Immuno Flashcards
infant with diarrhoea, failure to thrive and skin infections (candida). atrophy of thymus and mucosa-associated lymphoid tissue noted. Diminished T cells, non-functional b cells
Severe combined immunodeficiency
child with recurrent bacterial infections. blood count shows neutropenia. NBT test is normal
Kostmann syndrome
autosomal dominant condition with neutropenia every 3 weeks or so
cyclic neutropenia
condition with a very high neutrophil count, but absent pus formation. NBT test positive. Delayed umbilical cord sloughing
leukocyte adhesion deficiency
child with recurrent chest infections. normal t cell count, but diminsished b cell count, as well as IgA, IgM and IgG. Absent lymph nodes and tonsils. B cells cannot mature
Bruton’s x-linked a-gammaglobulinaemia
patient with diarrhoea, fever, tiredness. chest infections since diarrhoea, Crohn’s history
protein-losing enteropathy
child with recurrent chest infections, cleft lip, hypocalcaemia. Reduced T cells, IgG, IgA, absent thymus. Normal B cells, IgM. Also cardiac abnormalities and oesophageal atresia.
Di George’s syndrome
Elevated IgM, no IgG, IgA or IgE
Hyper IgM syndrome
child with recurrent chest infections and eczema. also easy bruising, nose bleeds and gi bleeds,reduced IgM, normal IgG, elevated IgA and IgE
Wiskott-Aldrich syndrome
20 year old with recurrent pneumonia. predisposed to autoimmune diseases, as well as increased risk of lymphoma and granulomas. MHC class 3 mutation. Reduced B and T cell functionality, reduced IgM, IgA, IgG and IgE.
Common variable immunodeficiency
Child recurrent skin infections and fungal infections. Chronic inflammation with non-caseating granulomas. NBT test negative. Lymphadenopathy, hepatosplenomegaly, pus. Normal neutrophil count. NADPH oxidase deficiency.
Chronic granulomatous disease
Sclerosing cholangitis with hepatomegaly and jaundice. MHC 1 deficiency –> CD8 T cell deficiency
Type 1 bare lymphocyte syndrome
Sclerosing cholangitis with hepatomegaly and jaundice. MHC 2 deficiency –> CD4 T cell deficiency
Type 2 bare lymphocyte syndrome
Recurrent mild resp/ GI infections, anaphylaxis to transfusions
Selective IgA deficiency
Sickle cell anaemia patients are vulnerable to which type of infection
Encapsulated bacteria (S. pneumonia)
Autosomal recessive condition resulting in severe sepsis a few days after birth. Absolute deficiency in both granulocytes and lymphocytes
Reticular dysgenesis
ADA deficiency cell count abnormalities
Low B, T and NK cells
Disease resulting in reduced activation of macrophages, so no granulomas can form. Patient susceptible to intracellular pathogens (TB, salmonella)
Interferon gamma receptor deficiency
Most important HLA antigens to match
HLA-A, HLA-B, HLA-DR
Name a monogenic auto-inflammatory disease
Familial mediterranean fever
Pathogens you are susceptible to in chronic granulomatous disease
catalase positive (pseudomonas, listeria, aspergillus, candida, E. coli, s. aureus, serratia)
What do all patients with C2 deficiency have
SLE
severe skin disease, increased infections
Patients with increased susceptibility to infection in MBL deficiency
premature infants, chemotherapy, HIV, Ab deficiency
alternative complement pathway deficiencies lead to increased infections with…
encapsulated bacteria
SLE pathogenesis
production of immune complexes leading to consumption of C3 and C4
Ix for classical pathway activity
CH50
Ix for alternative pathway activity
AP50
factors of classical complement pathway
C1q, C1r, C1s, C2, C4
most common classical pathway deficiency
C2
common pathway factors
C3, C5-9
deficiency of common pathway factors leads to infections with…
N. meningitidis
S. pneumoniae
H. influenzae
5 month old girl with recurrent fungal infections, diarrhoea and failure to thrive. Family history of early infant death. Bloods show absent B cells, T cells and NK cells
ADA deficiency
What protects SCID infant for first 3 months
maternal IgG
autoinflammatory conditions are a defect in which type of immunity
innate
autoimmune conditions are a defect in which type of immunity
adaptive
familial mediterranean fever symptoms
periodic fevers and serositis
familial mediterranean fever pathogenesis
MEFV mutation –> abnormal TNFa/ IL1 signalling
familial mediterranean fever treatment
colchicine
