Immunology Flashcards
(181 cards)
1
Q
how does lacterferrin stop bacteria?
A
starves bacteria of iron
2
Q
what are the different innate immune cells?
A
- polymorphonuclear cells (neutrophils, eosinophils, basophils)
- monocytes and macrophages
- dendritic cells
3
Q
macrophage name in: kidney, neural tissue, connective tissue
A
kidney: mesangial cell
neural tissue: microglia
connective tissue: histiocyte
4
Q
forms of oxidative killing
A
- NADPH oxidase = forms ROS
- Myeloperoxidase = forms hydrochlorus acis (oxidant and anti-microbial)
5
Q
what is the job of NK cells?
A
cytotoxic
kills altered self cells e.g. malignancy or virus-infected virus
regulates inflammation and promote DC function
6
Q
following phagocytosis, DC will?
A
upregulate expression of HLA molecules
express co-stmulatory molecules
migrate via lymphatics to lymph nodes (mediated by CCR7)
7
Q
what do CD4+ T cells (Helper T cells) do?
A
recognise peptides derived from extracellular proteins (presented on HLA class II = HLA-DR, DP, DQ)
8
Q
what are the CD4 subsets?
A
Th1 Th17 Treg TFh Th2
9
Q
what do Th1 cells do?
A
help CD8 T cells and macrophages
10
Q
what do Th17 cells do?
A
help neutrophil recruitment
enhance generation of auto-Abs
11
Q
what do TFh cells do?
A
promote germinal centre reactions
12
Q
what are Th2 cells?
A
helper T cells
13
Q
what do CD8+ cytotoxic T cells do?
A
recognise peptides derived from intracellular proteins HLA class 1 (A, B, C) important in defence against viral infections and tumours
14
Q
what are the features of the classical complement cascade?
A
- activated by immune complexes
- dependent on activation of immune response
- C1, C2, C4
15
Q
what are the features of the MBL pathway?
A
direct binding of MBL to microbial cell surface
C4, C2
16
Q
what are the features of the alternative pathway?
A
- directly triggered by binding of C3 to bacterial cell wall components
- not reliant on acquired immune response
- B, I, P factors
17
Q
what is the amplification step of alternative pathway?
A
activation of C3 comvertase
18
Q
what ligands and chemokine are important in directing DC trafficking to lymph nodes?
A
CCL19 and CCL21 are ligands for CCR7
19
Q
what is reticular dysgenesis and the gene mutation?
A
AK2 mutation
failure of stem cells to differentiate along myeloid/lymphoid lineage
20
Q
what is Kostmann syndrome and the mutation?
A
AR severe congenital neutropaenia
HCLS1-associated protein X-1
21
Q
what is the mutation in cyclic neutropaenia?
A
neutrophil elastase
22
Q
what is the problem in leukocyte adhesion deficiency?
A
deficiency of CD18
23
Q
what is the colour change in Nitroblue tetrazolum test?
A
yellow to blue
24
Q
what is the change seen in dihydrorhodamine (DHR) test?
A
becomes fluorescent
25
what is the phenotype on NK cell deficiencies?
increase risk of VIRAL infections
| e.g. severe chicken pox, disseminated CMV
26
what is the most common complement deficiency and the phenotype?
C2
| Phenotype: SLE, severe skin disease, increase risk of infection
27
what are nephritic factors?
- autoAbs directed against components of complement pathway
| - they stabilise C3 convertases (which break down C3) = C3 activation and consumption
28
what are nephritic factors associated with?
glomerulonephritis
| partial lipodystrophy
29
what is C1q deficiency?
- inherited complement deficiency
- SLE in childhood
- CH10 low, normal levels of C3 and C4
30
what is the phenotype of C7 deficiency?
meningococcus meningitis
| FH of sibling dying young
31
what is basophillic stippling?
presence of aggregated ribosomal material
32
causes of basophillic stippling
- beta-thalassaemia trait
- lead poisoning
- alcoholism
- sideroblastic anaemia
33
causes of target cells?
3 H's
Hepatic pathology
Hyposplenism
Haemoglobinopathies
34
what are howell jolly bodies? cause?
nuclear remnants visible within red blood cells
| cause: hyposplenism
35
what are causes of hyposplenism?
