Innate Immunity: Nonspecific Defenses of the Host

Innate Immunity: Nonspecific Defenses of the Host

Introduction to Innate Immunity

Innate immunity is the body's first line of defense against invading pathogens, providing rapid, nonspecific protection. Unlike adaptive immunity, innate immunity is present at birth and does not require previous exposure to a pathogen. It includes physical barriers, cellular defenses, and various chemical mediators.

• Innate Immunity: Defenses against any pathogen; rapid and present at birth.

• Adaptive Immunity: Immunity or resistance to a specific pathogen; slower to respond, has memory component.

• Immunity: The ability to ward off disease.

• Susceptibility: Lack of resistance to a disease.

Physical Barriers of Innate Immunity

The body employs several physical barriers to prevent the entry of pathogens. These include the skin, mucous membranes, and associated structures.

• Skin: Composed of the dermis (connective tissue) and epidermis (tightly packed epithelial cells containing keratin). Shedding and dryness inhibit microbial growth.

• Mucous Membranes: Line the gastrointestinal, respiratory, and genitourinary tracts. Mucus traps microbes and prevents tracts from drying out.

• Lacrimal Apparatus: Drains tears and washes the eye, removing microbes.

• Ciliary Escalator: Transports microbes trapped in mucus away from the lungs.

• Other Mechanisms: Earwax, urine flow, vaginal secretions, peristalsis, defecation, vomiting, and diarrhea help expel pathogens.

Chemical Barriers of Innate Immunity

Chemical factors in body fluids and secretions further inhibit microbial growth and survival.

• Sebum: Forms a protective film and lowers the pH (3–5) of skin.

• Lysozyme: Present in perspiration, tears, saliva, and urine; destroys bacterial cell walls.

• Gastric Juice: Low pH (1.2–3.0) destroys most bacteria and toxins.

• Vaginal Secretions: Low pH (3–5) inhibits microbes.

Role of Normal Microbiota

Normal microbiota play a crucial role in innate immunity by competing with pathogens for space and nutrients, producing substances harmful to pathogens, and altering environmental conditions to inhibit pathogen survival.

• Microbial Antagonism (Competitive Exclusion): Normal microbiota outcompete pathogens.

• Commensalism: One organism benefits, the other is unharmed.

• Probiotics: Live microbial cultures administered to exert a beneficial effect.

Cellular Components of Innate Immunity

Leukocytes (White Blood Cells)

Leukocytes are the primary cells involved in innate and adaptive immune responses. They are classified as granulocytes or agranulocytes based on the presence of granules in their cytoplasm.

• Granulocytes: Neutrophils, basophils, eosinophils, and mast cells.

• Agranulocytes: Monocytes (macrophages, dendritic cells), lymphocytes (T cells, B cells, NK cells).

Normal White Blood Cell Counts

White blood cell (WBC) counts are used to assess immune status. Abnormal counts may indicate infection, autoimmune disease, or other conditions.

• Neutrophils: 60–70%

• Lymphocytes: 20–25%

• Monocytes: 3–8%

• Eosinophils: 2–4%

• Basophils: 0.5–1%

Mechanisms of Innate Immunity

Phagocytosis

Phagocytosis is the process by which certain cells (phagocytes - neutrophils and monocytes - macrophage ) ingest and destroy microbes and cellular debris. Key steps include chemotaxis, adherence, ingestion, and digestion.

• Chemotaxis: Chemical signals attract phagocytes to microorganisms.

• Adherence: Attachment of a phagocyte to the surface of the microorganism.

• Ingestion: Opsonization (coating with serum proteins) enhances ingestion.

• Digestion: Microorganism is digested inside a phagolysosome.

Inflammation

Inflammation is a local response to infection or injury, characterized by redness, heat, swelling, pain, and loss of function. It serves to contain and eliminate injurious agents and initiate tissue repair.

• Stages of Inflammation:

  1. Vasodilation and increased permeability of blood vessels

  2. Phagocyte migration and phagocytosis

  3. Tissue repair

• Mediators: Histamine, kinins, prostaglandins, leukotrienes, cytokines

Fever

Fever is an abnormally high body temperature, often caused by infection. Cytokines reset the hypothalamus to a higher temperature, which can inhibit pathogen growth and enhance immune responses.

• Benefits: Inhibits growth of some microbes, increases production of immune cells, and speeds up tissue repair.

Antimicrobial Substances

The Complement System

The complement system consists of serum proteins that enhance the ability of antibodies and phagocytic cells to clear microbes and damaged cells. It can be activated by three pathways: classical, alternative, and lectin.

• Classical Pathway: Triggered by antibodies binding to antigens.

• Alternative Pathway: Triggered by complement proteins binding directly to pathogen surfaces (eg: opsinization in phagocytosis)

• Lectin Pathway: Triggered by lectin binding to microbial carbohydrates (lectin is a protein that can recognise and bind to specific sugars (carbohydrates).

Outcomes of Complement Activation:

• Cytolysis: Formation of membrane attack complex (MAC) that lyses pathogens.

• Opsonization: Enhances phagocytosis by marking pathogens for ingestion.

• Inflammation: Complement proteins trigger release of histamine and other mediators.

Interferons

Interferons are cytokines produced by cells in response to viral infections. They help protect neighboring cells by inducing the production of antiviral proteins.

• IFN-α and IFN-β: Induce antiviral proteins in neighboring cells.

• IFN-γ: Activates neutrophils and macrophages to kill bacteria.

Iron-Binding Proteins

Iron-binding proteins (e.g., transferrin, lactoferrin, ferritin, hemoglobin) sequester iron, making it unavailable to microbes. Some bacteria produce siderophores to compete for iron.

Antimicrobial Peptides (AMPs)

AMPs are short peptides produced in response to microbial molecules. They inhibit cell wall synthesis, form pores in microbial membranes, and have broad-spectrum activity.

Summary Table: Leukocytes and Their Functions

Innate or Adaptive	Cell Type	Description	Function
Innate	Basophil	Granulocyte	Releases histamines that cause inflammation.
Innate	Eosinophil	Granulocyte	Kills parasites with oxidative burst.
Innate	Mast cell	Granulocyte	Antigen-presenting cells; produce antibacterial peptides.
Both	Neutrophil	Granulocyte	Phagocytizes bacteria and fungi.
Both	Monocyte	Agranulocyte	Precursor to macrophages; some are fixed in certain organs and produce cytokines.
Both	Dendritic cell	Agranulocyte	In skin and respiratory and intestinal mucosa; phagocytizes bacteria and presents antigens to T cells.
Both	Natural killer (NK) cell	Lymphocyte	Kills cancer cells and virus-infected cells.
Adaptive	Plasma cell, B cell	Agranulocyte (lymphocyte)	Recognizes antigens and produces antibodies.
Adaptive	T cells	Agranulocyte (lymphocyte)	Secrete cytokines, kill virus-infected cells, and regulate immune responses.

Conclusion

Innate immunity provides essential, immediate defense against pathogens through physical and chemical barriers, cellular responses, and antimicrobial substances. Understanding these mechanisms is crucial for comprehending how the body prevents and controls infections before the adaptive immune system is activated.