DOCSLIB.ORG

Immune Pathology Immune System Functions Reactivity to Tolerance Nonshared Ag to Self-Ag

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Immune Pathology Immune System Functions Reactivity to Tolerance Nonshared Ag to Self-Ag Immune Pathology Immune system functions reactivity to tolerance nonshared Ag to self-Ag reduction pErVeRsIoN malfunction immunodeficiency hypersensitivity autoimmune diseases Hypersensitivity Hypersensitivity - excessive or inadequate manifestation adaptive immune of reactions Can manifest as local and systemic reactions Hypersensitivity Type Synonym Immunological mechanisms I IgE-mediated, anaphylactic, IgE-mediated degranulation of mast reaginic, HIS (blood cells dyscrasia) II antibody-dependent Cytotoxic antibodies activate cytotoxicity complement, which leads to cell lysis III immune complex Immune complexes activate leukocytes IV cell-mediated, delayed-type Cytokine production by hypersensitivity macrophages and lymphocytes V antibody-dependent Antibodies alter functional state of functional changes cells by interacting with its receptor Type I hypersensitivity • Speed ​​of reaction - seconds or minutes • IgE-mediated • Chemical mediators of damage - vasoactive products of mast cells / basophils (histamine, arachidonic acid derivatives) • Mechanism - accumulation of of neutrophils, unstriated muscle spasm Type I hypersensitivity • bronchial asthma (some forms) • anaphylactic shock • Urticaria • Quincke's edema • dietary allergy • nasal allergy • allergic conjunctivitis Mast cell Аг Synthesis and secretion: leukotrienes (LTC4, LTB4), prostaglandins (PGD2), degranulation: IL-3, 4,5,6 histamine Platelet-activating factor serotonin (PAF) eotoxin Type I hypersensitivity Morphological manifestations IHS: • exudative alterative inflammation (many eosinophils infiltrate) • dilation of blood vessels, increased vascular permeability • unstriated muscle spasm Type II hypersensitivity • Speed ​​of reaction – hours or days • Mediated by IgG, IgM • Chemical mediators of damage – complement • Mechanism - phagocytosis, lysis of target Type II hypersensitivity Types: • Cytotoxicity, complement-mediated • Antibody-dependent damage to connective tissue Type II hypersensitivity Mechanisms of complement-mediated cytotoxicity: 1. Lysis 2. Opsonization phagocytosis Example: some hemolytic anemia (blood transfusion of differ group, hemolytic disease of fetus and newborn) Membrane attack complex Ат Аг Osmotic lysis Complement Opsonization С3b-R Fc-receptor Macrophage Phagocytosis Type II hypersensitivity Antibody-dependent damage to the connective tissue • Circulating antibodies are fixed on connective tissue Ag and thus stimulate inflammation Examples: Goodpasture's syndrome, bullous pemphigoid Type III hypersensitivity • Speed ​​of reaction – hours or days • Mediated by IgG, IgM, IgA as part of immune complexes • Chemical mediators of damage - complement and its fractions • Mechanism - accumulation of of neutrophils, macrophages, release of lysosomal enzymes Type III hypersensitivity • most of glomerulonephritis • Systemic lupus erythematosus (SLE) (vasculitis and nephritis) • Rheumatoid arthritis (RA) • some vasculitides • Arthus reaction (experimental vasculitis) Type III hypersensitivity Morphological manifestations: • vascular injuries (vasculitis with large numbers of neutrophils, edema and hemorrhage into surrounding tissue) • Mesenchymal dysproteinosis (mucoid swelling, fibrinoid swelling, fibrinoid necrosis) Deposition of IC Complement IC activation basal membrane endotheliocyte Blood vessel neutrophil proteases proteolysis of BM 4 Secretion of proteases Chemotaxis and and active O2 neutrophils activation tissue damage Type IV hypersensitivity • Speed ​​of reactions – days • Mediated by T-and NK-cells • Chemical mediators of damage - lymphokines, monokines • Mechanism - the action of lymphocytes and macrophages, granulomas formation Type IV hypersensitivity • diseases associated with formation of granulomas (tuberculosis, syphilis, leprosy, sarcoidosis, Crohn's disease, etc.) • contact dermatitis (poison ivy) • transplant rejection reaction • autoimmune thyroiditis (Hashimoto) • insulin-dependent diabetes mellitus Type IV hypersensitivity Morphological manifestations of DTHS (delayed-type hypersensitivity): • productive inflammation, often with formation of granulomas. In infiltrate dominated lymphocytes, monocytes, macrophages Type V hypersensitivity Antibody-dependent functional changes: • The antibodies attach to the receptors and, thus, or block them (miastenia gravis), or stimulate (Graves' disease) • does not occur death of cell-target Examples: Ab acetylcholine receptor - miastenia gravis, Ab to thyroid-stimulating hormone receptor - Graves' disease (diffuse thyrotoxicosis). acetylcholine Ab to acetylcholine receptor acetylcholine receptor Immunodeficiency states Immunodeficiency states - a group of diverse syndromes caused by isolated or multiple defects of the immune system. Characterized by increased susceptibility to infections, leading to severe, acute and chronic diseases. Immunodeficiency states Primary immunodeficiency – genetically determined disease Secondary immunodeficiency – immunodeficiency which arose as a result of an illness of previously healthy person Primary immunodeficiency Depending on the affected section are divided onto groups: 1. B-cell deficiency 2. T-cell deficiency 3. combined ID 4. phagocyte defects 5. complement defects Primary immunodeficiency Epidemiology overall incidence of symptomatic PIDS - 1:10 000 Predominant pathology of B cells - 50% PIDS (frequency of IgA deficit - 1:400) pathology of T-cells - 30% phagocyte defects - 18% complement deficiency - 2% About 80% of patients younger than 20 years 70% - affected males (X-linked). B-cell deficiency Main manifestation - Ab deficiency and consequently increased sensitivity to bacterial infections • X-linked agammaglobulinemia (Bruton's syndrome) • common variable immunodeficiency • IgA deficiency • IgG subclass deficiency • etc. X-linked agammaglobulinemia (Bruton's syndrome) Panhypogammaglobulinemia of boys, characterized by low IgG, low or lack of other Ig-s, unchanged cellular immunity and outbreaks of infections in the age of 6 months, when mother’s Ab-s disappear X-linked agammaglobulinemia (Bruton's syndrome) Genetic defect associated with the inability to differentiate B- cells from pre-B cells. Hypersensitivity to pyogenic infections High risk of vaccinal poliomyelitis Autoimmunity: RA, SLE, etc. morphologically : • No germinal centers in lymph nodes and spleen • No plasma cells • Poorly developed palatine tonsils Selective IgA deficiency Absence or abrupt decrease of serum IgA at normal level of other Ig and intact cellular immunity The most common and lightest ID (up to 1:400) In the majority are asymptomatic IgA in secretions also not detected, its deficiency can be compensated by other Ig May occur recurrent respiratory infections, chronic diarrhea, allergic or autoimmune diseases T-cell deficiency The main manifestation - deficiency of cellular immunity and, consequently, increased sensitivity to viral and fungal infections • syndrome Dee Georgie • chronic mucocutaneous candidiasis • etc. Dee Georgie syndrome Synonyms: thymic hypoplasia, syndrome of 3rd and 4th pharyngeal recess Congenital ID, which is characterized by: • hypocalcemic tetany • congenital disorders of the heart and great vessels • specific face shape • increased susceptibility to infections • hypoplasia of the thymus and parathyroid glands • partial or total T-cells ID • normal B-cells immunity Dee Georgie syndrome Low-set ears, cleavage at the middle of face, jaw hypoplasia, hypertelorism and a shorter longitudinal groove between the nose and upper lip. Microscopically: None thymus-dependent area of lymph nodes and spleen Tetany begins to manifest in 1-2 days after