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Flashcards in Immunology (finished) Deck (326):
1

Which immune deficiency is this? CD4: low CD8: low B cells: normal or low IgM: normal or low IgG: low IgA: low

SCID

2

Which immune deficiency is this? CD4: low CD8: low B cells: normal IgM: normal IgG: low

DiGeorge

3

Which immune deficiency is this? CD4: low CD8: normal B cells: normal IgM: normal IgG: low

BLW

4

Which immune deficiency is this? CD4: normal CD8: normal B cells: low IgM: low IgG: low IgA: low

Bruton's

5

Which immune deficiency is this? CD4: normal CD8: normal B cells: normal IgM: high IgG: low IgA: low

HyperIgM

6

Which immune deficiency is this? CD4: normal CD8: normal B cells: normal IgM: normal IgG: normal IgA: low

Selective IgA deficiency

7

Which immune deficiency is this? CD4: normal CD8: normal B cells: normal IgM: normal or low IgG: low IgA: low

CVID

8

Which immune deficiency is this? Neutrophil count - absent Leukocyte adhesion markers - normal Nitroblue test of oxidative killing - absent Pus - no

Kostmann syndrome (congenital neutropenia)

9

Which immune deficiency is this? Neutrophil count - normal Leukocyte adhesion markers - normal Nitroblue test of oxidative killing - abnormal Pus - yes

Chronic granulomatous disease

10

Which immune deficiency is this? Neutrophil count - increased during infection Leukocyte adhesion markers - absent Nitroblue test of oxidative killing - normal Pus - no

Leukocyte adhesion deficiency

11

What are the consequences of T cell deficiencies?

Increased susceptibility to viral, fungal and some bacterial infections. Early malignancy.

12

What is the treatment for T Cell deficiencies?

Infection prophylaxis Ig replacement if necessary Specific other treatments

13

What is bare lymphocyte syndrome?

Defect of regulatory factor X or Blass II transactivator. Absent expression of HLA molecules within the thymus -> lymphocytes fail to develop.

14

What are the 2 types of Bare Lymphocyte Syndrome?

Type I - MCH I absent - low CD8 cells Type II - MCH II absent - low CD4 cells

15

Which type of bare lymphocyte syndrome is more common and what are its features?

Type 2 - profound deficiency of CD4 but normal CD8 and B cells. B cell class switch needs CD4 so less IgA and IgG are made.

16

What is bare lymphocyte syndrome associated with?

Sclerosing cholangitis

17

When do children with bare lymphocyte syndrome become unwell?

By 3 months of age

18

What is DiGeorge's Syndrome?

Impaired development of the 3rd and 4th pharyngeal pouches (oesophagus, thymus, heart)

19

What ist he cause of DiGeorge's Syndrome?

22q11.2 deletion - 75% are sporadic

20

What are the features of DiGeorge's syndrome?

Low set ears, cleft lip and palate Low calcium Susceptible to viral infection Very low numbers of mature T cells due to absent thymus

21

How is DiGeorge's syndrome treated?

Thymus transplant

22

What are the consequences of B cell deficiencies?

Increased susceptibility to bacterial and some viral infections and toxins e.g. tetanus, diphtheria

23

What is the treatment for B cell deficiency?

Ig replacement Bone marrow transplant in some situations Vaccination not effective except in IgA deficiency

24

What causes Bruton's agammaglobulinaemia and what are its features?

X linked tyrosine kinase defect Mutation in BTK gene Failed production of mature B cells No antibodies Symptoms after 3-6 months

25

What is the cause/defect in Hyper IgM syndrome?

X linked condition - Xq26 CD40L, CD40, CICDA or CD154 defect

26

How does hyper IgM syndrome present?

Boys present in 1st year of life with recurrent bacterial infections especially pneumocystis carinii and failure to thrive

27

What is the pathophysiology of Hyper IgM Syndrome?

Activated T cells can't interact with B cells to class switch, therefore B cells can't make IgA and IgG but elevated IgM. Also less lymphoid tissue as no germinal centre development

28

What are the long term risks of Hyper IgM syndrome?

Autoimmunity and malignancy

29

What is the cause and defect of Common Variable Immune Deficiency?

Defect in B cell differentiation with many genetic causes. Low IgG, IgE and IgA

30

What are the features of common variable immune deficiency?

Failure to thrive Recurrent infections Autoimmunity Granulomatous diseases

31

What is the most common B cell deficiency?

Selective IgA deficiency

32

How common is selective IgA deficiency?

Affects 1 in 600 caucasians

33

What are the features of selective IgA deficiency?

70% asymptomatic but can cause recurrent gastrointestinal and respiratory infections

34

Where is IgA found?

Mucosal areas, saliva, tears, breast milk

35

Where is IgE found?

Allergy - histamine release from mast cells

36

What is special about IgG?

Can cross from the placenta to the foetus

37

Where is IgM found?

On the surface of B cells (immature B cells express only IgM)

38

What is the half life of human normal Ig?

18 days

39

What is the cause of severe combined immune deficiency?

Defects in lymphoid precursors e.g. adenosine deaminase gene, IL-2 receptor. 45% are X linked

40

What are the features of SCID?

Low or normal B cell numbers, reduced T cells, low antibodies Recurrent infections, failure to thrive, diarrhoea and early infant death

41

What is the treatment for SCID?

Bone marrow transplant the only established treatment

42

What is the consequence of phagocyte deficiency?

Increased susceptibility to bacterial and fungal infections often with deep abscesses

43

What is the main defect in Kostmann syndrome?

Severe congenital neutropenia

44

What is the cause of Kostmann syndrome?

Autosomal recessive - HAX1

45

How common is Kostmann syndrome?

1-2 cases per million

46

How does Kostmann syndrome present?

Recurrent infections shortly after birth

47

How is Kostmann syndrome diagnosed?

Chronically low neutrophils and bone marrow test showing an arrest of neutrophil precursor maturation

48

What is the treatment for Kostmann syndrome?

G-CSF, prophylactic antibiotics, BMT if G-CSF ineffective

49

What is the main defect in leukocyte adhesion deficiency?

Failure to express leukocyte adhesion markers

50

How does leukocyte adhesion deficiency present?

Neonatal bacterial infections, often life threatening High neutrophil count and delayed umbilical cord separation

51

What are the 2 types of leukocyte adhesion deficiency and what's the difference between them?

LAD1 - deficiency of the beta2 intern subunit (CD18) of the leukocyte adhesion molecule LAD2 - much rarer and has severe growth restriction and mental retardation

52

What is the treatment for leukocyte adhesion deficiency?

Bone marrow transplant

53

What is the main defect in chronic granulomatous disease?

Failure of oxidative killing - defect of NADPH oxidase leading to reduced reactive oxygen speciesydrogen peroxide

54

How can you test for chronic granulomatous disease?

Negative NBT test - NBT = a dye that changes from yellow to blue following interaction with hydrogen peroxide Dihydrorhodamine flow cytometry test - DHR is oxidise to rhodamine which is strongly fluorescent after interaction with hydrogen peroxide

55

What are the features of chronic granulomatous disease?

