Type I Immunopathology

Question 1

What normally happens during worm infestation?

Answer 1

1. ) Make IgE and IgG against worms. IgG binds to worm/ova (opsonizes,) activates complement, C3a and C5a attract neutrophils. This doesn’t work. :(
2. ) Worm sheds antigen -> diffuse to nearby mast cells (who have FceR loaded w/ anti-helminth IgE) -> antigen corsslings w/ IgE, mast cells release histamine -> smooth muscle contraction and peristalsis TO pOOP em out
3. ) MOST IMPORTANT!!!!!!!!!! late-phase response. Mast cells secrete ECF-A2 (which is prostaglandins and leukotrienes) -> attract huge number of eosinophils (which have Fc receptors for IgG, which, on step 1, coat the worm!) Eosinophils contain MAJOR BASIC PROTEINS which is hella toxic to helminths.
4. ) Th2 finds helminth antigens presented by APC, attracts both eosinophils and macrophages. Th2’s lymphokines (IL-4, IL-5, IL-13) activate M2 macrophages which heal damage and wall-off resistant invaders.

Question 2

Anaphylaxis

Answer 2

IgE binds strongly to FcR1 receptors, bound IfE are crosslinked by allergen, mast cells signalled to secrete histamine.

If systemic, causes vasodilation and broncho/gut constriction which is no good

Question 3

Allergic rhinitis

Answer 3

Runny nose and itchy eyes lol

Question 4

Eczema

Answer 4

chronic dry skin, bacterial secondary infection is common

Question 5

Oral Allergy Syndrome

Answer 5

food allergy, antigens pass through mucous membranes w/ rapid access to local mast cells.

Tingling tongue, mouth, lips, itching and swelling yay.

Question 6

Hyper IgE syndrome

Answer 6

We probs don’t have to know this

Also called Job Syndrome, autosomal dominant, inability to make IFNgamma effectively. Poor Th1 response, results in high serum IgE, skin abscesses, and fungal/pseudomonal penumonia

Question 7

What is IgE development dependent on?

Answer 7

Thf and IL-4. Takes 5-ever to make (7 yrs if you move to a new continent or w/e)

Question 8

Describe Immediate reaction in atopic state

Answer 8

IgE binds mast cells and basophil IgE receptor FceRI with small association factor

IgE laden mast cells must be triggered by cross-linking of antigen. (antigen must be at least divalent)

Degranulation releases histamine, heparin, enzymes and TNF. Responsible for hives, or the wheel and flare response

Question 9

Describe late phase reaction in atopic state

Answer 9

Activated mast cells initiates a series of enzymatic steps

1.) Phospholipase PLA2 cleaves arachidonic acid from membrane phospholipids.
(can be converted by cyclooxygenase pathway into prostaglandins and lipooxygenase pathway into leukotrienes.) 5-15 min. Anti-histamine

2.) This initiated inflammation, constricts bronchioles (ECF-A) and attracts eosinophils! 4-10 hrs. Anti-inflammatory

Question 10

Describe allergen skin testing

Answer 10

Drip the allergen on skin! Poke it through! See if u react.

Question 11

What is CAP-FEIA

Answer 11

Flourescent Enzyme Immunoassay, where allergen is fixed into a capsule, patient’s serum is added and unbound proteins are washed away. Bound IgE is quantified.

Question 12

Asthma! Tests, aggravators

Answer 12

Asthma is both bronchoconstrictive and inflammatory (leads to fibrosis)

Tested by spirometry: tests FEV1. Volume of air that can be exhaled from lungs in 1 sec. Measured at baseline, give bronchodilators and see if it improves.

Over time FEV1 decreases b/c fibrosis. To decrease this, use inhaled glucocorticoids.

Question 13

Potential treatments to type I immunopathology

Answer 13

Avoid it!

Anti-histamines!

Epinephrine! (for anaphylactic shock!)
Glucocorticoids! (mostly for topical/pulmonary inhalents b/c systemic has a lot of problems)

Leukotriene inhibitors!

LABAs (long acting beta-2 agonists -> rapidly reduce bronchoconstriction, given in combination w/ inhalable steroid)

IgE blocker (treatment for asthma for kids 12 and older who dont respond to steroids)

Immunotherapy - “allergy shots” maybe increase your tolerance, maybe desensitizes mast cell, maybe increases T-reg. Nobody knows!