birth Etiology: • disruption of normal development of derivatives pharyngeal recess on the eighth week of gestation. • deletion of chromosome 22 The degree of ID for different patients varies, can occur spontaneous function improvement of T-cells. Combined ID Group of diseases with congenital and often hereditary defect of T-and B-cell systems, aplasia of lymphoid tissue and dysplasia of thymus. • severe combined ID (SCID) • Swiss agammaglobulinemia • dysgenesis of reticulum • Combined ID with preservation of Ig (Nezelof syndrome) • etc. Combined ID • at an early age (up to 3 months) appear thrush, pneumonia, diarrhea, which untreated progresses to death before the age of 2 • pronounced deficiency of B-cells, Ig, T-cells • lymphopenia • common opportunistic infections • absence of radiologically detectable thymus lymph nodes aplasia Secondary immunodeficiency Causes: • severe infectious diseases • malabsorption • aging • malnutrition • treatment with immunosuppressive drugs (corticosteroids, cytotoxic drugs) • radiation therapy • AIDS • autoimmune diseases • malignant tumors • etc. AIDS HIV CD4 Proviral DNA T-helper AIDS Lymphoid Lymphoid hyperplasia depletion Morphology of immunity organs at secondary immunodeficiencies Thymus - is formed atrophy corresponding IV-V phase ATMT. In peripheral immune organs - devastation (delymphonyzation) of structural-functional areas. Autoimmune diseases Autoimmune disease - a group of diseases, which are based on development of immune responses in body's self-Ag Autoimmune diseases I. Organ-specific II. Organo-nonspecific • Hashimoto's thyroiditis • systemic lupus • autoimmune encephalomyelitis erythematosus • insulin-dependent DM • rheumatoid arthritis • Graves' disease • Sjögren's sicca [Mikulicz- • miastenia gravis Sjögren] syndrome • autoimmune pernicious anemia • Scleroderma systematica • autoimmune orchitis • inflammatory myopathies • autoimmune Addison's
Load more

Recommended publications
  • Difference Between Hypersensitivity and Autoimmunity Key Difference – Hypersensitivity Vs Autoimmunity
    Difference Between Hypersensitivity and Autoimmunity www.differencebetwee.com Key Difference – Hypersensitivity vs Autoimmunity Autoimmunity is an adaptive immune response mounted against self-antigens. In simple terms, when your body is acting against its own cells and tissues, this is called an autoimmune reaction. An exaggerated and inappropriate immune response to an antigenic stimulus is defined as a hypersensitivity reaction. Unlike autoimmune reactions that are triggered only by the endogenous antigens, hypersensitivity reactions are triggered by both endogenous and exogenous antigens. This is the key difference between hypersensitivity and autoimmunity. What is Hypersensitivity? An exaggerated and inappropriate immune response to an antigenic stimulus is defined as a hypersensitivity reaction. The first exposure to a particular antigen activates the immune system and, antibodies are produced as a result. This is called sensitization. Subsequent exposures to the same antigen give rise to hypersensitivity. Few important facts regarding the hypersensitivity reactions are given below They can be elicited by both exogenous and endogenous agents. They are a result of an imbalance between the effector mechanisms and the countermeasures that are there to control any inappropriate execution of an immune response. The presence of a genetic susceptibility increases the likelihood of hypersensitivity reactions. The manner in which hypersensitivity reactions harm our body is similar to the way that the pathogens are destroyed by immune reactions. Figure 01: Allergy According to the Coombs and Gell classification, there are four main types of hypersensitivity reactions. Type I- Immediate Type/ Anaphylactic Mechanism Vasodilation, edema, and contraction of smooth muscles are the pathological changes that take place during the immediate phase of the reaction.