Pneumonia, abscesses, suppurative arthritis and the diseases. Infections are with catalase positive organisms (can resist catalase negative organisms)

56

What are the catalase positive organisms?

PLACESS: Pseudomonas Listeria Aspergillus Candida E coli Staph aureus Serratia

57

What is the cause/inheritance of chronic granulomatous disease?

Lots of mutations but mostly X linked

58

What is the treatment or chronic granulomatous disease?

Trimethoprim, itraconazole and interferon - can sometimes use a stem cell transplant

59

What is the cause of cyclic neutropenia?

Mutations in the ELA1 gene

60

What are the features of cyclic neutropenia?

Episodic neutropenia occurring every 3 weeks and lasting several days

61

What is the treatment for cyclic neutropenia?

G-CSF

62

Which cytokines are commonly deficient (in cytokine deficiencies)

IFN gamma, IFN gamma receptor, IL12, IL12 receptor

63

What do IFN gamma, IFN gamma receptor, IL12, IL12 receptor do?

Involve din signalling between T cells and macrophages to stimulate TNF and activate NADPH oxidase

64

What are the consequences of cytokine deficiencies?

Predispose to infections caused by salmonella, atypical mycobacteria, TB and BCG Unable to form granulomata

65

What is the most severe form of SCID?

Reticular dysgenesis

66

What is deficient in reticular dysgenesis?

Absolute deficiency in: Neutrophils Lymphocytes Monocytes/macrophages Platelets

67

What is the prognosis/treatment for reticular dysgenesis?

Fatal in very early life unless treated with bone marrow transplant

68

What is the consequence of complement deficiency?

Increased susceptibility to encapsulated bacterial infections

69

What are the 4 complement pathways where there can be deficiencies?

Classical, lectin, alternative, common/terminal

70

What is lacking in a classical pathway complement deficiency?

C1q/r/s, C2 (commonest, C4

71

What is classical pathway complement deficiency associated with?

SLE - as classical pathway is involved in removing immune complexes

72

Which test is abnormal in a classical pathway complement deficiency?

CH50 testy compleet deficiency?

73

What is the common deficiency in the lectin complement pathway?

MBL in 10%

74

How common is lectin pathway complement deficiency and is it significant?

Very common, not really clinically significant

75

Which factors are involved in alternative pathway complement deficiency?

Factors B/I/P

76

What is the alternative complement pathway involved in?

Killing bacteria

77

What are the features of alternative pathway complement deficiency?

Infections with encapsulated bacteria: Strep pneumonia Group B strep Haemophilus influenza Neisseria meningitidis

78

Which test is abnormal in alternative pathway complement deficiency?

AP50 test

79

What is lacking in common/terminal pathway complement deficiency?

C3, 5, 6, 7, 8, 9 - so cannot form MAC to kill bacteria

80

What are the features of common and terminal pathway complement deficiency?

Susceptibility to bacterial infections - meningitis, pneumonia May be associated with membranoproliferative glomerulonephritis

81

Which test is abnormal in common and terminal pathway complement deficiency?

AP50 and CH50

82

What is the treatment for complement deficiency?

Vaccination Prophylactic antibiotics High levels of suspicion Screen family members

83

Describe a type 1 hypersensitivity reaction

Immediate reaction provoked by re exposure to an allergen

84

Which Ig mediates a type 1 hypersensitivity reaction?

IgE

85

What is the pathophysiology of a type I hypersensitivity reaction?

Mast cells release mediators resulting in vasodilation, increased permeability, smooth muscle spasm

86

What are the typical symptoms of a type 1 hypersensitivity reaction?

Angioedema, urticaria, rhino conjunctivitis, wheeze, diarrhoea and vomiting, anaphylaxis

87

What is the prevalence of asthma in 13-14 year olds in the UK?

30%

88

What is the prevalence of allergic rhinitis in 13-14 year olds in the UK?

20%

89

What is the prevalence of atopic dermatitis in 13-14 year olds in the UK?

15%

90

What is the prevalence of food allergy in 13-14 year olds in the UK?

2.3%

91

What % of children with asthma also have food allergy?

4%

92

What are the components of the 'atopic triad'?

Eczema, asthma, hay fever

93

What are some common type 1 hypersensitivity syndromes?

Atopic dermatitis Food allergy Oral allergy syndrome Latex fruit/food syndrome Allergic rhinitis Acute urticaria

94

What is the allergen in atopic dermatitis?

Irritants, food and environmental

95

What is the pathology in atopic dermatitis?

Defects in B defensive predispose to staph aureus superinfection

96

How is atopic dermatitis diagnosed and when does it present?

Clinical - 80% present in the first year of life

97

How is atopic dermatitis treated?

Emollients, skin oils, topical steroids, antibiotics, PUNA phototherapy etc

98

What is the allergen in food allergy?

Milk, egg, peanut, tree nut, fish, shellfish

99

What is the pathology in food allergy?

IgE (anaphylaxis, OAS), cell mediated (coeliac) or both (atopic dermatitis)

100

How is food allergy diagnosed and when does it resolve?

Food diary, skin prick test, RAST challenge. Usually resolves by adulthood

101

How is food allergy treated?

Dietitian, food avoidance, epicene, control asthma if present

102

What is the allergen in oral allergy syndrome?

Birch pollen and rosacea fruit, ragweed and melons, mugwort and celery (cross reactivity)

103

What is the pathology in oral allergy syndrome?

Exposure to allergen induces allergy to food. Symptoms are limited to the mouth but 2% get anaphylaxis

104

How is oral allergy syndrome diagnosed?

Skin prick testing can be useful but clinical

105

How is oral allergy syndrome treated?

Avoid food. If ingested, wash mouth and use antihistamine

106

What is the allergen in latex food/fruit syndrome?

Chestnut, avocado, banana, potato, tomato, kiwi, papaya, eggplant, mango, wheat, melon

107

What is the pathology in latex food/fruit syndrome?

Some foods have latex like components so latex allergy sufferers are allergic to them

108

How is latex food/fruit syndrome diagnosed?

Skin prick test

109

How is latex food/fruit syndrome treated?

Strike avoidance of causative food

110

What is the allergen in allergic rhinitis?

Seasonal (tree and grass pollen, fungal spores) or perennial (pets, house dust mite) or occupational (latex, lab animals)

111

What are the features of allergic rhinitis?

Nasal itch and obstruction, sneezing, anosmia, eye symptoms

112

How is allergic rhinitis diagnosed?

Clinical: pale bluish swollen nasal mucosa Skin prick test and RAST

113

How is allergic rhinitis treated?

Allergen avoidance Antihistamine Steroid nasal spray Sodium cromoglycate eye drops Oral steroids Ipratropium nasal spray Grass pollen desensitisation

114

What is the allergen in acute urticaria?

50% idiopathic 50% caused by food, drugs, latex, viral infections, and febrile illnesses

115

What are the features of acute urticaria?

IgE mediated reaction - wheals which completely resolve within 6 weeks

116

How is acute urticaria diagnosed?

Mainly clinical - sometimes skin prick test

117

How is acute urticaria treated?

