Immuno Flashcards
Burkitt’s translocation
t (8:14)
CML translocation
t (9;22)
APML translocation
t (15;17)
Mantel Cell Lymphoma translocation
t (11;14)
Follicular lymphoma translocation
t (14;18)
Infliximab
TNF alpha inhibitor
e.g. Crohn’s
Antiphospholipid Syndrome (Hugh’s Syndrome) Antibodies
Antibodies against:
- cardiolipin
- β2 glycoprotein
lupus anticoagulant
Autoimmune hepatitis ANTIBODIES [3]
Anti-smooth muscle antibody
Anti Liver Kidney microsomal-1 (anti-LKM-1)
Anti-Soluble Liver Antigen (anti-SLA)
Autoimmune haemolytic Anaemia ANTIBODIES
Anti-Rh Blood Group Antigen
Autoimmune Thrombocytopenic Purpura ANTIBODIES
Anti-Glycoprotein IIb-IIIa or Ib-IX Antibody
Churg-Strauss Syndrome (eGPA) ANTIBODIES
Perinuclear/protoplasmic-staining antineutrophil cytoplasmic antibodies (p-ANCA)
Coeliac disease ANTIBODIES
Anti-tissue transglutaminase antibody (IgA)
Anti- endomysial antibody (IgA)
Anti-gliadin
Key note: check IgA levels before
Congenital heart block in infants of mothers with SLE ANTIBODIES
Anti-Ro antibody
Dermatitis herpetiformis ANTIBODIES
Anti-endomysial antibody (IgA)
Dermatomyositis ANTIBODIES
Anti-Jo-1 (t-RNA Synthetase)
Diffuse Cutaneous Scleroderma ANTIBODIES
Antibodies to:
- Topoisomerase/Scl70
- RNA Polymerase I,II,III
- Fibrillarin (nucleolar pattern)
Goodpasture’s Syndrome ANTIBODIES
Anti-GBM Antibody
Graves’ Disease ANTIBODIES
Anti-TSH Receptor Antibody (stimulatory antibody)
Hashimoto’s Thyroiditis ANTIBODIES
Antibodies to:
- Thyroglobulin
- Thyroperoxidase
Limited cutaneous scleroderma (CREST) ANTIBODIES
Anti-centromere antibody
Microscopic Polyangiitis (MPA) ANTIBODIES
Perinuclear/protoplasmic-staining antineutrophil cytoplasmic antibodies (p-ANCA)
Mixed connective tissue disease ANTIBODIES
Anti-U1RNP antibody (speckled pattern)
Myasthenia Gravis ANTIBODIES
Anti-Ach Receptor Antibody
Pernicious anaemia ANTIBODIES [2]
Antibody to:
- gastric parietal cells (90%)
- intrinsic factor (50%)
Polymyositis ANTIBODIES
Anti-Jo-1 (t-RNA Synthetase)
Primary biliary cirrhosis ANTIBODIES
Anti-mitochondrial antibody
Rheumatoid Arthritis ANTIBODIES
Anti-CCP Antibodies, Rheumatoid Factor (less specific)
Sjogren’s syndrome ANTIBODIES
Anti-Ro, Anti-La antibody (speckled pattern), 60-70% have positive RF
Systemic Lupus Erythematosus ANTIBODIES
Antibodies to dsDNA+ Histones (Homogenous) and Ro La, Sm, U1RNP (speckled)
Type 1 Diabetes Mellitus ANTIBODIES
Antibodies to Glutamate Decarboxylase and pancreatic β Cells
Wegener’s Granulomatosis (GPA) ANTIBODIES
Cytoplasmic antineutrophil cytoplasmic antibodies (c- ANCA)
Type IV hypersensitivity diseases
T1DM
Crohns
Rheumatoid Arthritis
Multiple Sclerosis
Contact dermatitis
Mantoux test
Type III hypersensitivity diseases
SLE
Polyarteritis Nodosa
Mixed Essential cryoglobulinaemia
Serum sickness
Type II hypersensitivity diseases
Haemolytic Disease of the Newborn (HDN)
Autoimmune Haemolytic Anaemia (+ ITP = Evan’s Syndrome)
Goodpasture’s Syndrome
Pemphigus Vulgaris
Graves’ disease
Myasthenia Gravis
Acute Rheumatic Fever
Pernicious Anaemia
Churg-Strauss Syndrome (eGPA)
Wegener’s Granulomatosis (GPA)
Microscopic Polyangiitis (MPA)
Chronic Urticaria
Type I hypersensitivity diseases [6]
Atopic dermatitis
acute urticaria
latex food syndrome
allergic rhinitis
food allergy
oral allergy syndrome
measure of mast cell degranulation
tryptase
cell findings in X-linked SCID
low/absent T cells and NK cells