    [Show full text]
  • Ii Vasclitides
    ا يمون وپات وژنز واسکوليتھااکلتا Vascliiitides: The Immunopa tho genes is دکتر محمدمھدی محمدی LMD, PhD, MPH ([email protected]) The 7th International 12th National Congress on Quality Improvement in Clinical Laboratories 28 Farvardin 1393 / 17April 2014 , Tehran, Iran A small spoonful of Terminology (in Farsi بيماريزايی) – .path·o·gen·e·sis, n • – the ppp(roduction and development of disease (events and reactions and other pathologic mechanisms) . Also, pa·thog·e·ny !?! (in Farsi بيماريزايی) _ .path·o·ge·nic·i·ty, n • – the disease-producing capacity of a pathogen. [PATHOGENIC + -ITY] • vir·u·lence, n. – the relative ability of a microorganism to cause disease; degree of pathogenicity. • Vasculitis, n. (vasculitides, plural) – a general term for vessel wall inflammation, systemic or localized, immune-mediated or directly invaded by microbes. • Infections may indirectly generate vasculitis, e.g. through IC formation or by X_reaction. Note that immunosuppressive therapy is only appropriate for --?– type! • WHAT R the IMMUNE MECHANISMS in VASCULITIS? افراط تعادل تفريط Immunodeficiency Allergy (& Infection) Defence Immunodeficiency Surveillance Autoimmunity (& Malignancy) Homostasis ?! Some Inter-related Concepts Immunological Vasculitis Hypersensitivity Auoimmunity Tolerance EDUCATION? Tolerance in different classic Txtbks of Immunology (Abbas, Benjamini, Janeway, Kuby, Roitt, Stites …) • Tolerance (by C&M Immunology): – Unresponsiveness of the adaptive immune system to antigens, as a result of inactivation or death of antigen-specific lymphocytes, induced by exposure to the antigens. – (()Active) Unresponsiveness of the (()HEALTHY) adappytive immune system to (selected) antigens, as a result of (i.e. MECHANISMS:) inactivation or death of antigen-specific lymphocytes, induced by exposure to those antigens. • Tolerance to self antigens is a normal feature of the adaptive immune system, but tolerance to foreign antigens may be induced undtiditiftider certain conditions of antigen exposure.
    [Show full text]
  • Hypersensitivity Reactions (Types I, II, III, IV)
    Hypersensitivity Reactions (Types I, II, III, IV) April 15, 2009 Inflammatory response - local, eliminates antigen without extensively damaging the host’s tissue. Hypersensitivity - immune & inflammatory responses that are harmful to the host (von Pirquet, 1906) - Type I Produce effector molecules Capable of ingesting foreign Particles Association with parasite infection Modified from Abbas, Lichtman & Pillai, Table 19-1 Type I hypersensitivity response IgE VH V L Cε1 CL Binds to mast cell Normal serum level = 0.0003 mg/ml Binds Fc region of IgE Link Intracellular signal trans. Initiation of degranulation Larche et al. Nat. Rev. Immunol 6:761-771, 2006 Abbas, Lichtman & Pillai,19-8 Factors in the development of allergic diseases • Geographical distribution • Environmental factors - climate, air pollution, socioeconomic status • Genetic risk factors • “Hygiene hypothesis” – Older siblings, day care – Exposure to certain foods, farm animals – Exposure to antibiotics during infancy • Cytokine milieu Adapted from Bach, JF. N Engl J Med 347:911, 2002. Upham & Holt. Curr Opin Allergy Clin Immunol 5:167, 2005 Also: Papadopoulos and Kalobatsou. Curr Op Allergy Clin Immunol 7:91-95, 2007 IgE-mediated diseases in humans • Systemic (anaphylactic shock) •Asthma – Classification by immunopathological phenotype can be used to determine management strategies • Hay fever (allergic rhinitis) • Allergic conjunctivitis • Skin reactions • Food allergies Diseases in Humans (I) • Systemic anaphylaxis - potentially fatal - due to food ingestion (eggs, shellfish,