Allergen avoidance, antihistamines

118

What is anaphylaxis?

Severe systemic allergic reaction with respiratory difficulty and hypotension

119

Which allergens cause IgE mediated mast cell degranulation in anaphylaxis?

Peanut Penicillin Stings Latex

120

Which allergens cause non-IgE mediated mast cell degranulation in anaphylaxis?

NSAIDs IV contrast Opioids Exercise

121

What is the management for anaphylaxis?

Elevate legs 100% oxygen IM adrenaline 500mcg Inhaled bronchodilators Hydrocortisone 100mg IV Chlorphenamine 10mg IV IV fluids SEEK HELP

122

How is a skin prick test done?

Positive control = histamine Negative control = diluent Positive test is a wheal ≥2mm greater than the negative control Discontinue antihistamines 48h before test (corticosteroids OK)

123

What are skin prick tests useful for?

Useful to confirm clinical history, and negative test excludes IgE mediated allergy

124

What does a RAST test measure

Levels of IgE in serum against a particular allergen

125

What is a RAST test useful for?

Confirms diagnosis of allergy and monitors response to anti-IgE treatment

126

How does a RAST test compare to skin prick testing?

Less sensitive/specific than a skin prick

127

What are the indications for a RAST test?

Can't stop antihistamines, anaphylaxis history, extensive eczema

128

What does a 'component resolved diagnosis' measure?

The IgE response to a specific allergen protein, whilst conventional tests measure response to a range of allergen proteins

129

What is the gold standard test for food allergy?

Double blind oral food challenge - increasing volumes of offending food/drug ingested under close supervision

130

What's the risk in a double blind food challenge test?

Severe reaction

131

What can you measure during an acute allergy episode?

Mast cell tryptate Peak at 1-2 hours and baseline by 6 hours

132

What is the general pathophysiology in Type II hypersensitivity disorders?

IgG or IgM antibody reacts with cell or matrix associated self antigen resulting in tissue damage, receptor blockade/activation

133

What are some examples of type II hypersensitivity disorders?

Haemolytic disease of the newborn Autoimmune haemolytic anaemia (+ ITP = Evans' syndrome) Autoimmune thrombocytopenic purpura Good pasture's syndrome Pemphigus vulgaris Graves disease Myasthenia graves Acute rheumatic fever Pernicious anaemia Churg-Strauss syndrome (eGPA) Wegener's granulomatosis Microscopic polyangiitis Chronic urticaria

134

Haemolytic disease of the newborn: Antigen = Pathology = Diagnosis is made by = Treatment is =

Haemolytic disease of the newborn: Antigen = on neonatal erythrocytes Pathology = maternal IgG mediated reticulocytosis and anaemia Diagnosis is made by = positive direct Coombs test Treatment is = maternal plasma exchange, exchange transfusion

135

Autoimmune haemolytic anaemia: Antigen = Pathology = Diagnosis is made by = Treatment is =

Autoimmune haemolytic anaemia: Antigen = Numerous autoantigens e.g. Rh blood group Ag Pathology = Destruction of RBCs by autoantibody + complement + FcR + phagocytes, anaemia Diagnosis is made by = Positive direct Coombs test, anti red cell Ab Treatment is = steroids

136

Autoimmune thrombocytopenic purpura: Antigen = Pathology = Diagnosis is made by = Treatment is =

Autoimmune thrombocytopenic purpura: Antigen = Glycoprotein IIb/IIIa on platelets Pathology = bruising/bleeding (purpura) Diagnosis is made by = anti-platelet antibody Treatment is = steroids, IVIG, anti-D antibody, splenectomy

137

Goodpasture's syndrome: Antigen = Pathology = Diagnosis is made by = Treatment is =

Goodpasture's syndrome: Antigen = non-collagenous domain of basement membrane collagen IV Pathology = glomerulonephritis, pulmonary haemorrhage Diagnosis is made by = anti GBM Ab, linear smooth IF staining of IgG deposits on BM Treatment is = corticosteroids and immunosuppression

138

Pemphigus vulgaris: Antigen = Pathology = Diagnosis is made by = Treatment is =

Pemphigus vulgaris: Antigen = epidermal cadherin Pathology = Non-tense blistering of the skin and bullae Diagnosis is made by = direct immunofluorescence showing IgG Treatment is = Corticosteroids and immunosuppression

139

Graves disease: Antigen = Pathology = Diagnosis is made by = Treatment is =

Graves disease: Antigen = TSH receptor Pathology = hyperthyroidism Diagnosis is made by = Anti-TSH-R Ab Treatment is = carbimazole and propylthiouracil

140

Myasthenia gravis: Antigen = Pathology = Diagnosis is made by = Treatment is =

Myasthenia gravis: Antigen = acetylcholine receptor Pathology = Fatiguable muscle weakness, double vision Diagnosis is made by = Anti-Ach-R Ab, abnormal EMG, tension test Treatment is = neostigmine, pyridostigmine, if serious use IVIG and plasmaphoresis

141

Acute rheumatic fever: Antigen = Pathology = Diagnosis is made by = Treatment is =

Acute rheumatic fever: Antigen = M proteins on group A strep Pathology = myocarditis, arthritis, Sydenham's chorea Diagnosis is made by = clinical, based on Jones criteria Treatment is = aspirin, steroids and penicillin

142

Pernicious anaemia: Antigen = Pathology = Diagnosis is made by = Treatment is =

Pernicious anaemia: Antigen = intrinsic factor and gastric parietal cells Pathology = low Hb, low B12 Diagnosis is made by = anti-gastric parietal cell Ab, anti-IF Ab, Schilling test Treatment is = dietary B12 or IM B12

143

Churg-Strauss syndrome: Antigen = Pathology = Diagnosis is made by = Treatment is =

Churg-Strauss syndrome: Antigen = medium and small vessel vasculitis Pathology = allergy -> asthma -> systemic disease (male predominancE) Diagnosis is made by = pANCA against myeloperoxidase, granolas, eosinophil granulocytes Treatment is = prednisolone, azathioprine, cyclophosphamide

144

Wegener's granulomatosis: Antigen = Pathology = Diagnosis is made by = Treatment is =

Wegener's granulomatosis: Antigen = medium and small vessel vasculitis Pathology = sinus problems, lung cavitation and haemorrhage, crescentic glomerulonephritis Diagnosis is made by = cANCA against proteinase-3, granulomas Treatment is = corticosteroids, cyclophosphamide, cotrimoxazole

145

Microscopic polyangiitis: Antigen = Pathology = Diagnosis is made by = Treatment is =

Microscopic polyangiitis: Antigen = pauci-immune necrotising small vessel vasculitis Pathology = purpura, lived, many different organs affected Diagnosis is made by = pANCA against myeloperoxidase Treatment is = prednisolone, cyclophosphamide, or azathioprine, plasmaphoresis

146

Chronic urticaria: Antigen = Pathology = Diagnosis is made by = Treatment is =

Chronic urticaria: Antigen = medications (NSAIDs), cold, food, pressure, sun, exercise, insect stings, bites, idiopathic Pathology = persistent itchy wheals lasting >6 weeks associated with angioedema in 50% cases. IgG against FceRI or IgG against IgE. Exclude urticarial vasculitis in those who respond poorly to antihistamine. Diagnosis is made by = Challenge test, ESR (raised in urticarial vasculitis), skin prick testing Treatment is = avoid precipitants. Check for thyroid disease. Preventative antihistamine. IM adrenaline for pharyngeal angioedema. 1% menthol in aqueous cream for pruritus (also Doxepin and cyclosporin)

147

What is the general pathology in type III hypersensitivity disorders?

