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Flashcards in Autoimmune Disease and Hypersensitivity Reactions Deck (176):
1

What is autoimmunity? 

A state that is present when an individual has made an immune response to self-antigens 

2

What provides evidence for autoimmunity in many cases? 

The presence of autoantibodies in serum 

3

What can autoantibodies in serum be helpful in? 

Diagonsing and monitoring autoimmune diseases 

4

What is meant by autoimmune disease?

The term applied to a disease in which autoimmunity is thought to play a significant pathological role, i.e. when the tissue damage results from the autoimmune response 

5

What are the types of autoimmune disease? 

  • Organ specific
  • Non-organ specific 

 

6

What is meant by organ specific autoimmunity? 

The target antigen is located in one organ 

7

What is meant by non-organ specific autoimmune disease? 

The target antigen is located on many different tissues/organs 

8

Give 10 examples of organ-specific autoimmune diseases

  • Hashimoto's
  • Thyrotoxicosis 
  • Primary myxoedema 
  • Chronic atrophic gastritis 
  • Pernicious anaemia 
  • Addisons's disease
  • Myasthenia gravis 
  • Type 1 diabetes mellitus 
  • Premature ovarian failure 
  • Male infertility 

9

Give 4 examples of intermediate/mixed autoimmune diseases

  • Goodpasture's syndrome 
  • Primary biliary cirrhosis 
  • Autoimmune haemolytic disease 
  • Ulcerative colitis 

 

10

Give 4 examples of non-organ specific autoimmune diseases

  • Systemic Lupus Erythematosus 
  • Rheumatoid arthritis 
  • Sjogren's syndrome 
  • Progressive systemic sclerosis 

 

11

What does the existence of autoimmune disesae show? 

Central tolerance is not fool proof

12

What is central tolerance? 

The mechanism by which auto-reactive B and T cells are deleted 

13

What is peripheral tolerance? 

Collective term for further immunological processes that act to avoid the activation of auto-active T and B lymphocytes 

14

What happens when peripheral tolerance breaks down? 

Autoimmunity can ensue

15

What are the potential mechaniams of immunologically mediated tissue injury? 

  • Defective immunoregulation 
  • Cytokine dysregulation 
  • Molecular mimicry
  • T cell bypass 
  • 'Hidden' self antigens 

 

16

What is the mechanism of injury in defective immunoregulation? 

Reduction in supressor/regulatory T cell number and/or function 

17

What diseases result from defective immunoregulation?

Thyroid, liver, GI, and other autoimmune diseases

18

What is the mechanism of injury in cytokine dysregulation? 

Cytokines provide additional signals to activate resting or tolerised autoreactive cells 

19

What disease results from cytokine dysregulation? 

Autoimmune thyroid disease following IL-2 therapy 

20

What is the mechanism of injury in molecular mimicry? 

Pathogen has cross-reactive epitopes with autoantigen; anti-pathogen immune response leads to anti-self response 

21

What diseases result from molecular mimicry? 

  • Coxsackie virus and glutamic acid decarboxylase in type 1 diabetes.
  • Adenovirus 12 and gliadin in coeliac disease 

 

22

What is the mechanism of injury in T cell bypass? 

Novel T cell carrier supplied for an associated T or B cell epitope for which tolerance exists, so T cell help via new carrier activates tolerised cell

23

What disease result from T cell bypass? 

Drug and virus induced auto-immune cytopenias 

24

What is the mechanism of injury of 'hidden' self antigens? 

Tolerance exists to cryptic antigens ('immunological ignorence'), and release or presentation of these breaks the tolerance 

25

What diseases result from 'hidden' self antigens? 

  • Sympathetic ophthalmia
  • Post myocardial complications
    • Dressler's syndrome
  • MS (myelin antigens)

 

26

What are hypersensitivity reactions? 

Excessive or over zealous immune responses that can lead to tissue damage

27

What are hypersensitivity reactions the basis of? 

Autoimmune disease 

28

What can hypersensitivity reactions occur in response to? 

  • Infectious agents
  • Environmental agents 
  • Self antigens 

 

29

Give an example of a disease caused by hypersensitivity to infectious agents

Fulminant hepatitis 

30

Give an example of a disease caused by hypersensitivity to environmental substances? 

Hayfever

31

What are the types of hypersensitivity reactions?

  1. Immediate hypersensitivity 
  2. Antibody mediated hypersensitivity 
  3. Immune complex mediated hypersensitivity 
  4. Delayed hypersensitivity 

 

32

What happens in immediate hypersensitivity? 

