Immuno Flashcards
1
Q
What are most deaths within 5 days of burns injuries related to?
A
Infection
2
Q
Reticular dysgenesis mutation and side effect
A
Adenylate kinase 2 gene (energy metabolism of mitochondria)
Bilateral sensorineural deafness
3
Q
Kostmann syndrome problem and mutation
A
Failure of neutrophil maturation in children
HCLS1-associated protein X-1
4
Q
Condition in which there is episodic neutropaenia every 4-6 weeks, and parents will have condition (autosomal dominant). Genetics and treatment.
A
Cyclic neutropaenia
Mutation in neutrophil elastase ELA-2
Responds to G-CSF
5
Q
Outline leukocyte adhesion deficiency cause
A
CD18 deficiency
Usually expressed on neutrophils to help bind to ICAM-1 on endothelial cells
Lack this, so fails to exit bloodstream
- High neutrophil count in blood
- Absence of pus formation
- Delayed umbilical cord separation
6
Q
Outline chronic granulomatous disease cause and features
A
NADPH oxidase deficiency - oxygen conversion to superoxide needed for hypochlorous acid
Impaired killing of intracellular microorganisms
Granulomas, lymphadenopathy, hepatosplenomegaly
Susceptible to catalase positive bacterie i.e. PLACESS (Pseudomonas, Listeria, Aspergillus, Candida, E. coli, S. aureus, Serratia)
7
Q
Chronic granulomatous disease investigations and definitive treatment
A
Negative nitro-blue tetrazolium test (NBT) normally turns from yellow to blue following interaction with hydrogen peroxide
In CGD it stays yellow
Dihydrorhodamine (DHR) flow cytometry test (gold standard). Oxidised by hydrogen peroxide to rhodamine, which is fluorescent, if normal
IFN-gamma therapy
HSCT in general for phagocyte deficiencies
8
Q
What problems can arise if there is a deficiency of IL-12 and IFN-gamma, and their receptors and why?
A
Susceptible to mycobacteria, BCG and salmonella
Normally:
• Infected macrophages produce IL-12 which leads to stimulatesd production of TNF-alpha and free radicals
• Activates NADPH oxidase
This oxidative pathway fails if you have deficiencies earlier on. Unable to form granulomas.
9
Q
What type of microorganisms are recurrent in Factor B/I/P deficiency (alternative pathway)?
A
Encapsulated bacteria
10
Q
What problems can arise with deficiency in the early classical pathway (C1/2/4), and which is the most common?
A
- Immune complexes fail to activate complement
- Failed clearance of apoptotic cells
- Increase in self-antigens -> autoantibodies
- Deposition of immune complexes
C2 most common deficiency - almost all have SLE, but C3 and C4 (goes down first) used to monitor SLE
11
Q
What is C1 esterase deficiency also known as?
A
Hereditary angioedema
C4 may also be low
12
Q
What causes secondary antibody dependent deficiency in the classical pathway?
A
Active lupus
Persistent production of immune complexes and consequent depletion of complement
13
Q
Which complement does MBL deficiency involve and how does it affect people?
A
C2 and C4
Increased infections in immunocompromised
14
Q
What non-pathogenic disease are patients with C3 deficiency at an increased risk of developing?
