Hypersensitivity Reaction

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Describe the hypersensivity reactions?

it means there is an excessive or aberrant immune response. In with it may be increased, maybe different class of immunoglobulin and it is either Th1/Th2 response

What are the two types of hypersensivity reactions?

1. foreign antigen
2. immune response to self

Describe the cells that are involved in Type I-type IV.

Type 1-IgE
Type II- IgM and IgG
Type III- Immune complex
Type IV- T cells

What is the type of hypersensivity reaction in which it is immediate and the cells involved are mast cells?

Type I

What is the type of hypersensitivity reaction in which it is antibody to self and the cells that are involved are complement, PMNs, macrophages?

Type II

What is the type of hypersensivity reaction in which it is Ag-Ab complex?

type III

What is the type of hypersensitivity reaction in which it is T cell mediated?

macrophages and cytokines

How long do you finally see an type 1 hypersensivity reaction?

seconds to minutes

Describe the IgE antibody reaction?

thats when there is a mast cell mediated vascular and smooth muscle reaction- in which there is inflammation.

What are hay fever, food allergies, bronchial asthma and anaphylaxis an example of what type of hypersensitivity reaction?

Type I

what are some common allergens of type I hypersensivity reaction?

proteins, foods, plant pollens, insects products, drugs and mold spores, animal hair and dander and Latex

what initiates type I hypersensitivity reaction?

Ag makes IgE to be produced and then IgE binds to the Fab receptors in the mast cells-- and that binding lead to cross-linking of receptors. And then mast cell mediators are released.

Type I hypersensitivity reaction stimulates what type of response? Th1 or Th2?

Th2 thats when the B cells produce IgE antibody.

what happens after B cells produce IgE antibody?

IgE binds to FcR on mast cells- and the subsequent allergen exposure--> release of granules by mast cells

Describe the what vasoactive amines, lipid mediators and cytokines released by the mast cells stimulate?

vasoactive amines/lipid mediators- they initiate immediate hypersensitivity reaction which happens minutes after repeated exposure to allergen

cytokines- they initiate late phase reaction- 6-24 hours after repeat exposure to allergen

what are some type I mast cell activation?

IgE binds to the FceR1 receptors-
mast cells get sensitized
cross-link Fc receptors
release of mediators

what is the Fc receptor involved in type I response?

FceR1

what cells carry FceR1 response?

mast cells and basophils

where are mast cells located

they are located in connective tissue all over the body

How are mast cells sensitized?

IgE coats the mast cell by binding to the receptor. And then mast cells are "sensitized".

Describe the affinity associated with FceR1?

it is very high

Describe IgE concentration and affinity in the serum?

IgE has a low concentration in the serum, but has a high affinity receptor= and it is critical for binding to mast cells

How many chains do FceR1 contain? and what are their purpose?

1 binds and 2 signal

what are signaling molecules of FceR1?

ITAMS

what is the result of phosphorylation of ITAMS?

1. granule with preformed mediators which lead to granule exocytosis in which we have release of vasoactive amines/proteases.
2. Lipid mediators- prostaglandins and lekotrienes
3. transcriptional activation of cytokine genes--> release of cytokines which lead to inflammation and recruitment

what happens wen you have granules which are preformed mediators released?

1. vasoactive amines- vascular dilation/smooth muscle contraction
2. proteases- tissue damage

Describe the lipid mediators?

prostaglandins- vascular dilation
Leukotrienes-smooth muscle contraction

Describe the transcriptional activation of cytokine genes?

they are cytokines in which leads to secretion and inflammation/recruitment

what are some of the ways to stimulate mast cells?

1. Allergen cross-linkage of cell bound IgE
2. antibody cross-linkage of IgE
3. anti-idiotype Ab
4. chemical cross-linkage of IgE- cross-linking chemical
5. cross-linkage of IgE receptors by anti-receptor antibody
6. enhanced Ca influx by ionophores that increases membrane permeability to Ca

Where do type I reactions occur? Where does inhaled antigens vs ingested antigens occur?

inhaled antigens- occurs in the bronchial submucosa
ingested antigens- occurs in the intestinal wall

Describe what happens when you have allergic rhinitis?

it is caused by increased mucous secretion; inflammation of the upper ways and sinuses

what happens when you have food allergies?

increased peristalsis due to the contraction of intestinal muscles

what causes bronchial asthma?

it causes bronchial hyperresponsiveness- which is caused by smooth muscle contraction- inflammation and tissue injury- caused by late phase reaction

what causes anaphylaxis reaction?

it is when you have a fall in blood pressure (shock) which is caused by vascular dilation- and this leads to airway obstruction- due to laryngeal edema

what is Wheal and flare reaction?

thats when you have swollen fluid filled area and the flare- redness around there.

how long does a wheal and flare reaction take?

this is when there is immediate- 5-15 min after injection of ag. It is irregular blanched area- that contains an elevated area- wheal.
erythema- in which there is a flare- dilation of blood vessels

what kind of response to allergic people have- Th1 or Th2?