Cross-linking of Antigen-specific IgE molecules on surface of mast cells or basophils 

33

What does the cross-linking lead to in immediate hypersensitivity? 

Degranulation of the cells and the release of vasoactive substances 

34

Over what time scale to immediate hypersensitivity reactions typically occur? 

In minutes 

35

What do immediate hypersensitivity reactions form the basis of? 

Most common types of allergies 

36

What does immediate hypersensitivity represent a component of? 

Childhood asthma 

37

What is anaphylaxis? 

A severe form of type I hypersensitivity reaction

38

What triggers anaphylaxis? 

The exposure of a pre-sensitised individual to an allergen, causing mast cell degranulation 

39

What does systemic mast cell degranulation lead to? 

  • Vasodilation 
  • Tissue oedema 
  • Airways obstruction 
  • Fall in blood pressure
  • Shock 

 

40

How should acute anaphylaxis be treated? 

Intramuscular adrenaline 

41

What is the purpose of intramuscular adrenaline in acute anaphylaxis? 

It promptly reverses the symptoms and signs with an increase in blood pressure and reversal of airways obstruction 

42

What happens in antibody mediated hypersensitivity? 

IgG antibodies reacting with antigen present on tissues or on the surfaces of cells 

43

What happens once the antibodies have bound with the antigens in antibody mediated hypersensitivity? 

They interact with complement or the FC receptor on phagocytic cells, activating these innate mechanisms leading to the induction of localised inflammatory response and tissue damage 

44

What is the timescale for antibody mediated hypersensitivity? 

The reactions may occur very quickly, but may also lead to prolonged activation 

45

Give 4 examples of antibody mediated hypersensitivity reactions

  • Goodpasture's syndrome
  • Haemolytic anaemias / Rhesus disease 
  • Stimulating Ab's
  • Blocking Ab's 

 

46

What happens in Goodpastures syndrome? 

There are autoantibodies to the basement membrane in the lung and kidney 

47

What disease is caused by the stimulation of antibodies? 

Grave's disease (stimulates TSH)

48

What diseases are caused by blocking antibodies? 

  • Myasthenia gravis (Blocks AchR)
  • Diabetes (blocks insulin receptor)

 

49

What happens in immune complex mediated hypersensitivity? 

Deposition of immune complexes, usually IgG antibodies 

50

What happens when immune complexes are deposited in various tissues in immune complex mediated hypersensitivity? 

They set up inflammatory reactions similar to Type II reactions (complement activation, phagocyte Fc receptor)

51

What are the most common sites of Type III reactions? 

  • Skin
  • Joints
  • Kidney

 

52

How does type III hypersensitivity in the skin present? 

Rash

53

How does type III hypersensitivity in the joints present? 

Arthritis 

54

How does type III hypersensitivity in the kidney present? 

Nephritis 

55

Give 3 examples of diseases caused by type III hypersensitivity

  • Systemic Lupus Erythematosus
  • Farmer's lung 

 

56

What happens in delayed hypersensitivity?

T cells activate macrophages or cytotoxic T cells 

57

What do activated macrophages/cytotoxic T cells cause? 

Tissue damage

58

59

What time scale do delayed hypersensitivity reactions typically occur over? 

Two to three days after exposure to antigen

60

What can cause delayed hypersensitivity reactions? 

  • External agents 
  • Autoimmune reactions 

 

61

Give two examples of diseases that are caused by a delayed hypersensitivity reaction to external agents 

  • Tuberculoid leprosy 
  • Contact dermatitis 

 

62

Give two examples of autoimmune diseases caused by delayed hypersensitivity

  • Coeliac disease 
  • Multiple sclerosis 

 

63

What causes coeliac disease? 

A delayed type hypersensitivity reaction taking place in the intestinal wall

64

What facilitates the reaction taking place in coeliac disease? 

The allele HLA-DQ2

65

What is the mechanism of disease in coeliac disease? 

Gluten is digested to gliadin, which is recognised as an antigen by HLA-DQ2 and presented to T cells. B cells then make autoantibodies to the transglutamase that is attached to the gliadin. The T cells interact with macrophages, activating them and causing the hypersensitivity, damaging the intestinal villi 

66

What is the appearance of the damaged intestinal villi in coaelic disease? 

Flattened 

67

What happens if gluten is withdrawn from the diet in coeliac disease? 

It reverses the process and the villi return to normal architecture 

68

What is immunotherapy? 

The manipulation of the immune response to treat disease 

69

What can immunotherapy involve? 