A
Connective tissue disease
15
Q
Which factors stabilised C3 convertases leading to glomerulonephritis and lipodystrophy
A
Nephritic factors
16
Q
What problems arise if there is a defect in the terminal common pathway
A
Failure to produce the membrane attack complex (MAC)
Can’t use complement to lyse encapsulated bacteria
Susceptible to N. meningitis, S. pneumonia, H. influenzae (vaccinate against these)
17
Q
Most common type of SCID
A
X-linked
Mutation of IL2 receptor gamma chain
18
Q
When does SCID present and why
A
Presents 3-6 months after birth, protected by IgG from mother across placenta, then colostrum, before
19
Q
SCID investigation findings
A
Flow cytometry - low B/T/NK cells
CXR - absent thymic shadow
20
Q
Second most common type of SCID and its treatment
A
Adenosine deaminase deficiency
PEG-ADA enzyme replacement therapy
21
Q
Cardiac abnormalities (tetralogy of fallot)
Abnormal facies (high forehead, low-set ears)
Thymic aplasia
Cleft palate
Hypoparathyroidism
condition, genetics, other features
A
DiGeorge syndrome
CATCH 22
22q11.2 deletion
(also developmental delay, PCP infection, atypical viral infection)
22
Q
DiGeorge syndrome investigation findings and management
A
Low T cells, normal B cells (immune function improves with age)
Thymic transplant
23
Q
Bare lymphocyte syndrome type II
- what is absent/low
- condition it is associated with
A
Regulatory protein issue
Absent MHC class II CD4+ deficiency No IgG or IgA (no class switching)
Association with sclerosing cholangitis
24
Q
Wiskott-Aldrich Syndrome mutation effect, features, Ig levels
A
Mutation affecting actin cytoskeleton arrangement, needed for T cell-APC interaction
Eczema, risk of lymphoma
High IgA, IgE
Low IgM
25
Outline Bruton's X-linked agammaglobulinaemia (XLA) cause and features
Defective B cell tyrosine kinase gene
Pro-B cell doesn't mature into pre-B cell
All immunoglobulins are low/gone (none after around 3 months), B cells are low
26
Outline selective IgA deficiency features
Most common primary antibody deficiency
• 2/3 asymptomatic
• Recurrent sinopulmonary infections, GI infections, risk of GI cancers
• Anaphylaxis with exposure to blood products (with IgA)
Low IgA (sometimes normal, as mainly low on mucosal surfaces)
Sometimes high IgE (compensate for low IgA, leading to allergic reactions)
Normal B cell levels
27
Selective IgA deficiency management
Depends on manifestation e.g. ABx for infections
Vaccination prophylaxis (only deficiency where this works)
28
Mutation in CD40L in activated T cells condition
Hyper IgM syndrome
CD40 involved in T-B cell communication
Inability of B cells to class switch
Production of only IgM
X-linked
29
Outline common variable immune deficiency, Ig levels and features
Group of disorders with unknown disease mechanism
Low everything apart from B cells and IgM
* Bronchiectasis
* Autoimmune disease
* Granulomatous disease
30
What does MEFV encode?
What does it interact with?
What diseases are mutations linked to?
```
Encodes pyrin (marenostrin)
Interacts with ASC -> procaspase 1 in the inflammasome complex
Mutations linked to autoinflammatory diseases e.g. Mediterranean fever
```
31
What does the NALP3/cryopyrin-inflammasome complex bind to in neutrophils?
ASC, activating procaspase 1
32
What type of pathogens are people with complement deficiencies susceptible to?
Encapsulated bacterial infections
33
What tests are used to diagnose complement deficiencies?
CH50 and AP50
34
```
CH50, AP50, C3, and C4 levels in the deficiencies of the following:
• C1q
• Factor B
• C9
• SLE
```
C1q - low CH50
Factor B - low AP50
C9 - both low
SLE - both normal (CH50 may be low)
C3 and C4 only low in SLE
35
What types of pathogens are people with T cell deficiencies more susceptible compared to antibody/CD4 T cell deficiencies?
Viral and fungal, as opposed to bacterial
36
Complement deficiencies general management
Vaccinate
Prophylactic Abx
Screen family
37
What is a type I hypersensitivity disorder and what is an important symptom?
Reaction to allergen re-exposure
IgE cross-links mast cells - histamine release
Anaphylaxis
38
```
What group are these diseases in?
Atopic dermatitis (infantile eczema)
Food allergy
Oral allergy syndrome
Latex food syndrome
Allergic rhinitis
Acute urticaria
```
Type I hypersensitivity
39
Atopic dermatitis defect. What does it also predispose to?
Defects in beta defensin
Predisposes to S. aureus superinfection
40
What causes oral allergy syndrome and how is it treated
Exposure to allergen e.g. birch pollen, seeded fruit
Induces allergy to food
If ingested, wash mouth and take antihistamines
41
What food causes latex food syndrome?
* Chestnut
* Avocado
* Banana
* Potato
* Kiwi
* Papaya
* Eggplant
* Mango
* Wheat
* Melon
42
```
Are the following IgE or cell-mediated:
• Anaphylaxis
• Oral allergy syndrome
• Coeliac
• Atopic dermatitis
```
Anaphylaxis - IgE
OAS - IgE
Coeliac - cell-mediated
Atopic dermatitis - both
43
What can trigger non-IgE mediated mass cell degranulation, leading to anaphylaxis?
