Immunology Chapter 12 2007 Thomson Wadsworth Immunity Bodys

Immunity • Body’s ability to recognize material as foreign and to • neutralize, eliminate,

Immunity • Susceptibility to infectious disease üGender, üage, ünutritional status, ühormones, üstress © 2007

Natural Resistance • Anatomical & Chemical barriers üSkin üLining of GI, respiratory, genitourinary tracts üMucous membranes üTears, urine, saliva üp. H of stomach üLow-level fever üHigh levels of oxygen (lungs) © 2007 Thomson - Wadsworth

Antigens and Immunogens • Antigens allow immune system to recognize potential pathogens and foreign cells • Antibodies – made in response to antigens • Immunogen – antigen that can induce an immune response ü Foreign to the host • Antigenic determinant – specific part of immunogen that elicits specific immune response © 2007 Thomson - Wadsworth

Antigens and Immunogens • Antigen characteristics üProteins, polysaccharides, lipids, nucleic acids üOf sufficient size üStructural stability üDegradable üComplex üForeign to the organism (immunogenic) © 2007 Thomson - Wadsworth

Immune System • Functions: ü Defense ü Homeostasis ü Surveillance • 4 basic requirements: ü Specificity ü Diversity ü Adaptivity ü Ability to respond to new stimuli • Recognizes then reacts © 2007 Thomson - Wadsworth

Immune System • Divisions üHumoral • Serum, B cells that become plasma cells üCellular

Immune System • Divisions – interdependant üSpecific • Each B and T cell programmed to attack one specific antigen üNonspecific • Stimulates specific immune system to seek out and target pathogens © 2007 Thomson - Wadsworth

Immune System • Divisions - specific immunity üActive • Synthesizes own antibodies üPassive • Receives antibodies from another üBoth can be natural or artificial • Active natural • Active artificial • Natural passive • Passive artificial © 2007 Thomson - Wadsworth

Cells of the Immune System • Formed in bone marrow • Originate from hematopoietic stem cells • Become RBCs or WBCs (leukocytes) • WBC outnumber RBCs 3: 1 • Deviations in WBC indicative of clinical conditions üSee Table 12. 2 © 2007 Thomson - Wadsworth

Cells of the Immune System • WBCs üMacrophages/monocytes üPolymorphonuclear leukocytes üLymphocytes © 2007 Thomson

Cells of the Immune System • Monocytes and Macrophages üMonocytes differentiate into macrophages üMacrophages • Fixed and wandering • See Table 12. 3 üImportant in removing pathogens üHighly specialized – phagocytosis üMajor antigen-presenting cells (APC) © 2007 Thomson - Wadsworth

Cells of the Immune System • Polymorphonuclear Leukocytes üIncrease or decrease in blood, large pool in bone marrow üDifferent nuclei from cell to cell • Neutrophil – stain purple • Eosinophils – stain bright red • Basophils – stain blue-black üProduce histamine © 2007 Thomson - Wadsworth

Cells of the Immune System • Other cells üMast cells • Mucosal surfaces üDendritic

Cells of the Immune System • Lymphoid cells üT cells • Helper • Cytotoxic • Suppressor T cell üHelper T cells (TH or T 4) • CD 4 Th 1 and Th 2 • CD 8 üB cells üNatural killer cells © 2007 Thomson - Wadsworth

Organs • Central üBone marrow üThymus • Peripheral (secondary) üLymphoid system • See Fig. 12. 4 • Lymph • To congregate antigens into a few lymphoid organs so an immune response can be initiated against intracellular pathogens © 2007 Thomson - Wadsworth

Organs • Peripheral (secondary) üSpleen üMALT, GALT, BALT • GALT includes Peyer’s patches •

Soluble Mediators • Complement cascades üResult in membrane attack complex üDefense against infected and tumor cells üTransplant rejection • Cytokines üProteins that affect behavior of other cells üAltered biological activity in target cell © 2007 Thomson - Wadsworth

Soluble Mediators • Cytokines üAutocrine • Acts on cell that produced it üParacrine • Acts on nearby cell üEndocrine • Acts at a distance üMore than one can be synergetic or antagonistic © 2007 Thomson - Wadsworth

Soluble Mediators • Cytokines üInterleukins (IL) • IL-2 most widely studied • See Table 12. 4 üInterferon (INF) • Alpha – antiviral • Gamma – immune regulation • Beta üTumor necrosis factor (TNF) © 2007 Thomson - Wadsworth

Antigen Recognition • Major Histocompatibility complex (MHC) üClass I – A, B, C üClass II – DR, DQ, DP • Combine 4 ways üPlay a role in susceptibility to diseases • Autoimmune • Infectious diseases © 2007 Thomson - Wadsworth

Antigen Recognition • Antibodies – assist in destruction or neutralization of the antigen •

Antigen Recognition • Ig. G üMost abundant, moves easily between serum and tissues, crosses placenta üSecond antibody made during infection • Ig. A üStops infectious organism at point of entry (nasal passages) © 2007 Thomson - Wadsworth

Antigen Recognition • Ig. M üSerum, large size limits mobility üFirst antibody found in new infections üSurface of B cells • Ig. D üFound on surface of B cells • Ig. E üAllergy to food and respiratory allergens © 2007 Thomson - Wadsworth