normal or elevated B cells
cell findings in ADA deficiency
low/absent T cells and NK cells
low/absent B cells
defect causing X-linked SCID
common gamma chain (IL-2RG) of the IL-2 receptor
Cytokine for T cells
IL-2
Cytokine for B cell differentiation in plasma cells
IL-4
Cytokines that induce fever
IL-1 and IL-6
what hypersensitivity does skin prick testing assess
type 1 IgE mediated e.g. allergic rhinitis
what hypersensitivity does patch testing assess
type IV e.g. contact dermatitis
Gold standard for food allergy
double-blind, oral food challenge
anti RANKL drug
denosumab
prevents development of osteoclasts which have the RANK receptor
Which cytokine is important in the pathogenesis of rheumatoid arthritis, anyklosing spondylitis and inflammatory bowel disease?
TNF alpha
live attenuated vaccines
MMR
Varicella
BCG
Oral polio (sabine)
Yellow Fever
Inactivated vaccines
Influenza quadrivalent
Polio Salk
Cholera
Pertussis
Rabies
Hep A
typically for boosters
As the pathogen cannot replicate, it usually requires multiple booster shots to provide immunity.
Conjugated vaccines
Neissiera meningitidis
Haemophilus influenzae
Streptococcus pneumoniae
For encapsulated bacteria.
Consist of bacterial polysaccharides conjugated to an immunogenic toxin
Subunit vaccines
Hep B
HPV
typically for viruses
contains proteins found on the surface of the viruses in addition to an adjuvant
Toxoid vaccines
Diphtheria
Tetanus
DNA/RNA vaccines
SARS CoV 2
What is the specific antigen recognised by the immune system in Goodpasture’s syndrome?
Type IV collagen
p-ANCA target
Myeloperoxidase
UC, Eosinophilic Granulomatosis with Polyangiitis, Primary Sclerosing Cholangitis or Microscopic Polyangiitis
c-ANCA target
Proteinase-3
[C is the third letter of the alphabet]
Granulomatosis with polyangiitis (Wegner’s)
Reticular dysgenesis
It is an autosomal recessive condition characterised by:
Severe, life threatening infections shortly after birth
Profound sensorineural deafness
Deficiency of the myeloid and lymphoid cell lineages
Anti-alpha-4-beta-1 integrin (binds to VCAM1 and MadCAM1 to mediate rolling/arrest of leukocytes), inhibits T cell migration
Natalizumab
Relapsing-remitting MS, Crohn’s disease
Risk: JC virus infection causing progressive multifocal leukoencephalopathy
What is the most common inherited immunodeficiency?
Selective IgA def
A lack of IgA leads to infections of mucosal surfaces
calcineurin inhibition drugs
cyclosporine and tacrolimus
intracellular pro proliferative molecule; prevents T cell
proliferation/function via reduced IL-2 expression
Rejection prophylaxis
(transplantation), SLE, psoriatic arthritis.
What lymphocyte lineage does azathioprine predominantly inhibit?
T cells
immunosuppressant that particularly inhibits T cell activation and proliferation
azathioprine
what must be checked before starting azathioprine?
TPMT polymorphism
They cannot metabolise the drug putting them at risk of bone marrow suppression
HLA associations in coeliac disease
HLA-DQ2 (90%)
HLA-DQ8
Th1 response
treatment for Kostmann syndrome
regular injections of granulocyte colony stimulating factor, which increases myelopoiesis and increases neutrophil levels
HLA association in Graves
HLA-DR3
most common transfusion reaction to packed red cells
Febrile non-haemolytic transfusion reaction I
Caused by white blood cells releasing cytokines such as IL-1 during storage.
