Hypersensitivities Types I and IV

Question 1

Anaphylaxis?

Answer 1

A severe, potentially life-threatening allergic reaction.

Question 2

´DTH Skin Test

Answer 2

´

´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)

Question 3

´Role of Cytokines in DTH

Answer 3

´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

Question 4

Common allergens associated with Type I hypersensitivity

Answer 4

Plant pollens

Insect bites

Drugs

Foods

Mold Spore

Animal hair and dander

Latex

Foreign serum

Vaccines

Question 5

Atopy Hypersensitivity Type I

What is it?

What are clinical examples?

Answer 5

• 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

Question 6

What happens once mast cells/basophils are degranulated?

Answer 6

○ 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

Question 7

What is the first line treatment for this condition?

Answer 7

Epinephrine (adrenaline) to reduce your body’s allergic response

Question 8

Primary mediators of Hypersensitivity Type I reactions

Answer 8

Are in the granules and aiding in the immediacy of the response. They don’t need to be synthesized.

Question 9

Granuloma formation

Answer 9

–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

Question 10

Systemic Hypersensitivity Type I

What is it?

What are clinical symptoms?

Answer 10

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

Question 11

In tissues, IgE binds to ___________. In blood, IgE binds to __________

Answer 11

Mast cells; basophils

Question 12

What are the three chains of the Fc Epsilon receptor?

Answer 12

Alpha

Beta

Gamma

Question 13

Late Asthma Responses

Answer 13

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

Question 14

________________ reverses the effects of histamines and serotonins

Answer 14

Epinephrine

Question 15

What biochemical manifestations arise from injection of epinephrine?

Answer 15

Cyclic AMP rises preventing mast cell degranulation

Question 16

Which cytokines lead to higher IgE production?

Answer 16

IL-4 and IL-13

Question 17

What happens during the effector phase of Hypersensitivity Type IV?

Answer 17

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.

Question 18

The TH1 cell will release__________,________, and _________.

Answer 18

interferon gamma, interleukin 2, and TNF-beta

Question 19

What symptoms might a patient present with during an anaphylatic reaction?

Answer 19

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

Question 20

Some drugs used to treat type I hypersensitivitity. What are their roles?

Answer 20

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

Question 21

Microorganisms that Induce Type IV hypersensitivity

Answer 21

Intracellular bacteria

Intracellular fungi

Intracelluar parasites

Intracellular viruses

Contact antigens

Question 22

Early asthma responses

Answer 22

Occurs within minutes of exposure to allergen

Involves histamine, leukotrienes and prostaglandins (PGD2) which leads to bronchoconstriction, vasodilation and mucus build-up

Question 23

Type I reactions can be _________ or ___________.

Answer 23

Local; systemic

Question 24

What are the two phases of Type IV hypersensitivity

Answer 24

Sensitization Phase- First encounter

Effector Phase- Second encounter

Question 25

What happens during the sensitization phase of Hypersensitivity Type IV?

Answer 25

Primary encounter with the antigen by APC

Th1 cells activated

Question 26

What contents are released from mast cells?

Answer 26

Histamine

Proteases

Heparin

Question 27

Which cytokine might be beneficial to a patient with lepromatous leprosy?

Why would a patient with leprosy be prone to asthma?

Answer 27

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

Question 28

Delayed Type Hypersensitivity (Type IV)

Answer 28

´When CD4 TH1 T cells encounter intracellular pathogens, they become activated to produce cytokines, which recruit and activate macrophages and induce an inflammatory reaction.