    [Show full text]
  • Hypersensitivity Reactions
    Color code: Important in red Extra in blue Hypersensitivity Reactions For team error adjustments, click here Objectives ➤ To know that hypersensitivity reactions are over and excessive immune responses that can be harmful to the body in four different ways ➤ To be familiar with inflammatory processes in Type I hypersensitivity reaction that mediate allergic inflammation ➤ To recognize that Type II hypersensitivity deals with immune responses against antigens that are integral parts of the cell membrane and are usually associated with autoimmune disorders ➤ To know that Type III hypersensitivity reactions are mediated by immune complexes and cause vasculitis ➤ To describe Type IV hypersensitivity is a purely cell mediated immune response associated with chronic inflammation What is hypersensitivity? Hypersensitivity: is an undesirable Protective immunity: desirable reaction by the immune system. reaction. Gell—Coombs Classification of Hypersensitivity Reactions Type I: Type IV: IgE mediated Type II: Type III: IgG mediated IgG mediated T cell (most (destruction (immune mediated allergic of cells) complex) immunity reactions) Type I Hypersensitivity ● Known as immediate hypersensitivity (mins-hrs) or an allergic reaction that may develop into an anaphylactic* reaction (a severe and life-threatening form). Antibody - Allergic (atopic): IgE - Non Allergic: IgG Features Cells Involved - Mast cells - Eosinophils - Basophils Antigen - Allergen (low molecular weight & high solubility) Ex: Pollens, Dust mites, Injected allergen (sting venom from
    [Show full text]
  • Hypersensitive Reactions
    Hypersensitive reactions For B.Sc Life Sciences VI Sem Paper Immunology Teacher: Dr. Renu Solanki There Are Several Components of Type I Reactions 1. Allergens: The majority of humans mount significant IgE responses only as a defense against parasitic infections. After an individual has been exposed to a parasite, serum IgE levels increase and remain high until the parasite is successfully cleared from the body. The term allergen refers specifically to nonparasitic antigens capable of stimulating type I hypersensitive responses in allergic individuals. 2. REAGINIC ANTIBODY (IGE): Serum IgE levels in normal individuals fall within the range of 0.1–0.4 µg/ml; even the most severely allergic individuals rarely have IgE levels greater than 1 µg/ml. IgE was found to be composed of two heavy and two light chains with a combined molecular weight of190,000.The higher molecular weight as compared with IgG (150,000) is due to the presence of an additional constant-region domain (see Figure 4- 13). This additional domain (C H 4) contributes to an altered conformation of the Fc portion of the molecule that enables it to bind to glycoprotein receptors on the surface of basophils and mast cells. Although the half-life of IgE in the serum is only 2–3 days, once IgE has been bound to its receptor on mast cells and basophils,it is stable in that state for a number of weeks. IgE Crosslinkage Initiates Degranulation Type I Reactions Can Be Systemic or Localized SYSTEMIC ANAPHYLAXIS LOCALIZED ANAPHYLAXIS (ATOPY) -ALLERGIC RHINITIS: ALLERGIC RHINITIS: Results from the reaction of airborne allergens with sensitized mast cells in the conjunctivae and nasal mucosa to induce the release of pharmacologically active mediators from mast cells; these mediators then cause localized vasodilation and increased capillary perme- ability.