- absent spleen (therapeutic, trauma)
| - poorly functioning spleen (IBD, coeliac, SCD, SLE)
36
what is the most common association of coeliac?
HLA-DQ2
37
what is the T cell response to gluten?
1. peptides from gluten deaminated by TTG
2. APCs take up deaminated gluten
3. presented via HLA (DQ2/DQ8) to CD4 cells
4. causes increase in IFN-gamma and IL-15
5. cytokines promote activation of IELs
6. IELs kill epithelial cells via KG2D receptor = gut damage
7. Primed T cells can help B cells with Abs that recognise gliadin to undergo germinal centre reactions = memory cells and plasma cells
38
what is the most accurate anti-bodies to measure in coeliac?
anti-TTG
| check if IgA deficient first
39
what are some other causes of villous atrophy?
- Chron's
- GvHD
- CVID
- nutritional def
40
what are the IELs in Coeliac compared to most T cells?
gamma delta T-cells
| most T cells are alpha-beta
41
what are other causes of increased IELs?
drugs
IgA def
post-infective malabsorption
giardiasis
42
what is the most dangerous side effect of coeliac?
multi-focal T cell lymphoma
43
what is X-linked SCID and mutation?
most common SCID
mutation: gamma cgain on Chr Xq13.1
inability to respond to cytokines = early arrest of T cells, NK cells, produce immature B cells
44
what is ADA deficiency?
16.5% of SCID
adenosine deaminase deficiency (needed by lymphocytes for cell metabolism)
failure of maturation along any lineages
45
features of DiGeorge
deletion of 22q11.2
CATCH features
normal B cells, low T cells
46
what are the features of Bare lymphocyte syndrome type 2?
deficiency of MHC II genes
low CD4
CD8/B cell normal
Low IgG and IgA
47
what does T lymphocytes deficiency lead to?
viral infections
fungal infections
some bacterial infections (especially intracellular e.g. TB, salmonella)
48
what is Bruton's X-linked hypogammaglobulinaemia?
abnormal B cell tyrosine kinase deficiency
| Pre-B cells cannot mature into mature B cells
49
what is the mutation in hyperIgM?
mutation in CD4 ligand gene
50
what is CVID?
unknown cause
| low IgG, IgA, IgE, recurrent bacterial infecitons
51
typical phenotype of CVID
adult with bronchiectasis
recurrent sinusitis
atypical SLE
52
what are the features of antibody deficiency?
bacterial infection
toxins
some viral infections
53
what can protein electrophoresis show?
gamma peak (all the Abs)
54
name 2 mixed pattern diseases
- ankylosing spondylitis
| - psoriatic arthritis
55
what are 3 rare monogenic auto-immune diseases?
- APS-1/APECED
- ALPS
- IPEX
56
regarding the inflammasome complex, what mutations cause increased inflamation?
- gain of function mutation in cryopyrin = increased inflammation
- loss of function mutation in pyrin-marenostrin = increased inflammation
57
what is the mutation in familial mediterranean fever?
- mutation in MEFV gene
| - this encodes pyrin-marenostrin (expressed by netrophils)
58
association of FMF
AA amyloidosis
59
treatement of FMF
colchine
anakinra (IL1R antagonist)
etanercept (TNF-alpha inhibitor)
60
what is the cause of APECED? Associations?
defect in AIRE
| associated with AI conditions, candidiasis
61
what is the cause of IPEX? symptoms?
mutation in FoxP3
- immune dysregulation
- polyendocrinopathy (DM, hypothyroid)
- enteropatht
- dermatitis
62
what is the mutation in ALPS?
mutation in Fas pathway
63
what is mutation in Chron's disease?
IBD1 on Chr 16 = encodes NOD2
| NOD 2 expressed in cytoplasm of myeloid cells, is a microbial sensor
64
genetic association of Ankykosing Spondylitis and treatment?