NSAIDs
IV contrast
Opioids
Exercise
44
4 differentials of anaphylaxis
Hereditary angioedema (C1 inhibitor deficiency)
ACEi induced angioedema (lips and tongue)
Acute anxiety
Urticaria
45
What happens when a1, b1, and b2 receptors are stimulated?
a1 - vasoconstriction
b1 - increased HR and contractility
b2 - bronchodilation
46
Anaphylaxis treatment algorithm in adults
1. Lie flat (with or without legs elevated)
2. IM adrenaline 1mg/mL 1:1000
3. High flow 100% oxygen
4. IV fluid challenge (crystalloid)
5. IV chloramphenamine 10mg
6. IV hydrocortisone 200mg (prevents rebound anaphylaxis)
(call ambulance after using epipen)
47
What does a skin prick test show and how?
Wheal >=2mm
| IgE-mediated
48
What should you do in preparation for a skin prick test?
Stop antihistamines 48 hours before (corticosteroids are ok to continue)
49
What does a RAST (quantative specific IgE to putative allergen) test measure, how does it compare to skin prick, and when is it indicated?
Measures levels of IgE against particular allergen in serum
Monitors response to treatment
Less sensitive/specific than skin prick
Use if can't stop antihistamines, anaphylaxis hx, extensive eczema
50
What do component-resolved diagnostics measure?
IgE response to a spefic allergen protein (rather than range of proteins from allergen)
e.g. in peanut, ara h 2 (anaphylaxis to peanut), ara h 8 (localised oral reaction to peanut)
Can confirm primary sensitisation and cross reaction
51
What is the gold standard test for food allergy
Challenge test
Double-blind oral food challenge
Increasing volumes of offending food are ingested under close supervision
Risk of severe reaction
52
When should tryptase be measured following anaphylaxis?
ASAP
Ideally within 1-2 hours, no later than 4 hours
Specialist follow-up for baseline may be required
53
What is a type II hypersensitivity disorder?
IgG or IgM reaction against cells or extracellular matrix
54
Which antigens are targeted in the following type II hypersensitivity disorders:
• Haemolytic disease of the newborn
• Autoimmune thrombocytopaenic purpura
• Goodpasture's syndrome
• Pemphigus vulgaris
• Myasthenia gravis
• Acute rheumatic fever
• Eosinophilic granulomatosis with polyangitis (Churg-Strauss)
• Granulomatosis with polyangitis (Wegener's)
• Microscopic polyangitis
* HDN - erythrocytes
* ATP - Glycoprotein IIb/IIIa on platelets
* Goodpasture's - collagen type IV (BM, non-collagenous domain)
* PV - epidermal cadherin
* MG - ACh receptor
* Acute rheumatic fever - M proteins of Group A Strep
* eGPA - myeloperoxidase
* GPA - proteinase 3
* MPA - myeloperoxidase
55
Pathology, diagnosis, and treatment of haemolytic disease of the newborn
Maternal IgG attacks neonatal erythrocytes - reticulocytosis and anaemia
Positive direct Coombs test
Maternal plasma exchange, exchange transfusion
56
Diagnosis and treatment of autoimmune haemolytic anaemia
Positive direct Coombs test, anti erythrocyte cell ab
Steroids
57
Goodpasture's syndrome pathology and diagnosis
Glomerulonephritis, pulmonary haemorrhage
Anti glomerular basement membrane antibody
Linear smooth fluorescent staining of IgG on BM
58
Non-tense skin blisters, bullae
Fluorescent IgG deposition
Condition?
Pemphigus vulgaris
59
Graves treatment
Carbimazole and propylthiouracil
60
Myasthenia gravis diagnosis and treatment
Anti-ACh-R ab, abnormal ECG
Tensilon test - ACh esterase inhibitor injection, improvement in symptoms
Neostigmine, pyridostigmine (IVIG if serious)
61
What is used for diagnosis of acute rheumatic fever?
Jones criteria
62
What can pernicious anaemia lead to if left untreated?