anakinra (IL1-R antagonist)
etanercept (TNFa inhibitor)
name a polygenic autoinflammatory disease
crohn’s
name a mixed pattern disease
Ankylosing spondylitis
psoriatic arthritis
behcet’s
mixed pattern disease pathogenesis
HLA-B27 mutation affects CD8 T cells, Th17 cells, NK cells
name a polygenic autoimmune disease
rheumatoid arthritis, myasthenia gravis, pernicious anaemia, SLE
Goodpasture disease HLA association
HLA-DR15
Grave’s disease HLA association
HLA-DR3
SLE HLA association
HLA-DR3
T1DM HLA association
HLA-DR3/4
Rheumatoid arthritis HLA association
HLA-DR4
Name a monogenic autoimmune disease
APECED
IPEX
ALPS
APECED features
mutation of AIRE transcription factor means lack of negative T cell selection
autoimmune polyendocrinopathy candidiasis ectodermal dystrophy
IPEX features
mutation in FoxP3 required fpr T reg cell development
Treg cells CD25+, FoxP3x
immune dysregulation, polyendocrinopathy, enteropathy, X-linked
diarrhoea, diabetes, dermatitis
ALPS features
mutation in Fas pathway –> T cells not killed in thymus
large spleen + lymph nodes, autoimmune cytopenia, lymphoma
autoimmune lymphoproliferative syndrome
type 1 hypersensitivity mechanism
sensitisation in primary exposure
Ag cross links IgE on mast cells –> degranulation
type 1 hypersensitivity example
atopic eczema
anaphylaxis
type 2 hypersensitivity mechanism
antibody binds to surface antigen
type 2 hypersensitivity example
Graves, myasthenia gravis
type 3 hypersensitivity mechanism
antibody-antigen complexes deposit in tissue
type 3 hypersensitivity example
SLE, serum sickness
type 4 hypersensitivity mechanism
T cell mediated
CD4+ release cytokines
CD8+ kill target cells
type 4 hypersensitivity example
T1DM, contact dermatitis
live attenuated vaccines examples
MMR (HIV safe)
Varicella zoster
BCG (NOT HIV safe)
Yellow fever (NOT HIV safe)
oral polio, typhoid
inactivated vaccine example
polio (salk)
anthrax
influenza
hep a
component/ subunit vaccine example
Hep B
HPV
Influenza
Toxoid vaccine example
diptheria
tetanus
pertussis
conjugate vaccine example
N. meninigitidis
Haemophilus influenza B
Strep pneumoniae
DNA/ mRNA vaccine example
covid vaccines
human normal immunoglobulin uses
ITP, Kawasaki, GBS, measles
what is pavilizumab
monoclonal antibody for RSV
interferon alpha uses
Hep B, C and CML
Kaposi’s sarcoma
hairy cell leukaemia
multiple myeloma
interferon beta uses
behcet’s
relapsing MS
interferon gamma use
chronic granulomatous disease
which antibody is responsible for protecting against GI infections
IgA
ipilimumab receptor and indication
CTLA4
melanoma
moromonab receptor and indication
CD3
transplant rejection
dacilizumab receptor and indication
IL2
transplant rejection
denosumab receptor and indication
RANKL
osteoporosis, bone mets pain, hypercalcaemia
infliximab receptor and indication
TNF-alpha
IBD
how do corticosteroids cause immunosuppression
reduce traffic of neutrophils to sites (causes transient increase in plasma counts)
reduce phagocytosis and release of proteolytic enzymes
increase lymphocyte apoptosis
increase lymphocyte migration back into nodes, spleen etc
inhibit NF-kappaB
inhibit phospholipase A2
azathioprine MOA
stops DNA production (metabolised to purine analogue 6-mercaptopurine)
affects T cells more than B
azathioprine indication
transplantation
autoimmune and autoinflammatory diseases
mycophenolate MOA
blocks de novo guanosine synthesis
affects T cells more than B cells
mycophenolate indication
transplantation
autoimmune and vasculitis
mycophenolate side effects
HSV reactivation
JC virus reactivation –> progressive multifocal leukoencephalopathy (PML)
progressive neural demyelination condition
cyclophosphamide MOA
alkylates gaunine base –> stops DNA replication
affects B cells more than T cells
cyclophosphamide indication
multisystem connective tissue disease or vasculitis e.g. Wegener’s, SLE
GvHD
cyclophosphamide side effects
haemorrhagic cystitis + bladder cancer
haem malignancies
non-melanoma skin cancer
methotrexate indication
autoimmune RA
psoriasis
crohn’s
anti-tumour
methotrexate side effects
pneumonitis
pulmonary fibrosis
cirrhosis
what is plasmaphoresis
remove pathogenic Ab from plasma
indicated in type 2 hypersensitivity reactions (goodpasture, myasthenia gravis, Ab-mediated rejection)
what should you give with plasmaphoresis to prevent rebound Ab production