  • Enhancing immunity 
  • Suppressing immunity 

 

70

What immunotherapy enhances immunity? 

Vaccination

71

When is it required to suppress immunity? 

To treat allergies and autoimmune conditions 

72

What is the treatment for allergies? 

  • Anti-histamines 
  • Allergen desensitisation 

 

73

What are the major therapeutic effects of anti-histamines via? 

Blocking H1 histamine receptors, leading to inhibition of histamine mediated; 

  • Vascular permeability 
  • Smooth muscle contraction 
  • Reduction in exocrine secretions 
  • Reduction in sensory nerve stimulation 

 

 

74

What is sensory nerve stimulation in allergies responsible for? 

Itching, sneezing etc. 

75

Give 3 examples of anti-histamines

  • Cetirizine 
  • Terfanidine 
  • Loratidine 

 

76

When are allergies treated with allergen desensitisation? 

When they are severe 

77

What happens in allergen desensitisation? 

Regular, subcutaneous injections of the relevant antigen are given ovr a period of weeks or months 

78

What is the mechanism of antigen desensitisation? 

Not fully understood 

May be due to shifting T cell response towards Th1 / inducing IgG blocking antibodies 

79

How is asthma treated? 

  • ß2 adrenoagonists 
  • Corticosteroids 
  • Leukotriene receptor antagonists 
  • Sodium cromglicate

 

80

What do ß2-adrenoagonists do? 

Bronchodilate 

81

Give an example of a ß2-adrenoagonist?

Salbutamol

82

Give an example of a corticosteroid? 

Budesonide 

83

What do leukotriene receptor antagonists do? 

Blocks smooth muscle contraction, production of mucous, recruitment of inflammatory cells, promotion of inflammation and modulation of cytokine production 

84

Give an example of a leukotriene receptor antagonist

Montelukast 

85

What does sodium cromglicate do? 

Helps stabilise the mast cell membrane, preventing degranulation 

86

How do anti-inflammatory drugs work? 

Largely by blocking or suppressing functions of non-specific inflammatory cells, or pro-inflammatory mediators produced by these cells 

87

What inflammatory cells to anti-inflammatory drugs block/suppress? 

  • Monocytes 
  • Macrophages 
  • Granulocytes 

 

88

What properties do anti-inflammatory drugs sometimes also have? 

Immunosuppressive properties 

89

What anti-inflammatory drugs also have immunosuppressive properties? 

Steroids 

90

What is meant by immunsuppressive? 

Inhibition of specific immune cells and their mediators 

91

What is the result of some types of anti-inflammatory drugs also having immunosuppressive properties? 

The distinction between the two is not always clear 

92

What do corticosteroids represent? 

A major class of anti-inflammatory and immunosuppressive drugs in clinical use 

93

What are corticosteroids structurally related to? 

The glucocorticoid steroid hormone cortisol 

94

How can corticosteroids be administered? 

  • Topically
    • Creams
    • Inhalers 
    • Drops
  • Systemically 
    • Oral 
    • Parenteral 

 

95

What are the immunomodulatory effects of corticosteroids? 

  • Leukocyte trafficking 
  • Functional effects 

96

What is the effect of leukocyte trafficking? 

  • Increased neutrophils
  • Reduced lymphocytes (especially T cells) and monocytes 

 

97

What are the functional immunomodulatory effects of corticosteroids? 

  • Inhibition of NFkB intracellular signalling pathway
  • Reduced cytokine release (IL-1, IL-2, and TNF-α)
  • Impaired leukocyte proliferation 
  • Suppressed phagocytosis and bacteriocidal activity 
  • Impaired antigen presentation 
  • Reduced arachidonic acid metabolism 

 

98

What are the types of corticosteroid drugs? 

  • Glucocorticoids 
  • Mineralocorticoids 

 

99

What are the side effects of glucocorticoids? 

  • Diabetes
  •  Cushing's
  • Adrenal suppression / acute adrenal insufficiency in abrupt withdrawal 
  • Osteoporosis
    • Avascular necrosis of head of femur 
  • Mental disturbances 

100

What are the side effects of mineralocorticoids?

  • Hypertension 
  • Sodium and water retention 
  • Potassium loss

 

101

What are the immunosuppressive side effects of corticosteroids? 

  • Increased susceptibility to infections 
  • Impaired wound healing

 

102

What are the other side effects of corticosteroids? 

  • Obesity and muscle wasting 
  • Growth arrest in children 

 

103

What do non-steroidal anti-inflammatory drugs (NSAIDs) represent? 

