Immunology Flashcards
(326 cards)
1
Q
Which immune deficiency is this?CD4: lowCD8: lowB cells: normal or lowIgM: normal or lowIgG: lowIgA: low
A
SCID
2
Q
Which immune deficiency is this?CD4: lowCD8: lowB cells: normalIgM: normalIgG: low
A
DiGeorge
3
Q
Which immune deficiency is this?CD4: lowCD8: normalB cells: normalIgM: normalIgG: low
A
BLW
4
Q
Which immune deficiency is this?CD4: normalCD8: normalB cells: lowIgM: lowIgG: lowIgA: low
A
Bruton’s
5
Q
Which immune deficiency is this?CD4: normalCD8: normalB cells: normalIgM: highIgG: lowIgA: low
A
HyperIgM
6
Q
Which immune deficiency is this?CD4: normalCD8: normalB cells: normalIgM: normalIgG: normalIgA: low
A
Selective IgA deficiency
7
Q
Which immune deficiency is this?CD4: normalCD8: normalB cells: normalIgM: normal or lowIgG: lowIgA: low
A
CVID
8
Q
Which immune deficiency is this?Neutrophil count - absentLeukocyte adhesion markers - normalNitroblue test of oxidative killing - absentPus - no
A
Kostmann syndrome (congenital neutropenia)
9
Q
Which immune deficiency is this?Neutrophil count - normalLeukocyte adhesion markers - normalNitroblue test of oxidative killing - abnormalPus - yes
A
Chronic granulomatous disease
10
Q
Which immune deficiency is this?Neutrophil count - increased during infectionLeukocyte adhesion markers - absentNitroblue test of oxidative killing - normalPus - no
A
Leukocyte adhesion deficiency
11
Q
What are the consequences of T cell deficiencies?
A
Increased susceptibility to viral, fungal and some bacterial infections. Early malignancy.
12
Q
What is the treatment for T Cell deficiencies?
A
Infection prophylaxisIg replacement if necessarySpecific other treatments
13
Q
What is bare lymphocyte syndrome?
A
Defect of regulatory factor X or Blass II transactivator. Absent expression of HLA molecules within the thymus -> lymphocytes fail to develop.
14
Q
What are the 2 types of Bare Lymphocyte Syndrome?
A
Type I - MCH I absent - low CD8 cellsType II - MCH II absent - low CD4 cells
15
Q
Which type of bare lymphocyte syndrome is more common and what are its features?
A
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
Q
What is bare lymphocyte syndrome associated with?
A
Sclerosing cholangitis
17
Q
When do children with bare lymphocyte syndrome become unwell?
A
By 3 months of age
18
Q
What is DiGeorge’s Syndrome?
A
Impaired development of the 3rd and 4th pharyngeal pouches (oesophagus, thymus, heart)
19
Q
What ist he cause of DiGeorge’s Syndrome?
A
22q11.2 deletion - 75% are sporadic
20
Q
What are the features of DiGeorge’s syndrome?
A
Low set ears, cleft lip and palateLow calciumSusceptible to viral infectionVery low numbers of mature T cells due to absent thymus
21
Q
How is DiGeorge’s syndrome treated?
A
Thymus transplant
22
Q
What are the consequences of B cell deficiencies?
A
Increased susceptibility to bacterial and some viral infections and toxins e.g. tetanus, diphtheria
23
Q
What is the treatment for B cell deficiency?
A
Ig replacementBone marrow transplant in some situationsVaccination not effective except in IgA deficiency
24
Q
What causes Bruton’s agammaglobulinaemia and what are its features?
A
X linked tyrosine kinase defectMutation in BTK geneFailed production of mature B cellsNo antibodies Symptoms after 3-6 months
25
What is the cause/defect in Hyper IgM syndrome?
X linked condition - Xq26CD40L, 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 thriveRecurrent infectionsAutoimmunityGranulomatous 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 antibodiesRecurrent 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 threateningHigh 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 moleculeLAD2 - 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 peroxideDihydrorhodamine 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:PseudomonasListeriaAspergillusCandidaE coliStaph aureusSerratia
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 BCGUnable to form granulomata
65
What is the most severe form of SCID?
Reticular dysgenesis
66
What is deficient in reticular dysgenesis?
Absolute deficiency in:NeutrophilsLymphocytesMonocytes/macrophagesPlatelets
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 pneumoniaGroup B strepHaemophilus influenzaNeisseria 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, pneumoniaMay 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?
