Test 2 Flashcards
Hypersensitivity
Normal exaggerated immune response to an antigen
Produces inflammation, cell destruction, and/or tissue damage
Hypersensitivity types:
Humoral (antibody) response
(Immediate hypersensitivity )
Cell mediated response
(Delayed hypersensitivity)
Allergen
Molecule that triggers a hypersensitivity reaction
Ex: animal dander, pollen, food, molds, drugs
Atopy
Immediate hypersensitivity mediated by igE antibodies
*Used as allergy interchangeably *
Ex: hay fever, food allergies, latex sensitivity ,
Types of hypersensitivity reactions :
Types I - III are humoral mediated(immediate)
Type IV - cell mediated [delayed]
Environmental substances
Immediate hypersensitivity reaction (humoral) associated w/ igE such as Rhinitis or asthma happens
If dust stimulated igG antibody production, farmers lung can be triggered
If diffuse into skin and act as a hapten, contact dermatitis (delayed hypersensitivity ) occurs
Eosinophil levels in blood and nasal secretions elevated = igE normal /elevated
Drugs
Can provoke hypersensitivity reaction mediated by IgG, IgE, T lymphocytes
Metals
Ex: nickel , chemicals
Cause type I hypersensitivity [humoral (immediate)]
Chemicals act as a hapten and bind to proteins/MHC
Infectious agents
Influenza , cause cytokines storm (high secretions of cytokine) & dam age to epithelial cells in RT
Streptococci , cause immune complex disease
Food allergies
LEAST COMMON FORM OF TYPE I HYPERSENSITIVITY
ANAPHYLAXIS - systemic type 1 reaction ; can cause shock/edema
Types of type I hypersensitivity
Metals Environmental substances Food allergies Drugs Infectious agents
Anaphylaxis reaction 3 stages :
- Antigen attaches to igE antibody on mast cells/basophiles
- Activated mast and basophils release mediators
- Effects of mediator release produce vascular changes and activation of platelets , eosinophils, neutrophils, and coagulation cascade
Anaphylactoid Reactions :
Not antigen-antibody mediated : substances act directly on mast cells or tissues, like anaphylotoxins of complement cascade [ C3a, C5a]
Direct chemical degranulation of mast cells may be cause [ infusion of macromolecules like proteins )
Atopic reaction
Exposure of skin,nose, or airway to an allergen produces specific ig antibodies
Exaggerated response by production of igE antibodies
The hallmark allergic disease
Infiltration of affected tissue by Th2 cells
Hypersensitivity reactions defined by
Principal mechanism responsible for cell tissue injury that occurs during immune response
Type 1 hypersensitivity:
-immediate hypersensitivity (anaphylactic)
-Mast cells (tissue basophiles ) cellular receptors for igE ; contain HEPARIN IN 1:6 RATIO W/ HISTAMINE
- basis of an allergic reactions caused by molecules released by mast cells when an allergen interacts with MEMBRANE BOUND IGE
- SYMPTOMS SKIN REDNESS, SNEEZING , WHEEZING WITHIN MINUTES
- localized reaction - immediate response to mediators from mast cell degranulation
-Generalized reaction : mediators like cytokines and vasoactive amines (histamines ]
- atopic food allergy March in children : most SES @ 2 YEARS , decrease after 3 years
- testing : skin puncture test (SPT),
Increase in igE in serum indicates allergy disorder
Greater the igE antibody value, greater chance of symptoms
IMUNNOCAP
Gold standard for allergen specific igE detection (in vitro)
Treatments:
Immunotherapy (hyposensitization) : allergy shots 3-: montelukast for asthma airway inflammation
Desensitization: best for one allergy
Mediators
Mediators of asthma and allergy formed by basophiles and released largely after stimulation w/ interleukin 3
Ex: Histamine
Leukotriene C4
Interleukin-4 & 13
Basophiles granulocytes(IL-3) are key effector cells in type 2 helper T (th2) cell responses ;
Histamine
Contraction of blood vessels and increase capillary permeability and mucus secretion in airway
Prostaglandins
Vasodilation and increased vascular permeability