B12 deficiency
Optic neuropathy
Peripheral neuropathy
Subacute combined degeneration of the spinal cord (sensory deficit, weakness, ataxia)
63
p-ANCA against myeloperoxidase, asthma, heart and kidney disease
eGPA
64
c-ANCA against proteinase 3, lung cavitations and haemorrhage, crescentic glomerulonephritis
GPA
65
p-ANCA against myeloperoxidase, purpura, livedo reticularis
Microscopic polyangitis
66
What are 3 types of antinuclear antibodies?
anti-
dsDNA
ENA (extractable nuclear antigen)
cytoplasmic
67
What does the presence of anti-dsDNA suggest?
SLE
68
Autoimmune polyendocrinopathy candidiasis-ectodermal dystrophy is caused by a mutation in which gene?
AIRE (autoimmune regulator)
69
Immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome is caused by a mutation in which gene?
FOXP3 - defective Treg cells
70
What are type III hypersensitivity disorders?
IgG or IgM immune complex mediated tissue damage
71
IgM against IgG +/- hep C antigens, joint pain
| Condition?
Mixed essential cryoglobulinaemia
72
Serum sickness cause and diagnosis
Reaction to proteins in antiserum (blood serum with antibodies) from non-human source or medications (most commonly penicillin)
Decreased C3
73
High WCC, ESR and CRP
'Rosary sign' small aneurysms on angiography
Systemic ischaemia, livedo reticularis, nodules
Hep B and C association
Condition?
Polyarteritis nodosa
74
SLE basic pathophysiology
Failure of immune complex and apoptotic cell clearance
Shift from Th1 to Th2 -> B cell hyperactivity -> autantibodies
75
Which autoantibodies are involved in SLE (6)?
```
Anti-Ro
Anti-La
Anti-Sm
Anti-U1-RNP
Anti-dsDNA
Anti-histones
```
76
What can hydralizine, procainamide and isoniazid all cause?
Drug-induced SLE
77
What is useful for SLE disease monitoring?
anti-dsDNA
| C4 first to drop
78
In SLE, what is the appearance of the basement membrane antibody on immunofluorescent exmination of the skin?
Granular lumpy-bumpy appearance
79
What is a type IV hypersensitivity disorder?
Delayed T-cell mediated hypersensitivity
80
Name 5x type IV hypersensitivity disorders?
```
T1DM
MS
Rheumatoid Arthritis (also type III - IgM vs Fc of IgG)
Contact dermatitis
Crohn's disease
```
81
What medical test can ellicit a type IV hypersensitivity reaction?
Mantoux test
82
T1DM antigens targeted
Pancreatic beta cell proteins (glutamate decarboxylase)
83
MS antigens targeted
Oligodendrocyte proteins (myelin basic protein, proteilopic protein)
84
MS diagnosis
Oligoclonal bands of IgG from CSF on electrophoresis
85
Rheumatoid arthritis HLA associations
HLA-DR1
| HLA-DR4
86
Which 2 enzymes are implicated in RA pathogenesis?
PAD2
PAD4
(Peptidylarginine deiminases)
They generate citrullinated autoantigens (arginine -> citrulline). Enzymes present in neutrophils and monocytes - so RA in inflamed synovium
87
More likely to get RA, SLE, T1DM, decreased T cell activation.
Condition?
PTPN22 (Protein Tyrosine Phosphatase Non-Receptor Type 22)
88
RA diagnosis
Anti-cyclic citrullinated protein - most specific (and generally most accurate)
Rheumatoid factor - slightly more sensitive but can be found in people with other AI diseases
89
Causes of contact dermatitis
Poison ivy
Nickel
Latex
90
What is a major genetic risk factor for Crohn's disease?
