Innate Immunity

Defense Mechanisms of the host

• Innate, natural defenses

  • Present at birth

  • Provide nonspecific resistance to infection

• Adaptive immunities

  • Specific

  • Must be acquired

• To protect the body against pathogens, the immune system relies on a multilevel network of physical barriers, immunologically active cells, and a variety of chemicals

First line of defense

• Any barrier that blocks invasion at the portal of entry

• nonspecific

• Skin and mucous membranes of respiratory, urogenital, eyes, and digestive tracts

• Outermost layer of skin is composed of epithelial cells and compacted, cemeented together, and impregnated with keratin; few pathogens can penetrate if intact

• Flushing effect of sweat glands

• Blinking and tear production

• Stomach acid

• Mucous coat impedes attachment and entry of bacteria

• Nasal hair traps larger particles

Second line of defense

• Protective cells and fluids

• Inflammation and phagocytosis

• Nonspecific

Third line of defense

• Acquired with exposure to foreign substance

• Produces protective antibodies and creates memory cells

• Specific

Nonspecific Chemical Defenses

• Sebaceous secretions

• Lysozyme - an enzyme that hydrolyzes the cell wall of bacteria, in tears

• high lactic acid and electrolyte concentration in sweat

• Skin’s acidic pH

• Hydrochloric acid in stomach

• Digestive juices and bile of intestines

• Semen contains an antimicrobial chemical

• Vagina has acidic pH

Genetic Defenses

• Some hosts are genetically immune to the diseases of other hosts

• Some pathogens have great specificity

• Some genetic differences exist in susceptibility

Structure and function of the organs of defense and immunity

• Immunology - The study of the body’s second and third lines of defense

• Functions of a healthy functioning immune system:

  • Surveillance of the body

  • Recognition of foreign material

  • Destruction of entities deemed to be foreign

Immune system

• Large, complex, and diffuse network of cells and fluids that penetrate into every organ and tissue

• Four major subdivisions:

  • Reticuloendothelial system (RES)

  • Extracellular fluid (ECF)

  • Bloodstream

  • Lymphatic system

White blood cells (leukocytes)

Innate capacity to recognize and differentiate any foreign material

Nonself

Foreign material

Self

Normal cells of the body

Pathogen-associated patterns (PAMPs)

Molecules shared by microorganisms

Pathogen recognition receptors (PRRs)

Receptors on WBCs for PAMPs

Reticuloendothelial system (RES)

• Network of connective tissue fibers that interconnects other cells and meshes with the connective tissue network surrounding organs

• Inhabited by phagocytic cells - mononuclear phagocyte system - macrophages ready to attack and ingest microbes that passed the first line of defense

Origin, composition, and functions of the blood

• Whole blood consists of plasma and formed elements (blood cells)

  • Serum - the liquid portion of the blood after a clot has formed - minus clotting factors

• Plasma

  • 92% water, metabolic proteins, globulins, clotting factors, hormones, and all other chemicals and gases to support normal physiological functions

Hemopoiesis

Production of blood cells

Steam cells

Undifferentiated cells, precursor of new blood cells

Leukocytes

• White blood cells

  • Granulocytes: lobed nucleus

  • Agranulocytes: unlobed, rounded nucleus

Granulocytes

• Neutrophils

  • 55-90%

  • Lobed nuclei with lavender granules

  • Phagocytes

• Eosinophils

  • 1-3%

  • Orange granules and bilobed nucleus

  • Destroy eukaryotic pathogens

• Basophils

  • 0.5%

  • Constricted nuclei

  • Dark blue granules

  • Release potent chemical mediators

  • Mast cells - nonmotile elements bound to connective tissue

Agranulocytes

• Lymphocytes

  • 20-35%

  • Specific immune response

  • B (humoral immunity) : activated B cells produce antibodies

  • T cells (cell-mediated immunity): activated T cells modulate immune functions and kill foreign cells

• Monocytes, macrophages

  • 3-7%

  • Largest of WBCs

  • Kidney-shaped nucleus

  • Phagocytic

  • Macrophages - final differentiation of monocytes

  • Dendritic cells - Trap pathogens and participate in immune reactions

Erythrocytes

• Develop from bone marrow stem cells

• Lose nucleus

• Simple biconcave sacs of hemoglobin

Platelets

Formed elements in circulating blood that are not whole cells

Lymphatic system

1. Provides an auxiliary route for return of extracellular fluid to the circulatory system

2. Acts as a drain-off system for the inflammatory response

3. Renders surveillance, recognition, and protection against foreign material

Lymphatic fluid

• Lymph is a plasma-like liquid carried by lymphatic circulation

• Formed when blood components move out of blood vessels into extracellular spaces