What protein is defective in X linked Severe Combined Immunodeficiency?
common gamma chain of IL-2R
A mutation in what protein is the most common cause of Hyper IgM syndrome?
CD40 (on B cells)
inability to class switch
risk of pneumocystitis
What is the basic pathophysiology of SLE
Due to the ineffective clearance of dead or dying cells from the body, leading to antibody complex formation.
When cells die, they are removed from the body by phagocytosis. If cells are not removed quickly, an immune response against antigens inside the cell may be mounted
drugs that blocks CD3 on T cells, mouse monoclonal antibody (OKT3)
Use?
Muromonab
Used to prevent active allograft transplant rejection
Anti-CD20 drug that depletes mature B cells (not plasma cells)
Use?
Rituximab
Lymphoma, rheumatoid arthritis, SLE
Anti-IL-6 receptor drug that reduces macrophage, T cell, B cell, neutrophil activation
Use?
Tocilizumab
Castleman’s disease, Rheumatoid arthritis
TNFalpha/TNFbeta receptor drug
also p75-IgG fusion protein, inhibits both cytokines.
Etanercept
Rheumatoid arthritis, Ankylosing spondylitis, Psoriasis and psoriatic arthritis
anti-IL-17A drug
Secukinamab
psoriasis, psoriatic arthritis, ankylosing spondylitis
drugs involved in IL-4 / 5/ 13 blockade treat which conditions?
Eczema, asthma, eosinophilic asthma
Inhibits phospholipase A2
prednisolone
tests for Sjogrens syndrome
Anti Ro and Anti-La
Schirmer test
what type of bacteria are you at risk of with chronic granulomatous disease?
Catalase positive
what pro inflammatory cytokine is released by T killer cells?
IFN gamma
what is the defect leading to cyclic neutropenia
gene coding for neutrophil elastase –> failure of neutrophil maturation
What is the role of Gp120 on HIV?
This receptor is responsible for initial binding to CD4 and a co-receptor, such as the CCR5 receptor.
What is the role of Gp41 on HIV?
Binding of gp120 exposes gp41.
gp41 then leads to fusion with the host cell membrane and viral entry into the cell.
Mutation in what cell surface receptor may confer immunity from HIV?
CCR5
HLA association of rheumatoid arthritis
HLA-DR4
NRTI
Zidovudine, Abacavir
Non-nucleoside reverse transcriptase inhibitor
Efavirenz
Protease inhibitor
Ritonavir
Integrase inhibitor
Dolutegravir
What is the confirmatory test for HIV infection?
Western blot after ELISA
what is the defect in Bruton’s agammaglobulinaemia
BTK (tyrosine kinase gene) for B cell development
what is released by neutrophils to attract other cells like macrophages?
IL-1
What monoclonal antibody targets alpha4 integrin and is used in the treatment of relapsing remitting multiple sclerosis?
Natalizumab
Diagnostic criteria for Common Variable Immunodeficiency
Decrease in serum IgG and a decrease in one of IgM or IgA.
There is a lack of antibody response to antigens or immunisation
More than 4 years old.
Treat with normal human immunoglobulin
what IL is secreted by activated CD4+T cells or activated T killer cells
IL-2
Treatment for Bruton’s
Normal human Ig
Key features of brutons
There is a notable lack of lymphoid tissue (lack of tonsils and adenoids) or lack of lymphadenopathy during infections.
what T cell response do parasites and helminths activate?
Th2 mediated by IL-4, Il-5, IL-13
what T cell are implicated in the development of allergic diseases, such as asthma or eczema
T helper 2 cells
mediated by IL-4, Il-5, IL-13
A correctable/reversible deformity suggests Jaccoud’s arthropathy which is part of which disease?
SLE rather than a diagnosis of rheumatoid arthritis.
drug that binds to IL-12 and IL-23
Ustekinumab
psoriasis, psoriatic arthritis
drugs that binds just IL-23
Guselkumab
psoriasis, psoriatic arthritis
what cell line does mycophenolate mofetil inhibit
T cells
which type of infections does a lack in IgA lead to?
mucosal surface infection e.g. Resp tract, ear, sinus
what are people with IgA def at risk of?
autoimmune disease e.g. coeliac disease
examples of adjuvants
Alum or Aluminium Hydroxide (prime naive B cells)
Bacterial products such as toxoids
Cytokines such as IL-1 or IL-2 In research
Freund’s complete adjuvant (dried Mycobacterium tuberculosis)
Immunoglobulins may bind to cell surface receptors on viruses, to prevent viral binding and entry of human cells.
