A sub-unit / conjugate vaccine
HIB
Inactivated preparations of the bacteria (vaccine example)
Whole cell typhoid
Vaccine that is made using recombinant DNA technology.
HepB
An antigen assembled in a multimeric form and saponin that provokes a strong serum antibody response.
Immune Stimulating Complex (ISCOMS)
The general name for a compound which increases the immune response without altering its specificity.
Adjuvant
A vaccine given only to sero-negative women
Rubella
A feature of immunological central memory
IL-2 Central memory (CM) T cells migrate efficienctly to peripheral LNs and produce IL-2,
Which live attenuated organism do BCG vaccines contain?
Mycobacterium bovis
Agent used in humans that promotes a predominantly antibody response through the release of Il-4 that primes naïve B-cells.
Alum
Live attenuated vaccine that is no longer given as standard in the UK since the rates of reverse mutation are higher than those of active disease. Excreted in the stools of immunised individuals.
Oral Polio
Subunit vaccine given to the elderly and immunocompromised
iNFLUENZA
Inactivated Vaccines
Hep A, Salk (polio), anthrax, cholrea, bubonic plague,rabies, pretussis
A water-in-oil emulsion containing mycobacterial cell wall components that could be used to increase the immune response of a vaccine.
Freud’s adjuvent
CpG (unmethylated)
Acts as an immunostimulatory adjuvant. Activates TLRs on APCs stimulating expression of costimulatory molecules.
A 3 year old girl is brought into AandE by her parents. She has had vomiting and diarrhoea since early yesterday evening when she was at a birthday party. On examination she has urticaria.
Food allergy
A 25 year old woman presents to her GP complaining of itchy, red wheals on her torso which have been present for 7 weeks. She can not remember how they started but has noticed they are worse in the heat and when she exercises.
Chronic urticaria
A 40 year old man presents to his GP complaining of loss smell and nasal itching and discharge. On examination his nasal mucosa are swollen and have a bluish tinge. His symptoms improve with a corticosteroid spray
Allergic rhinitis
A 55 year old man with history of angina was advised to take a tablet before a long flight. After taking the pill, he suddenly finds that he has difficulty breathing, feels nauseous and is itching.
Mast cell degranulation - caused by taking aspirin before a flight.
A 24 year old medical student develops worsening swelling of the hands and feet and abdominal pain before her final year medical exams. She says that similar milder episodes have occurred preciously.
Idiopathic angioedema
A 26 year old male who has been suffering from ‘flu-like’ symptoms with fever presents to the GP after developing skin rash in the last few days.
Acute urticaria - Severe acute urticaria is effectively treated with a short course of oral anti-histamines
A 35 year old woman presents with persistent itchy wheels for the last 2 months. She noticed that when this is at its worst, she also has a fever and feels generally unwell. After an acute attack, she has bruising and post-inflammatory residual pigmentation at the site of the itching.
Urticarial vasculitis. Urticarial rashes that last more than 24 hours in a single site, resolve with bruising or skin depigmentation
may raise the possibility of an underlying vasculitis.
This 45 year old woman presents to AandE with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine.
Acute angioedema - This woman has angioedema of the tongue, without symptoms suggestive of a generalised allergic reaction. Isolated angioedema may be allergic in origin, but 94% of cases angioedema presenting to AandE are drug induced and the majority of these are associated with ACE inhibitors (eg captopril).
A 22 year old woman presents with an intermittently itchy and desquamating skin rash on her abdomen which is unresponsive to antihistamines
Contact hypersensitivity
A 19 year old male presents to AandE with increasing breathlessness. On examination his blood pressure is 90/55 mmHg and his respiratory rate is 28/min. He shows you a generalised red itchy skin rash, and examination of his chest reveals bilateral inspiratory and expiratory wheezes throughout.. Treatment?
IM adrenaline 1mL of 1:1000. Plus 100% O2, inhaled bronchodilators, IV fluids, hydrocortisone and chlorphenamine.
A 40 year old man complains of loss of smell with nasal itching and discharge over 4 weeks. He also describes morning sneezing. He is otherwise in good health. On examination his nasal mucosa are swollen and hyperaemic. Treatment?
Oral antihistamines and intranasal corticosteroids are the mainstay of treatment of mild allergic rhinitis
This 45 year old woman presents to AandE with tongue swelling and acute respiratory tract obstruction. She has longstanding hypertension and received a renal transplant two years previously. She has no history of allergic disease. On examination her blood pressure is stable, and examination of her lung fields reveal normal breath sounds. Her current medication includes cyclosporine, azathioprine, captopril and nifedipine. Treatment?
