Immune

Question 1

Why does SCID only present at 3 months of age?

Answer 1

• Why 3 months? Because prior to 3 months, there is active transport of maternal IgG across placental to help protect baby

Question 2

Describe ADA def SCID. What will the T, B and NK cells be?

Answer 2

ADA deficiency

• 16.5% of all SCID
• Autosomal recessive
• Adenosine deaminase (ADA)
  
  • Enzyme required for cell metabolism in lymphocytes
  • Lack of this enzyme → accumulation of toxic productions e.g adenosine, 2deoxyaenosine, deoxyadenosine-triphosphate which kills lymphocyte
• Phenotype
  
  • Low/absent T
  • Low/absent B
  • Low/absent NK

Question 3

What is the most common form of SCID? Describe the molecular protein and clinical picture.

Answer 3

X-linked SCID

• Most common form of SCID
• 45% of SCID
• Mutation in gamma chain of IL2 receptor on chromosome Xq13.1
  
  • This is shared between receptors for IL2, IL4, IL7, IL9, IL15 and IL21
  • Inability to respond to cytokines, causing early arrest of T cell and NK cell development, production of immature B cells
• Phenotype
  
  • Low/absent T
  • Low/absent NK
  • Normal or increased B but low Igs (because immature)

Question 4

Clinical phenotype of SCID

Answer 4

• Infection of all types
  
  • Candidate and diarrhoea common early features
  • Bacterial, viral, fungal, protozoal
• Failure to thrive
• Unusual skin disease
  
  • Colonisation of infant’s empty bone marrow by maternal lymphocytes
  • Graft v host disease
• FH of early infant death

Question 5

• Clinical features
  
  • High forehead
  • Low set, abnormally folded ears
  • Cleft palate, small mouth and jaw
  • Hypocalcaemia
  • Oesophageal atresia
  • Underdeveloped thymus
  • Complex congenital heart disease

Answer 5

DiGeroge Syndrome

• Deletion of 22q11.2 → developmental defeat of pharyngeal pouch (blue box)
• Underdeveloped thymus → reduced T cells but normal B cells
• Immune function is usually only mildly impaired and improves with age

Question 6

Common clinical picture of a T cell def (primary or secondary)

Answer 6

• Viral infections (CMV)
• Some bacterial infections (esp intracellular pathogens)
  
  • Mycobacteria TB, Salmonella, Listeria
• Parasite infections
  
  • Toxoplasma
• Fungal infection
  
  • Pneumocystitis jiroveci (also associated with hyperIgM even though this is a B cell problem because of abnormal T cell function present in this condition)
• Early malignancy
• CD4 deficiency will impact development of T cell dependent antibody response

Question 7

Common clinical picture of a B cell def (primary or secondary)

Answer 7

• Lack of antibodies!
• Bacterial infections
  
  • Eep encapsulated bacteria (H.influexa, Strep pneu, Strep pyrogens, Pseudomonas)
• Some viral - enterovirus
• Toxins
  
  • Tetanus, diphtheria

Question 8

Skin barrier against infection (4)

Answer 8

• Tightly packed keratinised cells
  
  • Limits colonisation by microbes
• Physiological factors
  
  • Low pH
  • Low oxygen tension
• Sebaceous glands
  
  • Hydrophobic oils repel water and microbe
  • Lysozyme destroys structural integrity of bacterial cell wall
  • Ammonia and defensives have anti-bacterial properties
• Commensal bacteria
  
  • Compete of pathogenic microbes for scarce resources
  • Produce fatty acids and batericidins that inhibit growth of pathogen

Question 9

Mucosal barriers against infection (2)

Answer 9

• Secretes mucus
  
  • Physical barrier to trap invading pathogens
  • Secretory IgA prevents bacteria and viruses attaching to and penetrating epithelial cells
  • Lysozyme and antimicrobial peptides directly kill invading pathogen
  • Lactoferrin acts to starve invading bacteria of iron
• Cilia
  
  • Trap pathogens and contribute to removal of mucus
  • Assisted by physical manoeuvres such as sneezing and coughing

Question 10

Cells of the innate immune system (7 types and 4 classes)

Answer 10

• Polymorphs - neutrophils, eosinophils, basophils
• Monocytes and macrophages
• NK cells
• Dendritic cells

Question 11

Soluble components of innate immune system (3-4 types)

Answer 11

• Complement
• Acute phase protein e.g. CRP
• Cytokines and chemokines
  
  • Cytokines increase vascular permeability
  • Chemokine’s attract neutrophils

Question 12

Receptors expressed on polymorphs - neutrophils, eosinophils and basophils (4)

Answer 12

• Expresses cytokines and chemokine receptors - detect inflammation
• Expresses pattern recognition receptors - detect pathogens
• Express Fc receptors for Ig - detect immune complexes

Question 13

Function of polymorphs (innate immunity)

Answer 13

• Capable of phagocytosis/oxidative and non-oxidative killing - particularly neutrophils
• Release enzymes, histamine, lipid mediators of inflammation from granules
• Secrete cytokine and chemokine to regulate inflammation

Question 14

Describe oxidative killing in macrophages and neutrophils

Answer 14

• NAPDH oxidase complex convert oxygen to ROS - superoxide and H2O2
• Myeloperoxidase catalyses production of hydrochlorous acid from H2O2 and chloride
• Hydrochlorous acid is a very effective oxidant and anti-microbial

Question 15

Describe non-oxidative killing by phagocytes e..g neutrophils and macrophages

Answer 15

• Release of bactericidal enzymes e.g lysozyme and lactoferrin (depletes pathogen of iron) into phagolysosome
• Enzymes are present in granules
• Each has unique antimicrobial spectrum
• Results in broad coverage against bacteria and fungi

Question 16

How does phagocytes recognise a pathogen?