VaccinationProphylactic antibioticsHigh levels of suspicionScreen 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 dermatitisFood allergyOral allergy syndromeLatex fruit/food syndromeAllergic rhinitisAcute 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 mucosaSkin prick test and RAST
113
How is allergic rhinitis treated?
Allergen avoidanceAntihistamineSteroid nasal spraySodium cromoglycate eye dropsOral steroidsIpratropium nasal sprayGrass pollen desensitisation
114
What is the allergen in acute urticaria?
50% idiopathic50% 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?
PeanutPenicillinStingsLatex
120
Which allergens cause non-IgE mediated mast cell degranulation in anaphylaxis?
NSAIDsIV contrastOpioidsExercise
121
What is the management for anaphylaxis?
Elevate legs100% oxygenIM adrenaline 500mcgInhaled bronchodilatorsHydrocortisone 100mg IVChlorphenamine 10mg IVIV fluidsSEEK HELP
122
How is a skin prick test done?
Positive control = histamineNegative control = diluentPositive test is a wheal ≥2mm greater than the negative controlDiscontinue 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 tryptatePeak 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 newbornAutoimmune haemolytic anaemia (+ ITP = Evans' syndrome)Autoimmune thrombocytopenic purpuraGood pasture's syndromePemphigus vulgarisGraves diseaseMyasthenia gravesAcute rheumatic feverPernicious anaemiaChurg-Strauss syndrome (eGPA)Wegener's granulomatosisMicroscopic polyangiitisChronic urticaria
134
Haemolytic disease of the newborn:Antigen = Pathology = Diagnosis is made by = Treatment is =
Haemolytic disease of the newborn:Antigen = on neonatal erythrocytesPathology = maternal IgG mediated reticulocytosis and anaemiaDiagnosis is made by = positive direct Coombs testTreatment 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 AgPathology = Destruction of RBCs by autoantibody + complement + FcR + phagocytes, anaemiaDiagnosis is made by = Positive direct Coombs test, anti red cell AbTreatment is = steroids
136
Autoimmune thrombocytopenic purpura:Antigen = Pathology = Diagnosis is made by = Treatment is =
Autoimmune thrombocytopenic purpura:Antigen = Glycoprotein IIb/IIIa on plateletsPathology = bruising/bleeding (purpura)Diagnosis is made by = anti-platelet antibodyTreatment 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 IVPathology = glomerulonephritis, pulmonary haemorrhageDiagnosis is made by = anti GBM Ab, linear smooth IF staining of IgG deposits on BMTreatment is = corticosteroids and immunosuppression
138
Pemphigus vulgaris:Antigen = Pathology = Diagnosis is made by = Treatment is =
Pemphigus vulgaris:Antigen = epidermal cadherinPathology = Non-tense blistering of the skin and bullaeDiagnosis is made by = direct immunofluorescence showing IgGTreatment is = Corticosteroids and immunosuppression
139
Graves disease:Antigen = Pathology = Diagnosis is made by = Treatment is =
Graves disease:Antigen = TSH receptorPathology = hyperthyroidismDiagnosis is made by = Anti-TSH-R AbTreatment is = carbimazole and propylthiouracil
140
Myasthenia gravis:Antigen = Pathology = Diagnosis is made by = Treatment is =
Myasthenia gravis:Antigen = acetylcholine receptorPathology = Fatiguable muscle weakness, double visionDiagnosis is made by = Anti-Ach-R Ab, abnormal EMG, tension testTreatment 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 strepPathology = myocarditis, arthritis, Sydenham's choreaDiagnosis is made by = clinical, based on Jones criteriaTreatment is = aspirin, steroids and penicillin
142
Pernicious anaemia:Antigen = Pathology = Diagnosis is made by = Treatment is =
Pernicious anaemia:Antigen = intrinsic factor and gastric parietal cellsPathology = low Hb, low B12 Diagnosis is made by = anti-gastric parietal cell Ab, anti-IF Ab, Schilling testTreatment 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 vasculitisPathology = allergy -> asthma -> systemic disease (male predominancE)Diagnosis is made by = pANCA against myeloperoxidase, granolas, eosinophil granulocytesTreatment is = prednisolone, azathioprine, cyclophosphamide
144
Wegener's granulomatosis:Antigen = Pathology = Diagnosis is made by = Treatment is =
Wegener's granulomatosis:Antigen = medium and small vessel vasculitisPathology = sinus problems, lung cavitation and haemorrhage, crescentic glomerulonephritisDiagnosis is made by = cANCA against proteinase-3, granulomasTreatment is = corticosteroids, cyclophosphamide, cotrimoxazole
145
Microscopic polyangiitis:Antigen = Pathology = Diagnosis is made by = Treatment is =
Microscopic polyangiitis:Antigen = pauci-immune necrotising small vessel vasculitisPathology = purpura, lived, many different organs affectedDiagnosis is made by = pANCA against myeloperoxidaseTreatment 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, idiopathicPathology = 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 testingTreatment 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 cryoglobulinaemiaSerum sicknessPolyarteritis nodosaSystemic lupus erythematosus
149
Mixed essential cryoglobulinaemia:Antigen = Pathology = Diagnosis is made by = Treatment is =
Mixed essential cryoglobulinaemia:Antigen = IgM against IgG +/- hep C antigensPathology = Joint pain, splenomegaly, skin, nerve and kidney involvement, associated with hep CDiagnosis is made by = Mixture of clinical biopsiesTreatment 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 inflammationTreatment 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 antigensPathology = fever, fatigue, weakness, arthralgia, skin, nerve and kidney involvement, pericarditis and MI, associated with Hep BDiagnosis 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, RNPPathology = 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?