HLA-B27
| Tx: Anti-TNFa, anti-IL17
65
HLA association of Goodpastures
HLA-DR15
66
HLA association of Graves
HLA-DR3
67
HLA association of SLE
HLA-DR3
68
HLA association of T1DM
HLA-DR3/DR4
69
HLA association of RA
HLA-DR4
70
what is the function of PTPN22? what happens if he is mutated?
PTPN22 suppresses T cell activation
| if mutated = fail to control T cell activation
71
what does CTLA4 do?
controls T cell activation
72
difference between a T2SR and a T3SR
T2: antibody reacts with cellular antigen
T3: antibody reacts with soluble antigen to form immune complex
73
what is the autoantigen in pemphigus vulgaris?
auto-antigen against epidermal cadherin
74
what are the autoantigens in SLE and RA (T3R)?
SLE: DNA, histones, RNP
RA: Fc region of IgG
75
what does sensitisation show?
shows risk of allergic disorder but does not define allergic disease
76
how do helminths/allergens/venoms trigger immune response?
cause functional change which is recognised
| causes Th2 response
77
what are the 3 different responses to allergens?
1. Th2/Th9/ILC2 cells
2. Follicular Th2 cells
3. mast cell
78
what is the process of Th2/Th9 and ILC2 cells response to allergens?
1. release of IL4, IL5, IL13
2. eosinophils and basophils activated
3. expulsion of parasites and allergens
79
what is follicular Th2 response to allergens?
1. IL4 released
| 2. causes B cells to produce IgE and IgG4
80
what is the mast cell response to allergen?
1. cross-linking of IgE
2. histamine/leukotrienes released
3. expulsion
(also responsible for symptoms of asthma, eczema and hayfever)
81
what is the difference between oral exposure and skin/resp exposure?
oral exposure = immune tolerance
| skin/resp exposure = IgE sensitsation
82
what is a positive skin prick test ?
wheal >3mm compared to negative control
83
what is the most frequent organ involved in anaphylaxis?
skin
84
what are the 4 mechanisms of anaphylaxis?
IgE
IgG
Complement
Pharmacological
85
what cells and mediators are involved in IgE anaphylaxis and an example?
mast cells/basophils
histamine and PAF
e.g. food
86
what cells and mediators are involved in IgG anaphylaxis and an example?
macrophages/neutrophils
histamine and PAF
e.g. biologicals and blood
87
what cells and mediators are involved in complement anaphylaxis and an example?
mast cells/macrophages
PAF, histamines
e.g. dialysis and PEG
88
what cells and mediators are involved in pharmacological anaphylaxis and an example?
mast cells
leukotrienes and histamines
e.g. NSAIDs
89
what is the influence of IM adrenaline on the different receptors?
- alpha 1: peripheral vasoconstriction
- beta 1: increase HR, contraction and BP
- beta 2: relaxes SM, decrease inflammatory mediators
90
what are the different IgE mediated food allergy syndromes?
- food associated exercise induced anaphylaxis (within 4-6 hrs)
- delayed food induced anaphylaxis to beef, pork, lamb
- oral allergy syndrome
91
what is the MOA of delayed food induced anaphylaxis?
IgE antibody to alpha 1, 3 galactose in gut bacteria
| induced by tick bites
92
what are the reactions in oral allergy syndrome?
pollen cross reacts to stone fruits/veg/nuts
93
what chromosome is HLA expressed on?
6
94
where are HLA class 1 and II expressed?
1: A, B, C = ALL cells
2: DR, DQ, DP = APC, upregulated in stress
95
what are the most immunogenic HLA?
A, B, DR
96
what is important to remember about APCs involved in activating T cells?
combo of both DONOR and RECIPIENT APCs
97
what are the histological features of T-cell mediated rejection?
- lymphocytic interstitial infiltration
- ruptured tubular BM
- tubilitis
98
what are the histological features of AB-mediated rejection?
presence of inflammatory cells within capillaries of kidney = capillaritis
= graft fibrosis
99
what are the different T cell immunosuppressants?
- calcineurin inhibitors e.g. tacrolimus/cyclosporine
- cell cycle inhibitors e.g. mycofenolate mofetil, azathioprine
- targeting TCR e.g. Anti-CD3 Ab (OKT3), anti-thymocyte
- Alemtuzimab (anti-CD52 Ab)
- Daclizumab (anti-CD25 Ab)
100
what is the MoA of targeting TCR?