Th2

What is released upon Th2 response?

cytokines favor IgE response in which you have IL-4 and IL-13 release

After what time period do you see type I reaction?

4-6 hours

How long does it stay for type I?

persists 1-2 days

what do mast cells produce?

TNFa and IL-1 and this leads to increased expression of cellular adhesion molecules on venular endothelial cells

what do mast cells produce to recruit neutrophils?

neutrophil chemotactic factor

What do mast cells in the late phase reaction produce?

IL-3, IL-5, IL-8 and GM-CSF

what is type I hypersensitivity reaction?

it is systemic anaphylaxis in which you have vasodilation and low blood pressure and that can be within minutes

what are the symptoms in systemic anaphylaxis?

1. restless
2. labored breathing
3. drop in blood pressure

A 4 y/o girl went to a party and died of anaphylactic shock. Which of the following id she likely responsible for?

brownies- people put peanutes

what is the reason for type II hypersensitivity reaction?

thats when you have autoantibodies against self antigens- and there is failure of self-tolerance

what is the mechanism of damage in type II?

1. complement system- C3a and C5a. It leads to chemotaxis of PMNs, basophils and eosinophils- and the vasoactive amines release from mast and bass
2. macrophages- TNF and IL-1

what are some types of Type II diseaseS?

1. transfusion reactions
2. hemolytic disease of newborn
3. good pasture syndrome
4. pemphigus
5. drug induced hemolytic anemia
6. certain types of glomerulonephritis

what type of reaction is massive intravascular hemolysis?

type II

what is the mechanism for erythroblastosis fettles and what is the reason?

thats when the IgG from the mother reacts to Rh factor on the fetal rbc- pregnancy 2

what is the purpose of good pasture disease?

thats when you have antibodies to glomerular basement membrane in which the IgG is produced and leads to the complement activated. You also get nephritis/proteinuria and the lung is also the target

What are some post-streptooccal infections?

thats type II- and it occurs in which rheumatic fever- in which the antibodies that cross react with an antigen in the heart muscle

Describe the type II reaction?

1. complement and Fc receptor mediated inflammation
2. opsonization/phagocytosis
3. abnorml physiologic responses without cell tissue injury

what is Graves Disease?

hyperthyroidism

what is Myasthenia gravis?

inhibitor of NT

What are some type III hypersensitivity reactions?

thats when the immune complexes are lodged in the vessel walls. And the
- you have injury that is caused by the anti-tissue antibody

IC complex mediated injury-> vasculitis

what causes type III reactions?

thats when you have complement activation with C3a and C5a activation
Cytokine production-TNFa, and IL-1

what pathway is activated by the IC formation?

classical C pathway and that activates the Fc receptor mediated phagocytosis and deposition in the blood vessels, renal glomeruli, and joint synovia which leads to inflammation

Arthus reaction is an example of what type of hypersensitivity?

type III- thats when you have C3b immune complex and complement activation in which you have a release of C3a, C4a and C5a and that leads to mast cell release- and histamine receptor- and leads to neutrophils release and C3a, c5a and c5b67 release which activates the neutrophil- and leads to the release of lytic enzymes/CR1

what are some examples of type III reactions?

autoimmune- in which there is SLE/RA

Name some infectious diseases caused by type III?

poststrep/some types of meningitis/hepatitis/mononucleosis/malaria/tyrp

what type of hypersensitivity is T cell mediated and what is it due to?

T cell mediated and it is due tot he response of environmental agents. And it is usually not systemic

type IV hypersensitivity?

thats when you have contact sensitivity to chemicals/posion ivy, tissue injury to microbes

what microbe do you have T cell mediated type IV?

M TB

contact dermatitis is an example of what type of hypersensitivity?

Type IV- and thats when you have activated T cells-- and after 48-72 hours- it leads to Eczema, lymphocytes and macrophages

Describe some mechanisms of type IV hypersensitivity?

CD4 and CD8 cells- and they release cytokines which activate the cells.

what cytokines are involved in the Type IV?

IFNgama, IL2 and TNFbeta

which cells are also involved?

macrophages, Inc MHCII and increase in TNF receptors

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