IM adrenaline 0.5mL of 1:1000 Intramuscular adrenalin should be used in patients with severe local angioedema with secondary acute respiratory tract obstruction. However this is not always effective in ACE inhibitor-induced angioedema, and some patients will require intubation. Always stop the causative agent!
Cytokines exertine anti-viral effect?
Interferon
Immunglobulin diner
IgA
MHC associated with Th1 and Th2 cells
MHC Class 2
Acts on hepatocytes to induce synthesis of acute phase proteins in response to bacterial infection
IL-6
Arise in the first few days after infection and are important in defence against viruses and tumors
Natural Killer Cells
MHC associated with cytotoxic T cells
MHC 1
Along with IgD, is one of the first immunoglobulins expressed on B cells before they undergo antibody class switching
IgM
The most abundant (in terms of g/L) immunoglobulin in normal plasma
IgG
Deficiencies in this predispose to SLE
Classical complement Pathway
Kostmanns syndrome is a congenital deficiency of which component of the immune system?
neutrophils
Which component of the innate immune system is usually one of the first to respond to infection through a cut?
Neutrophil
Which infection is most common as a consequence of B cell deficiency?
Bacterial
Meningococcal infections are quite common as a result of which deficiency of the component of the immune system?
Complement
Produced by the liver, when triggered, enzymatically activate other proteins in a biological cascade and are important in innate and antibody mediated immune response?
Complement
A complete deficiency in this molecule is associated with recurrent respiratory and gastrointestinal infections.
IgA
Leukocyte Adhesion Deficiency is characterised by a very high count in which of the above?
Neutrophils
Which crucial enzyme is vital for the oxidative killing of intracellular micro-organisms?
NAPDH oxidase
Which complement factor is an important chemotaxic agent?
C3a
What is the functional complement test used to investigate the classical pathway?
CH50
Graves reaction type?
Type II – Antibody mediated
SLE reaction type?
Type III – Immune complex mediated
RA reaction type?
Type IV – T-cell mediated
Asthma reaction type?
Not autoimmune
T1DM reaction type?
Type IV – T-cell mediated
ITP reaction type?
Type II – Antibody mediated
ABO reaction type?
Type II – Antibody mediated
Hepatitis C associated membranoproliferative glomerulonephritis type I. Reaction type?
Type III – Immune complex mediated
Goodpasture’s syndrome reaction type?
Type 2 antibody mediated
Myaesthenia gravis reaction type?
Type II – Antibody mediated
SLE antibody?
Anti-DNA
RA best diagnostic antibody?
Anti-CCP
PBC antibody?
Anti-mitochondrial
What is the auto-antigen target in Goodpastures?
Type 4 collagen
Pattern of antibody deposition in GBM in goodpastures?
Smooth linear
Common treatment of Goodpastures?
Prednisolone
Immune damage in Goodpastures is associated with the kidney and?
Lung
Gene defect in X-Linked Agammaglobulinaemia
Burtongs typrosine kinase BTK gene
DiGeorge Syndrome genetic defect?
Chromosome 22q11 deletion
SCID is associated with defects in which cytokine receptor?
IL-2
Wiskott-Aldrich syndrome is associated with what gene?
WASP gene
Bare lymphocyte syndrome is assocaited with the absence of what?
MHC (class 2 most commonly).
This region encodes for C2, C2 and Factor B
MHC class 3
Hyper IgM is associated with a defect in what gene?
CD40
A 25 year old woman comes to her GP about family planning. She is worried because she had an older brother who died before she was born and her grandmother lost two children which she things were both boys. Her GO thinks there may be a genetic disorder in her family affecting the IL-2 receptor. If correct she has a 50% of inheriting the trait from her mother and being a carrier herself. And there would be a 50% chance of passing it to her children. If inherited, her daughters would be carriers and her sons would require treatment which is usually a bone marrow transplant but gene therapy is sometimes used.
SCID
A jaundiced 8 month old child presents with failure to thrive, and a history of recurrent infections (viral, bacterial and fungal). On examination there is hepatomegally and blood tests show a raised alk phos and low CD4 count. A defect is found in the proteins that regulate MHC Class II transcription.
