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Immunology Flashcards

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1
Q

Autoimmune pancreatitis - check for?

A

IgG4 levels

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2
Q

IgG4 disease vs PSC

A

Both can have cholestatic LFT’s and biliary strictures

IgG4 likely to also have pancreatic involvement

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3
Q

When does T cell development occur in thymus?

A

In utero - have naive T cells (CD4/CD8) at birth

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4
Q

Process that occurs in thymus cortex?

A

Positive selection
- Addition of T cell receptor (random through rearrangement
- Ensuring T cell can bind MHC
- Tagging with CD4 or CD8 depending on which MHC it binds

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5
Q

Process in thymus medulla
- Deficiency of AIRE?

A

Negative selection
- TEst T cells to ensure no autoreactivity and appropriate activity against foreign
- Transcription genese make self antigens
- AIRE makes insulin, cascin - deficiency = autoimmune polyendocrine syndromes

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6
Q

Signal 1

A

Naive T cell receptor binds antigen/MHC
Binding proteins and STOP signal

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7
Q

Signal 2 -

A

Costimulation

Initial activation - CD80/86 on APC binding to CD28. Then APC produces CD40 to bind to CD40ligand

Suppression - subsequent production on T cells of CTLA4, PD-1
- CTLA4 binds CD80/86 with higher affinity

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8
Q

CD40ligand deficiency - disease?

A

Hyper IgM syndrome

No CD40ligand on T cells, so ineffective class swiitching on B cells

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9
Q

FK506?

A

Tacrolimus

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10
Q

Signal 3

A

IL-2 binding to CD25 receptor causing T cell
- differentiation (subsets)
- entering cell cycle and proliferation

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11
Q

Role of calcineurin

A

Dephosphorylates NFAT, which is a transcription factor that stimulates IL-2 production

Blocks release of NFAT, so IL-2 cannot be released

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12
Q

MoA of mTOR inhibitors

A

Bind FK binding protein
Inhibit IL-2 action including CDK and cyclin production

Induce cell cycle arrest in G1/S

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13
Q

TH1
- target
- cytokines

A

Intracellular (virus), autoimmunity

TNFa, IFNy, IL-2

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14
Q

TH2
- target
- cytokines

A

Parasites + allergy

IL-4, IL-5, IL-13

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15
Q

TH17
- target
- cytokines

A

Extracellular bacteria/fungi. Recruits neutrophils

IL-17A, IL-17F

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16
Q

Treg
- Target
- Cytokines

A

Suppressess immune system

TGFb, IL-10

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17
Q

How are CD8 cells stimulated to proliferate?

A

Binding antigen on MHC1

TH1 cells producing IL-2, IL-12 and IFNy to stimulated CD8 proliferation

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18
Q

Mechanism of CD8 cells causing cell death

A

Stimulate to form perforins, targeted cell killing by inducing apoptosis

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19
Q

Functions of antibodies

A

Stimulate complement via classical pathway (IgM and IgG)

Recruit immune cells - opsonisation + phagocytosis, antibody dependant cellular cytotoxicity

Neutralise pathogens

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20
Q

Class of antibody determined by?

A

Heavy chain type

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21
Q

Which antibodies form B cell receptors

A

IgM
IgD

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22
Q

Chromosome for heavy chain?

A

Chromosome 14

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23
Q

Antibody diversity
- When does it happen
- How

A

Occurs in antigen independant in bone marrow

VDJ recombination until functional antibody formed

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24
Q

Allelic exclusion

A

After VDJ recombination, once functional Ab produced, DNA locked so B cell can ony make one Ab