NOD2 cystosolic protein on chromosome 16
91
Crohn's diagnosis
Biopsy of lesion
92
HLA associations of the following:
Graves disease
T1DM
Coeliac
GD - HLA-DR3
T1DM - HLA-DR3/4
Coeliac - HLA-DQ2,8 (ate 8 too 2 much at Dairy Queen)
93
SLE HLA associations
HLA-DR2
HLA-DR3
2-3, S-L-E
94
Diseases associated with HLA-DR2
Multiple hay pastures have dirt
MS
Hay fever
Goodpasture's syndrome
SLE
95
Diseases associated with HLA-B27
PAIR - seronegative arthropathies
Psioriatic arthritis
Ankylosing spondylitis
IBD-associated arthritis
Reactive arthritis
96
CTLA4 is receptor for what
Receptor for CD80/86 from T cells
Inhibitory signal to control T cell activation
97
```
Calcinosis
Raynaud's
Oesophageal dysmotility
Sclerodactyly
Telangiectasia
```
condition and other features
Limited cutaneous scleroderma
CREST syndrome
Primary pulmonary hyperation
Skin involvement up to forearms + perioral
98
CREST syndrome diagnosis
Anti-centromere antibodies
99
Diffuse cutaneous scledorema presentation
CREST + GIT + interstitial pulmonary disease + renal cysts
Skin beyond forearms
100
Anti-topoisomerase
Anti-Scl-70
Anti-fibrillarin
Anti-RNA polymerase I-III
Nucleolar staining by indirect immunofluorescence
Condition?
Diffuse cutaneous scledorema
101
Xerostomia (dry mouth)
Keratoconjunctivitis sicca (dry eyes)
Dry nose
Dry skin
Condition
Sjorgen's syndrome
102
Sjorgen's syndrome diagnosis
Anti-Ro
Anti-La
Schirmer test - check for dry eye
103
IPEX presentation apart from
Nail dystrophy
Alopecia universalis
Bullous pemphigoid
Diarrhoea
Dermatitis
Diabetes mellitus
104
IPEX cure
BM transplant
105
Visible manifestation of coeliac disease
Dermatitis herpetiformis - extensor surface rash
106
Coeliac investigations
IgA anti-edomysial antibody (postive when eating gluten
IgA anti-transglutaminase antibody (specific, and most sensitive)
IgG anti-gliadin antibody (most persistant)
>=4 duodenal biopsies (gold standard, need to know baseline too)
Villous atorphy and enteropathy
>20 intraepithelial lymphocytes
107
Hashimoto's thyroiditis targeted antigen
Thyroglobulin
| Thyroperoxidase
108
Dermatomyositis and polymyositis autoantibodies
Anti-Jo-1 (against t-RNA synthetase)
109
Primary biliary cirrhosis autoantibody
Anti-mitochondrial antibody
110
Which autoantibody is a speckled fluorescent appearance seen with?
Anti-U1RNP
111
Human normal immunglobulin (IgG antibody replacement)
From how many donors?
Which 3 infections are always screened ford?
How often is it given?
>1000 donors
Screen for HIV, Hep B, Hep C
Every 3-4 weeks
112
What is specific immunoglobulin injection given for?
Post-exposure prophylaxis, passive vaccination
Ig for rabies, VZ, Hep B, tetanus
113
What can the following recombinant cytokines be used to boost the immune response to?
Interferon alpha
Interferon beta
Interferon gamma
alpha - Hep B, Hep C, Hairy cell leukaemia, chronic myelogenous leukaemia, malignant myeloma
beta - Bechets
gamma - CGD
114
Ipilimumab function
Antibody against CTLA4 (downregulatory immune checkpoint)
Allows T cell activation
Used for advanced melanoma
115
Pembrolizumab/nivolumab function
Antibody against PD-1 (promotes T cell apoptosis, prevents Treg apoptosis)
Allows T cell activation
Used for advanced melanoma
116
What are CD19-targeted (B cell) CAR T cells [therapy] useful for?
ALL
| AML too
117
John Cunnigham virus (JCV) can reactivate during immunosuppressive therapy. Which cells does it attack?
Oligodendrocytes
118
Prednisolone mechanism of action
* Inhibits phospholipase A2
* Reduced prostaglandin synthesis
* Inhibits phagocyte trafficking
* Lymphopaenia
* Decreased Ab production
119
• Alkylates guanine (DNA nucleotide)
• Damages DNA
• Affects B > T cells
Medication
Cyclophosphamide
120
Haemorrhagic cystitis
Bladder cancer
Teratogenic
Sterility
SE of which drug
Cyclophosphamide
121
Mycophenolate mofetil mechanism of action
* Inhibits IMPDH
* Blocks de novo nucleotide synthesis of guanine
* Affects T > B cells
122
Azathioprine mechanism of action
* Converted to 6-MP and 6-thioguanine
* Prevent de novo purine synthesis and also halt replication of DNA
* Affects T cells > B cells
123
Allograft regimen
Mycophenolate, prednisolone, tacrolimus
124
Methotrexate mechanism of action
Inhibits dihydrofolate reductase
| Decreases DNA synthesis
125
What is plasmapharesis and what is it used for?