Answer 16

• Recognition of pathogen by pattern recognition receptors
• Toll-like receptors and mannose receptors
• Generic pathogen-associated molecular patterns (PAMPS) such as bacterial sugar, DNA, RNA
• Fc receptors for Fc portion of Ig to allow recognition of immune complexes

Question 17

NK cell function (2)

Answer 17

1. When inhibitory signals are lost (altered) e.g when cells are infected or becomes malignant. NK cells become activated and kills those altered cells
2. Secrete cytokines to regulate inflammation - promote dendritic cell function

Background:

• Present within the blood and can migrate to inflamed tissue
• Innate immunity but a lymphocyte
• Inhibitory receptors for self-HLA and prevent inappropriate activation by normal self
• Activator receptors including natural cytotoxicity receptors that recognise heparin sulphate proteoglycans
• But generally inhibitory signal > activator signals

Question 18

Functions of T helper (CD4) cells (2)

Answer 18

1. Immunoregulatory functions via cell-cell interactions and expression of cytokines
2. Development of full B lymphocytes and some CD8+ lymphocyte response

Question 19

Functions of CD8 T cells

Answer 19

1. Specialised cytotoxic cells which kill cells directly (perforin, granzyme, Fas/FasL pathway)
2. Secrete cytokines e.g. IFN-y, TNF-a
3. Particularly impt. in the defence against viruses and tumours

Question 20

What is immunological memory

Answer 20

Response to successive exposures is qualitatively and quantitatively different

• pool of memory T/B cells that are more easily activated (T and B)
• Secretes more antibodies (B) that are of higher specificity IgG instead of IgM
• B memory cells do not require CD4+ help

Question 21

Express receptors that recognise peptides usually derived from intracellular proteins and expressed on HLA Class 1

Answer 21

CD8 T cells

Question 22

Subset of lymphocytes that express Foxp3 and CD25

Answer 22

T reg

Question 23

Subbed of cells that express CD4 and secret IFNa and IL2

Answer 23

Th1

Question 24

Play an important role in promoting germinal centre reactions and differentiation of B cells in to IgG and IgA secreting plasma cells

Answer 24

T follicular helper cells

Question 25

Describe central tolerance of B cells

Answer 25

Any premature B cell that recognises self is killed to avoid auto reactivity (not concept of intermediate binding etc as in T cell because they do not need to recognise HLA/own antigens)

Question 26

What is the germinal centre reaction in lymph nodes wrt to T and B cells (3)

Answer 26

1. APC prime CD4+ cells
2. CD4+ t cells help B cell differentiate via CD40L:CD40
3. B cell proliferation with somatic hypermutation and isotope switching

Result: IgE, IgG and IgA from B cell

Question 27

Structure of an antibody (light or heavy chain)

• Fab?
• Fc?

Answer 27

• Two heavy and two light chain
• Heavy change determine the class (IgM, IgG, IgA, IgE and IgD)
• Antigen recognised by Fab (light and heavy chain)
• Effector function is Fc (only heavy chain)

Question 28

Describe the classical compliment pathway

Answer 28

Antibody-Antigen complexes, results in change in antibody shape to expose binding site of C1, depends on adaptive immunity (late)

Question 29

Describe the MBL pathway

Answer 29

Mannose binding lectin: Activated by binding of MBL to microbial cell surface carbohydrates, directly stimulates the classical pathway involving C2 and C4 (but not C1), do not require adaptive immunity

Question 30

Describe the alternative complement pathway

Answer 30

• Alternative: Directly triggered by binding of C3 to bacterial cell wall component e.g. LPS and teichoic acid of Gram+, do not require adaptive immunity

Question 31

Functions of complement (5)

Answer 31

• Increase vascular permeability and cell trafficking to site of inflammation
• Opsonisation of immune complexes to keep them soluble - hence def in complements in SLE leads to autoimmunity as self antigens now persist and becomes ‘visible’
• Opsonisation of pathogen to promote phagocytosis
• Activates phagocytes
• Promote mast cell/basophil degranulation

Question 32

What are cytokines and chemokine

Answer 32

Cytokines are small protein messengers with immunomodulatory function
Chemokines are subset of cytokines with chemoattractant properties

Question 33

Interaction of X and X with X is important for dendritic cell trafficking to lymph nodes

Answer 33

Interaction of CCL19 and CCL21 with CCR7 is important for dendritic cell trafficking to lymph nodes

CCL19 and CCL21 are ligands for CCR7 (receptor)

Question 34

Recurrent infections with high neutrophil counts on FBC but no abscess formation

Answer 34

leukocyte adhesion deficiency

Question 35

Recurrent infections with hepatosplenomegaly and abnormal DHT

Answer 35

Chronic granulomatous disease

Question 36

Recurrent infections with no neutrophils on FBC

Answer 36

Kostmann syndrome

Question 37

infection with atypical mycobacterium. Normal FBC

Answer 37

IFN gamma receptor deficiency

Question 38

Meningococcus meningitis with FH of sibling dissing of same condition aged 6

Answer 38

C7 deficiency

Question 39

Membranoproliferative nephritis and bacterial infections, abnormal fat distribution

Answer 39

C3 deficiency with presence of a nephritic factor

Question 40

Severe childhood onset SLE with normal levels of C3 and C4

Answer 40

C1q deficiency

Question 41

Recurrent infections with receiving chemotherapy but previously well

Answer 41

MBL deficiency

Question 42

Failure to produce ALL myeloid or lymphoid cells (ultimate failure)