IgG or IgM immune complex (Ab vs soluble Ag) mediated tissue damage

148

What are some examples of type III hypersensitivity disorders?

Mixed essential cryoglobulinaemia Serum sickness Polyarteritis nodosa Systemic lupus erythematosus

149

Mixed essential cryoglobulinaemia: Antigen = Pathology = Diagnosis is made by = Treatment is =

Mixed essential cryoglobulinaemia: Antigen = IgM against IgG +/- hep C antigens Pathology = Joint pain, splenomegaly, skin, nerve and kidney involvement, associated with hep C Diagnosis is made by = Mixture of clinical biopsies Treatment is = NSAIDs, corticosteroids and plasmaphoresis

150

Serum sickness: Antigen = Pathology = Diagnosis is made by = Treatment is =

Serum sickness: Antigen = reaction to proteins in antiserum (penicillin) Pathology = rashes, itching, arthralgia, lemphadenoapthy, fever and malaise. Symptoms take 7-12 days to develop. Diagnosis is made by = low C3, blood shows immune completes or signs of blood vessel inflammation Treatment is = discontinuation of precipitant, steroids, antihistamines +/- analgesia

151

Polyarteritis nodosa: Antigen = Pathology = Diagnosis is made by = Treatment is =

Polyarteritis nodosa: Antigen = hep B, hep C virus antigens Pathology = fever, fatigue, weakness, arthralgia, skin, nerve and kidney involvement, pericarditis and MI, associated with Hep B Diagnosis is made by = clinical criteria and biopsy (raised ESR, raised WCC, raised CRP), 'rosary sign' (small bead like aneurysms) Treatment is = prednisolone and cyclophosphamide

152

Systemic lupus erythematosus: Antigen = Pathology = Diagnosis is made by =

Systemic lupus erythematosus: Antigen = main intracellular components: DNA, histones, RNP Pathology = M:F 1:9, 4 of these 11: serositis, seizures, aphthous ulcers, arthritis, photosensitivity, discoid rash, malar rash, haematology, kidney findings, antinuclear antibody (ANA positive), immunological finding (anti dsDNA, anti-sm) Diagnosis is made by = low C4 (low C3 only in severe disease), antibodies to dsDNA, histones (drug induced), Ro, La, Sm, U1RNP, high ESR, normal CRP

153

Which drugs can cause drug induced SLE?

Hydrazine, procainamide, isoniazid

154

What is the general pathology of type IV hypersensitivity disorders?

Delayed hypersensitivity, T cell mediated

155

What are some examples of type IV hypersensitivity disorders?

T1DM MS Rheumatoid arthritis Contact dermatitis Mantoux test Crohn's

156

Type 1 diabetes: Antigen = Pathology = Diagnosis is made by = Treatment is =

Type 1 diabetes: Antigen = pancreatic beta cell proteins (glutamate decarboxylase, GAD) Pathology = insulitis, beta cell destruction Diagnosis is made by = blood glucose, ketonuria, glutamate decarboxylase antibodies, islet cell antibodies Treatment is = insulin via injections or continuous infusion

157

MS: Antigen = Pathology = Diagnosis is made by = Treatment is =

MS: Antigen = oligodendrocyte proteins (myelin basic protein, proteolipid protein) Pathology = demyelinating disease, perivascular inflammation, paralysis, ocular lesions Diagnosis is made by = CSF shows oligoclonal bands of IgG on electrophoresis Treatment is = corticosteroids, interferon beta

158

Rheumatoid arthritis: Antigen = Pathology = Diagnosis is made by = Treatment is = Is also hypersensitivity type:

Rheumatoid arthritis: Antigen = antigen in synovial membrane Pathology = chronic arthritis, rheumatoid nodules, lung fibrosis Diagnosis is made by = X ray, rheumatoid factor (85% sensitive), anti CCP (95% specific), increased ESR, increased CRP Treatment is = analgesia, steroids, DMARDs Is also hypersensitivity type: III - IgM Ab vs Fc region of IgG

159

Contact dermatitis: Antigen = Pathology = Diagnosis is made by = Treatment is =

Contact dermatitis: Antigen = environmental chemicals, poison ivy, nickel Pathology = dermatitis with usually short lived itching, blisters and wheals Diagnosis is made by = clinical or use patch test Treatment is = if no resolution use corticosteroids or antihistamines

160

Mantoux test: Antigen = Pathology =

Mantoux test: Antigen = tuberculin Pathology = skin induration indicates TB exposure

161

Crohn's disease: Pathology = Diagnosis is made by = Treatment is =

Crohn's disease: Pathology = Th1 mediated chronic inflammation in skip lesions in GIT. NOD2 gene mutation in 30% Diagnosis is made by = biopsy of lesion. Can affect any part of GIT from mouth to anus Treatment is = antibiotics, anti-inflammatory drugs, e.g. mesalazine, TNF alpha antagonists, e.g. infliximab, steroids

162

HLA ASSOCIATIONS: ankylosing spondylitis Susceptibility allele = Relative risk (fold) =

HLA ASSOCIATIONS: ankylosing spondylitis Susceptibility allele = HLA B27 Relative risk (fold) = 87

163

HLA ASSOCIATIONS: Goodpasture's syndrome Susceptibility allele = Relative risk (fold) =

HLA ASSOCIATIONS: Goodpasture's syndrome Susceptibility allele = HLA DR15/DR2 Relative risk (fold) = 10

164

HLA ASSOCIATIONS: Grave's disease Susceptibility allele = Relative risk (fold) =

HLA ASSOCIATIONS: Grave's disease Susceptibility allele = HLA DR3 Relative risk (fold) = 4

165

HLA ASSOCIATIONS: SLE Susceptibility allele = Relative risk (fold) =

HLA ASSOCIATIONS: SLE Susceptibility allele = HLA DR3 Relative risk (fold) = 6

166

HLA ASSOCIATIONS: Type 1 diabetes Susceptibility allele = Relative risk (fold) =

HLA ASSOCIATIONS: Type 1 diabetes Susceptibility allele = HLA-DR3/DR4 Relative risk (fold) = 25

167

HLA ASSOCIATIONS: Rheumatoid arthritis Susceptibility allele = Relative risk (fold) =

HLA ASSOCIATIONS: Rheumatoid arthritis Susceptibility allele = HLA-DR4 Relative risk (fold) = 4

168

What is PTPN22 and what is this polymorphism associated with?

Tyrosine phosphatase expressin lymphocytes - associated with development of RA, SLE, T1DM

169

What is CTLA4 and what is this polymorphism associated with?

