Innate Immunity

Overview of Immune Responses

The immune system protects the body from pathogens through coordinated physiological processes. Immune responses are classified as either innate or adaptive immunity, both of which recognize diverse pathogens, eliminate invaders, and discriminate between self and foreign antigens.

• Innate Immunity: Inborn, ancient protection found in all eukaryotes; provides generalized, nonspecific responses.

• Adaptive Immunity: Found only in vertebrates; matures over time, tailors responses to specific pathogens, and exhibits memory.

• Immune: Specific protection conferred by adaptive responses.

• Susceptible: Not immune to a pathogen and may develop infection.

Collaboration Between Innate and Adaptive Immunity

Immunity consists of three collaborating lines of defense: barrier defenses, cellular and molecular defenses, and adaptive defenses.

Role of Normal Microbiota

Normal microbiota are symbiotic microbes that live in and on the body, shaping immune responses and conferring protection. They train the immune system to tolerate nonpathogens and self-tissues, and changes in microbiota composition may lead to immune confusion, allergies, or autoimmunity.

• Hygiene Hypothesis: Suggests reduced microbial diversity negatively affects immune responses.

• Germ-free animal studies show microbe-free environments lead to underdeveloped immune systems.

First-Line Defenses

Types of Barriers

First-line defenses prevent pathogen entry and are categorized as mechanical, chemical, and physical barriers.

• Mechanical Barriers: Flushing, rinsing, and trapping actions (e.g., tears, urine, saliva, mucus membranes).

• Chemical Barriers: Molecules that attack microbes or create hostile environments (e.g., lysozyme, stomach acid, fatty acids).

• Physical Barriers: Structural blockades (e.g., skin, epithelial tissue).

Antimicrobial Peptides (AMPs)

AMPs are proteins that destroy a wide spectrum of pathogens by disrupting membranes, targeting intracellular components, and stimulating leukocytes.

• Defensins: Mammalian AMPs that rapidly kill invaders by inserting into cell membranes.

Second-Line Defenses

Lymphatic System

The lymphatic system collects, circulates, and filters body fluids, playing a crucial role in immune function. Lymphatic capillaries take up interstitial fluid, which is then called lymph and filtered in lymph nodes before returning to the blood.

Primary and Secondary Lymphoid Tissues

• Primary: Thymus (T cell maturation), bone marrow (B cell maturation, blood cell production).

• Secondary: Lymph nodes (filter lymph), spleen (filters blood), MALT (mucosa-associated lymphoid tissue).

Leukocytes

Leukocytes are essential for immune responses and are classified as granulocytes (with granules) and agranulocytes (without granules).

White Blood Cell Counts

Differential WBC count is a clinical measure to diagnose infections or immune disorders. Leukocytosis indicates increased leukocytes.

Phagocytes

Phagocytes (macrophages, dendritic cells, neutrophils) clear invaders by engulfing and destroying them. Some microbes evade phagocytosis using virulence factors.

Granulocytes

• Neutrophils: Most numerous, first responders, release AMPs, phagocytize pathogens.

• Eosinophils: Combat parasites and allergens, moderate phagocytic activity.

• Basophils: Release histamine, combat parasites, involved in allergies.

• Mast Cells: Reside in tissues, release histamine, conduct phagocytosis.

Agranulocytes

• Monocytes: Largest, mature into macrophages, increase in chronic infections.

• Macrophages: Highly phagocytic, fixed or wandering.

• Dendritic Cells: Highly phagocytic, modulate immune responses.

• Lymphocytes: NK cells (innate), B and T cells (adaptive).

Molecular Second-Line Defenses

Cytokines

Cytokines are signaling proteins that coordinate immune actions. Types include chemokines (attract WBCs), interleukins (activate immune responses), interferons (antiviral signals), and tumor necrosis factors (stimulate inflammation).

Iron-Binding Proteins

Iron-binding proteins (hemoglobin, ferritin, lactoferrin, transferrin) limit iron availability to pathogens. Some microbes produce siderophores to steal iron or use hemolytic strategies.

Complement System

The complement system consists of over 30 proteins that work in a cascade to boost immune defenses. Activation occurs via classical, alternative, or lectin pathways, leading to opsonization, membrane attack complex (MAC) formation, and inflammation.

• Opsonization: Tags invaders for phagocytosis.

• MAC: Causes cytolysis.

• Inflammation: Promotes immune cell recruitment.

Complement Regulation

Complement proteins are regulated by self-destruct features and regulators of complement activation (RCAs) to prevent tissue damage.

Inflammation and Fever

Inflammation

Inflammation is a protective response essential for healing. It develops when tissues are damaged and involves blood-clotting cascades to curb blood loss and limit pathogen spread.

• Main Goals: Recruit immune defenses, limit spread, deliver nutrients for recovery.

• Cardinal Signs: Redness, pain, localized heat, swelling, loss of function.

Phases of Inflammation

• Vascular Changes: Vasodilatation and increased vessel permeability; exudate accumulates.

• Leukocyte Recruitment: Chemoattractants recruit neutrophils and monocytes; margination and diapedesis allow leukocytes to exit vessels.

• Resolution: Inflammation signals decrease, tissue repair begins, leukocytes undergo apoptosis, pus may form.

Chronic Inflammation

Chronic inflammation is harmful, exacerbates tissue injury, and is linked to diseases such as atherosclerosis, cancer, and neurodegenerative disorders.

Fever

Fever (pyrexia) is a systemic innate response characterized by elevated body temperature. Pyrogens (e.g., bacterial toxins, cytokines) signal the hypothalamus to raise the body's temperature.

• Benefits: Enhances interferon effects, increases phagocyte efficiency, limits pathogen growth, promotes tissue repair.

• Low-grade fever: Considered protective; may not require treatment.

• Antipyretics: Drugs like aspirin, ibuprofen, acetaminophen reduce fever by limiting prostaglandin production.

• High fever: Life-threatening; can denature essential enzymes and proteins.