Bare lymphocyte syndrome
Patient X’s GP writes inquiring about whether to vaccinate. The patient suffers from recurrent respiratory tract infections and has been diagnosed with one of the B-cell maturation defects. For which one is immunisation still effective?
Selective IgA deficiency
For which disorder would a bone marrow transplant be unhelpful but a thymic transplant may provide a cure?
DiGeorge
In acute rejection, release of this substance from CD8+ lymphocytes helps kill target cells
Granzyme B
Risk factor for chronic allograft rejection
Hypertension
Transplanting an ABO incompatible kidney will result in what type of rejection
Hyeracute
Treatment of acute antibody mediated rejection
IVIG and plasmapheresis
Treatment of acute cell mediated rejection
High dose steroids
The 3 most important HLA types to screen for in renal transplantation when matching donor and recipient, in order of importance
HLA DR > B > A
Immune agent prevents DNA replication of T cells
Mycophenolate mofetil
immune agent causes a transient increase in neutrophils
Steroids
Can cause gingival hypertrophy as a side effect
Ciclosporin
Corticosteroids, as well as being directly lymphotoxic in high doses, inhibit T-cell function via which other mechanism?
Blocking cytokine synthesis
The antiproliferative drug cyclophosphamide inhibits lymphocyte proliferation by which mechanism?
Inhibition of DNA synthesis (b cells more than t cells)
Plasmapheresis may be indicated in which condition?
Goodpastures
A condition where antigen desensitization therapy may be indicated.
Bee/wasp venom allergy
SE steroids?
Hypertension
SE ciclosporin?
HTN and reduced GFR
SE azathioprine
bone marrow depression
SE methotrexate?
Pneumonitis, pulmonary fibrosis and cirrhosis
SE Immunoglobulin?
Anaphylaxis
Expresses Foxp3 and CD25 and secretes IL-10. Deficient in the monogenic autoimmune disease known as IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome)
T reg Cells
In the immature form these cells are adapted for recognition and uptake of pathogens. Maturation is associated with expression of CCR7, migration to lymph nodes and enhanced capacity for antigen presentation.
Dendritic cells
These cells can be rapidly mobilised from bone marrow. They express pathogen recognition receptors and Fc receptors and are able to engage in oxidative and non-oxidative killing. They do not express HLA class II molecules and so do not activate CD4 T cells. They are the predominant cell type in synovial fluid taken from patients with gout
Neutrophils
These cells may be formed following a germinal centre reaction involving isotype switching and affinity maturation of receptors. They are long-lived and reside in bone marrow.
Plasma cells
These cells express CD3 and secrete IL-17 and IL-22. They are thought to be important in some auto-immune conditions including rheumatoid arthritis.
Th17 cells
These cells may be resident in peripheral tissues (eg Kupffer cells in liver, microglia in neural tissue) express pathogen recognition receptors and Fc receptors and are able to engage in oxidative and non-oxidative killing. They are an important source of cytokines such as IL-1 and TNF-alpha and are thought to play an important role in some auto-inflammatory and auto-immune diseases.
Macrophage
The normal function of these cells is to express cytokines in response to recognition of specific peptides presented by HLA class II molecules. Depletion of these cells during HIV infection is an important factor in development of AIDS.
CD4 cells
Functions of the spleen?
Red pulp - reservoir of red cells and platelets. Filtering of phagocytosis and particulate matter.
White pulp - reservoir of lymphocytes and 2nd lymphoid organ.
Marginal zone - screen circulation of pathogens clears microorganisms and viruses.
Increased risk of what infections without a spleen?
Encapsulated bacteria - Strep pneumonia, HIB, Neisseria Meningitidis.
Malaria (as spleen clears infected RBCs)
Vaccines required after splenectomy?
Pneumonia, HIB, Meningococcus, Influenza
Prophylactic treatment after splenectomy?
Prophylactic Pen V for at least 2y. Also carry medic alter bracelet and take antibiotics when travelling.
Conditions associated with hyposlenism?
Haematological: SCD, Thal, lymphoproliferative, post BMT.
GI: coeliac and IBD
CTD: SLE
Play a role in protective immunity against HIV infection by killing virus infected cells via perforin and FAS.
CD8 T cells
Acts as a co-receptor for HIV entry to cells
CCR5
Directs homing of dendritic cells to lymph nodes
CCR7
Cells Are often infected by HIV if they express CD4
Marophages
Antibodies against this target are partially protective against HIV infection
gp120
Is quantitation of complement useful in assessment of type IV autoimmune diseases?