Receptor for CD80/CD86 expressed by T cells, transmits inhibitory signal to control T cell activation; associated with SLE, T1DM, autoimmune thyroid disease

170

What are the features of limited cutaneous scleroderma (CREST syndrome)?

Calcinosis

Raynaud's

Oesophageal dysmotility

Sclerodactyly

Telangiectasia

and primary pulmonary hypertension

Skin involvement is up to forearms only, and perioral

171

How do you diagnose CREST syndrome?

Anti centromere antibodies

172

What are the risks in CREST syndrome?

High risk of lung fibrosis and renal crisis

173

What are the features of diffuse cutaneous scleroderma?

CREST + 

GIT

Interstitial pulmonary disease

Renal problems

174

What antibodies do you see in diffuse cutaneous scleroderma?

Anti-topoisomerase/Scl70

RNA Pol I, II, III

Fibrillarin

175

Is diffuse cutaneous scleroderma more common in women or in men?

Female:male 4:1

176

In whom is Sjogren's syndrome most common?

M:F = 1:9

Onset in late 40s

177

What are the features of Sjogren's syndrome?

Xerostomia (dry mouth)

Keratoconjunctivitis sicca

Nose and skin involvement

May affect kidneys, blood vessels, lungs, liver, pancreas, PNS

May get parotid or salivary gland enlargement

178

What antibodies are there in Sjogren's syndrome?

Anti-Ro and anti-La

179

What test can you do in Sjogren's syndrome other than antibodies?

Schirmer test to measure tear production

180

What does IPEX syndrome stand for?

Immune dysregulation

Polyendocrinopathy

Enteropathy

X-linked inheritance syndrome

+ autoimmune diseases

181

What are the features of IPEX syndrome?

Eczematous dermatitis

Nail dystrophy

Autoimmune skin conditions e.g. alopecia universalis, bullous pemphigoid

182

What is the prognosis in IPEX syndrome?

Most affected children die within the first 2 years of life

183

How is IPEX syndrome inherited?

X-linked recessive - exclusive expression in males

184

How can you treat IPEX syndrome?

Bone marrow transplant is the only cure, but you can use immunomodulators to help

185

What is the basic pathophysiology in coeliac disease?

Failure of tolerance to gluten -> villous atrophy and enteropathy

186

What are the features of coeliac disease?

GIT discomfort, constipation, diarrhoea, bloating, fatigue

Iron, B12, folate, fat, vitamins A, D, E + K + calcium deficiencies

187

What antibodies are associated with coeliac disease?

  • IgA EMA (anti-endomysial) - disappears with exclusion diet, 95% specific, 85% sensitive
  • IgA TGT (anti transglutaminase) - 95% specific, 90-94% sensitive
  • IgG anti-gliadin - most persistent, 30-50% specific, 57-80% sensitive

188

What's associated with coeliac disease?

  • Dermatitis herpetiformis
  • Down's
  • North Africa 20/1000
  • 95% have DQ2 or DQ8 (two eight or not to eat)

189

What's the gold standard test for coeliac disease?

Duodenal biopsy - but not 1st line

190

What are the 4 extractable nuclear antibodies?

Ro

La

Sm

U1RNP

191

What autoantibody is associated with antiphospholipid syndrome?

Against:

  • Cardiolipin
  • Beta2 glycoprotein
  • Lupus anticoagulant

192

What autoantibody is associated with autoimmune hepatitis?

  • Anti-smooth muscle
  • Anti liver kidney microsomal 1 (anti-LKM-1)
  • Anti soluble liver antigen (anti-SLA)

193

What autoantibody is associated with autoimmune haemolytic anaemia?

Anti-Rh blood group antigen

194

What autoantibody is associated with autoimmune thrombocytopenic purpura?

Anti glycoprotein IIb-IIIa or Ib-IX antibody

195

What autoantibody is associated with Churg-Strauss syndrome (eGPA)?

Peri-nuclear/protoplasmic staining anti neutrophil cytoplasmic antibodies (pANCA)

196

What autoantibody is associated with coeliac disease?

  • Anti tissue transglutaminase (IgA)
  • Anti endomysial (IgA)

197

What autoantibody is associated with congenital heart block in infants of mothers with SLE?

Anti-Ro antibody

198

What autoantibody is associated with dermatitis herpetiformis?

Anti-endomysial antibody (IgA)

199

What autoantibody is associated with dermatomyositis?

Anti-Jo-1 (tRNA synthetase)

200

What autoantibody is associated with diffuse cutaneous scleroderma?

Antibodies to topoisomerase/Scl70, Rna Pol I, II, III, fibrillarin (nucleolar pattern)

201

What autoantibody is associated with Goodpasture's syndrome?

Anti-GBM antibody

202

What autoantibody is associated with Grave's disease?

Anti-TSH receptor antibody

203

What autoantibody is associated with Hashimoto's thyroiditis?

Antibodies to thyroglobulin and thyroperoxidase

204

What autoantibody is associated with Limited cutaneous scleroderma (CREST)?

Anti centromere antibody

205

What autoantibody is associated with microscopic polyangiitis (MPA)?

Perinuclear/protoplasmic-staining anti neutrophil cytoplasmic antibodies (pANCA)

206

What autoantibody is associated with mixed connective tissue disease?

Anti-U1RNP antibody (speckled pattern)

207

What autoantibody is associated with myasthenia gravis?

Anti-Ach receptor antibody

208

What autoantibody is associated with pernicious anaemima?

Antibody to gastric parietal cells (90%) and intrinsic factor (10%)

209

What autoantibody is associated with polymyositis?

Anti-Jo-1 (tRNA synthetase)

210

What autoantibody is associated with primary biliary cirrhosis?

Anti-mitochondrial antibody

211

What autoantibody is associated with rheumatoid arthritis?

Anti-CCP antibodies

Rheumatoid factor (less specific)

212

What autoantibody is associated with Sjogren's syndrome?

Anti-Ro

Anti-La (speckled pattern)

60-70% Rheumatoid factor positive

213

What autoantibody is associated with SLE?

  • dsDNA
  • Histones (homogenous)
  • Ro
  • La
  • Sm
  • U1RNP (speckled)

214

What autoantibody is associated with type 1 diabetes mellitus?

Antibodies to glutamate decarboxylase and beta cells

215

What autoantibody is associated with Wegener's granulomatosis (GPA)?

Cytoplasmic antineutrophil cytoplasmic antibodies (cANCA)

216

What is the target of anti T cell monoclonal antibodies?

Resting T cells

217

Which immune therapies target T cell proliferation (involving IL-2)?

Antiproliferative agents

Inhibitors of cell signalling

Corticosteroids

218

Which immune therapies target the effector functions of T cells e.g. production of TNFalpha + antibodies from B cells?

  • Anti TNFalpha monoclonal antibodies
  • Anti-IL-12/23 monoclonal antibodies
  • Plasmaphoresis
  • Corticosteroids

219

How would you choose a regime to suppress T Cells?