T1DMMSRheumatoid arthritisContact dermatitisMantoux testCrohn'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 destructionDiagnosis is made by = blood glucose, ketonuria, glutamate decarboxylase antibodies, islet cell antibodiesTreatment 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 lesionsDiagnosis is made by = CSF shows oligoclonal bands of IgG on electrophoresisTreatment 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 membranePathology = chronic arthritis, rheumatoid nodules, lung fibrosisDiagnosis is made by = X ray, rheumatoid factor (85% sensitive), anti CCP (95% specific), increased ESR, increased CRPTreatment is = analgesia, steroids, DMARDsIs 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, nickelPathology = dermatitis with usually short lived itching, blisters and wheals Diagnosis is made by = clinical or use patch testTreatment is = if no resolution use corticosteroids or antihistamines
160
Mantoux test:Antigen = Pathology =
Mantoux test:Antigen = tuberculinPathology = 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 anusTreatment is = antibiotics, anti-inflammatory drugs, e.g. mesalazine, TNF alpha antagonists, e.g. infliximab, steroids
162
HLA ASSOCIATIONS: ankylosing spondylitisSusceptibility allele = Relative risk (fold) =
HLA ASSOCIATIONS: ankylosing spondylitisSusceptibility allele = HLA B27Relative risk (fold) = 87
163
HLA ASSOCIATIONS: Goodpasture's syndromeSusceptibility allele = Relative risk (fold) =
HLA ASSOCIATIONS: Goodpasture's syndromeSusceptibility allele = HLA DR15/DR2Relative risk (fold) = 10
164
HLA ASSOCIATIONS: Grave's diseaseSusceptibility allele = Relative risk (fold) =
HLA ASSOCIATIONS: Grave's diseaseSusceptibility allele = HLA DR3Relative risk (fold) = 4
165
HLA ASSOCIATIONS: SLESusceptibility allele = Relative risk (fold) =
HLA ASSOCIATIONS: SLESusceptibility allele = HLA DR3Relative risk (fold) = 6
166
HLA ASSOCIATIONS: Type 1 diabetesSusceptibility allele = Relative risk (fold) =
HLA ASSOCIATIONS: Type 1 diabetesSusceptibility allele = HLA-DR3/DR4Relative risk (fold) = 25
167
HLA ASSOCIATIONS: Rheumatoid arthritisSusceptibility allele = Relative risk (fold) =
HLA ASSOCIATIONS: Rheumatoid arthritisSusceptibility allele = HLA-DR4Relative 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)?
CalcinosisRaynaud'sOesophageal dysmotilitySclerodactylyTelangiectasiaand primary pulmonary hypertensionSkin 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 + GITInterstitial pulmonary diseaseRenal problems
174
What antibodies do you see in diffuse cutaneous scleroderma?
Anti-topoisomerase/Scl70RNA Pol I, II, IIIFibrillarin
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 = 1:9Onset in late 40s
177
What are the features of Sjogren's syndrome?
Xerostomia (dry mouth)Keratoconjunctivitis siccaNose and skin involvementMay affect kidneys, blood vessels, lungs, liver, pancreas, PNSMay 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 dysregulationPolyendocrinopathyEnteropathyX-linked inheritance syndrome+ autoimmune diseases
181
What are the features of IPEX syndrome?
Eczematous dermatitisNail dystrophyAutoimmune 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, fatigueIron, 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?