Leukotriens
Erythema and wheal formation
Type 2 hypersensitivity
- cytotoxic reactions due to IgG or igM antibodies directed to cell surface antigens
3 Mechanisms :
1.antibody dependent , complement mediated cytotoxic reactions - destruction of cell CYTOLYSIS - transfusion reactions
- hemolytic Reactions
2.ANTIBODY DEPENDENT , CELL MEIDATED CYTOTOXICTY
3. Antireceptor antibodies - disturb natural function of receptors EX: HYPERACUTE GRAFT REJECTION
Transfusion reactions
hemolytic reactions after antibody dependent , complement mediated cytotoxic reactions
Hemolytic - infusion of incompatible erythrocytes; (acute- immediate & most dangerous ) or 1 of 2 delayed reactions ( 7 to 10 days later, low RBC, anamnestic antibody response ) & associated w/ decreased RBC survival & anamnestic antibody response
Reactions occur w/ as little as 10 to 15 ml of incompatible blood ;
Symptoms:
fever and chills ; release of thromboplastic substances into circulation and induce disseminated vascular coagulation and acute renal failure
Hemolytic disease of the fetus and newborn ( HDFN)
Excessive destruction of fetal RBCs by maternal antibodies ; jaundice or anemia
Most frequently ABO Incompatibility when mother is O and baby Is type a , sometime b
IgG, only immunoglobulin transported to fetus
*Transplacental hemorrhage TPH *
All RH negative pregnancies should receive rh IgG
Autoimmune hemolytic anemia
Type 2 hypersensitivity reaction directed against self antigen on rbcs
Cold autoimmune hemolytic anemia(cold autoagglutinatins): usually igM ; 1/3 rd of cases ; best @ room temp.
Warm autoimmune hemolytic anemia:
IgG, most cases of autoimmune anemia; react best at 37 C
Autoantibodies
Damage solid tissue components
Ex: Good pastures syndrome
Graves’ disease
Wegeners granulomatosis
Type II hypersensitivity and antibodies
Antibodies stimulate target organ functions without causing organ damage
Wegeners granulomatosis - stimulation of cells lead to tissue damage
Prevention : check donor and recipient & immunization
Plasmapheresis - reduce # of antibody in patients circulating blood
Type II reaction testing :
DAT ( direct antiglobulin test ) : detects AHG , IF POSITIVE repeated using monospecific anti IgG and anti C3 reagents
If there’s an autoimmune hemolytic anemia caused by igM , only C3d assay would be positive
Platlet agglutination if thrombocytopenic purpura suspected
Type III Reactions
Immunecomplex reactions deposition of immune complexes into blood vessels walls/tissues
Circulating immune complexes ACTIVATE COMPLEMENT
Ex: glomerulonephritis n systemic lupus (SLE)
heart valves and renal glomeruli two sites where immune complexes are deposited
Type III Reactions :
Farmers Lung and Arthus reaction Glomerulonephritis SLE (systemic lupus erythematosus) - autoimmune disorder characterized by autoantibodies (glomerulonephritis develops) Serum sickness Autoimmune diseases
Type III Reaction testing & treatment :
Specific assays
- quantitation of complement C3 and C4 components
Treatment : Avoidance of antigen and corticosteroids
Type IV Reactions : DTH
Cell mediated ( Delayed hypersensitivity ) Caused by soluble factors and lymphokines NOT antibody and complement
DTH : Delayed type hypersensitivity
Can be a Physiological reaction to pathogens that are difficult to clear m most extreme DTH Reactions
Ex: mycobacterium tuberculosis & hepatitis B virus
Tumor necrosis factor-alpha (TNF-A) - STIMULATES MOST OF DANAGE IN DTH REACTIONS
HALLMARK EXAMPLE OF OCCUPATIONAL TYPE 4 HYPERSENSITIVITY = ALLERGIC CONTACT DERMATITIS
TUBERCULIN TYPE HYPERSENSITIVITY
Type 4 Testing :
Skin test for TB
Reaction in people exposed or acquired TB microorganism. Doesn’t mean you have it
Tb antigen is injected intradermally ; obs. 48 - 72 hours
TREATMENT: AVOIDING ANTIGEN & ANTI-INFLAMMATORY DRUGS / corticosteroid
HYPSERNSITIVTY : A.C.I.D.
ACID A - ANAPHYLAXIS C - cytotoxic I- immunecomplex D- Delayed type hypersensitivity