One from each group:

  • Inhibitors of cell signalling (tacrolimus, ciclosporin)
  • Antiproliferative agents (azathioprine, mycophenolate mofetil, methotrexate, cyclophosphamide)
  • Blocker of cytokine production (prednisolone)

220

What are some examples of anti-T cell monoclonal antibodies?

Muromonab CO3

Basiliximab

Tocilizumab

Abatacept

221

What are some examples of anti-proliferative agents?

Cyclophosphamide

Mycophenolate mofetil

Azathioprine

222

What are some examples of inhibitors of cell signalling?

Tacrolimus

Ciclosporin

Sirolimus

223

What is infliximab?

An anti-TNFalpha monoclonal antibody

224

What is uskekinumab?

An anti-IL-12/23 monoclonal antibody

225

Muromonab CD3:

  1. Method of action
  2. Indications
  3. Side effects

Muromonab CD3:

  1. Method of action - blocks CD3 on T cells
  2. Indications - for active rejection
  3. Side effects - fever, leucopenia

226

Basiliximab:

  1. Method of action
  2. Indications
  3. Side effects

Basiliximab:

  1. Method of action - blocks CD25 (alpha chain of IL-2 receptor)
  2. Indications - prevents rejection in transplantation
  3. Side effects - GI disturbance

227

Tocilizumab:

  1. Method of action
  2. Indications
  3. Side effects

Tocilizumab:

  1. Method of action - blocks IL-6 receptor
  2. Indications - Rheumatoid arthritis if anti TNF drugs have failed
  3. Side effects - infections

228

Abatacept:

  1. Method of action
  2. Indications
  3. Side effects

Abatacept:

  1. Method of action - anti CTLA4 Ig, blocks co stimulation of T cells
  2. Indications - rheumatoid arthritis if anti TNF drugs have failed
  3. Side effects - infections and cough

229

Cyclophosphamide:

  1. Method of action
  2. Indications
  3. Side effects

Cyclophosphamide:

  1. Method of action - akylates guanine base of DNA, affects B > T cells
  2. Indications - multi system connective tissue disease e.g. SLE and cancer
  3. Side effects - hair loss, bone marrow suppression, sterility, haemorrhagic cystitis

230

Mycophenolate mofetil:

  1. Method of action
  2. Indications
  3. Side effects

Mycophenolate mofetil:

  1. Method of action - blocks de novo nucleotide synthesis, affects T>B cells
  2. Indications - autoimmune disease, vasculitis, transplantation
  3. Side effects - bone marrow suppression, herpes

231

Azathioprine:

  1. Method of action
  2. Indications
  3. Side effects

Azathioprine:

  1. Method of action - metabolised to 6-mercaptopurine in the liver, blocks de novo purine synthesis
  2. Indications - inflammatory and autoimmune diseases, transplantation
  3. Side effects - bone marrow suppression (measure TPMT), hepatotoxicity

232

Tacrolimus:

  1. Method of action
  2. Indications
  3. Side effects

Tacrolimus:

  1. Method of action - inhibits calcineurin which norally activates the transcription of IL-2, therefore decreases IL-2
  2. Indications - mainly rejection prophylaxis in transplantation
  3. Side effects - diabetes

233

Ciclosporin:

  1. Method of action
  2. Indications
  3. Side effects

Ciclosporin:

  1. Method of action - inhibits calcineurin which norally activates the transcription of IL-2, therefore decreases IL-2
  2. Indications - mainly rejection prophylaxis in transplantation
  3. Side effects - gingival hypertrophy

234

Sirolimus:

  1. Method of action
  2. Indications

Sirolimus:

  1. Method of action - blocks clonal proliferation
  2. Indications - mainly rejection prophylaxis in transplantation

235

Infliximab:

  1. Method of action
  2. Indications
  3. Side effects

Infliximab:

  1. Method of action - binds to TNF alpha
  2. Indications - psoriasis, Crohn's, rheumatoid arthritis, others
  3. Side effects - TB, lymphoma, autoimmune phenomena

236

Uskekinumab:

  1. Method of action
  2. Indications
  3. Side effects

Uskekinumab:

  1. Method of action - binds to p40 subunit of IL-12 and IL-23
  2. Indications - psoriasis
  3. Side effects - infections and cough

237

What is the method of action of prednisolone?

Inhibits phospholipase A2:

  • Decreases platelet activating factor
  • Decreases arachidonic acid
  • Decreases trafficking of phagocytes (hence transient increase in phagocyte count)

 

Lymphopenia, apoptosis of T + B cells, decreased antibodies

238

What are the indications for prednisolone?

Used as anti inflammatory and in autoimmune disease

239

What are the side effects of prednisolone?

  • Diabetes
  • Central obesity
  • Adrenal suppression
  • Cataracts
  • Glaucoma
  • Pancreatitis
  • Osteoporosis
  • Moon face
  • Acne
  • Hirsutism
  • Neutrophilia

240

What happens in plasmaphoresis?

Each time, 50% of patient's plasma is replaced with donor's

241

What are the indications for plasmapharesis?

Goodpasture's

Myasthenia 

Antibody mediated rejection

242

What are the side effects of plasmapharesis?

Reboud antibody production limits its efficacy

243

What does rituximab do and what is it used for?

Anti CD20 - so decreases B cells (not plasma cells).  Used for lymphoma and autoimmune disease

244

What does methotrexate do and what is it used for?

Inhibits dihydrofolate reductase (DHFR) and therefore decreases DNA synthesis. Used in autoimmune disease e.g. RA, psoriasis, Crohn's etc.  Also used in chemotherapy and as an abortifacent

245

What are the main side effects of methotrexate?

Teratogenicity and hepatotoxicity

246

What does alemtuzumab (Campath) do and what is it used for?

Monoclona antibody that binds to CD52 found on lymphocytes, resulting in depletion.  OFten used in CLL and a new variant is being used for multiple sclerosis.

247

What is a side effect of alemtuzumab?

Increased susceptibility to CMV infection

248

What does natalizumab do and what is it used for?

Anti alpha-4 integrin; used in MS and Crohn's

249

Which polymorphism leaves someone unable to metabolise azathioprine?

TPMT polymorphism

250

What are the 4 main ways to boost the immune system?

  1. Vaccination
  2. Human normal immunoglobulin
  3. Specific immunoglobulin (passive vaccination)
  4. Recombinant cytokines

251

What is human normal immunoglobulin and how is it given?

From >1000 donors who have been screened for HIV, Hep B and hep C, it contains preformed IgG against a full range of organisms.

Given every 3-4 weeks, the half life is 18 days.

252

What is human normal immunoglobulin used for?

Primary antibody deficiencies (CVID, Brutons etc), secondary deficiencies (CLL, multiple myeloma, BMT), and passive vaccination

253

What are some of the diseases you can get specific immunoglobulins for?

Ravies, varicella zoster, hep B, tetanus

254

What is the use of recombinant cytokines?

Boost immune response to cancer and some pathogens

255

What are some examples of recombinant cytokines?

  • Interferon alpha
  • Interferon beta
  • Interferon gamma

256

What is interferon alpha given for?

