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1.3 POM Immunology > Hypersensitivity > Flashcards

Hypersensitivity Flashcards

1
Q

What is an antigen?

A

Substance that can stimulate an antibody response

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2
Q

What is an antibody?

A

Y shaped heterodimeric protein that binds to an antigen
- Immunoglobin
- BCR when bound to B cells

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3
Q

What is an adjuvant?

A

Substance enhancing immune response to an antigen

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4
Q

What is an allergen?

A

Anitgen/substance that stimulates an allergic reaction (type 1 hypersensitivity)

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5
Q

What is a hapten?

A

Molecule that can become antigenic when associated with a larger carrier protein

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6
Q

What is hypersensitivity?

A

Adverse/excessive pathological immune response

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7
Q

What is an immunogen?

A

Self-adjuvanting antigen (causes immune response on its own)

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8
Q

What is an immune complex?

A

Antibody-antigen complex

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9
Q

What is immunogenicity?

A

Ability of a substance to stimulate an immune response

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10
Q

What are DAMPs?

A

Damage Associated Molecular Patterns
- Molecules released by non-apoptotic cell death —> activates innate immune system

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11
Q

What are PAMPs?

A

Pathogen Associated Molecular Patterns
- Common molecular patterns in pathogens and microbes (not found in host cells) —> stimulates innate immune response

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12
Q

What are PPRs?

A

Pattern Recognition Receptors
- Receptors for DAMPs and PAMPs

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13
Q

What are the 2 causes of hypersensitivity?

A
  1. Foreign antigens —> allergies
  2. Self antigens —> autoimmune disease
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14
Q

What are the 2 consequences of hypersensitivity reactions?

A
  1. Inflammation —> pain
  2. Tissue damage (can be fatal)
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15
Q

How many classifications of hypersensitivity are there?

A

4
- Type I, II, III, IV

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16
Q

What do all hypersensitivity reactions require?

A

Adaptive immunological memory to antigen

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17
Q

Which type of immune response is involved in hypersensitivity?

A

Adaptive

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18
Q

What are the 5 antibody isotopes?

A
  1. IgG
  2. IgD
  3. IgE
  4. IgA
  5. IgM
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19
Q

What is the structure of IgG antibodies?

A

Normal
- V-L, V-H, C-L
- C-γ1, 2, 3
- Double bond

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20
Q

What is the structure of IgD antibodies?

A

Normal
- V-L, V-H, C-L
- C-δ1, 2, 3
- Single bond

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21
Q

What is the structure of IgE antibodies?

A

Normal
- V-L, V-H, C-L, C-γ2, C-γ3
- C-ε1, 2, 3, 4
- 2 bonds

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22
Q

What is the structure of IgA antibodies?

A

Dimer —> 2 connected by J chain
- V-L, V-H, C-L
- C-α1, 2, 3
- single bonds
(like 2 IgDs)

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23
Q

What is the structure of IgM antibodies?

A

Pentamer —> 1 J chain + 4 disulfide bridges
- V-L, V-H, C-L
- C-μ1, 2, 3, 4
(like 5 IgEs)

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24
Q

What is the function of IgG3?

A

Activate phagocytosis
- Complement and FcR mediated phagocytosis

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25
Q

What is the function of IgE?

A

Stimulate mast cell degranulation

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26
Q

What is special about IgA?

A

Can cross mucosal epithelium

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27
Q

What is clonal expansion of T cells?

A

Rapid proliferation when naive T cell encounters antigen

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28
Q

What does clonal expansion of T cells result in? (2)

A
  1. Effector T cells
  2. Memory T cells
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29
Q

What is the main function of Treg cells?

A

Immune tolerance

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30
Q

What is the main function of Th17 cells?

A

Extracellular bacteria and fungi immune response

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31
Q

What is the main function of Th2 cells?

A

Allergic and anti-helminth response

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32
Q

What is the main function of Tfh cells?

A

B cell help in germination centres

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33
Q

What is the main function of Th1 cells?

A

Control intracellular pathogen response

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34
Q

What is type 1 hypersensitivity?

A

Allergic reaction (immediate/anaphylactic hypersensitivity)

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35
Q

What type of hypersensitivity are allergic reactions?

A

Type I

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36
Q

What are 4 examples of diseases caused by type 1 hypersensitivity?

