Hypersensitivity (Final Exam)

Hypersensitivity is an _______ of the immune response to self or pathogenic antigens.

exaggeration

Hypersensitivity occurs at the ______ exposure.

second

Autoimmunity occurs when the adaptive immune response responds to ______.

self antigens

This occurs when self ______ and ______ fails.

tolerance, regulation

______ is one cause of hypersensitivity.

Autoimmunity

Type I hypersensitivity relates to ______.

allergies

What are the key players in Type I hypersensitivity?

- IgE

- Mast cells

- Basophils and eosinophils

What are the 2-3 phases of Type I hypersensitivity?

Sensitization, Activation, and in some cases Late Phase

Durin the Sensitization phase, APCs present allergen to ______ cells.

Th2

This skews antigen-specific B cells to class switch to ______ Ab.

IgE

IgE is produced towards an antigen and binds to the ______ on mast cells (and basophils).

Fc𝛆RI

Binding of IgE to Fc𝛆RI increases its ______.

half-life (to 10+ days)

During the Activation phase, adjacent cell-bound IgE/receptor molecules are crosslinked with ______.

antigen

This causes rapid ______ of the cell.

degranulation

This is causes by what factors?

- Histamine!!!

- Heparin

- Eosinophil/neutrophil chemokines

- Prostaglandins, leukotrienes and cytokines

The chemical mediators in the Activation phase of Type I hypersensitivity cause ______ symptoms.

"allergy"

During the Late Phase of hypersensitivity, newly synthesized molecules within the ______ trigger a reaction 6-8 hours after antigen exposure.

mast cell/basophil

The Late Phase of Type I hypersensitivity happens in ______.

only some individuals

______ are the primary mediator of the Late Phase.

eosinophils

______ damage can occur due to the Late Phase, along with ______ changes due to remodeling.

Tissue, structural

What are some genetic and environmental influences on Type I hypersensitivity reactions?

- Several hundred genes

- Hygiene hypothesis

- Antibiotics?

- Cigarette smoking

- Diesel exhaust

What are some S/Sx of a Type I hypersensitivity reaction?

- Rhinitis/hay fever

- Asthma

- Food allergies

- Urticaria/hives

- Eczema

- Systemic anaphylaxis

These clinical manifestations of Type I hypersensitivity are caused by the release of ______ mediators.

inflammatory

Treatment of Type I hypersensitivity includes ...

- Antihistamines, bronchodilators

- Omalizumab

- Allergy immunotherapy

Omalizumab is an ______ medication. How does it work?

anti-IgE

It binds to the site that the Fc𝛆RI would bind

Allergy immunotherapy includes the administering of small amounts of ______ under the skin or orally to induce ______.

antigen, tolerance

In vivo ______ can be used to test for Type I hypersensitivities.

skin tests

These can be percutaneous or intradermal and are less expensive than ______ yet still sensitive.

serology

A positive skin test shows ______ at the site of antigen compared to a control

wheel and flare

______ is another lab test for Type I hypersensitivity.

IgE serology

______ test and ______ test used to be used for IgE serology, but are not used much now due to radioactive-labeled Abs.

Redioallergosorbent (RAST), Radioimmunosorbent (RIST)

______ IgE and ______-specific formats of IgE serology are currently available and in use.

Total, antigen

IgE allergen-specific ______ can also be used in the lab, which can test against close to 1800 allergens.

immunoassay

______ and ______ formats of IgE allergen-specific immunoassay are also available.

Microarray, POC

Total serum IgE testing frequently shows a value above ______ in those with allergies.

100 kU/L

Total serum IgE testing is better for monitoring ______.

allergy treatment

Type II hypersensitivity uses ______ directed against antigens found on cell surfaces.

IgG/IgM

These are ______ self-antigens, or heteroantigens.

altered

What are the 3 possible outcomes of Type II hypersensitivity?

- Cell with the antigen is destroyed

- Function of the cell is inhibited

- Function of the cell is increased above normal

In Type II hypersensitivity when the cell is damaged/destroyed, what mechanisms can be used to do this?

- Classical complement and cell lysis

- Opsonization of cell

- Ab-dependent cellular cytotoxicity

In Type II hypersensitivity when cellular function is inhibited, binding of an Ab to antigen on a cell blocks the interaction of another ______.

ligand:receptor pair

An example of this is in the disease ______, where there are autoantibodies to ACH.

Myasthenia Gravis

In Type II hypersensitivity when cellular function is increased, binding of an Ab to antigen on a cell ______ the cell.

stimulates

This causes ______ of cellular products.

overproduction

An example of this is in the disease ______, where autoantibody binds to TSH receptor.

Grave's Disease (hyperthyroidism)

Clinical manifestations of Type II hypersensitivity

- Transfusion reactions

- HDFN

- Autoimmune Hemolytic Anemia

- Organ/tissue specific autoimmune diseases

What are some organ/tissue specific autoimmune diseases that portray Type II hypersensitivity?

Grave's, Mysthenis Gravis, Hashimoto's Thyroiditis, Goodpasture's, Type I Diabetes

In the lab, Type II hypersensitivity can be tested for in the ______, relating to transfusion reactions.

blood bank

In addition, detection can be ______-specific.

disease

Type III hypersensitivity is similar to Type II in which IgM/IgG is directed against self or heteroantigen, except in Type III the antigen is ______ antigen.

soluble

______ between Ab and soluble antigen mediates Type III hypersensitivity reactions.

Immune complexes

These complexes deposit in ______, causing inflammation.

tissues

Type III hypersensitivity is dependent on ______ concentration and balance.

Antibody:Antigen

(too much of either will inhibit the reaction)

In Type III hypersensitivity, neutrophil/macrophages ______ are released, causing tissue damage.

granules

Clinical manifestations of Type III hypersensitivity

- Serum sickness

- RA and SLE

In RA and SLE, autoantibodies to ______ complexes in tissues.

Fc(IgG)

______ is also a type of Type III hypersensitivity.

Group A Strep (glomerulonephritis)

Lab testing for Type III hypersensitivity is mainly ______-specific.

disease

Otherwise, ______ levels can be measured for flare ups and treatment efficacy.

complement C3

Type IV hypersensitivity is ______, occurring 2-3 days after exposure.

delayed

______ is predominantly present in Type IV hypersensitivity reactions, but what other cells play a role?

Th1

CD8 T cells and APCs

Type IV hypersensitivity reactions can include a 1-2 week ______ phase

sensitization

Type IV hypersensitivity is triggered by ______ antigens or ______ antigens.

intracellular (ex. mycobacterium), contact (ex. poison ivy/oak, metals)

Upon first exposure, cells are ______.

sensitized

Upon second exposure, ______ is mounted.

immune response

A clinical manifestation of Type IV hypersensitivity is ______.

contact dermatitis

With contact dermatitis, ______ cells in the skin uptake and process antigens on the skin.

Langerhan

Then, these Langerhan cells migrate to T cell zones of ______.

lymph nodes

It is suspected that the substance/antigen acts as a ______.

hapten

The duration of the Type IV hypersensitivity reaction depends on the ______ of antigen and the degree of ______.

concentration, sensitization

In the lab, a ______ test or a ______ test can be performed to determine metal allergies.

patch, blood

A skin test can be used for ______.

Mycobacterium tuberculosis

A positive Type IV hypersensitivity test means there has been infiltration of sensitized ______ and ______ to the site.

T cells, macrophages,