A wide group of drugs that is one of the most frequently prescribed worldwide 

104

What properties do NSAIDs have? 

Both analgesic and anti-inflammatory properties 

105

Give 4 types of NSAID

  • Salicyclic acid 
  • Propionic acid derivatives 
  • Non-Propionic acid derivatives 
  • Selective COX-2 inhibitors 

 

106

What is the best known and most common type of NSAID?

Salicyclic acid 

107

Give an example of a salicyclic acid

Aspirin 

108

Give two examples of propionic acid derivatives? 

  • Ibuprofen 
  • Naproxen 

 

109

Give two examples of non-propionic acid derivatives

  • Indomethacin 
  • Diclofenac 

 

110

Give two examples of selective COX-2 inhibitors

  • Celocoxib
  • Etoricoxib 

 

111

What are the main anti-inflammatory properties of NSAIDs due to? 

The inhibition of cyclooxygenase in the production of prostaglandins 

112

What is the major side effect of older NSAIDs? 

GI toxicity 

113

What is the major side effect of newer NSAIDs? 

CVS effects 

114

What kind of molecule is TNF-α? 

A pro-inflammatory cytokine 

115

What does TNF-α play a central role in? 

The pathogenesis of a number of autoimmune diseases

116

Give two examples of diseases where TNF-α plays a crucial role in the pathogenesis

  • Rheumatoid arthritis 
  • Crohn's disease 

 

117

Give two drugs used against TNF-α related diseases

  • Infliximab 
  • Etanercept 

 

118

What is infliximab? 

A humanised monoclonal antibody against TNF-α

119

What is infliximab used to do? 

Treat Crohn's disease and rheumatoid arthritis 

120

What is etanercept? 

Soluble, recombinant, human TNF-α receptor fusion protein 

121

What is etanercept used to do? 

Treat rheumatoid arthritis 

122

What is a side effect of anti-TNF-α drugs? 

Reactivation of latent tuberculosis 

123

What does the reactivation of latent TB with ant-TNF-α drugs show? 

The important protective effect of TNF-α in this condition 

124

Why were cytotoxic and anti-proliferative drugs introduced into clinical practice? 

For the treatment of cancer in the 1950's 

125

What properties was it discovered that cytotoxic and anti-proliferative agents had? 

Immunosuppressive 

126

What can the immunosuppressive properties of cytotoxic and anti-proliferative drugs be used to do? 

Treat autoimmune disease and try and inhibit organ transplant rejection 

127

What are side effects of cytotoxic and anti-proliferative drugs due to? 

The agents targeting all proliferating cell types

128

What are the side effects of cytotoxic and anti-proliferative agents? 

  • Cytopenias 
  • GI toxicities 
  • Reduced fertility 

 

129

Give 4 examples of cytotoxic and anti-proliferative agents

  • Azathioprine 
  • Methotrexate 
  • Cyclophosphamide 
  • Mycophenolate Mofetil 

 

130

What do azathioprine and methotrexate act on? 

Cells in the S phase 

131

At what cell stage is cyclophosphamide toxic? 

All 

132

What does cyclophosphamide predominantly act on? 

Active cells rather than resting 

133

What does Mycophenolate Mofetil do? 

New anti-proliferative agent that blocks the synthesis of guanine nucleotides 

134

What is the advantage of Mycophenolate Mofetil? 

It has a degree of selectivity for lymphocytes 

135

Why does Mycophenolate Mofetil have a degree of selectivity for lymphocytes? 

As proliferating lymphocytes rely heavily on the de nova generation of guanine 

136

Give 8 immunological diseases in which cytotoxic drugs are used

  • Organ transplant rejection 
  • Rheumatoid arthritis 
  • Systemic lupus erythematosus 
  • Systemic Vasculitis 
  • Wegener's Granulomatosis
  • Polymyositis 
  • Membranous and membroproliferative glomerulonephritis 
  • Inflammatory bowel disease 

 

137

Give 3 examples of T-cell selective immunosuppressants

  • Cyclosporine 
  • Tacrolimus 
  • Rapamycin

 

138

What is the mechanism of action of cyclosporine and tacrolimus? 

They are calcineurin inhibitors, blocking nuclear factor of activated T cells (NFAT). 

They inhibit transcription of IL-2, and so inhibits unwanted T-helper responses 

139

What is the mechanism of action of rapamycin? 

Blocks cellular protein called mTOR

Inhibits IL-2 production 

Also has anti-proliferative effects 

140

What is a potential use for the anti-proliferative effects of rapamycin? 