A
  1. Asthma
  2. Allergic rhinitis
  3. Urticaria
  4. Atopic dermatitis
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37
Q

What are the general rules for deciding hypersensitivity type occurring?

A
  1. Type I —> allergic reaction
  2. Type II —> antibody issues
  3. Type III —> response not cleared (autoimmunity)
  4. Type IV —> delayed inflammation
38
Q

Which antibodies mediate type 1 hypersensitivity?

39
Q

Why do people have allergies?

A

Produce IgE antibodies against common multivalent antigens
- IgE rarely found in circulation of non-allergic people

40
Q

What are the 5 common types of allergen?

A
  1. Foods
  2. Plants
  3. Animal dander
  4. Drugs
  5. Insect products
41
Q

How are allergies diagnosed?

A

Skin prick test —> see if stimulates inflammation

42
Q

Which 2 Th cells are stimulated by IgE in type 1 hypersensitivity?

A
  1. Th2 cells
  2. Tfh cells
43
Q

Which 2 cytokines are involved in type 1 hypersensitivity?

A
  1. IL-4
  2. IL-13
44
Q

What are the effects of IL-4 and IL-13 in type 1 hypersensitivity?

A

Promote B cell switch to antigen-specific IgE production

45
Q

Which cells do IgE antibodies bind to and why?

A
  1. Mast cells
  2. Basophils
    - High infinity IgE receptors (FcεRI)
46
Q

What happens when cell bound IgE encounters an allergen?

A

Crosslinking —> degranulation

47
Q

What are the 6 steps of type 1 hypersensitivity?

A
  1. IgE encounters cognate antigen
  2. IgE activates Th2 and Tfh cells
  3. IL-4 and IL-13 released
  4. Stimulates B cell switch to antigen-specific IgE —> lots of antibodies
  5. IgE bind to mast cells and basophils
  6. Cell-bound IgEs stimulate degranulation —> antimicrobial chemicals released
48
Q

What are the 10 mediator molecules of type 1 hypersensitivity?

A
  1. Histamine
  2. Serotonin
  3. ECF-A (eosinophil)
  4. NCF-A (neutrophil)
  5. Proteases
  6. Platelet-activating factor
  7. Leukotrienes
  8. Prostaglandins
  9. Bradykinin
  10. Cytokines
49
Q

Which 2 molecules lead to an allergic reaction in type 1 hypersensitivity?

A
  1. Histamine
  2. Cytokines
50
Q

What are the 3 phases of a type 1 hypersensitivity reaction and which cells are involved?

A
  1. Early phase —> mast cells
  2. Later response —> neutrophils
  3. Late response —> eosinophils and Th2 cells
51
Q

When do the early, later and late responses occur in type 1 hypersensitivity?

A
  1. Early —> minutes
  2. Later —> hours
  3. Late —> 3-4 days
52
Q

What is type II hypersensitivity known as?

A

Antibody-mediated cytotoxic hypersensitivity

53
Q

Which 2 antibodies are involved in type II hypersensitivity and what do they do?

54
Q

What are 4 examples of a cause of type II hypersensitivity?

A
  1. Mismatched blood transfusion
  2. Haemolytic disease of newborns
  3. Immune thrombocytopenia
  4. Graves disease
55
Q

How can blood transfusions cause type II hypersensitivity?

A

Wrong type —> wrong antibodies

56
Q

How can haemolytic diseases of newborns cause type II hypersensitivity?

A

HTRs and HDFN

57
Q

Why can immune thrombocytopenia cause type II hypersensitivity?

A

Antibodies produced again platelet surface proteins

58
Q

Why can Graves disease cause type II hypersensitivity?

A

Thyroid stimulating antibodies —> bind to thyrotropin receptor —> over secretion of thyroid hormones

59
Q

Can type II hypersensitivity be caused by foreign and self antigens?

60
Q

What are the 3 mechanisms of type II hypersensitivity diseases?

A
  1. Anti-receptor activity
  2. ADCC
  3. Classical complement cascade
61
Q

What is ADCC?

A

Antibody Dependant Cell-mediated Cytotoxicity
- Bind to FcRs (constant region of IgGs and IgMs) of granulocytes and NK cells

62
Q

What happens if ADCC antibody-antigen complexes form resulting in type II hypersensitivity? (2)

A
  1. Lysis of target cells
  2. Release of inflammatory mediators (cytokines and chemokines)
63
Q

Which cells are involved in type II hypersensitivity reactions?