* Device separates whole blood into components
* Plasma treated to remove immunoglobulins or replaced with colloid fluid
* Reinfused
Severe antibody-mediated (Type II) disease
Antibody-mediated rejection
126
What needs to be coadministered with plasmapharesis and why?
Anti-proliferative agent e.g. cyclophosphamide
Rebound antibody production limiting efficacy and risking anaphylaxis
127
Tacrolimus and cyclosporin mechanism of action
* Inhibits calcineurin
* Reduced IL-2 transcription
* Reduced T cell proliferation
128
Immunosuppresant with gingival hypertrophy side effect
Cyclosporin
129
Sirolimus mechanism of action
mTOR (protein kinase) inhibitor
| Blocks clonal proliferation of T cells
130
Tacrolimus, cyclosporin and sirolimus indication
Rejection prophylaxis in transplantation (renal)
131
Tofacitinib mechanism and indication
JAK inhibitor
Suppresses STAT-1 dependent genes
Rhematoid arthritis
Psoriatic arthritis
132
Apremilast mechanism and indications
PDE4 inhibitor
Decreased cytokine production
Psoriasis
Psoriatic arthritis
133
Basiliximab mechanism
Anti-CD25 (alpha chain of IL-2)
134
Abatacept mechanism and indication
CTLA4 Ig, binds to CD80/86
Inhibits T cell activation
Rheumatoid arthritis
135
Rituximab mechanism
Anti-CD20
| Depletes mature B cells (not plasma cells)
136
Natalizumab mechanism and indication
Anti-alpha4 integrin (binds to VCAM1) - mediates rolling of leukocytes
Relapsing-remitting MS
137
Tocilizumab mechanism and indication
Anti-IL6
Castleman's disease
138
Muromonab mechanism and indication
Anti-CD3 on T cells (mouse monoclonal antibody (OKT3))
Active allograft transplant rejection
139
Horse or rabbit-derived antibodies against human T cells and their precursors
Anti-thymocytes globulin (ATG)
140
Daclizumab mechanism and indication
IL2 receptor antibody against CD25
Transplant rejection prophylaxis
141
Efalizumab mechanism
Anti-CDIIa
142
Alemtuzumab (Campath) mechanism
Antibody against CD52 on lymphocytes
143
What does infliximab, adalimumab, certolizumab, and golimumab target and what are their indications?
Anti-TNF alpha
RA, AS, psoriasis, psoriatic arthritis, IBD
144
How is etanercept different to other TNF alpha inhibitors?
It acts as a decoy receptor that binds to TNF anlpha
145
Mechanism of ustekinumab and indications?
Anti-IL12 -> less Th1 diff -> less CD8+
Anti-IL23 -> less Th17 diff -> less B cells
Binds to p40 subunit
Psoriasis, psoriatic arthritis
146
Secukinumab mechanism
Anti-IL17A
147
Denosumab mechniasm, indications, and a side effect?
Anti-RANK ligand - inhibits osteoclast diferentiation
Osteoporosis, MM, bone mets
Avascular necrosis of jaw
148
What are injection recall reactions?
Injection site reaction at previous sits
149
Are injection site and infusion reactions IgE mediated?
Infusions are, injection generally more cellular
150
How often is allergen desensitisation carried out and what is it useful for?
Escalate weekly until maximal dose
Maintenance dose monthly for 3-5 years
Bee venom, wasp venom, grass pollen, dust mite
Not food or latex
151
Where are isografts, allografts, and xenografts from?
Isograft - twin
Allograft - same species
Xenograft - different species
152
Which allografts can be taken from a living donor?
Bone marrow
Kidney
Liver
153
How do T cells and B cells recognise antigens differently
T cells - antigen with MHCs on APCs
| B cells - just antigen
154
Importance of HLA type
A
B
DR
DR > B > A
155
HLA chromosome
Chr6
156
Where do T and B cells cause damage in a renal transplant?