    [Show full text]
  • Biochemistry Hypersensitivity IV and V
    Description of Module Paper : 16 Immunology Module : 30 Hypersensitivity IV and V Principal Investigator Dr. Sunil Kumar Khare,Professor Dept. of Chemistry, I.I.T. Delhi Paper Coordinator Dr. M.N.Gupta, Emeritus Professor and Dept. of Biochemical Engg. and Content Writer Biotechnology, I.I.T. Delhi Content Reviewer: Dr. Prashant Mishra, Professor Dept. of Biochemical Engg. and Biotechnology, I.I.T. Delhi 1 Immunology Biochemistry Hypersensitivity IV and V Subject Name Biochemstry Paper Name 16 Immunology Module Name/Title 30 Hypersensitivity IV and V Dr. Vijaya Khader Dr. MC Varadaraj 2 Immunology Biochemistry Hypersensitivity IV and V 1. Objectives To understand the three types of class IV hypersensitivity reaction: contact dermatitis, tuberculin reaction and granulomatous hypersensitivity reaction. To explain how machanistically all the three types follow the same route. To learn how certain diseases caused by infectious agent have involvement of type IV hypersensitivity To understand type V hypersensitivity reactions which occur because of chronic stimulation 2. Concept map 3 Immunology Biochemistry Hypersensitivity IV and V Type IV hypersensitivity is also called delayed type as results are seen from 48 hrs-28 days ! In the three variants of type IV, the delay is of different time periods. We will also look at the type V hypersensitivity which was introduced as a separate class after Coombs and Geller classification. This hypersensitivity is involved in some autoimmune diseases. Contact with some substances can cause contact dermatitis. Injection of some antigens derived from infectious agents can be used as a test for hypersensitivity towards that microbe. When some microbes persist, it causes formation of granulomes.
    [Show full text]
  • Candida Albicans, 152 Ascaris Lumbricoides, 172 Borrelia
    Index AIDS, 117 Arteritis C-s (Chiirg-Strauss) syndrome, CDC surveillance case giant cell (GCA), 218-219 213-214 definition for, 119 temporal,218-219 Candida albicans, 152 ocular manifestations of Arthritis Candidiasis, 152-153 infection with, 117-125 psoriatic, 207-208 Cataract surgery, 81-83 retinal manifestations of, rheumatoid, see Rheumatoid CDC surveillance case 119 arthritis definition for AIDS, 119 AKC (atopic keratoconjunc- AS (ankylosing spondylitis), Cell tivitis),188-189 198-200 aqueous, 19 Alkylating drugs, 72-73 Ascariasis, 172 defined,3-4 Amoebiasis, 162-163 Ascaris lumbricoides, 172 Chest radiograph, 50 Anaerobic endophthalmitis, Atopic keratoconjunctivitis Chorioretinitis, defined, 4 chronic, 269-270 (AKC), 188-189 Chorioretinopathy, ANCA autoantibodies, 49-50 Autoimmune uveitis, serpiginous, 248-249 Angle signs, 22-23 experimental (EAU), 241 Choroid disorders, 247-252 Animals causing uveitis, 182- Azathioprine, 73 Choroidal signs, 29 183 Choroiditis, 29 Ankylosing spondylitis (AS), defined,4 198-200 Bacterial diseases causing multifocal, and panuveitis Anterior chamber signs, 19- uveitis, 134-144 (MCP) syndrome, 247-248 20 Bacterial endophthalmitis, punctate inner (PIC), 248 Anterior uveitis, 9 infectious, 267-269 vitiliginous, 240 Antiphospholipid antibodies Band keratopathy, 17, 19 Chiirg-Strauss (C-S) (APLA),49 BARN (bilateral acute retinal syndrome,213-214 APMPPE (acute posterior necrosis syndrome), 115- Cicatricial pemphigoid (CP), multifocal placoid 117 191-193 pigment epitheliopathy), Beh-;et's disease, 200-202
    [Show full text]
  • Hypersensitivity Reaction Types
