Chapter 16 - Summer 2024 - Student PDF

Because learning changes everything.® Chapter 16 Disorders in Immunity Talaro’s Foundations in Microbiology Eleventh Edition Barry Chess © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  The Immune...

Because learning changes everything.® Chapter 16 Disorders in Immunity Talaro’s Foundations in Microbiology Eleventh Edition Barry Chess © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC.  The Immune Response _________________: the study of disease states associated with underreactivity and overreactivity of the immune response Allergy, hypersensitivity – an exaggerated, misdirected expression of immune responses to an allergen (antigen) Autoimmunity – abnormal responses to self antigens Immunodeficiency – deficiency or loss of immunity Cancer – both a cause and effect of immune dysfunction © McGraw Hill, LLC 2  Immune System Disorders © McGraw Hill, LLC 3  Allergy/Hypersensitivity Reactions TABLE 16.1 Classification of Immunopathologies Caused by Overreactions to Antigens Type Systems and Mechanisms Involved Examples IgE-mediated; involves mast cells, Anaphylaxis, allergies such as I Immediate allergies basophils, and allergic mediators hay fever, asthma IgG, IgM antibodies act upon cells with Blood group incompatibility, Antibody-mediated II complement and cause cell lysis; pernicious anemia; incompatibilities includes some autoimmune diseases myasthenia gravis Antibody-mediated inflammation; Systemic lupus Immune complex circulating IgG complexes deposited in erythematosus; rheumatoid III diseases basement membranes of target organs; arthritis; serum sickness; includes some autoimmune diseases rheumatic fever Infection reactions; contact T-cell-mediated Delayed hypersensitivity and cytotoxic IV dermatitis; graft rejection; hypersensitivities reactions in tissues some types of autoimmunity © McGraw Hill, LLC 4  Type I Allergic Reactions Type I allergies share a similar physiological mechanism, are immediate in onset, and are associated with exposure to specific antigens Two levels of severity: _________ – any chronic local allergy such as hay fever or asthma _____________ – a systemic, often explosive reaction that involves airway obstruction and circulatory collapse © McGraw Hill, LLC 5  Type I Allergic Reactions Factors affecting allergy onset: Generalized predisposition to allergies is familial – not to specific allergen Allergy can be affected by age, infection, and geographic area Atopic allergies may be lifelong or may be “outgrown”; may also develop later in life © McGraw Hill, LLC 6  Nature of Allergens and Their Portals of Entry Allergens have immunogenic characteristics Typically enter through epithelial portals – respiratory, gastrointestinal, skin Organ of allergic expression may or may not be the same as the portal of entropy © McGraw Hill, LLC 7  Table 16.2 © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. 8  Stages in the Development of Allergy © McGraw Hill, LLC 9  Stages in the Development of Allergy Primary contact/Sensitization __________ dose – provided on first contact with allergen, generally no signs or symptoms Antigen processed by dendritic cells activates TH in lymph nodes Interaction between TH and B cells produce plasma cells that produce IgE immunoglobulin which attaches to mast cells and basophils Primes the immune system for next encounter with allergen © McGraw Hill, LLC 10  Stages in the Development of Allergy © McGraw Hill, LLC 11  Stages in the Development of Allergy 2. Provocation ___________ dose – subsequent exposure with the same allergen precipitates first allergy symptoms Allergen binds to the IgE-mast cell complex and triggers degranulation Degranulation releases mediators with physiological effects such as vasodilation and bronchoconstriction © McGraw Hill, LLC 12  Cellular Reactions in Allergic Response © McGraw Hill, LLC 13  Role of Mast Cells and Basophils They have an ubiquitous location in tissues: Mast cells are located in the connective tissue of virtually all organs; high concentration in lungs, skin, GI, and genitourinary tract Basophils circulate in blood and migrate into tissues Each cell can bind 10,000-40,000 IgE Their cytoplasmic granules contain physiologically active cytokines, histamine, etc. They degranulate or release the contents of the granules when stimulated by allergen © McGraw Hill, LLC 14  Cytokines, Target