• diagnosis
• inheritance pattern
• enzyme mutation
• treatment

Answer 42

• Reticular dysgenesis - autosomal recessive severe SCID
  
  • Mutation in mitochondrial energy metabolism enzyme adenylate kinase 2 (AK2)
• Fatal early unless treated wth BM transplant

Question 43

• Failure to produce neutrophils (more specific failure) - 2 types
• diagnosis
• inheritance pattern
• enzyme mutation

Answer 43

• Specific failure of neutrophil maturation in bone marrow (failure of differentiation)
• Kostmann syndrome - autosomal recessive severe congenital neutropenia
  
  • Classical form due to mutation in HCLS1-associated protein X1 (HAX1)
• Cyclic neutropenia - autosomal dominant episodic neutropenia every 4-6 weeks
  
  • Mutation in neutrophil elastase (ELA-2)

Question 44

Kostmann syndrome - mutated enzyme

Answer 44

HCLS-1 associated protein X1 (HAX1)

Question 45

Cyclic neutropenia - mutated enzyme

Answer 45

Mutation in neutrophil elastase (ELA-2)

• Cyclic neutropenia - autosomal dominant episodic neutropenia every 4-6 weeks
  
  • Mutation in neutrophil elastase (ELA-2)

Question 46

• Defect of phagocyte migration

Answer 46

Leukocyte adhesion deficiency (Deficiency of CD18 - beta2 integrin subunit)

Question 47

pathophy of leuckotee adhesion deficiency

Answer 47

• Leukocyte adhesion deficiency (Deficiency of CD18 - beta2 integrin subunit)
• CD18 combines with CD11 to form LFA-1 which is expressed on neutrophils
• LFA-1 binds to ICAM-1 on endothelial cells to allow neutrophils to adhere and transmigrate
• When CD18 is absent, neutrophils cannot interact with adhesion molecules and fail to exit from blood stream
• You get high neutrophil counts in blood but absence of pus formation

Question 48

Failure of oxidative killing mechanism

Answer 48

Chronic granulomatous disease

Question 49

Pathophy of CGD (chronic granulomatous disease)

Answer 49

• Chronic granulomatous disease
  
  • Absent respiratory burst
  • Deficiency in NADPH oxidase
  • Inability to generate ROS required for killing
  • Excessive inflammation but cannot kill
  • Then form granulomas instead (because neutrophils are activated but don’t work/die by killing), lymphadenopathy+/- hepatosplenomegaly

Question 50

Investigation and treatment for chronic granulomatous disease

Answer 50

• Investigation for chronic granulomatous disease
  
  • Nitoblue tetrazolium (NBT) test - changes colour from yellow to blue if there is hydrogen peroxide produced by activated neutrophils
  • Dihyro-rhodamine (DHR) flow cytometry - fluorescence if rhodamine interacts wth H2O2

Treatment - IFNy to * increase the macrophage ability for killing by oxidative pathway (IFNy therapy)

Question 51

4 examples of primary immune phagocyte deficieies

Answer 51

1. Kostmann (congenital neutropenia)
2. Leukocyte adhesion deficiency (CD18-beta2 integrin subunit deficiency that is needed for form LFA- 1 on neutrophils)
3. Chronic granulomatous disease (no oxidative killing)
4. IL12/IFNy deficiency

Question 52

IL-12, IL12R, IFNy or IFNyR deficiency

Answer 52

• IL12-IFNy network - particularly impt for mycobacterial infection and salmonella
• Infected macrophage produce IL12
• IL12 induce T cell to produce IFNy
• IFNy feeds back to macropahge to produce TNF and free radical
• Activate NADPH oxidase (oxidative killing) by both macrophage and neutrophils

Question 53

Symptoms of phagocyte deficiency

Answer 53

• Recurrent infections for extracellular pathogens - skin and mouth
  
  • Bacterial (S.aureus, Enteric bacteria)
  • Fungal (Candida albicans, Aspergillus fumigateurs and flavus)
• Mycobacterial infections (particularly so if impaired cytokine network)
  
  • Mycobacterium TB
  • Atypical mycobacteria

Question 54

Treatment principles of phagocyte deficiencies (2)

Answer 54

• Agressive managent of infection
  
  • Infection prophylaxis
    
    • Septrin - Abx
    • Itraconazole - anti-fungal
  • Oral/IV Abx as needed
• Definitive therapy
  
  • Haematopoietic stem cell transplant
    
    • For chronic granulomatous disease (CGD), you can give IFNy to increase the macrophage ability for killing by oxidative pathway (IFNy therapy)

Question 55

Classical NK deficiency (name the genes mutation)

Answer 55

• Abnormalities described in GATA2 or MCM4 genes in subtypes 1 and 2

Question 56

Functional NK deficiency (name the gene mutated)

Answer 56

• Abnormality described in FCGR3A gene in subtype 1

Question 57

Clinical presentation of NK deficiency

Answer 57

• Frequent virus infection
  
  • herpes (Simplex, Varicella zoster, Epstein Barr, CMV)
  • Papillomavirus infection

Question 58

Name the classical complements

Answer 58

C1, 2, 4

Question 59

What condition is associated with classic complement deficiency?

Answer 59

SLE

• Complement fragments promote clearance of apoptotic/necrotic cells by phagocytes
  
  • Deficiency results in increase load of self antigens, particularly nuclear components
  • Which promote auto-immunity and formation of immune complexes
• Fragments also promote clearance of immune complexes by erythrocytes, by making them soluble
  
  • Deficiency results in deposition of immune complexes stimulating local inflammation
• Clinical features: SLE
  
  • usually very severe skin disease
  • Almost all patient with C2 deficiency have SLE

Question 60

Deficiency of MBL

What problems does it cause?