T cells - interstitial
| B cells - endothelial
157
Difference between direct and indirect transplant recognition
Direct
• Donor APC presenting its own antigen/MHC to recipient T cells
• Mainly acute rejection
Indirect
• Recipient APC presenting donor antigen to recipient T cells
• The normal function of immune system
• Mainly chronic rejection
158
Which 3 cells infiltrate the graft in to the effector phase of graft rejection?
CD4+
Then cytotoxic T cells punch holes in target cells
Then macrophages get involved
159
Hyperacute transplant rejection time and mechanism
Minutes - hours
Preformed antibodies activate complement
160
Acute transplant rejection time and mechanism
< 6 months
Cellular - CD4 activating type IV reaction - cellular T cell infiltrate
Antibody - B cell activation, antibodies attack vessels - vasculitis
161
Chronic transplant rejection time and risk factors
> 6 months
RF: miltiple acute rejections, HTN, hyperlipidaemia
(immune and non-immune mechanisms)
162
GvHD time, presentation and treatment
days-weeks
Rash, vomiting, bloody diarrhoea, jaundice
Cyclosporin, methotrexate
163
Acute vascular rejection is similar to a hyperacute reaction, but how does it differ?
Only after xenograft
Days - weeks
164
What type of test determines HLA type?
PCR
165
What is a crossmatch?
Tests if serum from recipient is able to kill donor lymphocytes - positive crossmatch is contraindication
166
What medication is given before transplant?
Alemtuzumab (anti-CD52)
Basiliximab (anti-CD25)
OKT3
167
2 steps of HSCT
Eliminate hosts immune system - total body irradiation; cyclophosphamide
Replace with own (autologous) or HLA-matched (allogeneic) bone marrow
168
Why is there a decrease in RA symptoms during pregnancy?
Shift from Th1 to Th2
169
Why is there a 20x increase risk of death from MI in individuals who have had a transplant?
Transplant and immunsuppression -> HTN and hyperlipidaemia post-transplant
Th2 effects
Increased risk of atheroscleoris
170
HIV infections per day
5000 (>10% children)
171
HIV cycle
RNA retrovirus
• Targets CD4+
• Gp120 (initial) and gp41 on HIV binds to CD4 and CCR5/CXCR4
• Reverse transcriptase converts RNA into DNA
• Integrase integrates viral DNA into host's DNA
• Viral proteins created and cut with proteases
172
What is the major structural protein of HIV?
Gag protein (group specific antigen)
>50% mass of viral particle
173
Which antibodies against HIV are neutralising and non-neutralising?
Neutralising - anti-GP120, anti-GP41
Non-neutralising - antip24 gag IgG
(still infectious when coated with abs)
174
Which chemokines can CD8+ produce to prevent HIV entry?
MIP-1a
MIP-1b
RANTES
175
Why are naive CD8+ not primed in HIV infection?
Infected CD4+ killed
Memory lost and failure to activate monocytes and dendritic cells
These then can't prime CD8+
176
How are HIV quasispecies produced?
Error-prone reverse transcriptase - escape immune response
177
Time from HIV infection to AIDS
Median: 8-10 years
Rapid progressors: 2-3 years
Long term non progressers: stable CD4+ and no symptoms after 10 years
178
What predicts HIV disease progression?
Initial viral burden
179
HIV screening test
ELISA - detects anti-HIV antibody
180
HIV confirmation test
Western blot - detects anti-HIV antibody
181
When is the HIV test correct and why?
~10 weeks incubation from infection
Patient has to have seroconverted
182
What testing is done following diagnosis of HIV?
Viral load - PCR to detect RNA
CD4 - FACS (flow cytometry)
Phenotypic resistance - viral replication measured under selective pressure of increasing concentrations of ART, compared to wild-type
Genotypic resistance - direct sequencing of amplified HIV genome
183
AIDS CD4 count
< 200 cells/uL
184
When should HIV treatment be commenced?
Immediately once diagnosis confirmed
| old guidelines start thinking CD4 <350 and commence <200
185
What does highly active anti-retroviral therapy (HAART) include?
2x nucleoside/tide RT inhibitors + protease inhibitor (or non-NRTI)
e.g. emtricitabine + tenofovir + efavirenz
186
When should zidovudine infusion be used in women with HIV during pregnancy?
