Innate and Adaptive Immunity

• Innate immunity provides resistance to disease
• Immunity is made of two intrinsic systems: innate (which is nonspecific), and adaptive (which is specific)

Innate (nonspecific) defense system

• Constitutes the first and second lines of defense
• First line of defense includes: external body membranes like skin and mucosae
• Second line of defense includes: antimicrobial proteins, phagocytes, and cells which inhibit the spread of invaders; inflammation is the most important mechanism

Adaptive (specific) defense system

• Third line of defense that attacks particular foreign substances

• Adaptive system reactions take longer than innate system reactions

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

• Innate and adaptive defenses are intertwined

• Consists of barriers, cells, degradative enzymes, attack molecules

• Innate defenses have specific pathways for certain substances

• Innate responses release proteins, alerting cells of adaptive system to foreign molecules

Innate (nonspecific) Immunity

• It does not distinguish one threat from another
• The same response occurs regardless of the type of invading agent
• Preset at birth
• Provides nonspecific resistance
• Prevents approach, denies entry, and limits spread of microbes and environmental hazards

Adaptive (specific) immunity

• Uses adaptive defenses

• Protects against particular threats

• Dependent on activities of specific lymphocytes

• Provides specific resistance

• The innate defense system uses the first and second lines of defense

• First line of defense is surface barriers: Skin and mucous membranes

• Second line of defense is internal defense: Phagocytes, natural killer cells, inflammation, antimicrobial proteins, and fever

First Line of Defense: Surface Barriers

• Surface barriers are skin and mucous membranes, along with their secretions
• Physical barrier to most microorganisms
• Keratin provides resistance to acids, bases, bacterial enzymes, and toxins
• Mucosae provide similar mechanical barriers
• Skin and mucous membranes produce protective chemicals to inhibit or destroy microorganisms
• Acid in skin and mucous secretions inhibits growth and is called the acid mantle
• Enzymes such as lysozyme, found in saliva, respiratory mucus, and lacrimal fluid, kill many microorganisms; enzymes in stomach kill many microorganisms
• Mucin is a sticky mucus that lines digestive and respiratory tract to trap microorganisms
• Defensins are antimicrobial peptides that inhibit microbial growth
• Lipids in sebum and dermicidin in sweat are toxic to some bacteria

Surface barriers and respiratory system

• Mucus-coated hairs in the nose trap inhaled particles
• Cilia of the upper respiratory tract sweep dust and bacteria-laden mucus toward the mouth
• Breached surface barriers trigger the internal second line of defense, protecting deeper tissues

The 2nd Line of Defenses: Cells and Chemicals

• The innate system becomes necessary if microorganisms invade deeper tissues
• Includes phagocytes, natural killer cells, inflammatory response, antimicrobial proteins, and fever
• Second-line cells possess pattern recognition receptors that recognize and bind tightly to microbial structures

Phagocytes:

• Phagocytes are major group of cells involved in the eating of other cells
• White blood cells ingest and digest foreign invaders
• Eosinophils, and neutrophils are examples of phagocytes
• Neutrophils are the most abundant phagocytes, die fighting, and become phagocytic on exposure to infectious material
• Macrophages develop from monocytes and are chief phagocytic cells, and most robust phagocytic cell
• Free macrophages wander through tissue spaces, examples include alveolar macrophages
• Fixed macrophages are permanent residents of organs, stellate macrophages (liver) and microglia (brain) are examples

Phagocytosis

• Process starts when a phagocyte recognizes and adheres to a pathogen’s carbohydrate "signature"
• Some microorganisms have external capsules to hide their surface carbohydrates, to evade phagocytosis
• Opsonization is when the immune system uses antibodies or complement proteins like opsonins to coat pathogens
• Opsonins act as "handles" for phagocytes which enhances phagocytosis
• Cytoplasmic extensions (pseudopods) bind and engulf particles into vesicles called phagosomes
• Phagosomes fuse with lysosomes, forming phagolysosomes
• Phagolysosomes are acidified and lysosomal enzymes digest particles

Natural Killer (NK) Cells

• Natural killer cells are nonphagocytic, large granular lymphocytes survey the blood and lymph
• Natural killer cells can kill cancer and virus-infected cells before the adaptive immune system is activated
• Attack cells that lack "self" cell-surface receptors
• Kill by inducing apoptosis(programmed cell death) in cancer cells and virus infected cells
• Secretes potent chemicals to enhance the inflammatory response
• Cells are also used to maintain cell division

Inflammation

• Four cardinal signs of acute inflammation are redness, heat, swelling, and pain
• Fifth sign includes possible impairment of function, seen if movement or use of area is hampered
• Stages of inflammation include inflammatory chemical release, vasodilation and increased vascular permeability, and phagocyte mobilization

Chemical Release

• Chemicals are released into the extracellular fluid (ECF) by injured tissues, immune cells, or blood proteins
• Histamine is a key inflammatory chemical released by mast cells
• Macrophages and epithelial cells of boundary tissues (respiratory tissues, intestine) bear special pattern recognition receptors, called Toll-like receptors(TLRs)
• 11 types of TLRs recognize infecting microbes
• Activated TLRs trigger release of cytokines that promote inflammation

Inflammatory Mediators

• Kinins, prostaglandins (PGs), and complement are examples of inflammatory mediators besides histamine
• They all cause vasodilation of local arterioles
• All make capillaries leaky
• Attract leukocytes to the area
• Trigger pain receptors and prompting release of inflammatory chemicals

Vasodilation

• Vasodilation causes hyperemia which is congestion with blood that leads to redness and heat
• Increased capillary permeability leads to exudate which is fluid containing clotting factors and antibodies that leak into tissue
• Results in local swelling (edema)
• Swelling pushes on nerve endings which results in pain
• Fluid in tissue sweeps foreign material into lymphatic vessels for processing in lymph nodes

Phagocyte Mobilization

• Inflammation triggers the release of neutrophils from the bone marrow
• Neutrophils circulate to inflammation sites and enter the inflamed area

Margination

• Before neutrophils penetrate tissue, they cling to the capillary wall, called margination
• Margination triggers a signal to the endothelial cells of capillary, allowing an opening

Diapedesis

• Neutrophils flatten to pass through endothelial cells, leaving the capillaries through diapedesis

Chemotaxis

• Neutrophils follow a trail of chemicals.
• Chemicals act as chemotactic agents in a process called chemotaxis

Antimicrobial Proteins

• Enhance innate defense, attacking microorganisms directly or hindering their ability to reproduce.
• Interferons and complement proteins are examples

Interferons

• Slow spread of viral infections by ‘interfering’ with viral replication
• Small proteins released by activated lymphocytes, macrophages, and virus-infected tissues
• Cells(Cell I) are first infected with a virus and stimulate the production of interferons
• The virus infected cells (Cell I) die, but the interferons produced by Cell I reach plasma membrane of nearby healthy cells (Cell H)
• Interferons bind to surface receptors of Cell H, and trigger production of antiviral proteins within Cell H
• Interferons stimulate Cell H to produce degradative enzymes that degrades mRNA and stop protein synthesis of the virus
• The virus then attempts to infect Cell H (that has produced antiviral proteins)
• Antiviral proteins prevent viral entry into Cell H; instead, they interfere with viral replication