Hypersensitivities Types I and IV Flashcards
Anaphylaxis?
A severe, potentially life-threatening allergic reaction.
´DTH Skin Test
´
´Antigen is injected intradermally and the individual is observed for a reaction at the site.
´A positive skin-test indicates that the individual has sensitized TH1 cells specific for the antigen in question.
´E.g., PPD Skin Test for exposure to Mycobacterium tuberculosis.
- ´Purified protein derived from cell wall of the organism is injected intradermally.
- ´The presence of a red, slightly swollen but firm lesion between 48 and 72hr is positive and indicates previous exposure to the organism. (could be to a vaccine, not necessarily to the pathogenic agent)
´Role of Cytokines in DTH
´IL-3, GM-CSF – induce localized hematopoiesis
´IL-1,TNFα upregulate adhesion molecule expression on endothelial cells to facilitate trafficking and extravasation of monocytes into tissue site
´Chemokines MCP-1, MIF attract monocytes to the site and hold them there.
´IFNγ,TNFβ activate macrophages
´IFNγ knock-out mice prove the importance of this cytokine in DTH
Common allergens associated with Type I hypersensitivity
Plant pollens
Insect bites
Drugs
Foods
Mold Spore
Animal hair and dander
Latex
Foreign serum
Vaccines
Atopy Hypersensitivity Type I
What is it?
What are clinical examples?
- reaction limited to a specific target tissue or organ
- Involves epithelial surfaces at the site of allergen entry
- Genetic predisposition
Clinical Examples
Rhinitis- Hay Fever
- Airborne Allergens
- Activation of local mast cells
- Symptoms: Watery exudation from eyes, nose and Upper Respiratory Tract, sneezing, coughing
Asthma
- Airborne or blood borne allergens
- Mast cell degranulation
- Reaction occurs in the lower respiratory tract instead of the nasal cavity
- Bronchoconstriction due to smooth muscle contraction, airway edma, mucus secretion and inflammation
- Atopic dermatitis
- Food allergies
What happens once mast cells/basophils are degranulated?
○ Smooth muscle will be acted on to cause contractions
○ Blood vessels will be dilated
○ Increase in mucus
○ blood platelets become activated
○ Nerve endings become sensitized
○ Recruitment of inflammatory cells, one of which is the eosinophil
What is the first line treatment for this condition?
Epinephrine (adrenaline) to reduce your body’s allergic response
Primary mediators of Hypersensitivity Type I reactions
Are in the granules and aiding in the immediacy of the response. They don’t need to be synthesized.
Granuloma formation
–fusion of macrophages forming giant cells. Occurs when antigen is not cleared
Giant cells displace normal tissue, and release high amounts of lytic enzymes which destroy surrounding tissue.
This can result in extensive necrosis
Systemic Hypersensitivity Type I
What is it?
What are clinical symptoms?
Usually initiated by a gut absorbed allergen
Occures within minutes
Symptoms
Within 1 min respiration labored, blood pressure drops precipitously, leading to anaphylactic shock
Smooth muscles of the GI tract and bladder contract, resulting in defecation and urination, respectively
bronchiole constriction; death by asphyxiation.
systemic vasodilation and smooth muscle contraction induced by mediators released by mast cells.
Allergens – venom from bee, wasp, hornet; ant stings, drugs (penicillin, insulin, antitoxins), seafood and nuts.
Epinephrine is the immediate treatment
In tissues, IgE binds to ___________. In blood, IgE binds to __________
Mast cells; basophils
What are the three chains of the Fc Epsilon receptor?
Alpha
Beta
Gamma
Late Asthma Responses
Occurs several hours later (2-8)
Additional mediators- cytokines (IL-4, IL-5, IL-16, TNFα, eosinophil chemotactic factor (ECF) and platelet activating factor (PAF)
Cause an increase in endothelial cell adhesion and recruitment of inflammatory cells , neutrophils and eosinophils into the site
Lymphocytes
________________ reverses the effects of histamines and serotonins
Epinephrine
What biochemical manifestations arise from injection of epinephrine?
Cyclic AMP rises preventing mast cell degranulation
Which cytokines lead to higher IgE production?
IL-4 and IL-13
What happens during the effector phase of Hypersensitivity Type IV?
Second encounter with antigen:
Secretion of cytokines; recruitment and activation of
macrophages
Although other cells (e.g., neutrophils) come in, the macrophage is the primary cell
Response is delayed for 24hr; peaks around 48-72hr.
This delay in time is that needed for cytokines to recruit and activate macrophages
This leads to an amplified response of cytokines, macrophages and other non-specific cells.
Activated macrophages have increased levels of phagocytosis, increased levels of lytic enzymes, increased expression of MHC II molecules and adhesion molecules.
This all leads to the macrophage being a better APC cell, and a more effective phagocyte and killer cell
The result of this is a heightened inflammatory response and the clearing of the pathogen.
The TH1 cell will release__________,________, and _________.
interferon gamma, interleukin 2, and TNF-beta
What symptoms might a patient present with during an anaphylatic reaction?
Skin reactions, including hives and itching and flushed or pale skin
Low blood pressure (hypotension)
Constriction of your airways and a swollen tongue or throat, which can cause wheezing and trouble breathing
A weak and rapid pulse
Nausea, vomiting or diarrhea
Dizziness or fainting
Some drugs used to treat type I hypersensitivitity. What are their roles?
Antihistamines- Block H1 and H2 receptors on target cells
Cromolyn sodium- Blocks Ca2+ influx into mast cells
Theophylline- Prolongs high cAMP levels in mast cells by inhibiting phosphodiesterase, which cleaves cAMP to 5’-AMP
Epinephrine- Stimulates cAMP production by binding Beta-adrenergic receptors on mast cells
Cortisone- Reduces histamine levels by blocking conversion of histidine to histamine and stimulates mast cell production of cAMP
Microorganisms that Induce Type IV hypersensitivity
Intracellular bacteria
Intracellular fungi
Intracelluar parasites
Intracellular viruses
Contact antigens
Early asthma responses
Occurs within minutes of exposure to allergen
Involves histamine, leukotrienes and prostaglandins (PGD2) which leads to bronchoconstriction, vasodilation and mucus build-up
Type I reactions can be _________ or ___________.
Local; systemic
What are the two phases of Type IV hypersensitivity
Sensitization Phase- First encounter
Effector Phase- Second encounter
What happens during the sensitization phase of Hypersensitivity Type IV?
Primary encounter with the antigen by APC
Th1 cells activated
What contents are released from mast cells?
Histamine
Proteases
Heparin
Which cytokine might be beneficial to a patient with lepromatous leprosy?
Why would a patient with leprosy be prone to asthma?
IFN-y
c. TH2 response
. In lepromatous leprosy IL-4 mediates isotype switching to IgE
i. Asthma is related to the IgE produced
ii. IL-10 enhances the IgG1 and IgG3 response
iii. IL-5 enhances total immunoglobulin levels →hypergammaglobulineemia in lepromatous leprosy
d. Regulatory CD8 T cells in periphery produce cytokines that inhibit the DTH responses
Delayed Type Hypersensitivity (Type IV)
´When CD4 TH1 T cells encounter intracellular pathogens, they become activated to produce cytokines, which recruit and activate macrophages and induce an inflammatory reaction.