  • Hepatitis C, hepatitis B
  • Kaposi sarcoma
  • Hairy cell leukaemia, chronic myelogenous leukaemia, malignant myeloma

257

What is interferon beta given for?

  • Relapsing MS
  • Mechanism of action is not known

258

What is interferon gamma given for?

Chronic granulomatous disease

259

How does allergen desensitisation work?

  • Supervised administration of an allergen, starting with a tiny dose and escalating every week until maximal dose reached
  • Maintenance dose given monthly for 3-5 years
  • Reduces clinical symptoms of monoallergic disorders

260

What allergies does allergen desensitisation work for? Which is it not very good for?

Bee and wasp venom, grass pollen, house dust mite.  Not good for food, latex

261

What are the advantages and disadvantages of allergen desensitisation?

Good: only treatment that alters the natural course of disease and reduces clinical symptoms

Bad: costly, laborious and risk of severe adverse reaction

262

What is HIV?

An RNA virus that targets CD4+ T helper cells as hosts (also CD4+ monocytes and dendritic cells)

263

What does the HIV virus bind to?

gp120 (initial binding)

gp41 (conformational change)

Most strains use CCR5 and CXCR4 chemokine co receptors

264

What comprises the innate response to HIV?

  • Non specific activation of macrophages, NK cells and complement
  • Stimulation of dendritic cells via TLR
  • Release of cytokines and chemokines

265

What comprises the adaptive response to HIV?

  • Neutralising antibodies: anti-gp120 and anti-gp41
  • Non-neutralising antibodies: anti-p24 gag IgG
  • CD8+ T cells can prevent HIV entry by producing chemokines MIP-Ia, and RANTES which block co receptors

266

How does HIV damage the immune response?

  • Remains infectious even when antibody coated
  • Atibated infected CD4+ helper T cells are killed by CD8+ T cells
  • CD4 T cell memory is lost and there is failure to activate memory CTL 
  • Monocytes and dendritic cells are therefore not activated by the CD4+ T Cells and cannot prime naïve CD8+ CTL (due to impaired antigen presenting functions)
  • Infected monocytes and dendritic cells are killed by virus or CTL
  • Quasispecies are produced by error prone reverse transcriptatse -> these escape from the immune response

267

What are the 7 stages in the life cycle of HIV?

  1. Attachment/entry
  2. Reverse transcription and DNA synthesis
  3. Integration
  4. Viral transcription
  5. Viral protein synthesis
  6. Assembly of virus and release of virus
  7. Maturation

268

What is the median time from infecrtion to development of AIDS?

8-10 years

269

How many HIV patients are 'rapid progressors' and how long do they take to develop AIDS?

10% - takes 2-3 years

270

How many HIV patients are 'long term non-progressors' and what does this mean?

<5% - stable CD4 counts and no symptoms after 10 years

271

What measure predicts disease progression in HIV?

The initial viral burden (set point)

272

How is HIV diagnosed?

Screening test - detects anti-HIV Ab via ELISA

Confirmation test detects Ab via Western Blot, but requires the patient to have seroconverted (started to produce Ab), which happens after a ~10 week incubation period

273

What tests should you do in HIV after diagnosis?

  • Viral load - with PCR to detect viral RNA
  • CD4 count via FACS (flow cytometry), used to assess course of disease, and onset of AIDS correlates with diminuation of number of CD4+ T Cells
  • Resistance testing - to antiretrovirals, done with phenotypic and genotypic assays

274

What CD4 count defines AIDS?

<200 cells/mL blood

275

When should you start treatment for HIV?

  • CD4 <200
  • Patient is symptomatic
  • Start thinking about it when CD4<350

276

What is HAART?

2 NRTIs and one PI (or NNRTI) e.g. emtricitabine + tenofovir + efavirenz

277

What ARV should you give in pregnancy?

Zidovudine - antepartum PO, IV for delivery.

PO to newborn for 6/52, reduces transmission from 26% to 8%

278

What are the limitations of HAART?

  • Doesn't eradicate latent HIV-1
  • Fails to restore HIV specific T cell responses
  • Toxicities
  • High pill burden
  • Adherence
  • Threat of drug resistance
  • QoL
  • Cost

279

What are two classes of HIV drugs that target the docking process?

Fusion inhibitors

Attachment inhibitors

280

Give an example of an HIV drug which is a fusion inhibitor, as well as its side effects

Enfuvirtide - local reactions to infections, hypersensitivity (0.1-1%)

281

What is an example of an HIV drug which is an attachment inhibitor?

Maravirox

282

What are some examples of NRTIs?

Zidovudine

Didanosine

Stavudine

Lamivudine

Zalcitabine

Abacavir

Emtricitabine

Epzicom

Combivir

Trizivir

283

What are the side effects of NRTIs?

  • Generally rare
  • Fever
  • Headache
  • GI disturbance
  • BMS (zidovudine)
  • peripheral neuropathy (zalcitabine, stavudine)
  • Mitchondrial toxicity (stavudine)
  • Hypersensitivity (abacavir)

284

What kind of drug is tenofovir?

Nucleotide RTI

285

What are the side effects of tenofovir?

bone and renal toxicity

286

What are some examples of non-NRTIs and their side effects?

  • Nevirapine - hepatitis and rash
  • Delavirdine - rash
  • Efavirenz - CNS effects

287

What are some examples of integration inhibitor HIV drugs?

Raltegravir

Elvitegravir

288

What are some examples of HIV drugs which are protease inhibitors?

  • Indinavir
  • Nelfinavir
  • Ritonavir
  • Amprenavir
  • Fosamprenavir
  • Lopinavir
  • Atazanavir
  • Saquinavir

289

What are the side effects of protease inhibitors?

  • Hyperlipidaemias
  • Fat redistribution
  • Type 2 diabetes

290

What are the 3 stages of transplant refection?

  1. Recognition
  2. Activation
  3. Effector function

291

Which antigens are recognised in transplant rejection?

  • HLA - A, B, DR
  • Minor HLA - other polymorphic self peptides
  • ABO blood antigens

292

What are the two types of rejection?

  • Direct: donor APC presenting antigen and/or MHC to recipient T Cells; acute rejection mainly invovles direct presentation
  • Indirect: recipient APC presenting donor antigen to recipient T cells i.e. the immune system working normally, as it would for an infection 

293

Which type of rejection (presentation) does chronic rejection usually involve?