• Made up of water, dissolved salts, 2-5% proteins

• Transports white blood cells, fats, cellular debris, and infectious agents

Lymphatic Vessels

• Lymphatic capillaries permeate all parts of the body except the CNS, bone, placenta, and thymus

• Thin walls easily permeated by extracellular fluid which is then moved through contraction of skeletal muscles

• Functions to return lymph to circulation; flow is one-direction - toward the heart - eventually returning to the blood stream

Lymphoid organs and tissues

• Classified as primary and secondary

• Primary lymphoid organs

  • sites of lymphocytic origin and maturation

  • thymus and bone marrow

• Secondary lymphoid organs and tissues

  • Circulatory-based locations such as spleen and lymph nodes

  • Collections of cells distributed throughout body tissues

  • Skin and mucous membranes

  • SALT, GALT, MALT

Thymus

• High rate of growth and activity until puberty, then begins to shrink

• Site of T-cell maturation

Lymph nodes

Small, encapsulated, bean-shaped organs stationed along lymphatic channels and large blood vessels of the thoracic and abdominal cavities

Spleen

• Structurally similar to lymph node

• Filters circulating blood to remove worn out RBCs and pathogens

Actions of the second line of defense

• Recognition

• Inflammation

• Phagocytosis

• Interferon

• Complement

Inflammatory response

• Characterized by:

  • Redness - increased circulation and vasodilation in injured tissues in response to chemical mediators

  • Warmth - heat given off by the increased blood flow

  • Swelling - increased fluid escaping into the tissue as blood vessels dilate - edema; WBCs, microbes, debris, and fluid collect to form pus; prevents spread of infection

  • Pain - stimulation of nerve endings

Diapedesis

Migration of cells out of blood vessels into the tissues

Chemotaxis

Migration in response to specific chemicals at the site of injury or infection

Fever

• Initiated by circulating pyrogens whcih reset the hypothalamus to increase body temperature; signals muscles to increase heat production and vasoconstriction

  • Exogenous pyrogens

    • Products of infectious agents

  • Endogenous pyrogens

    • Liberated by monocytes, neutorphils, and macrophages during phagocytosis

    • Interleukin-1 (IL-1) and tumor necrosis factor (TNF)

• Benefits of fever:

  • Inhibits multiplication of temperature-sensitive microorganisms

  • Impedes nutrition of bacteria by reducing the available iron

  • Increases metabolism and stimulates immune reactions and protective physiological processes

Activities of Phagocytosis

1. To survey tissue compartments and discover microbes, particulate matter, and dead or injured cells

2. To ingest and eliminate these materials

3. To extract immunogenic information from foreign matter

Neutrophils

• General-purpose

• React early to bacteria and other foreign materials, and to damaged tissue

Eosinophils

Attracted to sites of parasitic infections and antigen-antibody reactions

Macrophages

• Derived from monocytes

• Scavenge and process foreign substances to prepare them for reactions with B and T lymphocytes

Recognition of foreign cells

• Toll-like receptors - Protein receptors within cell membrane of macrophages

• Detect foreign molecules and signal the macrophage to produce chemicals to stimulate an immune response

Mechanisms of Phagocytic recognition, engulfment, and killing

• Chemotaxis and ingestion

  • Phagocytes migrate and recognize PAMPs

  • Phagosome

• Phagolysosome

  • Lysosome fused with phagosome (death ~30 minutes)

• Destruction and elimination

  • Oxygen-dependent system (respiratory burst)

  • Liberation of lactic acid, lysoszyme, and nitric oxide

Interferon

• Small protein produced by certain WBCs and tissue cells

  • Interferon alpha - lymphocytes and macrophages

  • Interferon beta - fibroblasts and epithelial cells

  • Interferon gamma - T cells

• Produced in response to viruses, RNA, immune products, and various antigens, they bind to cell surfaces and induce expression of antiviral proteins and inhibit expression of cancer genes

Complement

• Consists of 26 blood proteins that work in concert to destroy bacteria and viruses

• Complement proteins are activated by cleavage (cascade reaction)

• Pathways

  • Classical - Activated by the presence of antibody bound to microorganism

  • Lectin pathway - nonspecific reaction of a host serum protein that binds mannan

  • Alternative - begins when complement proteins bind to normal cell wall and surface components of microorganisms

Four stages of complement cascade

1. Initation

2. Amplification and cascade

3. Polymerization

4. Membrane attack