Type I-IV Hypersensitivity Reactions Flashcards

1
Q

What is the requirement for all four hypersensitivities?

A

There must be prior exposure to the antigen

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2
Q

When discussing hypersensitivity, what term is synonymous with antigen?

A

Allergen

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3
Q

What do each of the four hypersensitivities react to (in a broad sense)?

A

I- immediate hypersensitivity (IgE)
II- IgG and IgM
III- Immune complexes
IV- specific T-cells (Th1 and CTL)

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4
Q

What is the effector cell for Type I hypersensitivity?

What is the time frame for a type I reaction?

A

IgE in response to contact with an allergen

It has an immediate response and then a late response four to six hours later

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5
Q

In a type I hypersensitivity, after the allergen is bound by IgE, what happens?

A

The IgE binds with high affinity to mast cells and basophils to influence them to degranulate

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6
Q

What 3 allergic conditions are frequently associated with type I?

A

asthma, rhinitis (hay fever) atopic dermatitis (skin reaction)

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7
Q

What is the normal circulating level of IgE?

What does it elevate to in a type I hypersensitivity reaction?

A

less than 1 microg/ml

elevates to over 1000

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8
Q

What is the gist of the hygiene hypothesis?

A

In western cultures there are more allergies than in developing nations because antibiotic reduce normal flora, diet and sensitization promote Th2 phenotype.

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9
Q

Which phenotype Th1 or Th2 would have more sensitivity to allergens?

A

Th2

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10
Q

What four cells have FcepsilonRI high affinity receptors?

A
  1. mast
  2. basophil
  3. eosinophil
  4. langerhans
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11
Q

What chain of FceRI mediates IgE binding?

A

alpha

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12
Q

What are the two receptors for IgE? Which is high affinity?

A

FceRI - high affinity

FceRII- not crucial

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13
Q

What progenitor cell do mast cells arise from?

Where do they differentiate?

A

CD34+ progenitor cells in the bone marrow

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14
Q

What are the four cytokines that are mast cell growth factors?
What is the most important mast cell growth factor?

A

IL-3, IL-4, IL-9, IL-10

The most important mast cell growth factor is Stem cell factor (c-kit ligand)

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15
Q

What newly synthesized mediators do mast cells produce when bound by IgE/allergen?

A
  1. PAF
  2. Leukotrienes
  3. Prostaglandins
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16
Q

What preformed enzymes are released from mast cells when IgE/allergen bind?

A

histamines

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17
Q

What is the biological effect of histamine release?

A
  1. increases vascular permeability

2. smooth muscle contraction

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18
Q

What enzymes are released by mast cells?

What is their function?

A

tryptase, chymase, cathepsin carboxypeptidase remodel connective tissue

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19
Q

What cytokines are released from mast cells?

A

IL-4/ IL-13 to stimulate more IgE
IL-3/IL-5, GM-CSF to promote eosinophils
TNFa to inflame tissue

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20
Q

What are the 3 leukotrienes? What are their 3 effector functions?

A

C4, D4, E4 and they

  1. increase vascular permeability
  2. smooth muscle contraction
  3. secrete mucus
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21
Q

What does PAF do?

A

attracts leukocytes and activates neutrophils, eosinophils and platelets

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22
Q

What are the two ways to activate mast cells?

A
  1. IgE-Dependent

2. IgE-independent

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23
Q

What are the steps of IgE dependent mast cell activation?

A
  1. Allergen binds to membrane bound IgE
  2. IgE crosslinks to activate FceRI
  3. Mediator release of mast cell
24
Q

What are the two other names for IgE-Indenpendent mast cell activation?

A

“pseudoallergic” and “anaphylactoid”

25
Q

What are the two major anaphylatoxins that activate mast cells? What receptor do they bind to on the mast cell?

A

C3a and C5a to C3aR and C5aR respectively

26
Q

What “outside agents” can cause activation of mast cells (not IgE and not anaphylatoxin)?

A

opiates, radiocontrast media, venom

27
Q

When does the early phase reaction of type 1 hypersensitivity occur?
Late phase?

A

Early phase- immediately (minutes)

Late phase - after 4 to 6 hours

28
Q

What causes the late phase of a type 1 hypersensitivity reaction?

A

Influx of eosinophils, basophils, T cells, neutrophils

29
Q

What causes the early phase of a type 1 hypersensitivity reaction?

A

Direct effect of histamines, PAF, leukotrienes, and prostaglandins on blood vessels and smooth muscle

30
Q

What is it called if a type 1 hypersensitivity affects multiple organ systems (systemic)?

A

anaphylaxis - usually caused by food, drugs, insect stings

31
Q

What is the in vivo test for type I hypersensitivity?

A

“Prick Test”- put allergen on skin using a needle, wait 15 minutes, if wheal and flare appears–> the test is positive

32
Q

What is a wheal and flare?

A

Wheal is raised bump and flare is redness both due to histamine release from mast cells with IgE receptors

33
Q

How long does it take to get results from a Prick test? What hypersensitivity is it associated with?

A

15 minutes

Type I

34
Q

What is the in vitro test for Type I hypersensitivity?

A

ImmunoCAP or RAST which directly measure the presence of allergen specific IgE

35
Q

What would a tryptase test tell you?

A

That there was mast cell degranulation (not necessarily type I sensitivity, but can confirm allergy associated with anaphylaxis)

36
Q

What are the three broad categories for ways to treat type1 hypersensitivities?