Answer 60

• 30% of all individuals are heterozygote for mutant protein
• 6-10% have no circulating MB
• Do not seem to cause significant problem unless there is another additional immune impairment on top of MBL deficiency

Question 61

What problems does deficiency of Factor B, I, P (alt complement pathway) cause?

Answer 61

• Inability to mobilise complement rapidly against bacterial infections (recall that classical pathway is slower due to need for acquired immunity cos antibodies needed)
• Clinical features
  
  • Recurrent infections with encapsulated bacteria
• Very rare

Question 62

C3, C5-C9 deficiency cases? (3 classic infection)

Answer 62

• Severe susceptibility to bacteria infections
  
  • Neisseria meningitis
  • strep pneu
  • H. influenza

Question 63

2 cause son secondary complement deficiencies

Answer 63

Acute SLE
Nephritic factors

Acute lupus (SLE) causes persistent production of immune complexes leading to consumption of classical complements

• Nephritic factors are auto-antibiotics against components of the complement
  
  • Nephritic factors stabilise C3 convertases resulting in C3 activation and consumption
  • Often associated with glomerulonephritis (classical membranoproliferative)
  • May be associated wth partial lipodystrophy (lose fat on the upper half of body)

Question 64

Name the 2 functional tests for complement activity

Answer 64

CH50 - for classical pathway

AP50 - for alternative pathway

Question 65

Hereditary angioedema is deficient in which complement

Answer 65

C1

Question 66

Presentation of Familial Mediterranean Fever

Answer 66

Periodic fevers lasting 48-96 hours
Abdo pain (peritonitis)
Chest pain (pleurisy and pericarditis)
Arthritis

Question 67

Management of femilial mediterranean Fever

Answer 67

• Colchicine 500μg bd: binds to tubulin in neutrophils & disrupts neutrophil function (including migration & chemokine secretion)
  * Same as used in gout to limit inflammation by neutrophil
  • Anakinra (IL-1R antagonist)
    
    • Targets the cytokines coming out of the inflammasome complex
  • Etanercept (TNF-α inhibitor)
  • Type I IFN

Question 68

3 types of monogenic autoimmune dx

Answer 68

1. Impaired tolerance - APECED (cannot present self antigen at thymus to lymphocytes, failure of positive central selection)
2. Treg abnormality - IPEX (mutation in Foxp3 = no T-reg)
3. Impaired lymphocyte apoptosis (mutation in Fas pathway, lymphocytes, including self-selecting lymphocytes cannot die, can lead to lymphoma)

Question 69

Crohn’s disease - role of NOD2 (genetic polymorphism)

Answer 69

NOD2 is a gene located on Chr16 that encodes for IBD1 protein.
When mutated, it increases the risk of getting Crohn’s.
1 mutated copy = 1.5-3x likely to get CD
2 mutated comes = 44x likely to get CD
But in itself alone, is not sufficient to get CD. Hence 2xNOD2 mutations does not automatically give you Crohn’s. (genetic polymorphism of mutated NOD2 gives you susceptibility)

To get CD, also needs combination of environmental factors and other genetic influences

NOD2/IBD1 is found in the cytoplasm of myeloid cells i.e macrophages, neutrophils etc. It recognises microbial MURAMYL DIPEPTIDE to trigger NFkB and inflammation.

In Crohn’s this + other factors gives you pro-inflammatory cytokines in/around crypts. Leads to non-caseating granulomas and mucosal ulceration.

Question 70

Mx of Crohns (4)

Answer 70

Steroids
Anti-TNFa - infliximab, adalimumab
Azathioprine
Anti IL-12/23 - ustekinumab

Question 71

3 examples of mixed pattern auto inflammatory and autoimmune dx

Answer 71

AS
psoriatic arthritis
Behcet’s syndrome

Question 72

AS: * Enhanced inflammation occurs at specific sites where there are _____

Answer 72

Enhanced inflammation occurs at specific sites where there are high tensile forces (entheses - sites of insertions of ligaments or tendons to bone)

Question 73

Presentation of Ank Spond.

Answer 73

Young <40 with early morning stiffness

Typical patient: Young man <30 with gradual onset low back pain worst at night, spinal stiffness in morning relieved by exertion. Pain radiates from sacroiliac joint to back

• Progressive loss of spinal movement (spine flexion - kyposis and neck hyperextension - ? posture)
• Enthesitis: Achilles tendonitis, plantar fasciitis of tibial and ischial tuberosities and at iliac crest
• Acute irits: may lead to blindness
• Anterior CP due to costochondritis
• Fatigue

Key complications: (7A)

1. Atlanta-axial subluxation - due to dentate ligament of connective tissue dysfunction
2. Anterior uveitis/Acute iritis
3. Autoimmune arthritis
4. Amyloidosis
5. Aortic regurg
6. Achilles tendonitis, plantar fasciitis
7. Apical lung fibrosis

Question 74

Tx for ankylosing spond

Answer 74

• Non-steroidal anti-inflammatory drugs
• Immunosuppression (need to target the cytokine pathway)
  
  • Anti-TNFα
  • Anti-IL17
  • Anti-IL12/23

Question 75

HIV virus structure (genes and proteins)

Answer 75

2x ssRNA, retrovirus, 20-sided capsid with membrane around it

9 genes, 15 proteins
env → gp120 and gp41
pol → 3 enzymes: reverse transcription, integrate and aspirate protease
gag → p24 (capside formation)

Question 76

How HIV infect target cells

Answer 76

gp120 binds to CD4
co-receptors of CCR5 and CXCR4 on target cells
gp41 fusion of virus into cell