What is this function of immunoglobins known as?
neutralisation
What is the full chromosomal abnormality found in DiGeorge syndrome?
22q11.2 deletion
mechanism of hyper acute rejection
preformed antibodies against ABO therefore sensitisation must have occurred beforehand
treatment for allergic rhinitis
nasal corticosteroids
oral antihistamines e.g. cetrazine (half life 6 hours)
deficiencies in C2, C3 or C4 (classical pathway) predispose to
SLE
how can the function of the complement system be quantified
CH50 or CH100 tests
test the ability of a serum to lyse sheep erythrocytes
which Immunoglobulin is the most abundant in the serum
IgG
when is IgG created in response to an infection
after 5 days
highly specific
what are functions of IgG
Its functions include:
- activation of the classical pathway of complement via C1q
- neutralisation or antibody dependent cell-mediated cytotoxicity.
how is the response to treatment of anaphylaxis monitored
mast cell tryptase (mast cell activation marker)
What happens in graft versus host disease?
lymphocytes from a transplant donor attack cells and tissues of a transplant recipient.
Typically, this occurs when the recipient is heavily immunosuppressed (and cannot destroy the donor lymphocytes) or very young.
where is most of the damage in GvHD
mucosal surfaces in the area of the transplant
what drug may be used in GvHD
methotrexate
HLA classes A, B and C, which MHC class
1
HLA DR, DQ, which MHC class
2
what are the most important HLA classes in terms of transplant
HLA DR > B > A
in what fashion are HLA subtypes inherited
co-dominant (therefore all are expressed)
Up to 6 HLA subtypes may be inherited, 3 from each parent.
Skin sign seen in polyarteritis nodosa
livedo reticularis
what infection is polyarteritis nodosa associated with
Hep B
what is the classical appearance seen in biopsy in polyarteritis nodosa
Rosary bead (small aneurysms in the arterial wall)
where is the biopsy for polyarteritis nodosa usually taken?
sural nerve (calf)
what type of hypersensitivity reaction occurs in polyarteritis nodosa
type 3
what is the treatment for polyarteritis nodosa
prednisolone
cyclophosphamide
CD14 is typically a marker of what type of immune cell?
monocytes/macrophages
what does CD14 recognise
bacterial endotoxin lipopolysaccharide (LPS)
What key molecule in involved in the pathophysiology of septic shock
bacterial endotoxin lipopolysaccharide
Which type of immunoglobulin is primarily secreted into breast milk and is responsible for passive immunity in newborns?
IgA
IgA structure
dimeric, 4 antigen binding sites
main function of IgA
neutralisation
treatment of mild urticaria during blood transfusion
non-sedating antihistamine
What is the short-term treatment for severe, life threatening antibody mediated damage or dysfunction, for example myasthenic crisis, cyroglobulinaemia or antibody mediated rejection?
plasmapheresis
Plasmapheresis allows for blood to be cleared of harmful antibodies. This means it may be a short term treatment for Type II hypersensitivity reactions or diseases caused by antibodies.
why must serum IgA levels be checked when investigating coeliac disease
Anti-TTG and anti-endomysial antibodies are IgA subtype, therefore a concurrent IgA deficiency (1 in 600) would give a false negative result.
What is the only lymphocyte subset considered to be part of the innate immune system?
NK cells
how do NK cells go about with their ting
NK cells can recognise either lack of MHC (a common tactic of viruses to avoid the immune system, by preventing MHC expression)
or an imbalance in numerous cell surface receptors. Imbalances in cell surface receptors suggests that the cell may be infected, cancerous or dying.
features of Granulomatosis with polyangitis
rapidly progressive crescentic glomerulonephritis
bleeding (nose bleed, coughing blood due to lung cavitations) - 👃 🩸 IS KEY
elevated CRP
peripheral neuropathy
most common cause of b12 def
pernicious anaemia
CD19 is typically a marker of what immune cell?