Anti-CD3 Ab (OKT3), anti-thymocyte globulin
| = apoptosis of T cells
101
what is the MoA of alemtuzimab?
anti-CD52 Ab
| = lysis of T cells
102
what is the MoA of Daclizumab?
anti-CD25Ab
| = targets cytokine signals
103
name 2 types of B cell immunosuppression
- BAFF inhibitors
| - Proteasome inhibitors e.g. bortezemib
104
what is the MoA of BAFF inhibitors?
target cytokines that promote B cell activation
105
what is the MoA of proteasome inhibitors?
e.g. bortezemib
| = blocks production of Ab by plasma cell
106
induction transplant immunosuppressive regimen
OKT3.ATG
anti-CD52
anti-CD25
107
baseline transplant immunosuppressive regimen
calcineurin inhibitor
| mycophenolate +/- steroids
108
what is GvHD prophylaxis?
methotrexate
| cyclosporine
109
what are the neutralising Ab in HIV?
Anti-gp120
| anti-gp41
110
what are the non-neutralising Ab in HIV?
anti-pp24gagIgG
111
what are the 2 error prone steps in HIV replication?
1. reverse transcriptase (RNA to DNA)
| 2. transcription of DNA into RNA copies
112
what is the life cycle of HIV?
1. attachment and entry
2. reverse transcription and DNA synthesis
3. integration
4. viral transcription
5. viral protein synthesis
6. assembly of virus, release of virus
7. maturation
113
what is the screening vs confirmatory test for HIV?
HIV Ab ELISA = screening test
| HIV Ab Western blot = confirmatory test
114
what is the HIV ART therapy?
2 x NRTI + 1 NNRTI/boosted PI
115
what do NNRTI/NRTI end in?
- ine
116
what do PIs end in?
- avir
117
what is the target of the flu vaccine?
Ab against HA
118
what are the live vaccines
```
MMR
BCG
Yellow fever
typhoid
polio (sabin)
```
119
what are the toxoid (inactivated toxin) vaccines?
diptheria
| tetanus
120
what are the component/subunit vaccines?
Hep B
HPV
Influenza
121
what are the conjugate vaccines?
HiB
Meningococcus
Pnemococcus
122
what is the role of an adjuvant?
increase immune response
| mimic action of a PAMP
123
how does CAR-T therapy work?
chimeric receptors
| can influence both B and T cells
124
what diseases is CAR-T therapy being used in?
ALL and NHL
125
what are CTLA4 and CD28?
- both expressed on T cells
- both regulate same antigens on APCs (CD80, CD86)
CD28 = stimulatory signal
CTL4 = inhibitory signal
126
what is the MoA of ipilimumab?
Ab spcific to CTLA4 = blocks it
| interactions occur through CD28 = stimulatory = more T cells
127
ipilimumab indication
advanced melanoma
128
what is the MoA of pembrolizumab/nivolumab?
Ab specific to PD1
129
pembrolizumab/nivolumab indication
advanced melanoma
130
what can IFN alpha be used to treat?
```
hep B
Hep C
Kaposi sarcoma
CML
MM
```
131
what can IFN beta be used to treat?
Behcet's
132
how do corticosteroids decrease inflammation?
corticosteroids inhibit phospholipase A2
block arachidonic acid and prostaglandin formation
= decrease inflammation
133
effect of corticosteroids on lymphocyte function?