Question 77

3 modes of HIV transmission

Answer 77

Sexual - via mucosal surfaces esp when there is co-current other STI which already weakens mucosal barrier

Vertical - mother to child during brith or breast milk

Infected blood - sharing of needles, blood transfusion

Question 78

Describe the body’s immune response (both innate and adaptive) to acute HIV infection

Answer 78

1. Natural immunity kicks in within hours of infection
   - Inflammation, non specific activation of macrophages, NK cells and complement
   - release of cytokines and chemokine
   - stimulation of dendritic cells via toll like receptor

BUT HIV also cause NK cells to up regulate inhibitory receptors which makes them anergia/useless

2. Acquired immunity (B cells)
   - DC cells presents antigen to B cells
   - B cells undergo maturation and class switching at lymph nodes with hope from follicular T cells
   - IgG antibodies against gp120 and gp41 produced (protective0
   - IgG antibodies against p24 also produced

BUT HIV remains infectious even when covered by antibodies. Once it is coated, it can now enter cells via the Fc portion of antibodies

3. Acquired immunity (T cells)
   - CD4 needed to signal and help other immune cells. They are selectively lost later
   - CD8 cells can kill HIV infected cells but without CD4 helper, naive CD8 T cells cannot be primed and become effector T cells
   - lost of CD4, CD8 and B cell memory

Eventually APC such as dendritic cells and monocytes are also killed by HIV = no more antigen presentation to activate adaptive immune system

Question 79

Effect of HAART on HIV viral load and CD4 counts

Answer 79

• Monitored by two markers
  
  • Marker 1: Suppression of viral load
  • Marker 2: CD4 levels rising
• Initial CD4 rise - memory T cells redistributed
• Later CD4 rise is thymic naïve T cells → thymus regeneration

Question 80

Patterns of untreated HIV disease progression (4 types of people)

Answer 80

85% typical progressors AIDS within 10 years
10% rapid progressors AIDS within 3 years
<5% long term non-progressors - no AIDS but infected
Exposed seronegative - no HIV despite exposure

Question 81

Describe the clinical course of untreated HIV in terms of viral load, CD8 and CD4 from acute infection to long term

Answer 81

• During primary infection → viral load increases
• As the virus peaks → damage decline in CD4 lymphocytes (primary target of virus)
• But at the same time, CD8+ kicks in and have effector responses
• Hence for a while, the CD8+ seem to be effective against the target (direct killing or soluble mediators) as the oral load drops and pts is asymptomatic
• But virus (while being hunted by CD8) is still targeting the CD4 cells which is needed for full CD8 function
• When the CD4 falls below <200cells/ul, then the CD8 becomes ineffective → AIDS
  
  • Opportunistic infections and malignancies

Question 82

Steps in HIV viral replication in a cell

Answer 82

1. Attachment/Entry
2. Reverse Transcription & DNA Synthesis (RNA → DNA)
3. Integration (viral DNA → Host DNA)
4. Viral Transcription (Viral DNA → mRNA by host mechanisms)
5. Viral Protein Synthesis
6. Assembly of Virus & Release of Virus
7. Maturation (Chopping up polypeptide etc continues even after the virus is released fro the cell)

Question 83

Diagnosis HIV methods

Answer 83

Detection of HIV-1
* The HIV antibody ELISA is a screening test and the HIV antibody Western blot is a confirmatory test.

Detection of viral load via PCR
* The initial baseline plasma viral load (that is when the patient is first monitored for virus number) is a good predictor of the time it will take for AIDS to appear.

CD4 counts (to monitor disease severity and progression) 
* The onset of AIDS correlates with the diminution of the number of CD4 T cells (<200cells/ul) - characterised by opportunistic infection by bacteria and cancers 

HIV-1 resistance testing

• Two established assays for measuring resistance to antiretroviral drugs
  - Phenotypic: Viral replication is measured in cell cultures under selective pressure of increasing concentrations of antiretroviral drugs – compared to wild-type
  - Genotypic: Mutations determined by direct sequencing of the amplified HIV genome (so far limited to sequencing of RT and P)
• Both assays are available commercially (expensive)

Question 84

What is the role of HAART in HIV? What drugs are typically in a HAART regimen.

Answer 84

• The use of combination regimens of anti-retroviral agents has allowed:
  
  • Substantial control of viral replication
  • Increase in CD4 T cell counts
  • Improvement in their host defenses with a dramatic decline in opportunistic infections and deaths.
• HOWEVER, HAART does not eliminate the virus from the patient due to a reservoir of HIV in resting CD4 T cells and CD4 MO
• Only prevent viral replication

Which HAART regimen?

• 3 drugs from at least 2 different classes
• Two drugs backbone = one or more binding agents

Question 85

Give examples of drug for HIV/HHART

Answer 85

HIV entry 
Fusion inhibitors
* Enfuviritide (T-20)
CCR5 co-repcetor antagonists 
* Maraviroc

Pre-transcriptional
NRTI - nucleoside RTI 
* Zidovudine 
* Lamivudine (3TC)
* Didanosine (ddl) 
* Stravudine (d4T)
* Abacavir (ABC) 
* Emtricitabine (FTC) 
Nucleotide RIT 
* Tenofovir (TDF)
NNRTI 
* Nevirapine (NVP) - SE hepatitis and rash 
* Efavirenz (EFV) - SE CNS effects 
* Etravirine 
* Rilpirivirine 

Post-transcription 
Integrase inhibitors  
* Raltegravir 
* Elvitegravir
Protease inhibitors  
* ​Lopinarvir (LPV) 
* Ritonavir (RTV) - P450 inhibitors. Given with other Pis to reduce metabolism and boost effectiveness 
* Fosamprenair 
* Darunavir (DRV) 
* Atazanavir  - boosted PI 
* Saquinavir 
* Indinavir 
* Tipranavir 
All PI causes hyperlipidaemia, fat redistribution and T2DM

Question 86

Important side effects of some HIV drugs

• Tenofovir
• Efavirenz
• Abacavir
• Atazanavir

Answer 86

• Tenofovir: can affect kidneys
• Efavirenz: insomnia/vivid dreams, psychiatric symptoms
• Abacavir: need HLA B*5701 test first due to risk of hypersensitivity
• Atazanavir: jaundice.