B cells
how is ANA detected
indirect immunofluroscence
homogenous pattern of ANA staining
anti-dsDNA
“speckled” pattern of ANA staining
anti-centromere antibodies and hence CREST syndrome.
what other auto anitbody may be found in SLE
RF
what other auto antibody may be found in SLE
RF
what are the acute phase proteins
IL-1
IL-6
CRP
which interleukins are pyrogenic
IL-1
IL-6
where does CRP bind and what does it activate
binds to the surface of dead/dying cells
activates the classical complement cascade via C1q
what is found on CSF electrophoresis of a patient with MS
oligoclonal bands of IgG
What lymphocyte lineage does tacrolimus predominantly inhibit?
T cells
What lymphocyte lineage does cyclophosphamide predominantly inhibit?
B cells
when should you stop the transfusion in an allergic reaction
headache, severe widespread rash, airway involvement
Which cell type secretes immunoglobulins?
plasma cells
how is Transfusion Associated Circulatory (TACO) treated
diuretics
how is Transfusion Associated Circulatory (TACO) treated
diuretics
what malignancy is Sjogrens syndrome at greater risk of
Mucosa Associated Lymphoid Tissue lymphoma (of the parotid)
What is the most abundant leukocyte found in peripheral blood?
neutrophils
A tumour cell has mutated and no longer expresses endogenous peptides and MHC Class I on the surface. What immune cell would recognise and kill this mutated cell?
natural killer cells
do natural killer cells express B or T cell receptors
neither
Symptoms of TACO
shortness of breath (pulmonary oedema), peripheral oedema and hypertension.
6 acute transfusion reactions
Anaphylaxis
ABO incompatibility
bacterial contamination
febrile non-haemolytic transfusion reaction
TACO
Transfusion related acute lung injury
What virus is polyarteritis nodosa associated with?
Hepatitis B
which complement deficiencies are most likely to cause symptoms
C5b, C6, C7, C8 and C9 deficiencies are most likely to cause symptoms.
all involved in the MAC complex
Infections by what type of bacteria are more common in patients deficient in the complement protein C9?
Encapsulated bacteria include meningococcus (Neisseria spp.), Haemophilus spp. or pneumococcus (Streptococcus spp.)
What blood product is most commonly contaminated by bacteria?
platelets
max time period an infusion can occur for
4 hours
what type of collagen is a major component of kidney and lung basement membrane
type IV collagen
what two organs can Goodpastures affect
kidneys (glomerulonephritis)
lungs (pulmonary haemorrhage)
which fruits are commonly cause symptoms in latex food syndrome
banana
pineapple
avocado
what is the effect of histamine binding to H1 receptor on endothelial cell surfaces
vasodilation
features of myasthenia gravis
weakness, fatiguability, double vision
treatment of myasthenia gravis
neostigmine
What primary immunodeficiency is suggested in a patient with recurrent infections with E Coli, Staphylococcus Aureus, Listeria spp, Klebiella spp, Serratia marcescens and Candida species?
Chronic Granulomatous Disease
these are catalase positive organisms
oral vs oesophageal candidiasis
A white pseudomembrane which can be removed is highly suspicious for candidiasis. Often, it may be itchy, sore or bleed.
Oral candidiasis may be seen in patients with poor inhaler technique using inhaled corticosteroids for asthma or COPD.
Oesophageal candidiasis presents differently, usually with a difficulty in swallowing. In any patient with oral or oesophageal candidiasis, it is highly suspicious for an immunodeficiency - indeed oesophageal candidiasis is an AIDs defining illness.
What autoantibody, sometimes detectable in Graves’ disease, is a useful clinical marker in monitoring thyroid cancer?
Anti-thyroglobulin antibodies
What monoclonal antibody targets CD25 and is used in the prophylaxis and treatment of allograft rejection?
basiliximab
CD25, or the interleukin 2 receptor chain alpha, is one of the three components of the IL-2 receptor.