- lymphopaenia
- blocks cytokine gene expression
- decrease Ab production
- promotes apoptosis
134
what are the different anti-proliferative agents?
inhibit DNA synthesis
- cyclophosphamide
- mycophenolate
- aziothioprine
- methotrexate
135
MoA of cyclophosphamide
| SE
alkylate G base of DNA
| SEs: haemorrhagic cystitis
136
MoA of azathiorpine and a caution
metabolised to 6-mercatopurine
blocked de novo purine synthesis
Check TPMT
137
MoA of mycophenolate
| SE
block de novo nucleotide synthesis
prevents T cell > B cell
SE: PML (JC virus)
138
MoA of calcineurin inhibitors
| monitor what?
prevent T cell signalling
blocks IL2 production so prevents proliferation
monitor BP and renal function
139
PDE4 inhibitors and indications
prevent activation of TFs
| indication: psoriasis and psoriatic arthritis
140
effect of anti-thymocyte globulin
T cell depletion
141
MoA of Basiliximab
Ab against CD25 (IL-2 receptor)
| decrease T cell proliferation
142
MoA of abatacept
CTLA-4-Ig fusion protein
| decrease T cell activation
143
MoA of Natalizumab
antibody against alpha-4 integrin
| inhibit leukocyte migration
144
indication of Natalizumab
MS
145
what is the MoA of Tocilizumab
decrease activation of macrophages/ T cells/ B cells
146
indications of Tocilizumab
Castleman's disease (IL6 producing tumour)
| RA
147
MoA of Etanercept
TNF-alpha antagonist
| inhibits TNF alpha and beta
148
Etanercept indications
RA
| Ankylosing spondylitis
149
MoA of Ustekinumab
inhibition of IL12 and IL123 (binds p40 subunit)
150
Ustekinumab indication
psoraisis
| Chron's
151
MoA of Secukinumab
Ab to IL17A
152
indication of Secukinumab
psoraisis
| AS
153
what is osteoprotegrin?
binds RANKL
| regulated osteoclast resorption = natural decoy
154
what is a big risk of biological therapy?
auto-immunity
155
what antibodies are found in T1DM
anti-GAD
| anti-IA2
156
histology of T1DM
CD8 T cell infiltration of pancreas
157
genetic associations of RA
HLA DR4
HLA DR1
PAD 2 and PAD 4 polymorphism
158
what does PAD2 and PAD4 do?
increase citrullination = more citrullinated peptides
159
what strange things can cause increased citrinullation and so RA?
smoking
| gum infection with porphyromonas gingivalis
160
what can be seen in the joint in RA?
inflamed synovium = pannus
161
what is ANA?
Ab that bind to nuclear proeins
162
what is lupus nephritis? pattern detection?
immune complex deposition
| granular "lumpy bumpy" pattern
163
2 subtypes of ANA
dsDNA
| extractable nuclear antigen (ENAs)
164
different types of ENAs
ribonucleoprotein (Ro, La, Sm, U1RNP)
| enzymes
165
what provides a homogenous staining ?
dsDNA
166
what is dsDNA found in?
specific for SLE
| high titres = severe disease
167
what provides a speckled pattern?
Extractable nuclear antigens (Ribonucleoproteins)
168
Ribonucleoproteins associated with SLE
Ro
La
Sm
U1RNP
169
Ribonucleoproteins associated with Sjogren's
Ro
| La
170
antibodies in dermatomyositis
anti-Jo
| anti-Mi2
171
what is the pathophysiology of systemic sclerosis
inflammation with Th2 and Th17
| cytokines --> fibroblasts --> fibrosis
172
distinct features of CREST (limited)
- skin involvement does not progress beyond forearms
| - pulmonary HTN not fibrosis
173
Abs in diffuse vs limited (CREST)
diffuse = Scl70 (anti-topoisoerase)
| limited (CREST) = anti-centrometere
174
antibodies in polymyositis
anti-signal recognition peptide Ab
175
what are the small vessel (ANCA) associated diseases?
microscopic polyangiitis
granulomatosis with polyangiitis
Churg Strauss
176
what are the small vessel (immune complex) associated diseases?
anti-GBM
IgA
cyroglobuinaemia
177
cANCA
- cytoplasmic fluorescence
- Abs to enzyme proteinase 3
- Wegner's
178
pANCA
- perinuclear staining pattern
- Ab to myeloperoxidase
- microscopic polyangiitis and Churg Strauss
179
what is the problem in X-linked agammaglobulinaemia?
failure of pre-B cells to mature in bone marrow
180
describe what the PADI enzymes do
arginine to cirtrulline (deamination)
181
what is the treatment for RA
1st: methotrexate
2nd: Rituximab, abatacept, tocilizumab