Organs, and Allergic Symptoms Chemical mediators released by mast cells and basophils act alone or in combination; account for the scope of allergic symptoms Histamine, serotonin, leukotriene, platelet-activating factor, prostaglandins, bradykinin General targets include: skin, upper respiratory tract, GI tract, and conjunctiva Responses: rashes, itching, redness, rhinitis, sneezing, diarrhea, shedding tears © McGraw Hill, LLC 15  Cytokines, Target Organs, and Allergic Symptoms Systemic targets: smooth muscles, mucous glands, and nervous tissue Responses: vascular dilation and constriction resulting in change in blood pressure and respiration © McGraw Hill, LLC 16  Main Chemical Mediators ___________ – most profuse and fastest acting; stimulator of smooth muscle, glands, and eosinophils Response to chemical depends on the muscle location: constricts smooth muscles of small bronchi, intestines; relaxes vascular smooth muscles Serotonin – effects complement those of histamine Leukotrienes – “slow reacting substance of anaphylaxis”, produce prolonged bronchospasm, vascular permeability, and mucous secretion of the asthmatic individual © McGraw Hill, LLC 17  Main Chemical Mediators Prostaglandins – powerful inflammatory agents. Regulate smooth muscle contraction Bradykinin – causes prolonged contraction of the bronchioles, dilation of peripheral arterioles, increased capillary permeability, and increased mucus secretion © McGraw Hill, LLC 18  Reactions to Inflammatory Cytokines © McGraw Hill, LLC 19  Diseases Associated with Type I Allergy Atopic disease : Hay fever, rhinitis: seasonal, antigen may be inhaled, topical or ingested Allergic Asthma: severe bronchoconstriction Atopic dermatitis or Eczema : itchy inflamed skin Food allergy – intestinal portal can affect skin and respiratory tract Vomiting, diarrhea, abdominal pain Eczema, hives, rhinitis, asthma, occasionally anaphylaxis Drug allergy – side effect of treatment; any tissue can be affected; reaction from mild atopy to fatal anaphylaxis © McGraw Hill, LLC 20  Diseases Associated with Type I Allergy ©DermNet New Zealand Trust © McGraw Hill, LLC 21  Anaphylaxis ____________ – a reaction of animals injected with a foreign protein. Reinoculation showed acute symptoms—itching, sneezing, difficult breathing, prostration, convulsions, death Two types in humans: Cutaneous anaphylaxis – wheal and flare inflammatory reaction to the local injection of allergen Systemic anaphylaxis (anaphylactic shock) – sudden respiratory and circulatory disruption that can be fatal in a few minutes Allergen and route are variable (bee stings, antibiotics, or serum injection) © McGraw Hill, LLC 22  Diagnosis of Allergy Important to determine if a person is experiencing allergy or infection Skin testing (a): Source: Dr. Frank Perlman, M.A. Parson/CDC © McGraw Hill, LLC 23  Diagnosis of Allergy © McGraw Hill, LLC 24  Treatment and Prevention Methods Avoiding allergen © McGraw Hill, LLC 25  Treatment and Prevention Methods Use drugs that block the action of the lymphocytes, mast cells, or chemical mediators (antihistamines) Desensitization (or hyposensitization) therapy – injection of allergens stimulates high-levels of allergen-specific IgG to prevent IgE-allergen binding in mast cells © McGraw Hill, LLC 26  Type II Hypersensitivities Reactions that lyse foreign cells Involve antibodies, complement-mediated lysis of foreign cells Transfusion reactions ABO blood groups Rh factor – hemolytic disease of the newborn © McGraw Hill, LLC 27  Human ABO Antigens and Blood Types 4 distinct ___________________________ Genetically determined RBC glycoproteins; inherited as 2 alleles of A, B, or O 4 blood types: A, B, AB, or O Named for dominant antigen(s) Type O persons lack both A and B antigens Tissues other than RBCs also carry A and B antigens © McGraw Hill, LLC 28  Human ABO Antigens and Blood Types TABLE 16.3 Characteristics of ABO Blood Groups Incidence of Type in United States: Antigen Among those of Among Among Genotype Present on Antibody in African Blood Type Whites Asians Erythrocyte Plasma Caribbean (%) (%) Membranes Descent (%) AA, AO A A Anti-b 41 28 27 BB, BO B B Anti-a 10 27 20 Neither anti-a AB AB A and B 4 5 7 nor anti-b Neither A Anti-a and anti- OO O 45 40 46 nor B b © McGraw Hill, LLC 29  Antibodies Against A and B Antigens © McGraw Hill, LLC 30  Antibodies Against A and B Antigens Serum contains pre-formed