It used to be used in the treatment of allograft rejection, but now may be used for treatment of multiple sclerosis.
what do drugs that target CD25 stop the proliferation of
T cells
CD25, or the interleukin 2 receptor chain alpha, is one of the three components of the IL-2 receptor –> T cells
What disease is Tofacitinib used in? [3]
rheumatoid arthritis
psoriatic arthritis
ulcerative colitis
JAK1/3 inhibitor reduces the expression of pro-inflammatory cytokines that are responsible for cellular damage.
what drug can cause a benign leukocytosis
corticosteroids
lithium
inheritance of Kostmann syndrome
autosomal recessive
What predilection do Kostmann syndrome babies have to form
abscess formation
tightening of the skin on wrist, arm, trunk and around mouth
limited SS or diffuse SS?
diffuse
Chimeric Antigen Receptor T cells example
tisagenlecleucel against CD19
used for B cell Acute Lymphoblastic Leukaemias or large B cell lymphomas
which transciption factor do Treg express
FoxP3
what does Treg secrete to suppress the immune response
secreting IL-10
how can Treg inhibit the T cell response
inhibitory signal via CTLA4, competitively binding to CD28
drug that inhibits Tregs
Anti-CTLA4 antibodies (Ipilimumab)
causing an increase in immune system function. Useful in cancers
What monoclonal antibody targets CD52 and causes depletion of all lymphocyte subsets?
alemtuzumab
CD52 is found on both B and T cell lymphocytes at various stages of development.
Used for T cell lymphomas
which cell is response for the white material in pus
neutrophils
what cell has CD20
mature B cells
What condition may be precipitated by mutations in NOD2/CARD15?
Crohn’s Disease
antibody likely to be found in patient wtih SLE with recurrent clots
anti-cardiolipin
Used to treat severe ankylosing spondylitis not controlled by NSAIDs
etanercept
Used to treat malignant melanoma, involved in T cell checkpoints
ipilimumab or nivolumab
differential diagnosis for anaphylaxis
- C1 inhibitor deficiency (herediatory angioedema)
- ACEi induced angioedema
- anxiety
- urticaria
Woman with flushed face, problems breathing that has happened multiple times with enlarged liver
hereditary angioedema
Can lead to development of post transplantation lymphoproliferative disease
Epstein Barr Virus
Ankylosing spondylitis – they’ve tried NSAID and TNF inhibitor, what else can you target
IL-17
e.g. Secukinamab
what conditions can be treated with CAR-T therapy?
B cell cancers
ALL
Non-Hodgkin lymphoma
what CD does CAR-T therapy often target
CD19
What is the effect of the gene mutation in familial Mediterranean fever?
increased IL-1 production
Woman with periorbital purple rash (heliotrope) and rash on knees, which enzyme is elevated?
creatine kinase
dx: dermatomyositis
two key features of dermatomyositis
Heliotrope rash with eyelid oedema
gottrons papules
complication with cyclophosphamide
haemorrhagic cystitis
which cells are inhibted by MHC-1
NK cells
formula to express herd immunity threshold
1-1/R0
What is the effect of the gene mutation in familial mediterranean fever?
increased IL-1production
Drug that can be used in advanced melanoma and metastatic renal cancer
Ipilimumab
Pembrolizumab
Nivolumab
What protein on HIV initiates binding on which protein of its target cell?
Gp120 on HIV binds CD4 on T helper cells.
After binding, it undergoes conformation changes to enable binding to co receptors on host cells namely CCR5 (macrophages or T cells) or CXCR4 (T cells)
Which protein on HIV is prone to mutation
Gp120
Cell numbers in BLS 1
Low CD8
Normal CD4 therefore normal antibody levels
Normal B cells
Cell numbers in BLS 2
Low CD4
Normal CD8
Normal B cells
No antibodies produced as no CD4 to prime the B cells
ALL flow cytometry markers
CD34= precursor/stem cells
CD3, 4, 8 = T cells
CD19, 20, 22= B cells
TdT
AML flow cytometry markers
CD34= precursor/ stem cells
CD33, CD13, CD117, MPO= myeloid cells
Which cancers have the translocation t(9;22)
CML and ALL
what are the antibody levels in X-linked SCID, BLS 1 and BLS 2
X-linked SCID: low
BLS 1: normal
BLS 2: low
x-linked: no CD4 T cells to isotype switch
BLS 1: CD4 cells present to isotype switch
BLS2: no CD4 cells present to isotype switch
