Exam 4: Dr. Archer Hypersensitivity Reactions Flashcards

1
Q

What are hypersensitivity reactions?

A

Excessive, undesirable reactions produced by the normal immune system

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2
Q

What do hypersensitivity reactions often involve?

A

Initial exposure or “sensitization” to an antigen

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3
Q

What does subsequent exposure to a specific antigen lead?

A

The inappropriately excessive response (or hypersensitivity reaction)

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4
Q

Describe Type I hypersensitivity

A

Immediate hypersensitivity

2 phases– sensitization and re-exposure

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5
Q

Describe phase I (sensitization) of type I hypersensitivity

A

Antigens often encountered at the mucosal and cutaneous surfaces
IgE production in response to initial antigen encounter
Often asymptomatic with initial encounter

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6
Q

What are examples of type I hypersensitivity?

A

Dendritic cell within the bronchial epithelium may encounter an inhaled allergen
Langerhan cell within the epidermis may capture a percutaneously absorbed antigen

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7
Q

What happens to the cells that can be involved in a type I hypersensitivity after encounter with antigen?

A

The cells travel to the regional lymph nodes, with preferential signaling towards Th2 and the promotion of a humoral immune response

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8
Q

What happens to B cells during a Type I hypersensitivity reaction?

A

They are directed to a class switch towards IgE production

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9
Q

What happens to antigen specific IgE in a type I hypersensitivity reaction?

A

It binds to tissue mast cells
The IgE coated art cells then reside at the mucosal and cutaneous surfaces where the antigen was originally encountered. The individual is now sensitized

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10
Q

What is type I hypersensitivity mediated by?

A

IgE

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11
Q

What is the primary cellular component of type I hypersensitivity reactions?

A

Mast cells

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12
Q

What is phase 2 (re-exposure) of type I hypersensitivity?

A

Subsequent exposure to the same allergen causes “cross-linking”

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13
Q

When does cross-linking occur?

A

When antigen is bound by two or more IgE molecules

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14
Q

What does cross-linking initiate?

A

A signaling pathway within mast cells and triggers the release (or degranulation) of active substances

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15
Q

What are the active substance involved in type I hypersensitivity?

A
Histamine
Heparin
Leukotrienes
Prostaglandin D2
Platelet activating factor 
Eosinophil chemotactic facotr
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16
Q

Where does histamine come from?

A

Mast cells, as does eosinophil chemotactic factor

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17
Q

What is the clinical consequence of mast cell degranulation?

A

Vasodilation and vascular permeability of blood vessels, resulting in tissue edema
Contraction of smooth muscles
Interaction with local nerve endings
Platelet aggregation

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18
Q

Describe the late phase response of type I hypersensitivity

A

Recruitment of eosinophils and macrophages into the tissue

Presence of eosinophils

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19
Q

What is the hallmark of type I hypersensitivity?

A

Presence of eosinophils

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20
Q

What are the majority of type I hypersensitivity reactions like?

A

Localized and affects only the tissues which come in contact with the allergen

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21
Q

What are examples of localized type I hypersensitivities of the skin?

A

Atopic dermatitis
Flea allergy dermatitis
Equine “sweet itch”

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22
Q

What are examples of localized type I hypersensitivities of the respiratory tract?

A

Asthma

Allergic rhinitis

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23
Q

What are examples of localized type I hypersensitivities of the intestinal tract?

A

Food allergy

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24
Q

How can some type I hypersensitivities be classified?

A

Systemic, meaning they often cause an anaphylactic reaction

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25
Q

What are examples of systemic type I hypersensitivities?

A

Drugs or insect stings

Severe peanut allergy and seafood allergy in humans

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26
Q

What is feline asthma?

A

Lower airway disease limiting airflow

27
Q

What can happen in feline asthma that limits airflow?

A

Airway inflammation
Accumulating airway mucus
Airway smooth muscle contraction

28
Q

What happens in feline asthma that can reduce airway diameter?

A

Decreased airway pressure

Reduction in the volume of air through the airway

29
Q

What plays an important role in feline asthma?

A

Interactions between T cells and eosinophils within airways

30
Q

Describe vaccine adverse reactions

A

IgE mediated degranulation of mast cells in the skin

Histamine and leukotrienes are released to the deeper layers of the skin

31
Q

What is a type II hypersensitivity also known as?