No
Factors to monitors SLE disease?
Anti-DNA ab and Complement C3 and C4
Mutation in MEFV leads to failure to regulate neutrophil function
Familial Mediterranean Fever
Polygenic auto-inflammatory disease in which NOD-2 (CARD 15) mutations are common
Chrons
Mixed pattern disease with very high heritability (>90%) and a strong association with HLA-B27
Ankylosing Spondylitis
Polygenic auto-immune disease associated with polymorphisms in PAD enzymes (which citrullinate proteins). Environmental factors including smoking and gum infection are associated with disease.
RA
Monogenic auto-immune disease due to a mutation in Foxp3
IPEX (immune dysregulation polyendocrinopathy, enteropathy, X linked syndrome)
Antibody associated with congenital heart block in mothers with SLE?
Anti-Ro
Antibody associated with Lupus nephritis?
Anti-DNA
Antibody Associated with mixed connective tissue disease?
Anti-RNP
Antibody associated with Limited cutaneous systemic sclerosis?
Anti-centromere
Antibody associated with Sjogren’s?
Anti-Ro
Disease assocaited with anti-smooth muscle antibody?
Autoimmune hepatitis
Disease assocaited with anti-endomysial and anti-TTG antibodies?
Coeliac AND dematitis herpatiformis
Disease associated with anti-mitochondrial antibody?
Primary Biliary Cirrhosis
Allograft rejection type Mediated predominantly by antibodies which usually form after the transplantation
Acute vascular rejection
Allograft rejection type Both immunological and non-immunological mechanisms contribute
Chronic rejection
Allograft rejection Due to presence of pre-formed antibodies
Hyperacute rejection
Allograft rejection Mediated by activation of CD4 T cells which provide help for a CD8 T cell and B cell response and occurs within 1-4 weeks
Acute cellular rejection.
Vaccines contraindicated in immunecompromised?
MMR, Polio, BCG, Yellow fever. MMR BOY (MMR, BCG, Oral polio, Yellow Fever).
Side Effects of Steroids?
Psychosis
Cataracts, glaucoma, thin hair, cushings, peptic ulceration, acne, hypertension, DM, poor wound healing, osteoporosis, proximal muscle wasting.
Use multiple immunosuppressive drugs to minimise toxicity? Combination for kidney transplant is? (3)
Tacrolimus
Mycophenolate
Corticosteroids
A 58 year old pharmacist presents with a 3 month history of skin itching associated with lethargy and loss of energy.
Physical examination is normal, but liver function tests reveal:
Total bilirubin = 36umol/l (0-17umol/l)
ALT = 28U/l (0-31U/l)
Alkaline phosphatase 420U/l (30-130). Which autoantibody?
Anti-mitochondrial (PBC)
A 56 year old prison officer presents with a history of recurrent nose bleeds, haemoptysis and joint pain associated with profound lethargy.
On examination, he has crackles in his upper left lung field, and a cavitating left lung lesion is demonstrated on chest radiography.
Urine dipstick is positive for protein and blood. Which autoantibody?
Anti-neutrophil cytoplasmic antibody
A 22 year old woman presents with joint pain and fatigue. She has an intermittent, skin-sensitive rash, and also complains of mouth ulcers. Physical examination is otherwise normal.
Urine dipstick is positive ++ protein and ++ blood.
Full blood count shows a normocytic normochromic anaemia.
Which auto-antibody?
Anti-dsDNA
A 30 year old plumber attends his GP complaining of feeling tired all the time. He has type I diabetes, which is currently well controlled, and a history of irritable bowel syndrome. A full blood count shows a microcytic hypochromic anaemia, and iron studies confirm iron deficiency. Vitamin D levels are within the insufficient range.
Which auto-antibody?
Anti-TTG
A 44 year old builder presents with a history of fingers intermittently becoming very cold and white with recent development of a gangrenous tip of his finger. The skin over his fingers feels ‘tight’ and you note telangectasia on his hands.
Which auto-antibody?
Anti-centromere
A 19 year old student presents with a chronic, extremely itchy rash consisting of papules and vesicles which is distributed symmetrically over the extensor surfaces of her elbows, legs and buttocks. You suspect dermatitis herpetiformis.
Which auto-antibody?
Anti-intrinsic facotor??