antibodies that react with blood of another antigenic type – agglutination; possible transfusion concern Type A contains Abs that react against B antigens Type B contains Abs that react against A antigens Type O contains Abs that react against A and B antigens Type AB contains no Abs that react against A or B antigens © McGraw Hill, LLC 31  Interpretation of Blood Typing Kathy Park Talaro © McGraw Hill, LLC 32  Transfusion Reactions © McGraw Hill, LLC 33  Hemolytic Disease of the Newborn © McGraw Hill, LLC 34  Hemolytic Disease of the Newborn and Rh Incompatibility When a mother is Rh_ and her unborn child is Rh+, fetal RBCs can leak into the mother’s circulation during childbirth. This sensitizes the mother’s immune system The first Rh+ child is usually not affected, but a second contact with this factor in a subsequent pregnancy can be fatal Hemolytic Disease of the Newborn (HDN) – in a second pregnancy maternal anti-Rh antibodies can affix to fetal RBCs and cause hemolysis Prevention requires the use of passive immunization of the mother with antibodies against the Rh antigen to prevent sensitization © McGraw Hill, LLC 35  Type III Hypersensitivity Reaction of soluble antigen with antibody and the deposition of the resulting complexes in basement membranes of epithelial tissues Immune complexes become trapped in tissues and incite a damaging inflammatory response Arthus reaction – localized dermal injury due to inflamed blood vessels Serum sickness – systemic injury initiated by antigen- antibody complexes that circulate in the blood © McGraw Hill, LLC 36  Pathogenesis of Immune Complex Disease The figure of “Pathogenesis of Immune Complex Disease.” © McGraw Hill, LLC 37  Immunopathologies Involving T Cells Type IV Hypersensitivity Delayed hypersensitivity as symptoms arise one to several days following the second contact with an antigen In general, type IV diseases result when T cells respond to antigens displayed on self tissues or transplanted foreign cells Examples: delayed allergic reactions to infectious agents, contact dermatitis, and graft rejection © McGraw Hill, LLC 38  Immunopathologies Involving T Cells SCIENCE PHOTO LIBRARY/age footstock © McGraw Hill, LLC 39  Contact Dermatitis The figure of “Contact Dermatitis.” © McGraw Hill, LLC 40  Contact Dermatitis The figure of “Contact Dermatitis” continues on this slide. 1. Lipid-soluble catechols are absorbed by the skin. 2. Dendritic cells close to the epithelium pick up the allergen, process it, and display it on MHC receptors. 3. Previously sensitized TH1 (CD4+ ) cells recognize the presented allergen. 4. Sensitized TH1 cells are activated and secrete cytokines (IFN, TNF). 5. These cytokines attract macrophages and cytotoxic T cells to the site. 6. Macrophages release mediators that stimulate a strong, local inflammatory reaction. Cytotoxic T cells directly kill cells and damage the skin. Fluid-filled blisters result. © McGraw Hill, LLC 41  Contact Dermatitis (b): BW Folsom/Shutterstock © McGraw Hill, LLC 42  T Cells and ________________________________ Host rejection of graft Host T cells release interleukin-2 to expand TH and TC cells specific for donor antigens. TC cells release lymphokines that begin the rejection Graft rejection of host Graft versus host disease(GVHD) Any host tissue bearing MHC foreign to the graft is attacked © McGraw Hill, LLC 43  T Cells and Organ Transplantation © McGraw Hill, LLC 44  T Cells and Organ Transplantation © McGraw Hill, LLC 45  Classes of Grafts Classified according to the degree of MHC similarity between donor and host: Autograft – recipient also serves as donor Isograft – tissue from identical twin is grafted Allograft – genetically different individuals but of the same species (humans) Xenograft – individuals of different species Rejection can be minimized by tissue matching HLA antigens Mixed lymphocyte reaction Tissue typing © McGraw Hill, LLC 46  Autoimmunity In certain type II & III hypersensitivities, the immune system has lost tolerance to autoantigens and forms autoantibodies and sensitized T cells against them Disruption of function can be systemic or organ specific: Systemic lupus erythematosus Rheumatoid arthritis Endocrine autoimmunities Myasthenia gravis Multiple sclerosis Susceptibility is determined by genetics and influenced by gender and environmental factors © McGraw Hill, LLC 47  The Origins of ______________ Disease