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 Delayed
Appears and recedes rapidly Appears slowly, lasts longer Induced by Ag/haptens by any route Induced by infection, injection of
Ag/hapten , intradermally, or by skin contact
Circulating Ab present and responsible
for reaction Circulating AB may be absent and not responsible reaction * cell mediated reaction
Passive transfer possible with serum No transfer with serum; transfer possible w/ T-cells or transfer factor Desensitization easy but short lived Desensitization difficult but long lasting Classification:Hypersensitivity reactions
Immediate hypersensitivity -anaphylaxis
-atopy
-antibody mediated cell damage
-arthus phenomenon: immune complex hypersensitivity reaction -serum sickness
-infection (tuberculin type) -contact dermatitis type 4 Types
I- Anaphylactic/immediate hypersensitivity II- Cytotoxic hypersensitivity reaction
III- Immune Complex Hypersensitivity Reaction (like anti tetanus serum) IV- 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
-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
>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 48-72 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 complex-mediated reaction or a cell complex-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%