RoLaSmU1RNP
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 antibodiesRheumatoid factor (less specific)
212
What autoantibody is associated with Sjogren's syndrome?
Anti-RoAnti-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 agentsInhibitors of cell signallingCorticosteroids
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 CO3BasiliximabTocilizumabAbatacept
221
What are some examples of anti-proliferative agents?
CyclophosphamideMycophenolate mofetilAzathioprine
222
What are some examples of inhibitors of cell signalling?
TacrolimusCiclosporinSirolimus
223
What is infliximab?
An anti-TNFalpha monoclonal antibody
224
What is uskekinumab?
An anti-IL-12/23 monoclonal antibody
225
Muromonab CD3:
* Method of action
* Indications
* Side effects
Muromonab CD3:
* Method of action - blocks CD3 on T cells
* Indications - for active rejection
* Side effects - fever, leucopenia
226
Basiliximab:
* Method of action
* Indications
* Side effects
Basiliximab:
* Method of action - blocks CD25 (alpha chain of IL-2 receptor)
* Indications - prevents rejection in transplantation
* Side effects - GI disturbance
227
Tocilizumab:
* Method of action
* Indications
* Side effects
Tocilizumab:
* Method of action - blocks IL-6 receptor
* Indications - Rheumatoid arthritis if anti TNF drugs have failed
* Side effects - infections
228
Abatacept:
* Method of action
* Indications
* Side effects
Abatacept:
* Method of action - anti CTLA4 Ig, blocks co stimulation of T cells
* Indications - rheumatoid arthritis if anti TNF drugs have failed
* Side effects - infections and cough
229
Cyclophosphamide:
* Method of action
* Indications
* Side effects
Cyclophosphamide:
* Method of action - akylates guanine base of DNA, affects B > T cells
* Indications - multi system connective tissue disease e.g. SLE and cancer
* Side effects - hair loss, bone marrow suppression, sterility, haemorrhagic cystitis
230
Mycophenolate mofetil:
* Method of action
* Indications
* Side effects
Mycophenolate mofetil:
* Method of action - blocks de novo nucleotide synthesis, affects T>B cells
* Indications - autoimmune disease, vasculitis, transplantation
* Side effects - bone marrow suppression, herpes
231
Azathioprine:
* Method of action
* Indications
* Side effects
Azathioprine:
* Method of action - metabolised to 6-mercaptopurine in the liver, blocks de novo purine synthesis
* Indications - inflammatory and autoimmune diseases, transplantation
* Side effects - bone marrow suppression (measure TPMT), hepatotoxicity
232
Tacrolimus:
* Method of action
* Indications
* Side effects
Tacrolimus:
* Method of action - inhibits calcineurin which norally activates the transcription of IL-2, therefore decreases IL-2
* Indications - mainly rejection prophylaxis in transplantation
* Side effects - diabetes
233
Ciclosporin:
* Method of action
* Indications
* Side effects
Ciclosporin:
* Method of action - inhibits calcineurin which norally activates the transcription of IL-2, therefore decreases IL-2
* Indications - mainly rejection prophylaxis in transplantation
* Side effects - gingival hypertrophy
234
Sirolimus:
* Method of action
* Indications
Sirolimus:
* Method of action - blocks clonal proliferation
* Indications - mainly rejection prophylaxis in transplantation
235
Infliximab:
* Method of action
* Indications
* Side effects
Infliximab:
* Method of action - binds to TNF alpha
* Indications - psoriasis, Crohn's, rheumatoid arthritis, others
* Side effects - TB, lymphoma, autoimmune phenomena
236
Uskekinumab:
* Method of action
* Indications
* Side effects
Uskekinumab:
* Method of action - binds to p40 subunit of IL-12 and IL-23
* Indications - psoriasis
* 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'sMyasthenia 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?
* Vaccination
* Human normal immunoglobulin
* Specific immunoglobulin (passive vaccination)
* 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 symptomsBad: 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?
* Attachment/entry
* Reverse transcription and DNA synthesis
* Integration
* Viral transcription
* Viral protein synthesis
* Assembly of virus and release of virus
* 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?
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 ELISAConfirmation 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?
275
When should you start treatment for HIV?
* CD4
* Patient is symptomatic
* Start thinking about it when CD4
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 inhibitorsAttachment 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?
ZidovudineDidanosineStavudineLamivudineZalcitabineAbacavirEmtricitabineEpzicomCombivirTrizivir
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?
RaltegravirElvitegravir
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?
* Recognition
* Activation
* 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