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25
Immature B cell leaving BM characterised by?
IgM and IgD
26
Which antibody crosses placenta?
IgG
27
Which antibodies activate complement
IgM IgG
28
Which IgG subclass does not bind complement
IgG4
29
Function of IgA
Ab found in secretions - first point of defence in areas exposes to outside world
30
Function of IgE
Embed in mast cells (sensitising event) Can then be stimulated by re-exposure to antigen to cause mast cel degranulation
31
B2 cells - antigen dependant class switching process
B cell receptor binds antigen, displays on MHC 2 Co-stimulates CD4 cells, matures an forms subsets T cell subset produces different cytokines for class switching - TH1 --> IgG - TH2 --> IgE and IgA
32
B2 Somatic hypermutation
B cell receptor binds atigen, DNA uncocked, random mutations to produce higher affinity B cell receptor Highest affinity receptor selected, proliferates. Becomes: - Plasma cell - Memory cell - skips this process next time for faster immune response
33
B1 cells (t cell independant)
Can bind lipopolysaccharide antigens. Lie in marginal zones of spleen. Only produce IgM, provide limited immune response to encapsulated organisms
34
MAC components
C5b - C9
35
Common complement pathway componentns
All 3 pathways end in C3 convertase - converts C3 to c3a and c3b C3b can then also form C5 convertase - converts C5 to c5a and c5b
36
General principles of a and b in complement
A - inflammation (anaphylotoxin B - binds - opsonin or initiates mac
37
Classical pathway complement - Recognises? - Componenets
Immune complexes and damaged cells C1q, C1r, C1s C2 and C4 (C2 a and b)
38
Role of CRP
Activation of complmenet system
39
Lectin pathway - good at recognising?
MASPS Mannin (mannose binding lectin) - found on fungi Lectin - found on carbohydrate residues, encapsulate bacteria
40
Regulator of MAC
CD55 and CD59
41
Disease with lack of CD55 and CD59 - Features - Rx
PNH Haemolysis, VTE and organ ischaemia Eculizumab
42
Inhibition of factor C3b and C3 convertase
Factor I - C3b Factor H - C3 convertase
43
aHUS pathophys and ttraetment
Factor H and I deficiency, dysregulated alternative complement pathway Rx - Eculizumab
44
Pathophys and tests for C1 esterase deficienc
Lack of inhibition of bradykinin formation --> angio-oedema Tests - low C4, low C1 esterase, high C1 Rx - C1 esterase concentrate, bradykinin receptor antagonist
45
Antibody most potent activator of complement
IgM
46
IgA forms
Monomer plasma DImer external body surface
47
Complmenet responsible for opsonisation/opsonins
C3b
48
REgulators of alternative pathway
Factor H Factor I Properdin
49
Normal TOtal IG's Abnormal vaccination response
Specific antibody deficiency
50
Most common manifestation of 2nd immunodeficiency cause by chronic systemic steroid use
Bacterial bronchopneumonia
51
CVID malignancy highest risk
NHL
52
Recurrent infection with catalse positive bacteria
Staph, Burhilderia, Serratia, fungal Phagocyte deficiency --> Chronic granulomatous disease
53
Recurrent infections Bowel obstructions Early childhood
Chronic granulomatous disease
54
Test for CGD
Oxidative burst test - Dihydro rhodamine assay
55
Recurrent infections Food allergies Severe eczema
Hyper IgE syndrome
56
Hereditary angiooedema cf histamine mediated - timing -
Bradykinin - 48-96 hours No urticaria Non responsive to antihistamines, steroids, adrenaline
57
CR3/CR4 deficiency
Leukocyte adhesion deficiency Umbilical cord takes long time to fall off
58
CR3/CR4 deficiency
Leukocyte adhesion deficiency Umbilical cord takes long time to fall off
59
IL-5
Mepoluzimab
60
IL-5R
Benralizumab
61
IL4- Ra
Dupilumab
62
IgE
Omalizumab
63
Indications for desensitisation
Antibiotic - done in hospital Aeroallergin - allergic rhinitis, asthma
64
Contraindications for desensitisation
Type 3 or 4 SJS/TENS/AGEP
65
Cause of thunderstorm asthma
Rye grass
66
Contraindications to skin prick testing for IgE
Recent antihistamine use Dermatographism or serious skin condition
67
When to use allergen specific IgE
High risk anaphylaxis Specific allergen Recent antihistamines
68
Type 3 drug reactions - Cause - Presentations
Immune complex Serum sickness Vasculitis Lupus Nephritis
69
Type 2 drug reactions - Cause - Presentations
