Fire Ant Stings and Other Mishaps: Immnology

Donna Sullivan, PhDFire Ant Stings and Other Mishaps: ImmnologyHost Defensive Systems21st line of defense - intact skinmucous membranes and their secretions2nd line of defense - phagocytic white blood cellsinflammation-complementfever-interferon3rd line of defense- B and T lymphocytesantibodiesnonspecific

specificPhysical or anatomical barriers3Outermost layer of skin is composed of epithelial cells compacted, cemented together and impregnated with keratinFlushing effect of sweat glandsDamaged cells are rapidly replacedMucous coat impedes attachment and entry of bacteriaBlinking and tear productionStomach acidNasal hair traps larger particles

Chemical Defenses4Sebaceous secretionsLysozyme, an enzyme that hydrolyzes the cell wall of bacteria, in tearsHigh lactic acid and electrolyte concentration in sweatSkins acidic pHHydrochloric acid in stomachDigestive juices and bile of intestinesSemen contains antimicrobial chemicalVagina has acidic pH

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DIFFERENTIATION OF CELLS6LeucocytesGranulated: granules, lobed nucleiNeutrophilsEosinophilsBasophilsAgranulated: un-lobed, round nucleiMonocytesMacrophages, dendritic cellsLymphocytesT cells, B cells7GRANULOCYTESNeutrophils (PMNs)Strongly phagocytic, important in controlling bacterial infectionsUsually first cells to arrive at siteEosinophilsWeakly phagocytic, main role in allergic reactions, destruction of parasitesBasophilsNon phagocyticCell surface receptors for IgEMediated allergic and antiparasitic responses due to release of histamine8DIFFERENCES BETWEEN NEUTROPHILS AND MACROPHAGESNEUTROPHILSRapid increase in production (and in blood) during acute phase of infectionOnly found in inflamed tissuesSingle mature formRapidly form pusShort-lived; die after phagocytosisMACROPHAGESOnly slight increase in blood during inflammationFound in healthy tissuesMultiple mature formsSlowly form granulomas (with T cell help)Long-lived-survive after phagocytosis9MONOCYTES/MACROPHAGESReleased from bone marrowCirculate in blood and enter tissues where they mature into macrophageActivated macrophageInitiated by phagocytosis of particulate antigens10CELLS OF THE MONOCYTE- MACROPHAGE SYSTEMBRAIN - MICROGLIALLUNGS - ALVEOLARBLOOD - MONOCYTESJOINTS - SYNOVIAL AKIDNEY - MESANGIALSPLEEN - MACROPHAGESLIVER - KUPFFERLYMPH NODES -RESIDENT & RECIRCULATING MACROPHAGESBONE MARROW - PRECURSORSCONNECTIVE TISSUE - HISTOCYTES10Macrophages (and neutrophils) are from a myeloid precursor type of stem cell11MACROPHAGES: FUNCTIONStand guardInitiate early innate immune responseEducate the specific immune systemPresent antigen associated with Class II MHC to CD4 TH cellsCall in the troopsSecrete cytokines that promote immune responsesJoin the battlePhagocytose and inactivate microbesSecrete antibacterial substances, inflammatory mediators, and complement components12

Phagocytosis13NATURAL KILLER CELLSPrimary targets of NK cell killing are virus infected and tumor cellsMay depend on reduced expression of Class I MHC molecules, alterations in surface carbohydratesMechanism of killingDirect cytotoxicityAntibody dependent cellular cytotoxicity (ADCC) 14Stages Of InflammationBlood vessels dilate in response to chemical mediators and cytokinesEdema swells tissues, helping prevent spread of infectionWBCs, microbes, debris and fluid collect to form pusPyrogens may induce feverMacrophages and neutrophils engage phagocytosis15Developmental Stages of Monocytes and Macrophages

16INFLAMMATIONTissue damage due to trauma, caustic agents, microbesMediated primarily by immune system cells, cytokinesAcute inflammationChronic inflammation17Rubor, Calor, Tumor, DolorRubor: Redness caused by increase circulation and vasodilation in injured tissuesCalor: Warmth, heat given off by increased flow of bloodTumor: Swelling, caused by increased fluid escaping into the tissuesDolor: Pain, causes by stimulation of nerve endings18

TRAUMA AND INFLAMMATION19TRAUMA AND INFLAMMATION

20TRAUMA AND INFLAMMATION

21TRAUMA AND INFLAMMATION

22TRAUMA AND INFLAMMATION

23Activities Of PhagocytesStand guardTo survey tissue compartments and discover microbes, particulate matter and dead or injured cellsJoin the BattleTo infest and eliminate these materialsEducate Specific Immune SystemTo extract immunogenic information from foreign matter24

Chemical Mediators25ComplementConsists of 26 blood proteins that work in concert to destroy bacteria and virusesComplement proteins are activated by cleavageClassical pathwayAlternative pathway26Complement

