Immunoglobulins and Allergic Reactions Ige antibodies are involved in allergic disorders -IgE molecules bind to allergens allergy-inappropriate

and often harmful immune system response to substances that are normal harmless substances allergen-substance that causes manifesta- tions of allergy atopy- term often used to describe IgE-mediated disease, genetically determined allergic disorders Allergen triggers the B cell to make IgE antibody, which attaches to the mast cell; when that allergen reappears, it binds to the IgE and triggers the mast cell to release its chemicals Mast cells release: heparin and histamine Allergic and Hypersensitivity Reactions -Does not occur with the first exposure; reaction follows a re-exposure after (2nd contact)sensitization in a predisposed individual -mediated by IgE antibodies; maybe associated with IgG and IgM -maybe immediate or delayed depending upon how much time elapsed Immediate Appears and recedes rapidly Induced by Ag/haptens by any route Circulating Ab present and responsible for reaction Passive transfer possible with serum Desensitization easy but short lived Classification:Hypersensitivity reactions Immediate hypersensitivity -anaphylaxis -atopy -antibody mediated cell damage -arthus phenomenon: immune complex hypersensitivity reaction -serum sickness Delayed Hypersensitivity Delayed Appears slowly, lasts longer Induced by infection, injection of Ag/hapten , intradermally, or by skin contact Circulating AB may be absent and not responsible reaction * cell mediated reaction No transfer with serum; transfer possible w/ T-cells or transfer factor Desensitization difficult but long lasting

-infection (tuberculin type) -contact dermatitis type 4 Types IIIIIIIVAnaphylactic/immediate hypersensitivity Cytotoxic hypersensitivity reaction Immune Complex Hypersensitivity Reaction (like anti tetanus serum) Delayed hypersensitivity reaction (example PPD/mantoux test)

Hypersensitivity -a reflection of excessive or aberrant immune response -sensitization:initiates the buildup of antibodies

TYPE I anaphylactic Reactions -occurs within minutes of exposure to antigen

-antigens combine with IgE antibodies bound to mast cells and basophils, causing them to undergo degranulation and release several mediators: histamine: dilates and increases permeability of blood vessels (swelling and redness), increases mucus secretion (runny nose), smooth muscle contraction (bronchi) prostaglandins: contraction of smooth muscle of respiratory system and increased mucus secretion leukotrienes: bronchial spasms **anaphylactic shock- massive drop in blood pressure, can be fatal in minutes Types of IgE mediated allergic response: -atopic->allergic rhinitis, food allergies, asthma food allergies->1st manifestation of a propensity for allergic disease -anaphylactic Allergies >result from IgE mediated by hypersensitivity reactions; characterized by manifestations associated with histamine released >maybe localized or systemic -local: rhinitis, contact dermatitis (skin), and food allergies (GIT) -systemic:anaphylaxis TYPE I Reactions (IgE Mediated) >Anaphylaxis*classical immediate reaction *sensitization -most effective when Ag introduced parenterally -may occur by any route exposure to Ag -minute quantities are enough -interval of 2-3 wks needed between sensitizing and shocking dose -once sensitized it remains so for long time -shocking dose most effective by IV route *the shocking Ag must be same or similar to sensitizing Ag cutaneous anaphylaxis <if small shocking dose is given ID to sensitized host, there is a local wheal & flare reaction (local anaphylaxis) >used for -testing for hypersensitivity -identification of allergens for atopy >precaution-keep adrenalin injection ready to compact severe fatal reaction TYPE I Reactions

>Humans itching of scalp and tongue, flushing of skin, difficulty in breathing, nausea, vomiting, diarrhea, acute hypotension, loss of consciousness, death (rare) -causes:serum therapy, antibiotic, insect stings -tx:adrenalin 0.5ml (1 in 1000solution) sc/im repeated up to 2ml in 15 min physiologic response to immunologic dysfunction 1. uticaria (hives) cutaneous manifestation characterized by wheal and flares; caused by localized release of histamine 2. rhinitis ->inflammation of the mucous membranes of the nasal passages 3. angioedema->generalized swelling due to release of histamine and increased capillary permeability 4. bronchoconstriction -> swelling of the airway and constriction of bronchial smooth muscle caused by release of vasoactive agents 5. pruritis- itching associated with erhythema and uticaria 6. hypotension->due to the release of vasoactive agents and loss of intravascular volume secondary to increased capillary permeability 7. leukocytopenia->abnormal decrease in WBCs occurring secondary to disruption in cell development 8. opportunistic infection->secondary infections or malignant processes associated with immune system deficiencies Nursing Interventions: >Maintain Airway if with mucosal edema of the respi tract is evident >provide supportive care of the cardiovascular system >administer antihistamines to reduce the histamine reaction >in acute situations where anaphylaxis is present, administer epinephrine to reverse symptoms >administer fluid to replace intravascular volume lost due to edema or diarrhea >monitor and evaluate possible causes of the allergic reaction >educate the patient and family members regarding avoidance of the allergen and appropriate treatment >be persistent because the identification and treatment of allergies is often frustrating TYPE II Cytotoxic Reaction (example: blood type incompatibility) Antigen * foreign IgM = response to infection, activates complement system IgG=chronic infection -involve activation of complement by IgG or IgM binding to an antigenic cell -antigenic cell is lysed/destroyed. -transfusion reactions: Type III Immune Complex Reaction (examples:rheumatoid arthritis, glomerulonephritis) -involve reactions against soluble antigens circulating in serum