cyclophosphamide
name some calcineurin inhibitors
tacrolimus
ciclosporin
calcineurin inhibitor MOA
stop IL2 expression, blocking T cell proliferation
calcineurin inhibitor indication
transplantation
calcineurin inhibitor side effects
nephrotoxic
HTN
neurotoxic
diabetogenic
gum hypertrophy (ciclosporin)
name an mTor inhibitor
sirolimus
mTor inhibitor MOA
inhibit IL2 signaling pathway
mTor inhibitor indication
transplantation
mTor inhibitor side effects
HTN
less nephrotoxic than calcineurin inhibs
name some JAK inhibitors
tofacitinib
ruxolitinib
JAK inhibitor MOA
reduced production of inflammatory molecules
JAK inhibitor indication
RA
Name a PDE4 inhibitor
apremilast
PDE4 inhibitor MOA
increase cAMP, reduce cytokine production
PDE4 inhibitor indication
psoriasis
psoriatic arthritis
basiliximab MOA
target IL-2R
prevent T cell proliferation
natalizumab MOA
target alpha4 integrin
prevent T cell migration
natalizumab indication
MS
rabbit anti-thymocyte MOA
prevent T cell proliferation
rituximab MOA
target CD20 on B cells, only epxressed on mature cells, not plasma cells
antobody level remains as plasma cell population in tact
deplete b cells for 6 months
rituximab indication
B cell lymphomas
RA
SLE
rituximab side effects
progressive multifocal leukoencephalopathy
abatacept MOA
target CTLA4-Ig infused protein
enhance CTLA4 (which is an inhibitory checkpoint for T cell activation)
abatacept indication
RA
abatacept side effects
infection - TB, hep B/C
which HLA antigens are expressed on all cells
HLA class 1 (A, B, C)
which HLA antigens are expressed on antigen presenting cells
HLA class 2 (DR, DQ, DP)
MHC class 1 present antigens to which class of T cells
CD8+
MHC class 2 present antigens to which class of T cells
CD4+
order of importance in HLA matching
DR > B > A
hyperacute rejection pathology
preformed antibodies activate complement
thrombosis, necrosis
hyperacute rejection treatment
prevent via HLA and ABO matching beforehand
acute T cell mediated rejection pathology
type IV hypersensitivity, cell infiltration
acute T cell mediated rejection treatment
T cell suppression - rabbit anti-thymocyte globulin or basiliximab
acute antibody mediated rejection pathology
antibody attacks endothelium
vasculitis
acute antibody mediated rejection treatment
rituximab (b cell suppression), Ab removal
chronic rejection pathology
fibrosis, glomerulonephropathy, bronchiolitis obliterans
chronic rejection treatment
prevent further organ damage
GvHD symptoms
rash, N&V, abdo pain, diarrhoea, bloody stool, jaundice
GvHD prophylaxis
cyclosporine, methotrexate, irradiate transfused blood products
Disease associated with anti-CCP (cyclical citrullinated peptide)
RA
Disease associated with anti-smooth muscle
autoimmune hepatitis
primary sclerosing cholangitis
Disease associated with ant-Jo1
dermatomyositis
dermatomyositis symptoms
heliotrope rash around eyes
gottron’s papules on dorsum of finger joint
difficulty climbing stairs, rising from chair
raised ESR, CK
Disease associated with anti-centromere
limited systemic scleroderma
limited systemic scleroderma symptoms
raynauds, oesphageal dysmotility, sclerodactyly, telangiectasia
raised ESR, hypergammaglobinaemia, reduced Hb
Disease associated with anti-topoisomerase
diffuse systemic scleroderma
diffuse systemic scleroderma symptoms
CREST + renal, cardiac and pulmonary involvement
Disease associated with pANCA
churg-strauss syndrome
churg-strauss symptoms
eosinophilia, asthma, chronic sinusitis, malaise, fatigue, weight loss
Disease associated with anti-double stranded DNA
SLE
Disease associated with anti-parietal cell
pernicious anaemia
Disease associated with anti-Ro/ anti-La
sjogren’s syndrome (also SLE)
Disease associated with anti-mitochondrial
primary biliary cirrhosis (pruritis, reduced absorption of soluble vitamins)
Disease associated with anti-glutamic acid decarboxylase
T1DM
Disease associated with cANCA
wegener’s granulomatosis
wegener’s granulomatosis symptoms
epistaxis
saddle nose deformity
pulmonary haemorrhage
glomerulonephritis
treat with lifelong corticosteroid immunosuppression
Disease associated with anti-endomysium, anti-ttg and anti-gliadin
coeliac
Disease associated with anti-cardiolipin
antiphospholipid syndrome
SLE
syphilis
Disease associated with anti-RNP