Question 87

When to initiate HAART? Which HAART regimen?

Answer 87

• New BHIVA 2016 guidelines suggest all patients on HAART regardless of CD4 count as they get better outcomes. Previously only when CD counts are <350 or <200
  Choices: 2 NRTIs + PI (or NNRTI)

Question 88

Limitations and complications of HAART regimens

Answer 88

• Effective HAART does not eradicate latent HIV-1 in the host
  
  • Potential for immunotherapy
• Fails to restore HIV-specific T-cell responses
• Is dogged by the threat of drug resistance
• Significant Toxicities
• High pill burden
  
  • More drugs needed to control the SE of HIV-drugs
• Adherence problems
• Quality of life issues
• Cost (~40%)

Question 89

Vaccination herd immunity formula

Answer 89

1/R0 where R0 i the average number of people 1 infected person can infect on average

Question 90

3 situations for vaccinations

Answer 90

Young
Travel - HepB/HepC/TB/VZV/typhoid/rabies/cholera
Elderly - Pneumo PPV, flu, shingles

Question 91

Principles of why vaccines work

Answer 91

Immune memory
Exposure of immune system → exquisite specificity
Memory B and T cells = more easily activated and long-lived
Persistence of existing IgG

Question 92

4 methods of immune-boosting

Answer 92

1. Vaccination
2. Replacing missing component e.g. BMT/antibodies/T cells
3. Cytokine therapy
4. Block immune checkpoints to allow greater activation of T cells

Question 93

Ipilimumab -MOA what disease is it used for

Answer 93

anti-CTLA4
CTLA4 is an T cell inhibitor. Antibody to it allows T cell activation
Used in advanced, met melanoma

Question 94

Pembrolizumab & nivolumab - MOA and what disease is it used for

Answer 94

anti-PD1
PD1 ligand is expressed by APC and tumour cells
Activation of PD1 = negative regulator of T cell
Pembrolizumab and nivolumab

Question 95

Cytokine therapy how does it work and what types are there/for what disease

Answer 95

Boost immune response to cancer and some pathogens

IFNa

• HepB, HepC, Kaposi
• hairy cell leukaemia, CML, multiple myeloma

IFNb
- relapsing MS

IFNy
- Chronic granulomatous disease

Question 96

How does general antibody replacement work? Where does it come from and how is it administer? how frequent

Answer 96

Plasma from healthy donors (screened and irradiated) are pooled
All the Ig present in the blood are administered by IV or SC to the recipient every 3-4 weeks

Question 97

What disease can be treated by general antibody replacement

Answer 97

Primary immune def - Bruton’s, hyperIgM, CVID

Secondary antibody def - Haem cancers e.g. CLL/multiple myeloma

Question 98

EBV T Cell replacement - what is this a treatment for?

Answer 98

Patients who are post BMT who are unable to control persistent EBV infection causing EVG related B cell lymphoproliferative disease

Question 99

Immunoboosting therapies - T cell replacement (what 2 types of viral specific T cell replacements are there?)

Answer 99

CMV → for CMV retinitis (pizza topping chorioretinitis)

EBV-specific CD8 T cells (EBV Burkit’s lymphoma)

Question 100

Explain the 3 MOA of steroids

Answer 100

1. Phospholipase A2 inhibitor - prevent production of prostaglandin and leukotriene
2. Inhibits phagocyte (e.g. neutrophil) migration and function - transient neutrophilia
3. Inhibits lymphocyte function - sequestrated in lymphoid tissue (CD4 > CD8 > B)

Question 101

Steroids are synthetic glucocoticosteroids which has/has no mineralocorticoid function. The equivalent endogenous dose is ____

Answer 101

NO mineralocorticoid activity

5-7.5 mg is the equivalent to endogenous steroid produciton

Question 102

SE of steroids

Answer 102

Metabolic
- diabetes, obesity, Cushingnoid, abnormal lipids, abnormal LFT, osteoporosis

Others

• cataracts
• glaucoma
• AVN
• peptic ulcers
• myositis

Question 103

Name 3 anti proliferative drugs that can be used in immunosuppression

Answer 103

Cyclophosphamide
Azathioprine
Mycophenolate mofetil

Question 104

MOA of cyclophosphamide

Answer 104

Alkylates guanine in DNA and stop cell proliferation
Inhibits B>T cells
At high doses inhibit all rapidly proliferating cells

Question 105

SE of anti proliferative drugs e.g. cyclophosminde, azathioprine and myophenolate mofetil

Answer 105

Bone marrow suppression

Infection (worst with cyclophosmiade_

Question 106

What enzyme polymorphism should be checked before prescribing azathioprine

Answer 106

TPMT

Polymorphism can mean some patient cannot metabolise drug → toxic accumulation

Question 107

MOA of azathioprine (3)

Answer 107

Metabolised by liver into 6 mercaptopurine
1. Which blocks de novo purine synthesis
2. Inhibits T cell activation
3. Inhibits T cell proliferation
Drug is then broken down by TPMT
T>B cell (same as mycophenolate mofetil) but different from cyclophosmiade which is B>T