-usually involve IgA antibodies -antibody-antigen immune complexes are deposited in organs, activate complement, and cause inflammatory damage -glomerulonephritis:inflammatory kidney damage -occurs when slightly high antigen-antibody ratio is present Type IV- delayed or cellular reaction Examples: graft versus host disease, contact dermatitis, hashimoto, hyperthyroidism, sarcoidosis Helper T-cell will stimulate the presenting of antigen to the macrophage The macrophage will stimulate the cytotoxic reaction -involve reactions by t- memory cells *first contact sensitizes person *subsequent contacts elicit a reaction -reactions are delayed by on e or more days (delayed type hypersensitivity) *delay is due to migration of macrophages and T-cells to site of foreign antigens -reactions are frequently displayed on the skin: itching, redness, swelling, pain. *tuberculosis skin test *poison ivy *metals *latex in gloves and condoms (3% of health care workers) *anaphylactic shock may occur two types: tuberculin and contact dermatitis tuberculin type*id inoculation of PPD in sensitized individuals leads to induration and inflammation in 4872 hou/rs contact dermatitis-Ag possibly enters thru sebaceous glands -lesions wary from macules & papules AUTOIMMUNE RESPONSE Autoimmunity >refers to a disruption in the bodys ability to tolerate its own cells; instead it recognizes these cells as antigens >occurs when the immune system reacts against its own cells by forming auto-antibodies, which then destroys its own tissue >once the tissue is recognized as foreign, a tissue specific reaction, an immune complexmediated reaction or a cell mediated reaction occurs

>bodys tolerance to self antigens decreases with age; incidence of auto-immune diseases increase with age Autoimmune Disorder Theories 1. Molecular Mimicry >due to presence of cross reacting Ags-Presence of epitopes with identical peptide sequences in some infecting micro-organisms & self Ags, e.g. >following anti-rabies immunization in humans with the neural vaccine of infected sheep brain- due to the presence of organ specific Ags >following streptococcal infection streptococcal M proteins and the heart muscle 2.Polyclonal B-Cell Activation >Non-specific activation of multiple B Cell clones by certain stimuli like *chemicals 2-mercaptoethanol *bacterial products PPD *enzymes trypsin *antibiotics- nystatin *micro-organisms mycoplasma, EBC, malaria >multiple non-specific Abs are formed during such conditions 3. Breakdown of Immunological Homeostasis >cessation of tolerance to self Ag. >Enhanced helper T-cell and decreased suppressor T-cell functions 4. Released of Sequestered Ags >sequestered Ags- certain Ags are present in closed systems (compartments) and are not accessible to the immune apparatus. E.g. *lens protein of the eye is enclosed in its capsule & does not circulate *sperm Ags- spermatozoa develop at puberty, no tolerance during fetal life Causes: >Presence of previously hidden antigen >secondary to infectious diseases >as a result of alterations in suppressor T-cell function >persistence of primitive thymus >familial/hereditary Immune Complex-Mediated Reactions >Antigen-Antibody complexes form and deposit in tissues >Complement activation occurs -> neutrophil digestion of immune complexes; lysosomal enzyme release >tissue destruction is diffused, affecting a number of target organs Cell Mediated Reactions >mediated by sensitized T-cells and antibodies >cytotoxic T-cells destroy the host tissue directly >lymphokine-producing T cells have a widespread effect by attracting phagocytic cells to the tissue

Tissue Specific Reactions: >IgG and IgM are the antibodies most commonly affected >tissue is destroyed through the action of antibodies on the cells plasma membrane >tissue destruction occurs by way of complement-mediated cell lysis, macrophages, phagocytosis, and antibody-dependent cell mediated cytotoxicity complement-> series of enzymatic proteins in the serum that when activated, destroys bacteria and other cells Disorders of Immunity: Autoimmune Diseases Examples of autoimmune diseases: >multiple sclerosis- white matter of brain and spinal cord are destroyed >myasthenia gravis-impairs communication between nerves and skeletal muscles >Type I diabetes mellitus- destroys pancreatic beta cells that produce insulin >rheumatoid arthritis- destroys joins >systemic lupus erythematosus (SLE) affects kidney, heart, lung, and skin >glomerulonephritis impairment of renal function Systemic Lupus Erythematosus (SLE) >a chronic, inflammatory multisystem disorder characterized by periods of remissions and exacerbations >an autoimmune disease which affects collagen/connective tissues Etiology and Incidence: >idiopathic >genetics predisposition to the disease >family history of other autoimmune disorders >hypersensitivity reactions to drugs/substances *Phenergan, apresoline, isoniazid, quinidine, phenytoin >history of viral infection >affects women (20-30y/o) >higher incidence on negroid and mongloid descent Diagnostics: >CBC ->pancytopenia >ESR -> increased (inflammation) >ANA: antinuclear antibody testing >Anti-DNA-> most specific >LE factor Panophysiologic manifestations: 1. SLE is characterized by formation of antibodies (IgG and IgM) against the bodys nucleic acid, phospholipids, WBCs, RBCs, 2. 3.Neutrophils attempt to phagocytize the AN-ab complexes are ineffective 4.Lysosomal enzymes are released, further propagating the tissue damage

5.The glomerular basement membrane of the kidneys is particularly susceptible to complex deposition, as a result there is a high incidence of renal failure secondary to SLE 6.Deposition of complexes also occur in the brain, heart, lung, GI tract, spleen, cells 7.10 year survival rate = 50%