Innate Immunity

DefStructure and Function of the Organs and Immunity

  • the study of the body’s second and third lines of defense is called immunology

  • functions of a healthy functioning immune system:

    1. surveillance

    2. recognition of foreign material

    3. destruction of entities deemed to be foreign

Defense Mechanisms of the Host

  • host defenses

    • innate, natural defenses: present at birth

      • provide nonspecific resistance to infection

      • defenses against any pathogen

    • adaptive immunities: specific, acquired

  • innate- first line of defense

    • any barrier that blocks invasion at the portal of entry

    • nonspecific

  • innate- second line of defense

    • protective cells and fluids

    • inflammation and phagocytosis

    • nonspecific

  • acquired- third line of defense

    • acquired with exposure to foreign substance

    • produces protective antibodies and creates memory cells

    • specific


Physical or Anatomical Barriers: First Line of Defense

  • skin and mucous membranes

    • outermost layer

    • tight junctions between cells

    • blinking and tear production

    • stomach acid

    • nasal hair

    • ear wax

    • mucous coat

    • normal flora: compete for nutrients, change pH, stimulate production of antimicrobial compounds


  • washing/ removal methods (move ‘em on out)

    • normal turnover- cells shed

    • flushing effect of sweat glands

    • blinking and tear production

    • flow of saliva

    • mucous coat impedes attachment and entry of bacteria

    • cilia sweep material out of respiratory tract

    • urination, defecation, vomiting, menstruation, ejaculation

    • bleeding of a wound

    • coughing, sneezing, runny nose

Ciliary Escalator

  • cilia in the lungs beat mucous and microbes trapped in mucous upward and out of the lungs

Nonspecific Chemical Defenses

  • sebaceous secretions- oil; sweat

  • lysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tears, sweat, saliva, and urine

  • acidic pH- sweat, skin (3-5), stomach (1.2-3), intestinal, vagina (3-5), urine

  • digestive juices/enzymes and bile of intestines

  • semen contains an antimicrobial chemical, seminalplasmin

  • lactoferrin, transferrin- transport of iron

    • play ‘keep-away’

    • also can bind bacterial cell envelope- inhibit H+ transport

First Line of Defense: Chemical

  • antimicrobial peptides (over 100 identified)

    • psoriasin (skin, tongue) sequesters zinc, especially control E. coli

    • SP-A, SP-D, galectins, pentraxins= opsonins= promote phagocytosis

    • defensins, histatins, cathelicidins

      • bind phospholipids found on outer layer of cell membrane of prokaryotes, some protozoa, not animals

      • disrupt membrane, inhibit ATP production, may enter and inhibit biosynthesis

  • many also promote wound healing


Genetic Defenses

  • some species genetically resistant to certain diseases of other species

  • structure or presence of a biomolecule differs between species; eg. sugar linkages in carbohydrates of glycoproteins control influenza virus binding

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

    • slight variation on cell receptors can alter pathogen ability to enter

    • intensity of immune response may differ


Second Line of Defense


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

  • 4 major subdivisions of immune system:

    1. reticuloendothelial system (RES)

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

      • inhabited by phagocytic cells-mononuclear phagocytic system - macrophages that are ready to attack and ingest microbes that cross the first line of defense


    1. extracellular fluid (ECF)

    2. bloodstream

    3. lymphatic system

Body Compartments that Participate in Second Line of Defense

Lymphatic System

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

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

  3. surveillance, recognition, and protection against foreign material

Lymphatic Fluid

  • lymph - 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


Lymphoid Organs

  • classified as primary and secondary

  • primary lymphoid organs

    • site of cell production and maturity

    • bone marrow-production of blood cells, maturation of B- cells

    • thymus- site of T-cell maturation

  • secondary lymphoid organs

    • sites where cells will hangout and survey for disease

    • lymph nodes, tonsils

    • spleen - filters circulating blood to remove worn out RBCs and pathogens

Origin, Composition, and Functions of the Blood

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

    • serum is 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 physiology functions

