Innate Immunity Overview

Innate Immunity

• Innate immunity is the body's first line of defense against any microbial infection or foreign material
• It provides protective mechanisms that don't require a prolonged induction period
• It recognizes non-self structures but not self, avoiding autoimmunity
• Pattern recognition receptors (PRRs) recognize pathogen-associated molecular patterns (PAMPs)
• It detects immunological danger in the form of damage-associated molecular patterns (DAMPs)
• Innate immunity is activated rapidly by microbes and subsequently activates adaptive immunity
• Innate immunity is present from birth and is non-specific
• It does not improve after exposure to antigens
• It is available quickly and is antigen-independent
• It has limited diversity and no immune memory
• Physical barriers such as skin, form a hostile environment against microbes.
• The dry, acidic surface of skin and continual loss of outer dead skin layers remove potential pathogens.
• Cells of the stratum corneum create a tight barrier preventing toxins and bacteria from entering.
• Sebaceous glands in dermis produce sebum to maintain pH between 3-5, inhibiting potential pathogen growth.
• Sweat regulates body temperature to flush microbes and waste and lysozyme inhibits microbial growth
• Mucous membranes are linings of the respiratory, digestive, and genitourinary tracts
• Continuously produce mucus, a viscous glycoprotein which traps microbes and debris
• Epithelial cells with inner connective tissue secrete mucus and prevent desiccation, trapping microbes.
• Enzymes within mucus kill microbes, the acidic environment of the stomach also kills microbes.
• Mucus-coated nose hairs trap microbes, the ciliary escalator in the lower respiratory tract pushes outward microbes; sneezing/coughing speeds the process
• Epiglottis covers the larynx preventing food and microbes from entering.
• Tears from lacrimal glands wash over the eye and drain into lacrimal ducts, containing lysozyme breaking down bacterial cell walls.
• Urine flushes out microbes and contains uric acid, urea and lysozyme.
• Acidic environment of vagina has lactic acid secreted by bacteria maintaining a pH 4.4-4.6 to kill microbes.
• Saliva from salivary glands constantly cleans teeth and mouth, containing lysozyme and aggregate bacteria
• Gastric juice with HCl, mucus, and enzymes with a low pH of 1.5-3 kills most microbes and toxins.
• Small intestine mucus prevents attachment and entry. Pancreatic enzymes, bile, intestinal enzymes, and secretory IgA help.
• M cells endocytose pathogens aiding presentation to B & T lymphocytes
• peristalsis moves food, defecation eliminates waste, vomiting responds to toxins
• Blood-brain barrier, blood-placenta barrier, and blood-thymus barrier protect privileged organs.
• Recognition of signals indicates 'all is well' and prevents immune response against host tissues.

Normal Flora

• "Normal microbiota" are microorganisms living on the body, inhibiting pathogen growth
• Commensal microbes are not pathogenic except under specific circumstances.
• The skin and gastrointestinal tract are colonized by over 500 microbial species
• They defend their territory through physical advantage, nutrient competition, and inhibitory substances like acid and toxins.

Second Line of Defense

• Formed elements of blood: platelets involved in blood clotting, erythrocytes transport oxygen/carbon dioxide, leukocytes include granulocytes and agranulocytes (e.g., neutrophils, basophils, eosinophils, monocytes, macrophages, dendritic cells, and natural killer cells.)
• Phagocytes (e.g., neutrophils, monocytes, macrophages) perform phagocytosis, engulfing and destroying microbes through chemotaxis, adherence, ingestion, and digestion.

Soluble Factors

• Acute-phase proteins increase plasma protein levels (e.g., C-reactive protein, mannose-binding protein) in response to cytokines produced by macrophages after exposure to microorganisms.
• These proteins bind bacterial surfaces and activate complement.
• Interferons (alpha, beta, gamma), chemokines (chemotactic activity), and enzymes (lactoperoxidase, lactoferrin, myeloperoxidase) are part of the soluble factors.
• Complement (serum proteins C1-C30; C5b-C9 form membrane attack complex).

Complement Activation

• Complement activation occurs through the classical, alternative, or lectin pathways.
• Classical pathway is activated by antibodies, alternative pathway by microbial surfaces, and the lectin pathway by microbial surfaces.

Inflammation

• Inflammation is a reaction to injury, from infection or physical/chemical trauma, to restore homeostasis.
• Acute inflammation is rapid and resolves quickly (infection removed) while chronic inflammation persists longer.
• Inducing factors include endogenous factors (tissue necrosis, hypersensitivity, bone fracture) and exogenous factors (mechanical injury, burns, chemical injury, and infectious agents).
• Hallmark signs are tumor (swelling), rubor (redness), calor (heat), and dolor (pain).
• Inflammatory response steps:

1. Vasodilation & increased vessel permeability, histamine released kins, prostaglandins, leukotrienes, cytokines, and clotting factors
2. Phagocyte migration and phagocytosis, phagocytes migrate to site of infection (diapedesis), phagocytic cells engulf microbes
3. Tissue repair, damaged tissue replaced, inflammatory response clears infection site and prevents infection, and phases are inflammatory, proliferative, and re-modeling

Antigens and Antibodies

• Antigens are substances/molecules recognized as foreign by the immune system
• Immunogens are antigens that trigger an immune response. All immunogens are antigens but not all antigens are immunogens.
• Epitopes/antigenic determinants are the smallest portion of an antigen recognized by B and T receptors.
• An antigen can have multiple epitopes.
• An epitope on a monovalent antigen is different from a bivalent antigen.
• A single antibody only recognizes one epitope at a time, not the whole antigen.
• T-independent antigens are antigens capable of directly stimulating B cells to produce antibodies without the help of T helper cells.
• These antigens have repeated epitopes, activating B cell clones for other antigens (polyclonal activation).
• T-independent antigens are generally more resistant to degradation.
• Antigens can be proteins, polysaccharides, nucleic acids, or lipids. Exogenous/endogenous antigens (external/internal body origin)
• Autoantigens are normal proteins/protein complexes (DNA, RNA) recognized as non-self by the immune system.
• These antigens cause issues when the immune system has lost immunological tolerance (e.g., Nucleoproteins, Nucleic acids).
• Complete antigens have antigenic properties, to generate immune responses by themselves, high molecular weight.

Incomplete Antigens (Haptens)

• Haptens are incomplete antigens, unable to induce an immune response on their own but can react with specific antibodies when combined with larger molecules (carrier molecules).
• Haptens are often small molecules that become immunogenic after binding to a carrier molecule.
• Haptenic determinants are new determinants created by the hapten.
• The type of carrier molecule determines if the response will be T-independent or T-dependent.

Explore the fundamental aspects of innate immunity, the body's first line of defense against infections. This quiz covers its functions, mechanisms, and the role it plays in activating adaptive immunity. Test your knowledge on how innate immunity distinguishes between self and non-self structures.