    put together by Alex Yartsev: Sorry if i used your images or data and forgot to reference you. Tell me who you are. [email protected] ypersensitivity Reactions ripped shamelessly fffrfrrromom a website which can no longer be recalled Type I - immediate hypersensitivity Mediated by IgE antibodies and produced by the immediate release of histamine, arachidonate and derivatives by basophils and mast cells. This causes an inflammatory response leading to an immediate (within seconds to minutes) reaction. Some examples: • Allergic asthma • Allergic conjunctivitis • Allergic rhinitis ("hay fever") • Anaphylaxis • Angioedema • Urticaria (hives) Type II - antibody-dependent hypersensitivity In type II hypersensitivity, the antibodies produced by the immune response bind to antigens on the patient's own cell surfaces. IgG and IgM antibodies bind to these antigens to form complexes that activate the classical pathway of complement activation for eliminating cells presenting foreign antigens (which are usually, but not in this case, pathogens). That is, mediators of acute inflammation are generated at the site and membrane attack complexes cause cell lysis and death. The reaction takes hours to a day. Some examples: • Autoimmune haemolytic anaemia • Goodpasture's syndrome • Pemphigus • Pernicious anemia • Immune thrombocytopenia • Transfusion reactions Type III - immune complex hypersensitivity In type III hypersensitivity, soluble immune complexes (aggregations of antigens and IgG and IgM antibodies) form in the blood and are deposited
    [Show full text]
  • Immune-Mediated Diseases in a Nutshell
    Immune-Mediated Diseases In a Nutshell Objectives Describe the epidemiology, clinical presentation, pathogenesis and pathologic changes of autoimmune diseases, including lupus erythematosis, rheumatoid arthritis, vasculitis, temporal arteritis and Wegener's granulomatosis Systemic Lupus Erythematosus Systemic lupus erythematosus: clinical features Febrile, multisystem inflammatory disease Variably affects wide range of organs and tissues, especially skin, kidneys, serosal surfaces, joints, heart Clinical course highly variable, often with multiple exacerbations and remissions Especially prevalent in young women, black Americans Prevalence: up to 1 to 2,500 persons Systemic lupus erythematosus: pathogenesis Autoantibodies develop against a variety of antigens: Nucleoproteins / nucleic acids DNA histones nonhistone RNA-binding proteins Blood cells erythrocytes platelets lymphocytes Phospholipids (e.g., “lupus anticoagulant”) Systemic lupus erythematosus: pathogenesis Antigen-antibody Antibody bound to immune complexes cells leads to lysis form via complement- mediated Complexes deposit in cytotoxicity or numerous sites, ADCC initiate complement cascade, and trigger inflammation Type III Hypersensitivity Type II Hypersensitivity Systemic lupus erythematosus: pathogenesis Possible causes of autoantibody production Intrinsic B cell defect Excessive helper T cell activity Deficient suppressor T cell activity Rheumatoid Arthritis Rheumatoid arthritis: clinical features Systemic, chronic inflammatory disease Principally affects joints: severe,
    [Show full text]
  • Hypersensitivity Mechanisms: an Overview
    Hypersensitivity Mechanisms: An Overview Stephen Canfield, MD, PhD Asst. Prof. Medicine Pulmonary, Allergy, and Critical Care Medicine 1 Origins of Hypersensitivity “Hypersensitivity” first used clinically in 1893: • attempting to protect against diphtheria toxin • test animals suffered enhanced responses, even death following second toxin exposure Emil von • at miniscule doses not harmful to untreated Behring animals The term “Allergy” is coined in 1906: • postulated to be the product of an “allergic” response • from Greek allos ergos (altered reactivity) Clemens von Pirquet os from Silverstein, AM. 1989. A History of Immunology. Academic Press, San Diego 2 First Task of the Immune System Dangerous Innocuou ? s? 3 Modern Use • Hypersensitivity: • Aberrant or excessive immune response to foreign antigens • Primary mediator is the adaptive immune system • T & B lymphocytes • Damage is mediated by the same attack mechanisms that mediate normal immune responses to pathogen 4 Mechanisms of Hypersensitivity Gell & Coombs Classification G&C Common Term Mediator Example Class Type I Immediate Type IgE monomers Anaphylaxis IgG/IgM Drug-induced Type II Cytotoxic Type monomers hemolysis Immune Complex IgG/IgM Type III Serum sickness Type multimers PPD rxn Type IV Delayed Type T cells Contact Dermatitis 5 Common to All Types Adaptive (T & B Cell) Immune Responses • Reactions occur only in sensitized individuals • Generally at least one prior contact with the offending agent • Sensitization can be long lived in the absence of re-exposure (>10 years)