Indirect

294

Hyperacute transplant rejection:

  • Time - 
  • Mechanism - 
  • Pathology - 
  • Treatment - 

Hyperacute transplant rejection:

  • Time - mins-hours
  • Mechanism - preformed Ab which activates complement
  • Pathology - thrombosis and necrosis
  • Treatment - prevention: cross match

295

Acute cellular transplant rejection:

  • Time - 
  • Mechanism - 
  • Pathology - 
  • Treatment - 

Acute cellular transplant rejection:

  • Time - weeks-months
  • Mechanism - CD4 activating a type IV reaction
  • Pathology - cellular infiltrate
  • Treatment - T cell immunosuppression

296

Acute antibody mediated transplant rejection:

  • Time - 
  • Mechanism - 
  • Pathology - 
  • Treatment - 

Acute antibody mediated transplant rejection:

  • Time - weeks-months
  • Mechanism - B cell activation; antibody attacks vessels
  • Pathology - vasuclitis, C4d
  • Treatment - Ab removal and B cell immunosuppression

297

Chronic transplant rejection:

  • Time - 
  • Mechanism - 
  • Pathology - 
  • Treatment - 

Chronic transplant rejection:

  • Time - months-years
  • Mechanism - immune and non immune mechanism
  • Pathology - fibrosis 
  • Treatment - minimise organ damage

298

Graft versus host disease:

  • Time - 
  • Mechanism - 
  • Pathology - 
  • Treatment - 

Graft versus host disease:

  • Time - days-weeks
  • Mechanism - donor cells attacking host
  • Pathology - skin (rash), gut (D+V, bloody stool), liver (jaundice)
  • Treatment - prevention/immunosuppression, corticosteroids

299

What needs to be done to match a transplant?

  • Determine donor and recipient blood group and HLA type - using PCR, and maximise similarity
  • Check recipient's pre formed Ab against ABO and HLA via CDC (complement dependent cytotoxicity) and FACS (flow cytometry), and luminex (like solid phase FACS to pick up Abs to individual HLAs)
  • Cross match via CDC and FACS; tests if serum from recipient is able to bind/kill donor lymphocytes - positive crossmatch is a contraindication for transplantation
  • After transplant check again for new antibodies against the graft

300

Other than matching the transplant, what can you do to prevent rejection?

  • Pre transplant induction agent to suppress T cell responses e.g. anti CD52 (alemtuzumab) or anti CD25 (basiliximab)
  • Use immunosuppressants post transplant to reduce rejection e.g. CNI and MMF
  • Treat episodes of acute rejection:
    • Cellular: steroids, IVIG
    • Antibody mediated: IVIG, plasma exchange, anti-C5

301

What are the post-transplant complications (other than rejection)?

  • Infection:
    • Increased risk of conventional infections
    • Opportunistic infections: CMV, BK virus, pneumocystis carinii
  • Malignancy 
    • Viral associated (x100): Kaposi's sarcoma (HHV8), lymphoproliferative disease (EBV)
    • Skin cancer x20
    • Other cancers e.g. lung, colon x2-3
  • Atherosclerosis
    • Hypertension, hyperlipidaemia
    • x20 increased risk of death from MI compared to age-matched general population

302

What is in the UK vaccination programme?

  • 2 months: DTaP/IPV/Hib/PCV/MenB
  • 3 months: DTaP/IPV/Hib/Men C/Men B/rotavirus
  • 4 months: DtaP/IPV/Hib/PCV/MMR
  • 12-13 months:Hib/MenC/PCV/MMR/MenB
  • 3 years 4 months: DTaP/IPV/MMR
  • 13-18 years:DT/IPV
  • Girls aged 12-13 years: HPV

303

What vaccinations are given to at risk groups in the UK?

  • Anthrax
  • Hep A
  • Hep B
  • Men ACWY
  • Rabies
  • Varicella if not immune
  • BCG (babies in high prevalence areas, HCWs)

304

What vaccinations should travellers from the UK consider?

  • Cholera
  • Hep A
  • Hep B
  • Japanese encephalitis
  • Tick born encephalitis
  • Typhoid
  • Yellow fever

305

Where are central memory T cells found and what do they do?

  • Lymph nodes and tonsils - roll along and extravasate in High Endothelial Venules (HEVs)
  • CCR7+ and CD62L+ allow entry via HEVs to lymph nodes
  • Produce IL-2 to support other cells
  • More central memory in CD4 population

306

Where are effector memory T cells found and what do they do?

  • Liver, lungs and gut
  • CCR7 -ve and CD62 low, therefore not found in lymph nodes
  • Effector - produce perforin and IFN gamma
  • More effector memory in CD8 population

307

What is the function of CCR7?

Binds CCL19 and CCL21 present on the luminal surface of endothelial cells in lympho nodes, which causes firm arrest and the initiation of extravasation

308

What is the function of CD62L?

Interacts with a molecule in HEV, which mediates attachment and rolling

309

What do B memory cells do?

Can differentiate into long lived plasma cells, which produce:

  • Quicker response
  • More antibodies
  • Higher affinity antibodies
  • More IgG
  • Generally better antibodies

310

What response do T helper cells produce?

  • Th1: cell mediated - involves cytokines IL-2, IFN gamma, TNF
  • Th2: humoral response, involves cytokines IL-4, IL-5, IL-6

311

What are the advantages of live vaccines?

  • Lifelong immunity with no booster required
  • Immune response to several antigens and protection against cross reactive strains

312

What are the disadvantages of live vaccines?

  • Careful in immunodeficient pateitns
  • Reversion to virulence
  • Harder to store

313

What are some examples of live vaccines?

  • Sabin polio (oral - no longer used)
  • MMR
  • Varicella
  • Yellow fever
  • BCG 
  • Typhoid

314

What are the advantages of inactivated vaccines?

  • Easy to store
  • Cheaper
  • Safe in ID patients
  • No mutation/reversion
  • Can eliminate wild-type virus from the community

315

What are the disadvantages of inactivated vaccines?

  • Poorer and hosrter immunity
  • Repeated boosters, adjuvants to combat this

316

What are the four different kinds of inactivated vaccines and examples of them?

  • Inactivated - salk (polio), anthrax, cholera, bubonic plague, Hep A, rabies, pertussis
  • Component - Hep B (HbS antigen), HPV (capsid), influenza (haemagglutinin, neuraminidase)
  • Conjugate - tetanus (exotoxin), Hib
  • Toxoid - diphtheria, tetanus

317

What is the point of adjuvants in vaccines?

They increase the immune response without altering the specificity of it

318

How does alum work as an adjuvant and why is it a good adjuvant?

  • Provides slow release antigen to help prime the immune response
  • Activates Gr1+ cells to produce IL-4 -> helps prime naive B cells
  • Generally safe, and mild, so is commonly used

319

What is CpG and how does it work as an adjuvant?

  • Unmethylated motif with 2 purines at the 5' end and 2 pyrimidines at the 3' end
  • Acts as an immunostimulatory adjuvant
  • Activates TLRs on APCs stimulating expression of costimulatory molecules

320

What is Complete Freund's adjuvant and what is it used for?

Water-in-oil emulsion containing mycobacterial cell wall components - mainly for animals, painful in humans

321

What is ISCOMS (immune staining complex)?

Experimental multimeric antigen with adjuvant built in

322

What is HBIG?

Hep B immunoglobulin

323

What is HRIG?

Human rabies immunoglobulin

324

What is HNIG?

Human normal immunoglobulin - Hep A and measles

325

What is daviluzimab?

Monoclonal antibody for RSV

326

How is the mantoux test done?

  • Inject 0.1ml of 5 tuberculin units intradermally, examine arm 48-72 hours later
  • Positive result is indicated by redness and an induration (swelling that can be felt) of at least 10mm in diameter
  • Implies previous exposure to tuberculin protein - could represent previous BCG exposure