Cancer therapy

141

What is the result of the cyclosporine and tacrolimus, and rapamycin working in different ways? 

They can be used together for greater effect 

142

What are cyclosporine, tacrolimus and rapamycin widely used in? 

The prevention of organ transplant rejection, and in certain T-cell driven autoimmune conditions 

143

What cytokines are biological immune response modifiers? 

  • Interferon-α
  • Interferon-ß
  • IL-2
  • Granulocyte Colony Stimulating Factor (G-CSF)

144

Give 5 conditions interferon-α can be used to treat 

  • Chronic Myelogenous Leukaemia 
  • Hairy cell Leukaemia 
  • Follicular lymphoma 
  • AIDS-related Kaposi's Sarcoma 
  • Chronic infections of hepatitis B and C

 

145

What can interferon-ß be used to treat? 

Relapsing, remitting multiple sclerosis 

146

What can IL-2 be used to treat? 

Metastatic renal cancer 

147

How can G-CSF be used clinically?

  • Mobilise granulocytes when neutropenia is a problem
  • Increase bone marrow progenitor cells in the blood for harvesting prior to stem cell transplantation

 

148

What has systemic administration of a number of cytokines proven to be? 

Highly toxic 

149

Give a potential toxic consequence of systemic administration of cytokines

Capillary leak syndrome in IL-2 therapy 

150

Give two examples of cytokine inhibitors

  • Infliximab 
  • Etanercept 

 

151

What do infliximab and etanercept inhibit? 

TNF-α

152

What is given in replacement immunoglobulin therapy? 

Intravenous immunoglobulin 

153

When is replacement immunoglobulin therapy used? 

Primary and secondary antibody deficiencies 

154

Give 4 diseases where intravenous immunoglobulin has a therapeutic benefit? 

  • Kawasaki disease 
  • Idiopathic thrombocytopenia
  • Guillain-Barre syndrome
  • Chronic Inflammatory Demyelinating Polyneuropathy

 

155

What are monoclonal antibodies? 

Antibodies of a single specificity 

156

What produces monoclonal antibodies? 

Fusion of an antigen specific B cell clone with an immortalised plasma cell line 

157

How are monoclonal antibodies produced? 

  1. Hyper-immunise mice with an antigen 
  2. Harvest splenic B-cells 
  3. Fuse with immortalised plasma cell line 
  4. Humanise antibodies 

 

158

What is meant by humanising antibodies? 

Engineering a human antibody so it contains the antigen specificity of the mouse antibody 

159

What are the potential mechanisms of action of therapeutic monoclonal antibodies? 

  • Neutralising the target antigen 
  • Induce complement mediated cell lysis 
  • Induce antibody dependant (NK-mediated) lysis of target cells 
  • Block cellular interactions of receptor ligand binding 
  • Induce apoptosis in target cells 
  • Conugated to radioisotopes to deliver to target cell 
  • Conjugated to cellular toxins to deliver to target cell

 

160

Give 8 examples of monoclonal antibodies used therapeutically

  • Infliximab 
  • Herceptin
  • Omalizumab 
  • Alemtuzumab
  • Palivisumab
  • Basiliximab
  • Bevacizumab
  • Rituximab 

 

161

What is the target antigen for infliximab? 

TNF-α

162

What diseases is infliximab used to treat? 

  • Rheumatoid arthritis 
  • Crohn's disease 

 

163

What is the target antigen for herceptin? 

Her-2 (EGF receptor)

164

What is herceptin used to treat? 

Her-2+ Breast cancer 

165

What is the target antigen for omalizumab? 

IgE

166

What is omalizumab used to treat? 

Severe allergic asthma 

167

What is the target antigen for alemtuzumab? 

CD52 (most WBCs)

168

What is alemtuzumab used to treat? 

Chronic lymphocytic leukaemia 

169

What is the target antigen for palivisumab?

RSV F-protein 

170

What is palivisumab used for? 

RSV prophylaxis in 'at risk' children 

171

What is the target antigen for basiliximab? 

CD25 (IL-2 receptor)

172

What is basiliximab used to treat? 

Organ transplant rejection 

173

What is the target antigen for bevacizumab? 

VEGF

174

What is bevacizumab used to treat? 

Tumour angiogenesis in colorectal cancer 

175

What is the target antigen for rituximab? 

CD20 (B-cell) 

176

What is rituximab used to treat? 

  • B-cell leukaemia/lymphoma 
  • Some severe autoimmune diseases