NCM 106 Lecture

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

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

Classification:Hypersensitivity reactions Immediate hypersensitivity -anaphylaxis -atopy -antibody mediated cell damage -arthus phenomenon: immune complex hypersensitivity reaction -serum sickness Delayed Hypersensitivity

-infection (tuberculin type) -contact dermatitis type 4 Types IIIIIIIV-

Anaphylactic/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 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 WBC’s 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 body’s 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

>body’s 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 cell’s 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 body’s 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%