mixed connective tissue disease
Disease associated with anti-nuclear
SLE, sjogren’s, autoimmune hepatitis, dermatopolymyositis
Disease associated with anti-intrinsic factor
pernicious anaemia
what does a high CH50 indicate
acute or chronic inflammation (ie RA)
IgE roles
parasitic infections
also involved in mast cell activation in type 1 hypersensitivity
coeliac HLA association
HLA DQ2
ankylosing spondylitis HLA association
HLA B27
goodpasture’s HLA association
HLA DR2
HLA DR3 association
Graves
SLE
myasthenia gravis
HLA DR4 association
T1DM
RA
post-streptococcal rheumatic fever mechanism
molecular mimicry
Di George’s mutation
22q11 deletion
IFN-gamma receptor deficiency susceptiblity
intracellular pathogens (salmonella, TB)
what other conditions is selective IgA deficiency linked to
autoimmune diseases (RA, SLE, coeliac)
what mutation causes hyper IgM
mutation in CD40 ligand on T cells (X linked condition)
what infection are hyper IgM patients susceptible to
pneumocystis jirovecci
what is the mutation in common variable immunodeficiency
MHC class 3 –> aberrant class switching
increased risk of lymphomas, granulomas
clinical features - bronchiectasis, sinusitis
bloods - normal IgM, decreased IgA, IgG, IgE
what Ig are type 1 hypersensitivity reactions mediated by
IgE
gold standard for investigating type 1 hypersensitivity reactions
skin prick test
what are serum tryptase levels useful for
diagnosing anaphylaxis
what is the first immune component to initiate the response in ABO incompatibility
C1
pemphigus vulgaris antibodies
anti-demoglein 1 and 3
what can antibodies directed at chlamydia trachomatis cause
reactive arthritis (arthritis, dysuria, conjunctivitis, uveitis)
which proteins are implicated in the pathogenesis of MS
proteolipid protein
myelin basic protein
what antigens are the target for T cells in rheumatoid arthritis
synovial membrane antigens
what is the name for a transplant from an identical twin
isograft
what is an allograft
donor is same species as recipient but not identical
what does ABO mismatch cause in transplantation
hyperacute rejection
cyclosporine A MOA
calcineurin inhibitor
azathioprine MOA
metabolised into 6-mercaptopurine - purine analogue that prevents DNA synthesis
daclizumab target
CD25 of IL2 receptors - used in kidney transplant pts
how does HIV bind to cell
gp120 binds to CXCR4 receptor on cd4 t cell
IgG can be used to treat…
bruton’s agammaglobinaemia
hyper IgM syndrome
haematopoietic stem cell transplant indications
SCID
leukaemia
MM
interferon-alpha uses
Hep B
Hep C
Kaposi sarcoma
CML
interferon-gamma uses
chronic granulomatous disease
interferon-beta uses
MS
severe mysthenic crisis management
plasmapheresis (also useful for goodpasture’s)
what cytokine is adalimumab specific to
TNF-alpha
infliximab MOA
TNF-alpha antagonist
TNF-alpha antagonist uses
RA, crohn’s, ankylosing spondylitis
denosumab MOA
antibody directed at RANK ligand –> inhibition of osteoclast function (prevent bone breakdown)
denosumab uses
MM
osteoporosis
bone metastases
dermatomyositis antibody
anti-jo1, anti-nuclear
dermatomyositis clinical features
heliotrope rash around eyes
gottron’s papules on dorsum of finger joints
weakness of proximal limb muscles
dermatomyositis immunofluoresence pattern
speckled
peripheral pattern on immunofluoresence
anti-dsDNA (SLE)
hashimoto’s thyroiditis antibodies
anti-thyroid peroxidase
anti-thyroglobulin
autoimmune hepatitis type 1 antibodies
anti-nuclear antibodies
anti-smooth muscle antibodies
autoimmune hepatitis type 2 (younger patients) antibodies
anti-liver kidney microsomal
primary biliary cirrhosis antibodies
anti-mitochondrial
autoantibodies to components of hemidesmosomes of the basement membrane
bullous pemphigoid
autoantibodies to type 7 collagen
epidermolysis bullosa
vitiligo antibodies
anti-melanocyte
epistaxis, haemoptysis, positive for cANCA
wegener’s granulomatosis
axial rigidity associated with a history of autoimmune disease and circulating anti-glutamic acid decarboxylase antibodies
stiff man syndrome
target for autoantibodies in GBS
ganglioside LM1(A)
assay for gold standard HIV diagnosis
western blot
rapdily progressive glomerulonephritis with nosebleeds/ haemoptysis
wegener’s granulomatosis
cd20
b cell
what should new diagnoses of t1dm be screened for
coeliac
