Innate and Adaptive Immune System

• Immunity offers resistance to disease through two intrinsic systems.

Innate (Nonspecific) Defense System

• Forms the first and second lines of defense
• The first line of defense involves external body membranes like skin and mucosae.
• The second line of defense includes antimicrobial proteins and phagocytes
• Other cells inhibit invaders, and inflammation is the most important mechanism.

Adaptive (Specific) Defense System

• This forms the third line of defense

• It attacks specific foreign substances

• Reacts slower compared to the innate system

• The immune system is a functional rather than an organ system

• Barriers, cells, degradative enzymes, and attack molecules are all defences that are intertwined

• Many defensive molecules are released and recognised by both

• Innate defenses use specific pathways for certain substances

• Innate responses release proteins that alert cells of the adaptive system to foreign molecules

Innate (Nonspecific) vs Adaptive (Specific) Immunity

• Innate immunity does not distinguish one threat from another
• It gives the same response regardless of the invading agent.
• It is preset at birth and provides nonspecific resistance, limits the spread of microbes and environmental hazards.
• Adaptive immunity uses adaptive defenses
• It protects against particular threats
• It depends on specific lymphocytes and provides specific resistance.

Innate Defenses

• The innate defense system uses the first and second lines of defense.
• Surface barriers include skin and mucous membranes.
• Internal defenses include phagocytes, natural killer cells, inflammation, antimicrobial proteins, and fever.

First Line of Defense: Surface Barriers

• Surface barriers are the skin and mucous membranes, along with their secretions.
• These are a physical barrier to most microorganisms
• Keratin is resistant to weak acids and bases, bacterial enzymes, and toxins.
• Mucosae provide similar mechanical barriers.
• Protective chemicals inhibit or destroy microorganisms

Protective Chemicals

• Include the acid mantle where acidity of skin and mucous secretions inhibits growth Include Enzymes like:
• Lysozyme in saliva, respiratory mucus, and lacrimal fluid kills microorganisms
• Enzymes in the stomach kill many microorganisms
• Mucin lines digestive and respiratory tracts, traps microorganisms
• Defensins are antimicrobial peptides that inhibit microbial growth
• Lipids in sebum and dermicidin in sweat that are toxic to some bacteria.

Respiratory System Modifications

• Respiratory system modifications stop pathogens.
• Mucus-coated hairs in the nose trap inhaled particles.
• Cilia in the upper respiratory tract sweep dust- and bacteria-laden mucus toward the mouth.
• Internal second line of defense triggers when surface barriers are breached by nicks or cuts protecting the deeper tissues

Second Line of Defenses: Cells and Chemicals

• Activated when microorganisms invade deeper tissues
• Includes phagocytes, natural killer (NK) cells, inflammatory response
• Also includes antimicrobial proteins (interferons and complement proteins), and fever.
• Second-line cells have pattern recognition receptors disarming microbes before harm.

Phagocytes

• It is a major group of cells that "eat" other cells.
• This includes white blood cells that ingest and digest foreign invaders.
• Examples include eosinophils and neutrophils.
• Neutrophils are abundant but die fighting and become phagocytic when exposed to infectious material.
• Macrophages are a type of phagocyte that develop from monocytes
• They are chief phagocytic cells.
• Free macrophages wander through tissue spaces, such as alveolar macrophages.
• Fixed macrophages are permanent residents of some organs, like stellate macrophages (liver) and microglia (brain).

Phagocytosis

• Process starts when phagocyte recognizes and adheres to pathogen's carbohydrate signature.
• Microorganisms evade phagocytosis with external capsules hiding surface carbohydrates.
• Opsonization enhances phagocytosis by coating pathogens with opsonins.

Steps of Phagocytosis

• Phagocytes adhere to pathogens or debris.
• Phagocytes form pseudopods that engulf particles, forming a phagosome.
• A phagosome fuses with a lysosome, forming a phagolysosome.
• Phagolysosome is acidified; lysosomal enzymes digest particles.
• Indigestible and residual waste is exocytosed from the phagocyte.
• Adherence, is first phase of phagocytosis, it is enhanced by opsonins.

Natural Killer (NK) Cells

• NK cells are nonphagocytic, large granular lymphocytes that survey the blood and lymph.
• They kill cancer and virus-infected cells before adaptive immune system activation.
• Attack cells that lack "self" cell-surface receptors.
• Induce apoptosis in cancer cells and virus-infected cells.
• Secrete chemicals that enhance inflammatory response.
• They monitor cell division to maintain cells.

Inflammation - Acute

• Four cardinal signs of acute inflammation are: redness, heat, swelling, and pain.
• A fifth sign is impairment of function.
• Inflammation is a tissue's response to injury in 3 key stages:
• Inflammatory chemical release
• Vasodilation and increased vascular permeability
• Phagocyte mobilization

Inflammation – Chemical Release

• Chemicals are released into the extracellular fluid by injured tissues, immune cells, or blood proteins.
• Histamine released by mast cells is a key inflammatory chemical.
• Macrophages and epithelial cells bear Toll-like receptors (TLRs)
• TLRs recognize specific classes of infecting microbes.
• Activated TLRs trigger the release of cytokines that promote inflammation.

Other Inflammatory Mediators

• Other inflammatory mediators include kinins, prostaglandins (PGs), and complement.
• All cause vasodilation of local arterioles.
• All make capillaries leaky.
• Many attract leukocytes to the area Have other inflammatory roles triggering pain receptors, or prompting the release of more inflammatory chemicals.

Inflammation - Vasodilation and Increased Vascular Permeability

• Vasodilation causes hyperemia
• Congestion with blood leads to redness and heat.
• Increased capillary permeability causes exudate
• Fluid contains clotting factors and antibodies to leak into tissue.
• Results in local swelling (edema).
• Swelling also pushes on nerve endings, resulting in pain.
• Pain results from toxins released by bacteria or from released prostaglandins and kinins.

Benefits of Edema

• Surge of fluid sweeps foreign material into lymphatic vessels for processing
• Delivers clotting proteins and complement to the area
• Clotting factors form a fibrin mesh that acts as a scaffold for repair, isolates the injured area.

Phagocyte Mobilization

• Inflammation triggers the release of neutrophils from the bone marrow.
• They circulate to the site of inflammation and enter the inflamed area.

Margination

• Before neutrophils penetrate into tissue, they cling to the capillary wall in process called margination
• Margination signals endothelial cells of the capillary to allow opening.

Diapedesis

• Neutrophils flatten to pass through endothelial cells and leave the capillaries.

Chemotaxis

• Neutrophils follow a trail of chemicals created by the inflammatory process.
• Chemicals act as chemotactic agents.
• Chemotaxis describes cells following a chemical signal.

Antimicrobial Proteins

• Enhance innate defense by attacking microorganisms, or hindering their reproduction
• Interferons and complement proteins are most important.

Interferons

• Slow the spread of viral infections by "interfering" with viral replication.
• Small proteins that activated lymphocytes, macrophages, and virus-infected tissues release.
• Cells (Cell I) are first infected by a virus and stimulate production of IF's.
• Virus infected cells (Cell I) die, but IF's produced by Cell I are secreted that reach the plasma membrane of nearby healthy cells (Cell H).
• IFs bind to surface receptors of Cell H triggering the production of antiviral proteins within Cell H.
• IFs stimulate Cell H to produce degradative enzymes, degrade mRNA and stop protein synthesis of the virus.
• The virus attempts to infect Cell H to produce antiviral proteins.
• Antiviral proteins cannot prevent viral entry into Cell H, instead interfering with replication causing the virus death.