A Survey of Blood Cells

  • hemopoiesis - production of blood cells

  • stem cells - undifferentiated cells, precursor of new blood cells

  • leukocytes - white blood cells

    • granulocytes : lobed nucleus

    • agranulocytes : unlobed, rounded nucleus

  • primary lymphoid organs - where immune cells develop

  • secondary lymphoid organs - where adaptive immune cells get activated




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


Leukocytes

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 differientiation of monocytes

    • dendritic cells: trap pathogens and participate in immune responses

Erythrocytes and Platelet Lines

  • erythrocytes (red blood cells): develop from bone marrow stem cells, lose nucleus, simple biconcave sacs of hemoglobin

  • platelets: formed elements in circulating blood that are not whole cells


Actions of the Second Line of Defense

  • recognition

  • inflammation

  • phagocytosis

  • interferon

  • complement


Inflammatory Response

  • classic signs and symptoms characterized by:

    • redness (rubor) - increased circulation and vasodilation in injured tissues in response to chemical mediators

    • warmth (calor) - heat given off by the increased blood flow

    • swelling (edema or tumor) - increased fluid escaping into the tissue as blood vessels dilate - edema; WBC’s, microbes, debris, and fluid collect to form pus; prevents spread of infection

    • pain (dolor) - stimulation of nerve endings


The Major Events in Inflammation


The Chemical Mediators of the Inflammatory Response

Unique Characteristics of Leukocytes

  • 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

    • reset the hypothalamus; signals muscles to increase heat production and vasoconstriction

    • exogenous pyrogens

      • products of infectious agents

    • endogenous pyrogens

      • liberated by monocytes, neutrophils, and macrophages during phagocytosis; interleukin-1 (IL-1) and tumor necrosis factor (TNF)



  • advantages

    • inhibits multiplication of temperature sensitive microorganisms

    • impedes nutrition of bacteria by reducing the availability of iron

    • increases body metabolism and stimulates immune reactions and protective physiological processes

  • disadvantages

    • tachycardia

    • acidosis

    • dehydration

    • 44-46ºC fatal (111-114ºF)

Phagocytosis

  • general activities of phagocytes:

    • to survey tissue compartments

    • to ingest and eliminate these materials

    • to extract immunogenic information from foreign matter


Phagocytes and Phagocytosis

  • neutrophils- general purpose; first line of defense to bacteria and foreign materials, and to damages 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

  • pattern recognition receptors (PRRs)

  • protein receptors within cell membrane of macrophages, Toll-like receptors (TLR) attach to Pathogen Associated Molecular Patterns (PAMPS)

  • signal the macrophage to produce cytokines


Phagocytosis


Extracellular Killing

  • eosinophils

    • bind structures on parasitic helminths

    • secrete what would be in lysosome- damage, may kill

  • neutrophils

    • secrete reactive oxygen species (kill nearby)

    • NETs- sticky DNA traps

  • NK Cells (totally different mechanism)

    • leukocytes, recognize our not-normal cells (virally infected or tumor), binding signals to secrete perforins, granzyme

Microbial Evasion of Phagocytosis

Interferon

  • small protein produced by certain WBCs and tissue cells

    • interferon alpha- lymphocyte and macrophages

    • interferon beta- fibroblasts and epithelial cells

    • interferon gamma- T-cells

    • produced in response to viruses, RNA, immune products, and various antigens; binds 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 complements of microbes


4 Stages in the Complement Cascade

  • initiation

  • amplification and cascade

  • polymerization

  • membrane attack

  • C3a and C5a- promoteinflammation and chemotaxis

  • C3b- opsonin

  • MAC- direct killing gram- bacteria maybe some virally infected cells

  • our cells have proteins in membrane to inactivate


Effects of Complement Activation

  • opsonization: enhanced phagocytosis

    • coats the pathogen with opsonin (marker)

  • membrane attack complex: cytolysis

    • forces fluid in the cell causing it to rupture

  • attract phagocytes

  • inflammation

Summary

  • immunology- study of immune system

  • first line of defense- mechanical barriers

    • structures and chemicals that keep foreign invaders out

    • skin, mucous membranes, tears, wax, sweat

  • second line of defense- cells and inflammation

    • white blood cells (excluding T and B cells)

    • inflammation (heat, redness, swelling and pain)

    • phagocytosis and complement