Immune Response • Modes of Attack üPhagocytosis üCell-mediated cytotoxicity üAntibodies üInflammation © 2007 Thomson

Immune Response • Phagocytosis üIngestion of pathogen and cell üPhagosome fuses with lysosome and forms phago-lysosome üPathogen destroyed or broken down üIf not broken down – granulomas form © 2007 Thomson - Wadsworth

Immune Response • Cell-Mediated Cytotoxicity ü Kill infected or tumor cells ü Perforin and enzymes secreted to induce apoptosis • Antibodies ü Neutralize bacterial toxins and viruses • Inflammation ü Initiate alternate complement pathways ü Component of allergies and autoimmune diseases © 2007 Thomson - Wadsworth

Progression of Immune Response • Primary immune response üSee Fig. 12. 8 • Secondary

Immunity to Infection • Specific types of pathogens üBacteria üViruses üProtozoans üHelminths © 2007

Altered and Foreign cells • Tumor üNaturally occurring, influence immune system • Transplant üRare

Altered and Foreign cells • Tumor (Cancer) üProgressive, uncontrolled growth of single cell üOut-competes with healthy cells for nutrients and space üAntigens unique to the tumor üImmune system attacks but some escape üNumerous approaches to cancer therapy © 2007 Thomson - Wadsworth

Altered and Foreign cells • Transplant üAutograft üIsograft üAllografts üXenografts © 2007 Thomson -

Altered and Foreign cells • Transplant Rejection üHost versus graft (HVG) • First set rejection – 11 -17 days • Second set rejection – months to years üGraft versus host (GVH) • Matching of MHC antigens is critical • Immunosuppression required • Unique challenges based on organ © 2007 Thomson - Wadsworth

Immunization • Passive – antibodies to prevent disease or decrease severity of symptoms üvaccinations übacteria, viruses, bites • Active – exposed to antigen to initiate antibodies and memory cells üinfluenza © 2007 Thomson - Wadsworth

Immunization • Types of vaccines üSee Table 12. 6 © 2007 Thomson - Wadsworth

Immunodeficiency • Most caused by malnutrition or genetics üMalnutrition – d/t lack of access and dietary choice üAffects through the life span üCritical nutrients • Vitamins A, C, B 6, E, essential fatty acids, beta-carotene, manganese, selenium, zinc, copper, iron, sulfur, manganese, germanium © 2007 Thomson - Wadsworth

Immunodeficiency • Most caused by malnutrition or genetics üCongenital/inherited üMales more likely - X recessive • X-linked agammaglobulinemia • Ig. A deficiency most common • Di. George syndrome • Wiskott-Aldrich syndrome • Bare lymphocyte syndrome • SCIDs – “bubble boy” © 2007 Thomson - Wadsworth

Immunodeficiency • Acquired Immunodeficiencies üFrom cancer treatment üHIV üFrom burns üFrom IBD © 2007

Tolerance • Immunological Tolerance üNonresponsiveness • Autotolerance üTolerance to one’s own antigens üBlocked by clonal deletion or clonal abortion • Induced • Central • Peripheral © 2007 Thomson - Wadsworth

Immune System Attack • Hypersensitivity (allergy) üType I, III – immediate hypersensitivities • Within

Immune System Attack • Type I / Ig. E üRespiratory allergens üSneezing, watery red eyes, runny nose, respiratory distress üOral inflammation, canker sores, cramps, nausea, diarrhea, gas üHives üAtopic to anaphylactic © 2007 Thomson - Wadsworth

Immune System Attack • Type I / Ig. E üHistamines are released early üLeukotrienes

Immune System Attack • Type I / Ig. E üAllergy testing/diagnosis • Skin scratch testing • Elimination diets • Placebo-controlled food challenge • RAST / RIST üAllergy shots • Regulated dose of allergen © 2007 Thomson - Wadsworth

Immune System Attack • Type I / Ig. E üFood allergies - 1 -2% of adults üMany confuse allergy with intolerance üAllergy – immune response üHistamines in cheese, wine, some fish may cause intolerances üLactose intolerance is most common üAlso yellow dye no. 5, MSG, sulfites © 2007 Thomson - Wadsworth

Immune System Attack • Common food allergens üPeanuts, tree nuts üShellfish üFood additives üMilk

Immune System Attack • Food allergens üIg. E response in gut üHistamines produced üSymptoms

Immune System Attack • Asthma – chronic airway inflammation and excessive airway sensitivity to various triggers üGenetic, environmental, lifestyle üSymptoms may be intermittent, although constant inflammation present üWheezing, cough, chest tightness, difficulty breathing, sputum production © 2007 Thomson - Wadsworth

Immune System Attack • Type II allergens üTransfusion reactions üHemolytic disease of newborns • Type III allergens üImmune complexes üInfectious diseases üAutoimmune disease • Type IV allergens üDelayed hypersensitivity © 2007 Thomson - Wadsworth

Autoimmunity • Adaptive response against self ü 5 -7% of adults, older, female üTestosterone, estrogen • Pathogenic immune cells crossreact with human cells • Autoantibodies produce lesions © 2007 Thomson - Wadsworth