Antibody Low cell counts due to multiple drugs - AIHA - ITP - Agranulocytosis Also Anti-GBM
70
Strongest associated with fatal food anaphylaxis?
Poorly controlled asthma - bronchocosntriction greatest cause of mortality
71
Atopy vs sensitisation vs allerg
Atopy - genetic tendency to produce specific IgE for allergens Sensitisation - IgE production following allergen exposure Allergy - allergen specific IgE and symptoms following exposure
72
Persistent hypotension on Beta blocker
Give glucagon
73
Manageement of aspirin induced respiratory disease
Due to COX1 inhibition Avoid COX1 inhibitors Intranasal corticosteroids Oral monteleukast
74
Synthetic TLR7 agonist
Imiquimod
75
Most common presentation of IgG deficiency
Normal phenotype
76
Low C4 - which cryoglobulinaemia?
Type 2 and Type 3
77
When is varicella infectious What precautions
1-2 days before rash --> rash cursted over Droplet
78
VZV vaccine PPx - When - Who to give
Exposure < 5 days Not immuncompromised, Not pregnant, > 12 months
79
VZV Ig - When - Who to give
Exposure < 10 days Pregnant or immunocompromised who have inadequate Ig levels (check Ig levels)
80
Dysregulated response to EBV infection
X linked lymphproliferative disease
81
Periodic fever syndrome
Inflammasomes
82
STAT3?
Hyper IgE syndrome - Prevents Th17 cell production
83
Common cytokine receptor gamma chain deficiency
SCID
84
Function of CRP
Bind phospholipi - recognise foreign pathogens and damaged cells Activates complement system
85
Benefit of conjugate vaccines
Elicites T cell response (polsaccharide bound to protein), elicits T cell response
86
Storiform fibrosis
IgG4
87
Allergy symptoms Recurrent pancreatitis or sclerosing cholangitis Good response to steroids
IgG4 disease
88
Only vaccine CI in egg allergy
Yellow fever
89
Bone tumour epiphysis
Chondroblastoma
90
Metaphysis bone cancers
Osteosarcoma
91
When to stop IVIG in 2nd hypogammagobulinaemia
When Ig levels normalised
92
MoA of fingolimod
Spingosine 1 phosphate receptor modulator Prevents leukocyte migration
93
A/E of fingolimod
Life threateing HSV Bradycardia
94
MoA of dupilumab Indication
Blocks apha subunit of IL-4 (blocks both IL-4 and IL-13) Eczema
95
MoA of tofactinib
inhibits JAK1 and JAK3 (in contrast to ruxolitinib)
96
Indications that can clear allergy status
>10 years with unknown reaction Childhood nonspecific exanthem > 10 years ago delayed reaction
97
Delayed anaphylaxis mammalian food Sensitised event?
Tick bites
98
Most common cancer immunodeficiencies?
Lymphoma
99
Management of chemotherapy induced diarrhoea 1st 2nd
1st - loperamide 2nd- SC octreotide
100
Fluoropyrimidine chemotherapy -severe toxicity with 1st dose - treatment - test for?
Uridine triacetate Check for polymorphisms in F DU metabolising enzymes
101
Features separating angioodema syndrome vs anaphylaxis
Angiooedema - No urticaria - Asymmetrical - Doesn't involve dependant areas
102
Clinical features of HAE
Young Recurrent abdominal attacks
103
Diagnostic HAE
Low C4 Normal C1q C1 inh -low - HAE 1 - normal but impaired function - HAE 2
104
Clinical features and associates Acquired angiooedema
Age > 40 Malignancy - NHL MGUS
104
Clinical features and associates Acquired angiooedema
Age > 40 Malignancy - NHL MGUS
105
Clinical features and associates Acquired angiooedema
Age > 40 Malignancy - NHL MGUS
106
Diagnostic acquired angiooedema
Low C4 Low C1 Inh Low C1q
107
Super antigen - Example - How it works
Exotoxins from staph (TSS) Can cross link MHC class II antigen presenting cell AND The adjacent T cell receptor
108
Mab with x - composition?
x is cool like a chimera chimeric
109
Mab with z - composition?
Humans get z scored humanised
110
Mab with m
man = human fully human
111
Amplifies normal alternative complement pathway
Foreign or damaged cells
112
B2 microglobulin - what structure?
MHC1
113
Where does class switching and somatic hypermutation take place?
Germinal centres - temporary structures formed in 2nd lymphoid organs
114
What does innate immune system detect?
Pattern recognition PAMP - microbes only DAMPS - damage associated peptides
115
HLH pathophys
Deficient CD8 and NK activity Unsuppressed macrophage activation

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