Sequestered antigen theory – during embryonic growth some tissues are immunologically privileged Forbidden clones – some clones were not subjected to the tolerance process, and they attack tissues carrying self molecules Theory of immune deficiency – according to it 1. Mutations in the receptor genes of some lymphocytes render them reactive to self, and 2. T-cell regulatory cells that normally maintain tolerance to self have become dysfunctional Molecular mimicry – some microbial antigens are similar to normal human cells. Microbial infection could stimulate antibodies that can cross-react with tissues © McGraw Hill, LLC 48  Autoimmune Diseases TABLE 16.4 Selected Autoimmune Diseases Type of Disease Target Characteristics Hypersensitivity Systemic lupus Inflammation of many organs; antibodies erythematosus Systemic II and III against red and white blood cells, platelets, (SLE) clotting factors, nucleus DNA Rheumatoid arthritis Vasculitis; frequent target is joint lining; and ankylosing Systemic III and IV antibodies against other antibodies spondylitis (rheumatoid factor) Excess collagen deposition in organs; Scleroderma Systemic II antibodies formed against many intracellular organelles Hashimoto's Thyroid II Destruction of the thyroid follicles thyroiditis Antibodies against thyroid-stimulating Graves' disease Thyroid II hormone receptors Stomach Antibodies against receptors prevent Pernicious anemia II lining transport of vitamin B12 © McGraw Hill, LLC 49  Autoimmune Diseases The “TABLE 16.4” continues on this slide. Type of Disease Target Characteristics Hypersensitivity Antibodies against the acetylcholine Myasthenia gravis Muscle II receptors on the nerve-muscle junction alter function Antibodies stimulate destruction of Type I diabetes Pancreas II insulin-secreting cells T cells and antibodies sensitized to Multiple sclerosis Myelin II and IV myelin sheath destroy neurons Goodpasture syndrome Antibodies to basement membrane of Kidney II (glomerulonephritis) the glomerulus damage kidneys Antibodies to group A streptococci Rheumatic fever Heart II cross-react with heart valve tissue © McGraw Hill, LLC 50  Systemic Autoimmunities Systemic lupus erythematosus (SLE), or lupus – All patients produce autoantibodies against a variety of organs and tissues Facial rash, skin lessions. Also affected: kidneys, bone marrow, nervous system, joints, muscles, heart, and GI tract Rheumatoid Arthritis (RA) – incurs progressive, debilitating damage to the joints (chronic inflammation) Lungs, eye, skin, and nervous systems may also be affected © McGraw Hill, LLC 51  Systemic Autoimmunities (a): ©DermNet New Zealand Trust; (b): ©Mediscan/Alamy Stock Photo (a): Source: Usatine, R. P., Smith, M. A., Mayeaux, E. J., & Chumley, H. S. The Color Atlas of Family Medicine (2nd ed.). www.accessmedicine.com. Copyright The McGraw-Hill Companies, Inc. All rights reserved.; (b): UnderhilStudio/Shutterstock © McGraw Hill, LLC 52  Endocrine Glands Autoimmunities Graves’ disease – attachment of autoantibodies to receptors on the follicle cells that secrete thyroxin, increases levels of hormone Hyperthyroidism Hashimoto’s thyroiditis – both autoantibodies and T cells are reactive to the thyroid gland and reduce levels of thyroxin Hypothyroidism Type I Diabetes mellitus – autoantibodies and sensitized T cells damage beta cells in the pancreas Reduction in insulin production Possibly due to molecular mimicry © McGraw Hill, LLC 53  Neuromuscular Autoimmunities Myasthenia gravis – autoantibodies bind to receptors for acetylcholine and block transmission of nerve impulses to muscle fibers Pronounced muscle weakness In some cases it can progress to complete loss of muscle function and death © McGraw Hill, LLC 54  Neuromuscular Autoimmunities Multiple sclerosis – myelin sheath of nerve cells is damaged by both T cells and autoantibodies Paralyzing neuromuscular disease Muscular weakness and tremors, difficulties in speech and vision, and some degree of paralysis Antigen triggering attack still unidentified © McGraw Hill, LLC 55  Immunodeficiency Diseases Components of the immune response system are absent Deficiencies involve B and T cells, phagocytes, and complement Dysfunctional immunities can be grouped into: Primary diseases– congenital; usually genetic errors Secondary diseases – acquired after birth; caused by natural or artificial agents © McGraw Hill, LLC 56 Primary