    [Show full text]
  • Diseases of the Immune System 813
    Chapter 19 | Diseases of the Immune System 813 Chapter 19 Diseases of the Immune System Figure 19.1 Bee stings and other allergens can cause life-threatening, systemic allergic reactions. Sensitive individuals may need to carry an epinephrine auto-injector (e.g., EpiPen) in case of a sting. A bee-sting allergy is an example of an immune response that is harmful to the host rather than protective; epinephrine counteracts the severe drop in blood pressure that can result from the immune response. (credit right: modification of work by Carol Bleistine) Chapter Outline 19.1 Hypersensitivities 19.2 Autoimmune Disorders 19.3 Organ Transplantation and Rejection 19.4 Immunodeficiency 19.5 Cancer Immunobiology and Immunotherapy Introduction An allergic reaction is an immune response to a type of antigen called an allergen. Allergens can be found in many different items, from peanuts and insect stings to latex and some drugs. Unlike other kinds of antigens, allergens are not necessarily associated with pathogenic microbes, and many allergens provoke no immune response at all in most people. Allergic responses vary in severity. Some are mild and localized, like hay fever or hives, but others can result in systemic, life-threatening reactions. Anaphylaxis, for example, is a rapidly developing allergic reaction that can cause a dangerous drop in blood pressure and severe swelling of the throat that may close off the airway. Allergies are just one example of how the immune system—the system normally responsible for preventing disease—can actually cause or mediate disease symptoms. In this chapter, we will further explore allergies and other disorders of the immune system, including hypersensitivity reactions, autoimmune diseases, transplant rejection, and diseases associated with immunodeficiency.
    [Show full text]
  • 1. Hypersensitivity What Is Hypersensitivity?
    Chapter 19: Disorders of the Immune System 1. Hypersensitivity 2. Autoimmunity 3. Transplant Rejection 1. Hypersensitivity What is Hypersensitivity? Hypersensitivity is an immunological state in which the immune system “over-reacts” to foreign antigen such that the immune response itself is more harmful than the antigen. All types of hypersensitivity involve: • the adaptive immune response • i.e., highly specific reactions via T or B cells • prior exposure to the antigen • the initial exposure sensitizes the individual but does NOT cause a hypersensitive reaction • hypersensitivity is only seen on secondary exposure 1 Types of Hypersensitivity Hypersensitivity following secondary exposure to antigen comes in 4 basic forms: *Type I: allergic reactions (“immediate” hypersensitivity) • IgE mediated and very rapid (2-30 minutes) *Type II: cytotoxic reactions • cell damage due to complement activation via IgM or IgG *Type III: immune complex reactions • cell damage due to excess antibody/antigen complexes Type IV: delayed cell-mediated reactions • cell damage involving T cells & macrophages * Types I-III are all antibody-mediated, Type IV is not! Type I: Allergic Reactions Allergic (anaphylactic) reactions involve the activation of mast cells or basophils through the binding of antigen to IgE on the cell surface: • mast cells & basophils have IgE receptors that bind the constant region of any IgE antibody • “cross-linking” of IgE molecules on the cell surface by binding to antigen triggers the release of “mediators” • mediators = histamine, prostaglandins & leukotrienes …more on Allergic Reactions The release of these mediators causes the redness, swelling, itching, mucus, etc, that characterize allergic reactions: Most allergic reactions are local: • itching, redness, hives in the skin, mucus, sneezing • usually due to inhaled or ingested antigens Systemic allergic reactions can be lethal: • severe loss of blood pressure, breathing difficulty (anaphylactic shock) • usu.
    [Show full text]