* Untreated women with unknown viral load
| * Considered if viral load > 50, use if over 1000 (on ART)
187
HIV ART for neonates
Zidovudine
2 weeks if very low risk
4 weeks if low risk
(6 weeks PO on path guide)
Combination PEP if higher risk
188
Why might amlodipine not work in a patient also taking efavirenz?
Efavirenz (NNRTI) is a CP450 inducer
Amlodipine broken down too quickly
189
Maraviroc is an attachment inhibitor. What does it target?
Blocks CCR5
190
What do the names of reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors end with respectively?
- ine
- gravir
- avir
191
When does PEP need to be taken?
<72 hours of exposure
Take for 4 weeks
192
How long can immunologic memory last?
up to 65 years
193
Where are effector memory cells found?
Liver
Lungs
GIT
194
Is CCR7 and CD62L present in central and effector memory cells?
CCR7+ in central and effector
CD62L high in central and low in effector
Allows migration via high endothelial venules to peripheral lymph nodes
195
What cytokines do central and effector memory cells produce?
Central - IL2
| Effector - perforin, IFN-gamma
196
Is there more effector memory in CD4 or CD8 population?
CD8
197
Which immunoglobulins are involved in B cell expansion/isotope switching, stimulated by antigens?
IgM - T cell independent
| IgG, IgA, IgE - T cell dependent
198
Outline difference between Th1, Th2, and Th17 (all T helper cells) response
Th1
• Cell mediated
• Help APCs (e.g. macrophages) and CD8+
Th2
• Humoral
• BCR takes up antigen, presented on MHC II, Th2 binds and activates B cell
Th17
• Neutrophil recruitment
• Targets fungal and bacterial infection
199
Cytokines produced in Th1, Th2, and Th17 response
Th1
• IL2
• IFN-gamma
• TNF
Th2
• IL4, 5, 6
Th17
• IL17, 21, 22
200
Where is the vaccine antigen processed if injected IV?
Spleen
201
How long does protection after BCG last?
10-15 years
202
Which cells should be targeted in a cancer vaccine?
APCs to express tumour antigen i.e. dendritic cells
203
Signs of immune senescence
* Accumulation of terminally differentiated effector memory T cells
* More senescence markers
* Reduced ability to respond to new antigens
* Low-grade inflamation
204
What types of pathogens are conjugated vaccines used against?
Encapsulated bacteria
205
Live attenuated vaccine benefits
* Long immunity
* Protects against cross reactive strains
* Activates all phases of immune system
206
3 examples of live attenuated vaccines
BCG
MMR
Typhoid
207
3 examples of inactivated vaccines
Salk (polio)
Hep A
Pertussis
208
2 examples of subunit vaccines
Hep B
| HPV
209
3 examples of conjugate vaccines
Hib
Meningococcus
Pneumococcus
210
2 examples of toxoid vaccines
Diptheria
| Tetanus
211
Disadvantage of DNA vaccines
Could lead to autoimmune diseases e.g. SLE
212
Can PWHIV have MMR, BCG or yellow fever vaccine?
Only MMR
213
What is the most common vaccine adjuvant and what does it do?
Alum
• Slows antigen release
• Activates Gr1+ cells to produced IL4
• Helps prime naive B cells
214
How does CpG adjuvant work?
Cystosine next to guanine in DNA
| Triggers TLRs on APCs
215
How does complete Freund's adjuvant work?
Water-in-oil emulsion containing mycobacterial cell wall components (mainly for animals)
216
How does ISCOMS (immune stimulating complex) adjuvant work?
Experimental
| Spherical open cage-like structures formed when mixing together cholesterol, phospholipids and saponins
217
Which interleukin can be used as an adjuvant?
IL12
218
How long do passive vaccines last? What can human normal Ig (HNIG) be used for?
3 weeks
Hep A, measles, ITP, Kawasaki, GBS
219
How is the mantoux test carried out?
Inject 0.1ml of 5 tuberculin units (purified protein derivative) intradermally
Examine arm 48-72 hours later
Positive result: >10mm induration (not including erythema) - means previous exposure to tuberculin
220
What is the aim of the BCG vaccine?
Stop activation of TB
Efficacious against miliary and meningeal TB
Only some protection against pulmonary TB
