consists of physical barriers, sensor systems, cellular defenses, and chemical mediators that act rapidly and nonspecifically to prevent infection and eliminate invaders.

First line of defense: Physical and chemical barriers that prevent pathogen entry.
Sensor systems: Cellular receptors and proteins that detect breaches in barriers and initiate immune responses.
Effector actions: Cellular and molecular mechanisms that destroy or remove invaders.

First Line of Defense

Physical Barriers

Physical barriers are anatomical structures that separate the internal environment from the external world, preventing pathogen entry.

Skin: The most visible and effective barrier, composed of the tough dermis and keratinized epidermis. The outer layers slough off, removing attached microbes.
Mucous membranes: Line the digestive, respiratory, and genitourinary tracts. Mucus traps microbes, and cilia or other mechanisms help expel them.

Diagram of body surfaces showing skin and mucous membranes as barriers

Chemical Barriers and Antimicrobial Substances

Both skin and mucous membranes are protected by a variety of antimicrobial substances:

Lysozyme: Enzyme that degrades peptidoglycan; found in tears, saliva, and phagocytes.
Peroxidase: Breaks down hydrogen peroxide to produce reactive oxygen; found in saliva, tissues, and phagocytes.
Lactoferrin: Sequesters iron, inhibiting microbial growth; present in saliva, phagocytes, blood, and tissue fluids.
Defensins: Antimicrobial peptides that disrupt microbial membranes; found on mucous membranes and in phagocytes.

Diagram of human body showing physical and chemical barriers

Normal Flora

Normal flora are non-pathogenic microorganisms that colonize body surfaces and provide protection by:

Competing with pathogens for binding sites and nutrients (competitive exclusion).
Producing substances that inhibit or kill pathogens.

Additional info: Disruption of normal flora (e.g., by antibiotics) can increase susceptibility to infections.

Sensor Systems

Pattern Recognition Receptors (PRRs)

Sensor systems detect signs of tissue damage or microbial invasion using pattern recognition receptors (PRRs), which recognize conserved microbial molecules.

Toll-like receptors (TLRs): Located on cell surfaces or endosomes; detect microbial components such as lipopolysaccharide (LPS), flagellin, peptidoglycan, and bacterial nucleic acids.
NOD proteins: Detect microbial molecules inside the cell.

Diagram of host cell with Toll-like receptors detecting microbial components

The Complement System

The complement system is a group of proteins circulating in blood and tissue fluids in an inactive form. Activation triggers a cascade of reactions leading to pathogen destruction. There are three main pathways of activation:

Alternative pathway: Triggered by C3b binding to microbial surfaces.
Lectin pathway: Initiated by mannose-binding lectins (MBL) binding to microbial carbohydrates.
Classical pathway: Initiated by antibodies binding to antigens.

Diagram of complement activation pathways and outcomes

Major Outcomes of Complement Activation

Inflammation: C3a and C5a induce vascular changes and attract immune cells.
Opsonization: C3b coats microbes, enhancing phagocytosis.
Lysis of foreign cells: Formation of the membrane attack complex (MAC) creates pores in microbial membranes, leading to cell lysis (especially effective against Gram-negative bacteria).

Diagram of membrane attack complex (MAC) formation

Cells of the Immune System

Blood Cell Formation (Hematopoiesis)

All blood cells, including immune cells, originate from hematopoietic stem cells in the bone marrow. Differentiation is regulated by colony-stimulating factors.

Red blood cells (erythrocytes): Carry oxygen.
Platelets: Involved in blood clotting.
White blood cells (leukocytes): Key players in host defense; divided into granulocytes, mononuclear phagocytes, dendritic cells, and lymphocytes.

Diagram of hematopoiesis and immune cell lineages

Granulocytes

Granulocytes are white blood cells with cytoplasmic granules. They include:

Neutrophils: Most abundant; primary phagocytes in innate immunity.
Basophils: Involved in allergic responses.
Eosinophils: Important in defense against parasitic worms and in allergic reactions.

Diagram of granulocyte differentiation

Mononuclear Phagocytes and Dendritic Cells

Monocytes: Circulate in blood; differentiate into macrophages in tissues.
Macrophages: Abundant in tissues such as liver, spleen, lymph nodes, and lungs; phagocytose microbes and debris.
Dendritic cells: Function as antigen-presenting cells, bridging innate and adaptive immunity by capturing antigens and presenting them to lymphocytes.

Lymphocytes

B lymphocytes (B cells): Produce antibodies; central to adaptive immunity.
T lymphocytes (T cells): Mediate cellular immunity.
Natural killer (NK) cells: Destroy infected or abnormal host cells without antigen specificity.

Cell Communication in Immunity

Surface Receptors

Surface receptors are membrane proteins that bind specific signaling molecules (ligands), transmitting signals into the cell to initiate responses.

Cytokines

Cytokines are chemical messengers that regulate immune cell function. Major classes include:

Chemokines: Direct cell movement (chemotaxis).
Colony-stimulating factors: Stimulate blood cell production and differentiation.
Interferons: Control viral infections and modulate immune responses.
Interleukins: Produced by leukocytes; regulate both innate and adaptive immunity.
Tumor necrosis factor: Induces inflammation and kills tumor cells.

Adhesion Molecules

Adhesion molecules enable immune cells to adhere to each other and to blood vessel walls, facilitating migration to sites of infection or injury.

Phagocytosis

Steps of Phagocytosis

Phagocytosis is the process by which phagocytes engulf and destroy microbes and debris. The steps include:

Chemotaxis: Phagocytes are attracted to infection sites by chemical signals.
Recognition and attachment: Phagocytes bind to microbes using receptors (often enhanced by opsonization with C3b).
Engulfment: The microbe is engulfed into a phagosome.
Phagosome-lysosome fusion: The phagosome fuses with a lysosome, forming a phagolysosome.
Destruction and digestion: Microbes are killed by toxic oxygen products and enzymes.
Exocytosis: Debris is expelled from the cell.

Diagram of phagocytosis steps

Inflammation

Initiation and Process

Inflammation is a localized response to tissue damage or infection, characterized by heat, pain, redness, swelling, and sometimes loss of function. It is initiated by:

Microbial products triggering TLRs on macrophages, leading to cytokine release.
Complement activation (C3a, C5a) attracting immune cells.
Tissue damage activating enzymatic cascades.

The inflammatory process involves vasodilation, increased vascular permeability, and migration of leukocytes (diapedesis) to the site of injury.

Diagram of inflammation process and diapedesis Diagram of phagocyte migration and pus formation during inflammation

Outcomes of Inflammation

Limits damage and restores tissue function.
Excessive inflammation can cause tissue damage, especially in sensitive organs (e.g., brain, spinal cord).

Apoptosis

Apoptosis is programmed cell death that eliminates cells without triggering inflammation. Apoptotic cells are engulfed by macrophages without inducing an inflammatory response.

Fever

Fever is a systemic response to infection, especially bacterial. It is triggered by pyrogens (endogenous cytokines or exogenous microbial products) and results in:

Inhibition of pathogen growth by raising body temperature above optimal levels for microbes.
Acceleration of immune responses and tissue repair.