A
  1. Environmental- avoid exposure to antigen
  2. Drugs- antihistamines, bronchodilators, corticosteroids, epinephrine, anti-IgE
  3. Immunologic intervention - immunotherapy and desensitization
37
Q

What are the similarities between type II and type III hypersensitivity?

A
  1. IgG and IgM
  2. exaggeration of normal immune response
  3. 4-24 hours
38
Q

What are the major differences between type II and type III hypersensitivity?

A

Type II- Ab is against surface antigens on cells and tissue and damage is localized
Type III- Ab is against soluble Ag that form complexes and the damage is to organs where immune complexes deposit

39
Q

What does the IgG or IgM interact with in Type II hypersensitivity? Which cells are these receptors located on?

A

FcR or complement receptors on:

  1. NK cells (IgG)
  2. Neutrophils (IgG)
  3. Eosinophils (IgE)
  4. Monocytes/macrophages (IgG)
  5. platelets (IgG, IgM)
40
Q

What are TYPEII sensitivities to circulating cell antigens?

To tissue antigens?

A
Circulating:
1. blood transfusion reactions
2. Autoimmune hemolytic anemia
Tissue:
1. Goodpasture's Syndrome-NC1 domain of collagen (lungs/pulmonary)
2. Myasthenia Gravis- against AchR
41
Q

What type of hypersensitivity would be associated with ADCC via FcR?

A

Type II- autoimmune hemolytic anemia:

  1. Circulating Ab binds antigen on RBC
  2. Fc of Ab binds to FcR
  3. RBC is lysed
42
Q

What is the target of Type III hypersensitivity?

What is the effector cell?

A

Target: immune complexes
Effector: neutrophils

43
Q

What is the pathophysiology of type III hypersensitivity?

A
  1. Immune complexes form
  2. Complement activates releasing anaphylatoxins (C3a, C5a) which attracts leukocutes and stimulates basophils/platelets to release histamine and vasoactive substances
  3. Vascular permeability increases
  4. Platelets aggregate causing microthrombus
  5. Immune complexes aggregate in thrombus
  6. Neutrophil tries to digest ICs but gets frustrated bc they are embedded in the vascular wall
  7. Frustrated neutrophil releases toxic metabolites
44
Q

What are the two tests for type III hypersensitivity?

A
  1. Arthus Reaction- acute hemorage/necrosis in skin of animal with lots of Ab that is injected with the antigen (in humans, it is a skin reaction to a booster vaccine when you didn’t need it)
  2. One-Shot experimental serum sickness
45
Q

What are the 3 phases of antigen metabolism in host?

In what phase and after how many days will the person show symptoms if they have type III hypersensitivity?

A
  1. Equilibration between antigen/extravascular space
  2. Catabolic clearance of antigen by endogenous proteins
  3. Ab clearance (formation of Immune Complex)
    Type III- sick in phase three (7days) after the presentation of the antigen
46
Q

What are clinical examples of type III hypersensitivity?

A
  1. Human serum sickness (or serum-like sickness that is drug derived)
  2. Lupus-
  3. hypersensitivity pneuomonitis (farmers lung)
47
Q

What are the typical symptoms (4) of serum sickness and after how many days will you see them?
What hypersensitivity is this associated with?

A
  1. Hives
  2. Joint swelling
  3. fever
  4. swollen LN

AFTER SEVEN DAYS *****

48
Q

What is the mediator of a type 4 hypersensitivity?

What is the time frame for these sensitivities?

A

Th and CTL cells (**NOT Ab derived)

48-96 hours (DAYS)

49
Q

What nomenclature (3) is associated with type 4 hypersensitivity?

A
  1. Tuberculin test
  2. Delayed-type hypersensitivity (DTH)
  3. Cell-mediated immunity
50
Q

What is the most common manifestation of Type 4 hypersensitivity?

A

contact dermatitis (skin allergy to metals, poison ivy, etc)

51
Q

What is a hapten?

A

A small allergen that links to self-protein to form an immunogenic hapten-carrier complex

52
Q

Describe the afferent phase of contact dermatitis.

A
  1. hapten binds to self-protein
  2. langerhan’s cell recognizes it and processes the allergen into peptides and expresses it as MHC II
  3. T-cells interact in the lymph node and become CD4, then langerhan’s cytokines expand and differentiate the T-cells
53
Q

What two types of cells are made in response to a hapten in type 4 hypersensitivity?

A

CD4 Th1

CD8

54
Q

Describe the efferent phase (second encounter with allergen) in contact dermatitis.

A
  1. allergen interacts with langerhans and keratinocytes which release cytokines
  2. adhesion molecules on vascular endothelium are upregulated bringing memory T-cells that had been circulating to the area
  3. LC present allergen to T-cells which secrete chemokines and cytokines to recruit cells that cause inflammation (monocytes/macrophages, effector T)
55
Q

What are the clinical features of eczema?

A
  1. weepy (oozy)
  2. scaly
  3. Itchy (ALWAYS)
  4. red
56
Q

What is the characteristic appearance of poison ivy?

A

straight line with oozing blisters

57
Q

What test is performed to verify type IV hypersensitivities?

A

Patch test- analagous to the type I prick test, except instead of 15 minutes you need to wait 48-96 hours bc type 4 is delayed-type hypersensitivity