The enzyme in de novo purine synthesis is PAT (PPRP amide transferase?)
The enzyme lost in Lesch Nylan in salvage/recycling pathway is HGRT

Question 108

Indications for azathioprine

Answer 108

Transplant
Autoimmune
Auto inflammatory
IBD

Question 109

Indications for cyclophosphamide

Answer 109

Vasculitis
CTD e.g. severe, neuropsych SLE
Anti-cancer

Question 110

Indications for mycophenolate mofetil

Answer 110

Alternative to azathioprine for transplant

Alternatie to cyclophosmiade for vasculitis and autoimmune conditions

Question 111

MOA of mycophoenolate mofetil

Answer 111

Blocks de no nucleotide synthesis (v guanine nucleoSIDE synthesis in azathioprine)
T>B

Question 112

Specific SE associated with cyclophosphamide

Answer 112

Haemorrhage cystitis - Due to toxic metabolic acrolein being excreted in the urine

And also hence bladder cancer (hame cancer from bone marrow suppression) and non-melanoma skin ca

Question 113

Cyclophosphamide has the worst SE wrt to infections what prophylaxis is needed?

Answer 113

PCP (pneumocystis jiroveci pneumonia) with co-trimoazole

Question 114

What specific infections is taking mycophenolate mofetil at risk of

Answer 114

Herpes reactivation and PML (from JC virus)

Progressive multifocal leukoencephalopathy

Question 115

Ustekinumab

Answer 115

Anti-p40 subunit of IL12 and IL23

used in psoriatic arthritis

Question 116

Secukinumab

Answer 116

anti-IL17a

Used in psoriatic arthritis and ankylosing spondylitis after anti-TNFa

Question 117

Denosumab

Answer 117

Anti-RANKL

Osteoporosis

Question 118

Tocilizumab

Answer 118

Anti-IL6 
Castleman syndrome (IL6 producing tour)

Question 119

Natalizumab

Answer 119

Anti-a4 integrin

MS

Question 120

Rituximab

Answer 120

Anti-CD20
Targets mature B cell but not plasma cells (hence low risk of infection)
Used in lymphoma, RA and SLE
Do not increase malignancy but exacerbates CVS disease

Question 121

Abatacept

Answer 121

Fusion protein of IgG Fc and CTLA-4
Binds CD80 and CD86 to prevent T cell priming
Used in RA (IV every 4 week) or SC weekly

Question 122

Basiliximab

Answer 122

Anti-CD25 (IL-2Ra chain)
Inhibits T cell proliferation
Used in prophylaxis of allograte rejection - iV before and after transplant

Question 123

Tofacitinib

Answer 123

JAK inhibitor

used in the state for RA

Question 124

Apremilast

Answer 124

PDE4 inhibitor, reduces cAMP and cytokine production

Used in psoriatic arthritis

Question 125

Cyclosporin and tacrolimus

Answer 125

Inhibits calcineurin and hence reduces IL2 production

Question 126

SE of cyclosporin and tarcolimus

Answer 126

nephrotox, neurotic, hypertension
Cyclosporin - gum hypertrophy and hirsutism
Tarcolimus - diabetogenic

Question 127

What is plasmapheresis

Answer 127

Removal of pathogenic antibody in pt blood by passing it though a cell separate. Cells returned to pt but ab in plasma removed

Used in severe antibody mediated dx e.g. Goodpastures (anti-GBM) and severe MG (anti-ACh) - dx due to type 2 hypersensitivity

Question 128

Pembrolizumab and nivolumab

Answer 128

anti-PD1 (PD1 is T cell negative regulator)
Hence pembrolizumab and nivolumab activate T cell and boost immune system
Used in advanced melanoma

Question 129

Ilipimumab

Answer 129

CTLA4 inhibitor
Increases T cell activation
used in advanced melanoma

Question 130

MOA of calcinuerin inhibitors

Answer 130

E.g. cyclosporin and tacrolimus
Activation of TCR → increase in intracellular Ca from ER
Ca binds to calmodulin
Cal modulate increase calcineurin which binds to NFATc
NFAT (transcription factor) up regulates transcription of IL2

Question 131

Anti-thymocyte globulin + SE

Answer 131

Rabbit Abs against human thymocyte globulin
Depletes host T cell
Used n allograft rejection, daily IV infusion

SE: infection, malignancy
leucopenia
infusion reaction

Question 132

Explain the oral v skin allergy concept

Answer 132

• Oral routes promote immune tolerance while skin induces IgE sensitisation
• Gut: Protein are partially degraded by digestion process → peptides formed of lower allergenicity. IgG responses formed to dietary protein which induced tolerance (Treg, IL10 and TGFb)
• Skin: when there is skin barrier disruption (e.g. filaggrin predisposes to more leaky skin binding), the pathogen/allergen gains access to the dermis. Activated skin dendritic cells are very potent in activating T cells. T cells help B cells to activate to form IgE responses → dermatitis.
• Dermatitis in children if unchecked in children is associated with future allergic disorder (allergic march)
• If the skin barrier is intact, no penetration of allergen into dermis and hence no immune response.
• Evidence LEAP study: Children at high risk of peanut allergy – early introduction of peanut into the diet reduces the risk of allergic responses. The likely explanation is that peanut is in the gut first, so an IgG response is formed before the IgE response.