27Specific immunitiesB and T lymphocytesSpecificity and memory28

29Lymphocyte Development and Differentiation

Antigen Presentation

Challenge of B and T Cells

B Cell Antibody Production

T Cell Responses31Preliminary conceptsCell receptors or markers confer specificity and identityMajor functions of receptors areTo perceive and attach to nonself or foreign moleculesTo promote the recognition of self moleculesTo receive and transmit chemical messages among other cells of the systemTo aid in cellular development.32How Are Receptors Formed?As a cell matures, certain genes that encode cell receptors are transcribed and translated into protein products with a distinctive shape, specificity and function.Receptor is modified and packaged by the endoplasmic reticulum and Golgi complex.It is ultimately inserted into the cell membrane, accessible to antigens, other cells, and chemical mediators.33

Receptor Formation in a Developing Cell34Major Histocompatibility Complex (MHC)Receptors found on all cells except RBCsAlso known as human leukocyte antigen (HLA)Plays a role in recognition of self by the immune system and in rejection of foreign tissueGenes for MHC are located on chromosome 6, clustered in a multigene complex of classes I, II, III35MHC Receptors

36Functions of MHCClass I markers that display unique characteristics of self molecules and regulation of immune reactionsRequired for T lymphocytesClass II receptors that recognize and react with foreign antigens. Located primarily on macrophages and B cellsInvolved in presenting antigen to T cellsClass III secreted complement components, C2 and C437Clonal Selection TheoryLymphocytes use 500 genes to produce a tremendous variety of specific receptorsUndifferentiated lymphocytes undergo genetic mutations and recombinations while they proliferate in the embryo forming a billion different clones with the ability to react with a tremendous variety of antigens.38Ability to React to Every Antigen Is Pre-ProgrammedLymphocyte specificity is preprogrammed, existing in the genetic makeup before an antigen has ever entered the system.Each genetically different type of lymphocyte expresses a single specificity.First introduction of each type of antigen into the immune system selects a genetically distinct lymphocyte and causes it to expand into a clone of cells that can react to that antigen.

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Structure of Antibodies41ImmunoglobulinsImmunoglobulin genes lie on 3 different chromosomesUndifferentiated lymphocyte has 150 different genes for the variable region of light chains and 250 for the variable region and diversity region of the heavy chainDuring development, recombination causes only the selected V and D genes to be active in the mature cell.42Gene Segments of ImmunoglobulinsHeavy chainsVariable (V)Diversity (D)Joining (J)Constant (C)Light chainsVariable (V)Joining (J)Constant (C)

44HYPERSENSITIVITY REACTIONSType I (immediate) hypersensitivity: IgE-mediated atopic (allergic) and anaphylactic reactionsType II hypersensitivity: Ab-dependent cytotoxicityType III hypersensitivity: Immune complex induced tissue damaging inflammationType IV (delayed) hypersensitivity:Cell-mediated cytotoxicity45

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TYPE II REACTIONS: Blood Typing and Transfusion Reactions47

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TYPE IV (DTH) REACTION: TB Skin Test

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IMMUNE REACTIONS DUE TO MATERNAL ANTIBODIESInsect StingsNormal reaction: local pain, erythema, swellingOnset 10-15 minutesSubsides in 1-2 hoursTherapy: cool compresses, analgesics51Insect StingsLarge, local reactionsPeak at 48 hoursDuration of 1 weekOccasional fatigue, nauseaNot IgE mediatedTherapy: antihistamines, prednisone52Insect StingsAnaphylaxis: IgE mediatedGeneralized urticaria, flushing, angioedema, cardiorespiratory symptomsOnset 15-20 minutes up to 72 hoursAdults have highest mortalityPrevention: avoidance, EpiPen, immunotherapy if skin test positive53Fire Ant StingsFire Ant StingsFerocious; potent venom; multiple stingsIntense pain followed by pruritisImmediate flare (2-5cm) and wheal (1cm)8-10 hours later a sterile pustule developsSystemic reactions (16%) rarely life threatening54Fire Ant StingsChance of being stung 50%ReactionsWheal & Flare 100%Pustule 96%Large local reaction 3.6-56%Secondary infection 54%Systemic 16%CutaneousLife-threatening 0.6-2%Deaths 32

http://afrsweb.usda.gov/fireant/venom.htm?pf=1

55Allergic Reaction: Possible CausesInsect bites/stings (bees, wasps, etc.)Food (nuts, crustaceans, peanuts, etc.)PlantsMedicationsOthers56FindingsSkinWarm, tingling feelingFace, mouth, chest, feet, and handsItchingHives

57Respiratory SystemTightness in throat/chestCoughRapid breathingLabored breathingRetractionsUse of accessory musclesSwelling of the airwayNoisy breathingInability to speak or coughHoarsenessStridorWheezing (audible without stethoscope)

RESPIRATORY FAILURE!RESPIRATORY ARREST!58Cardiovascular SystemIncreased heart rateDecreased blood pressureDecreased perfusion (shock) due to vasodilation

59Generalized FindingsItchy, watery eyesHeadacheSense of impending doomRunny nose60Other Signs and SymptomsDecreasing mental statusSigns of shock (hypoperfusion)Respiratory distress61Emergency Medical CarePatient has prescribed epinephrine?Facilitate administration of preloaded epinephrine.Reassess every 2 minutes.No auto-injectorCALL 911!!! Transport to ER62