Immunodeficiencies © McGraw Hill, LLC 57  Primary Immunodeficiencies ©Baylor College of Medicine, Public Affairs © McGraw Hill, LLC 58  Primary Immunodeficiencies © McGraw Hill, LLC 59  The Immune System and Cancer New growth of abnormal cells Tumors may be ________ (non-spreading) self-contained; or __________ (cancer) spreading from tissue of origin to other sites Appear to have genetic alterations that disrupt the normal cell division cycle Possible causes include: errors in mitosis, genetic damage, activation of oncogenes, or retroviruses © McGraw Hill, LLC 60  The Immune System and Cancer Immune surveillance, immune system keeps cancer “in check” by detecting and eliminating cancer cells Primarily by TC cells, natural killer (NK) cells, and macrophages © McGraw Hill, LLC 61 Medical Moment: Candidiasis CA = Candida albicans (predominately) Ubiquitous yeast Dimorphic: yeast and pseudohyphae Opportunistic infection Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Pathogenesis Virulence factors include: – Adherence molecules – stick to human cells and prosthetic devices) – Acid proteases and phospholipase – penetration and damage cells – Conversion to hyphal forms – increases tissue penetration Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Epidemiology Risk for invasive or systemic Candidiasis – Bone marrow/organ transplant, catheters, prolonged hospitalization, premature birth, hemodialysis, mechanical ventilation > 3 days, renal failure Host defects that increase risk: – Compromised mucocutaneous barriers (wounds, IV catheters, burns, ulcerations) – Decreased WBC’s (granulocytopenia, chronic granulomatomous disease) – Decreased complement and immunoglobulins – Decreased cell mediated immunity due to HIV, diabetes mellitus, corticosteriods – Use of broad spectrum antibiotics – decrease of normal flora Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Epidemiology, con’t Common fungal infection in immunocompromised persons 40-65% population have Candida in normal fecal flora 90% of HIV+ NOT on HAART therapy eventually develop oropharyngeal candidiasis (OPC) Blood borne Candida and disseminated Candidiasis have a ~25-30% mortality rate Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  66 Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Signs and Symptoms of a few types of Candida infections Systemic candidiasis = two presentations: candidemia and disseminated candidiasis – Candidemia – considered nosocomial, fever unresponsive to broad spectrum antibiotics, history of risk factors (25,000 cases per year in the USA) – Disseminated candidiasis – liver/spleen, peritonitis GI candidiasis – Oropharyngeal/Esophogeal = sore, painful mouth/tongue, dysphagia, white patches on oral mucosa, nausea, vomiting Chronic mucocutaneous candidiasis – Persistent infection of hair, nails, skin and mucous membranes most associated with endocrine disorders Cutaneous candidiasis syndrome: – Skin lesions of various forms from diffuse trunk, thorax and extremities to nails/nail bed infection Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Treatment of Candidiasis Systemic Candidiasis: – Txt = Fluconazole orally or IV OR Echinocandins IV (caspofungin, micafungin, anidulafungin) Oropharyngeal Candidiasis (thrush): – Txt = antifungal lozenges or fluconazole orally PREVENTION: – Early detection and treatment of oropharyngeal to prevent systemic spread in susceptible persons Copyright © McGraw-Hill Education. All rights reserved. No reproduction or distribution without the prior written consent of McGraw-Hill Education.  Because learning changes everything. ® www.mheducation.com © McGraw Hill LLC. All rights reserved. No reproduction or distribution without the prior written consent of McGraw Hill LLC. Chapter 16 Review  Compare and contrast the four types of immune system overreactions (Type I, II, III, IV).  What is the role of Mast Cells and Basophils?  Why can’t someone with type O blood receive a type AB blood transfusion?  Describe the mechanism that causes Rheumatoid arthritis.  Summarize the endocrine glands autoimmunities.  What are immunodeficiencies and how do they cause disease? Chapter 16 Review Vocabulary  Immunopathology  Histamine  Allergy/hypersensitivity  Atopic disease  Autoimmunity  Systemic anaphylaxis  Immunodeficiency  SCID  Cancer  DiGeorge Syndrome  Atopy  Benign  Anaphylaxis  Malignant  Sensitizing dose  Provocative dose