A

Cytotoxic or antibody mediated hypersensitivity

32
Q

What does type II hypersensitivity involve?

A

The destruction of a target cell

33
Q

What is the sensitization to in a type II hypersensitivity?

A

An antigen displayed in the surface of that target cell

34
Q

What are antibodies produced to in type II hypersensitivities?

A

Endogenous antigens or exogenous substances which attach to cell membranes and cause subsequent tissue damage

35
Q

What is type II hypersensitivity mediated by?

A

IgG (mostly) or IgM

36
Q

What is the pathophysiology of type II hypersensitivity?

A

Rapid destruction can occur via activation of the classical pathway of complement and the formation of the membrane attack complex
Can take longer where the target cell destruction involves NK cell destruction or macrophage phagocytosis of the ADCC pathway

37
Q

What are examples of type II hypersensitivities?

A

Immune-mediated hemolytic anemia (IMHA)
Transfusion reactions
Myasthenia gravis
Pemphigus

38
Q

What happens in IMHA?

A

Antibodies coat RBC and induce destruction

39
Q

What can cause intravascular hemolysis?

A

Severe damage by antibodies and complement

40
Q

What can macrophages do in IMHA?

A

Recognize the Fc portion of the antibody and remove the targeted RBC from circulation

41
Q

What is one of the hallmarks of IMHA?

A

Autoagglutination

42
Q

Describe Type A cats

A

Either no or only low levels of pre-formed anti-B alloantiboides

43
Q

Describe Type B cats

A

High levels of pre-formaed anti-A alloantibodies

44
Q

What happens if a type A cat receives type B blood?

A

Minor risk, but possible for transfusion reactions

45
Q

What happens if a type B cat receives type A blood?

A

Much greater risk for transfusion reaction

46
Q

What is the diagnosis of myasthenia gravis?

A

Identification of antibodies against acetylcholine receptors

47
Q

What is used to test for myasthenia gravis?

A

Tensilon test

48
Q

What is a type III hypersensitivity reaction also known as?

A

Immune complex hypersensitivity

49
Q

What does a type III hypersensitivity involve?

A

The formation of soluble immune complexes in the blood and subsequent tissue deposition and tissue damage

50
Q

What is the pathophysiology of type III hypersensitivity?

A

Excessive production of antigen specific IgG antibody sensitization
Re-exposure causes antibody binding to antigen in circulation and the formation of antigen/antibody complexes or “immune complexes”

51
Q

What happens in a type III hypersensitivity once immune complexes are deposited or “settle out” into tissues?

A

Initiate inflammatory response
Complement activation
Recruitment of inflammatory cells to the site of inflammation

52
Q

What can a high load of antigen re-exposure cause in type III hypersensitivity?

A

The formation of immune complexes within the circulation

53
Q

How long do complexes circulate in the bloodstream in type III hypersensitivity?

A

Until the deposit within the wall of the capillaries of differing tissues (kidneys, skin, joints)

54
Q

What can type III hypersensitivity be caused by?

A

Many infectious and inflammatory diseases

55
Q

What can complement fixation and triggering of inflammatory pathways within the vascular walls lead to in type III hypersensitivities?

A

Joint pain
Cutaneous lesions
Protein losing nephropathy

56
Q

What happens with antigenic causes in many cases of type III hypersensitivity?

A

It is not often determined and is described as “idiopathic” or “immune-mediated”

57
Q

What is type IV hypersensitivity also known as?

A

Cell mediated or “delayed” type hypersensitivity

58
Q

What does sensitization lead to in type IV hypersensitivity/

A

The generation of antigen specific T lymphocytes (Th1)

59
Q

What does subsequent exposure lead to in type IV hypersensitivity?

A

Activation of sensitized T lymphocytes and movement of these T lymphocytes to the site of antigen exposure which can lead to the release of inflammatory cytokines and recruitment of inflammatory cells

60
Q

What cells cause direct damage in type IV hypersensitivity?

A

Cytotoxic T cells

61
Q

What do helper T cells do in type IV hypersensitivity?

A

Secrete cytokines which activate cytotoxic T cells and recruit and activate monocytes

62
Q

What is the most significant manifestation of type IV hypersensitivity in humans and dogs?

A

Contact allergy

63
Q

What is contact allergy?

A

Initial topical sensitization followed by re-exposure leading to an inappropriate inflammatory response at the cutaneous site of challenge