A
  1. Granulocytes
  2. NK cells
64
Q

What are the 3 consequences of type II hypersensitivity reactions?

A

Tissue injury:
1. Inflammation (local or systemic)
Cell depletion:
2. Loss of function of tissue
3. Organ function imbalance

65
Q

What are the 3 steps of type II hypersensitvity?

A
  1. IgG or IgM antibodies bind to antigen
  2. Anti-receptor activity/ ADCC/ classical complement
  3. Lysis of target cells and inflammation
66
Q

What is type III hypersensitivity known as?

A

Immune complexe driven disease

67
Q

When do type III hypersensitivity reactions occur?

A

Immune complexes not cleared eg. self-antigens

68
Q

Which complexes cause type III hypersensitivity?

A

Immune complexes

69
Q

What is an example of type III hypersensitivity?

A

Autoimmunity

70
Q

What are the 6 symptoms of type III hypersensitivity?

A
  1. Fevers
  2. Rashes
  3. Joint pain
  4. Proteinuria - vasculitis, glomerulonephritis, arthristis
71
Q

What are 3 examples of diseases caused by type III hypersensitivity?

A
  1. SLE —> antibodies against nuclear DNA/proteins
  2. MS
  3. Rheumatoid arthritis
72
Q

What are 3 examples of foreign antigens causing type III hypersensitivity?

A
  1. Persistant hepatitis virus
  2. Drugs
  3. Serum sickness
73
Q

What is serum sickness?

A

Type III hypersensitivity from injection or administration of foreign proteins or antigens

74
Q

Which antibodies are involved in type III hypersensitivity?

75
Q

Which types of hypersensitivity result in inflammation?

A

All
- Type I, II, III —> immediate

76
Q

What is type IV hypersensitivity also known as? (2)

A
  1. Delayed-type hypersensitivity
  2. T cell mediated hypersensitivity
77
Q

What is different about type IV hypersensitivity and why?

A

Delayed inflammation
- Requires DCs —> APCs —> Naive T —> Memory T
- Time taken to generate antigen specific memory T cells

78
Q

When is peak immune response seen in type IV hypersensitivity?

A

2-3 days after inflammation

78
Q

How long do type IV hypersensitivity reactions take to occur and why?

A

Several weeks

79
Q

What are the 4 steps of type IV hypersensitivity reaction?

A
  1. Dendritic cell recognises foreign antigen —> APC
  2. Antigen presented to naive T cell —> activated
  3. T cell recruitment and expansion
  4. Antigen-specific memory T cells produced —> response
80
Q

What is are 7 examples of type IV hypersensitivity?

A

Th1 beased:
1. Poison ivy
2. Nickel salts
3. Hair dyes
4. Tuberclin test

Th2:
5. Asthma
6. Allergens

CTLs:
7. Graft rejection

81
Q

How does poison ivy stimulate type IV hypersensitivity?

A
  • Urishol acts as hapten —> binds to skin proteins —> antigen —> Th1 response
  • Re-exposure —> memory T produce IFNγ —> pro-inflammatory macrophage activation —> blister-like lesions
82
Q

Which cells drive inflammation in type IV hypersensitivity?

83
Q

What is an example of 2 pathogens causing type IV hypersensitivity?

A
  1. Measles
  2. M. tuberculosis
84
Q

Which type of hypersensitivity is involved in the tuberculin skin test?

85
Q

How many hypersensitivity types can be involved in the cause of 1 disease?

86
Q

What are the immune mediators of each type hypersensitivity?

A
  1. IgE
  2. IgG/M
  3. Immune complexes
  4. T cells
87
Q

What is the general mechanism of type I hypersensitivity?

A

Cell-bound IgE activates mast cell and basophil degranulation

88
Q

What is the general mechanism of type II hypersensitivity?

A

Antibodies against cell surface antigens destroy cells via ADCC or classical complement

89
Q

What is the general mechanism of type IV hypersensitivity?

A

Sensitised T cells activate macrophages via cytokines

89
Q

What is the general mechanism of type III hypersensitivity?

A

Antigen-antibody complexes cause neutrophil activation via complement

1.3 POM Immunology (13 decks)

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