Question 133

Clinical presentation of true allergy + common symptoms that are NOT due to allergy

Answer 133

• Symptoms occur within 3min or ≤3hrs after allergen exposure
• Typically ≥2 organ systems are involved:
• Skin: angioedema (swelling of lips, tongues, eyelids), urticaria (wheals or ‘hives’), flushing & itch
• Respiratory: cough, SOB, wheeze, sneezing, nasal congestion & clear discharge, red itch watery eyes
• GIT: nausea, vomiting and diarrhoea
• Vasculature & CNS: symptoms of hypotension (faint, dizzy, blackout), sense of
  impending doom
• Symptoms are reproducible after every exposure (don’t vary with time or dose or concentration of allergen)
• May be triggered by cofactors (e.g. exercise, EtOH, infection)
• Note symptoms reported by patients which are NOT assoc. with IgE allergic reactions:
  
  • Fatigue
  • Migraine - food related migraine is pharmacological effect not IgE mediated
  • Recurrent episodes of abdominal pain, diarrhoea, constipation and bloating
  • Hyperactivity
  • Depression
  • Confusion
  • Variation of symptoms with dose and route of allergen

Question 134

Investigations for ?allergy (both elective and acute)

Answer 134

• Skin prick test:
• Serum specific IgE test (RAST)
• Component-resolved diagnostics (CRD)
• oral Ag challenge test for food and drug allergy
• Serum mast cell tryptase levels

Question 135

Explain how a skin prick test is done

Answer 135

1. Discontinue antihistamines ≥48hrs before test
2. Expose patient to standardised solution of allergen extract through skin prick to forearm
3. Use standard skin test solutions, +ve (histamine) & -ve controls (diluent)
4. Measure local wheal & flare response to controls & allergens
5. +ve test if wheal ≥ 3mm greater than -ve control
6. More sensitive & specific than blood tests to diagnose allergy in routine clinical practice. Considered to be gold standard to support a diagnosis of allergy in routine allergy practice

Question 136

Describe how a RAST test is done

Answer 136

1. Allergen bound to sponge in plastic cap & patient’s serum is added
2. Specific IgE (if present) binds to allergen
3. Fluorescent tagged anti-IgE Ab is added
4. Amt.of IgE/anti-IgE is measured by fluorescent light signal
5. Much more expensive than skin prick test (£15 for a single test)

Question 137

Describe component-resolved diagnostics (CRD)

Answer 137

• Blood test to detect IgE to single protein components
• Useful for diagnosis of food allergies e.g. peanut, hazelnut (established) and milk (emerging)
• May reduce need for food challenges
• Two main types of food allergens:
  
  • Heat and protease labile, these allergens tend to cause low or minimal symptoms confined to oral cavity → safe for food challenge to take place
  • More stable allergens – resist enzymatic breakdown → systemic symptoms or anaphylaxis → food challenge not safe, allergen avoidance

Question 138

Describe Ag challenge test

Answer 138

• Gold standard for food and drug allergy - double blind placebo (gold standard) or open challenge
• Increasing vol. of food/drug ingested
• Must take place under close medical supervision (expensive) due to risk of severe reaction
• Difficult to interpret mild symptoms

Question 139

Describe levels of serum mast cell tryptase in anaphylaxis

Answer 139

• Peaks at 1-2hrs & returns to baseline by 6-12hrs
  
  • Failure to return to baseline may indicate systemic mastocytosis (clonal disease of mast cells)
• Serial measurement of serum tryptase (a highly specific marker for mast cell degranulation)
• Take samples 1, 3 & 24hrs post-episode of anaphylaxis
• The rise in tryptase concentration is directly proportional to fall in BP
• Blood histamine not very practical in routine practice
• Tryptase: pre-formed protein found in mast cell granules
  not useful for food induced anaphylaxis

Question 140

4 mechanisms of anaphylaxis

Answer 140

IgE - mast cells → histamines + platelet activating factor
IgG - macrophages/neutrophiles → histamine + platelet activating factor
Complement - mast cells/macrophages → PAF + histamine
Pharmacological - mast cells → leukotrienes and

NB IgG can induce anaphylaxis but require very high concentration of antigen and the antigen must be introduced systematically for it to cause anaphylaxis histamine e.g. blood transfusions, biologics, IgG transfusion

Question 141

Emergency management of anaphylaxis

Answer 141

• IM adrenaline 500ug → outer aspect of thigh and repeat if needed
• Adjust body position: sit up if SOB, supine if hypotension, lie on side if unconscious
• Oxygen 100%
• Fluid replacement
• Inhaled Bronchodilators
• Hydrocortisone 100mg IV (prevent late phase response)
  
  • Can get a late rebound, this has a slower mechanism of action and isn’t given to deal with the acute effects
• Chlorpheniramine 10mg IV (for skin rash)
• Get help, don’t panic

Question 142

Adrenaline MOA in anaphylaxis

Answer 142

• α1 receptors: causes peripheral vasoconstriction, reverses low BP and mucosal oedema
• β1 receptor: increase heart rate and contractility and BP
• β2: relaxation of bronchial smooth muscle & reduces release of inflammatory mediators

Question 143

Follow-up management of anaphylaxis

Answer 143

• Referral to:
  
  1. Allergy/immunology clinic
  2. Qualified dietician (if food-induced anaphylaxis)
  3. Venom immunotherapy & drug desensitisation as appropriate
• Investigate the cause of anaphylaxis
• Written information sheet on the following;
  
  • Recognition of symptoms
  • Avoidance of identifiable triggers
  • Indications for self-treatment with an Epipen
• Prescription of emergency kit to manage anaphylaxis
  1. Epipen: contains adrenaline (300μg for adults, 150μg for children) + prednisolone 20mg OD
  2. Antihistamine tablet: cetirizine 10mg OD
  3. Must call ambulance & attend A&E after using emergency kit
  4. All patients should be prescribed 2 pens
• Copy of management plan and training for patient, carers, school staff and GP+ Implement patient’s management plan in nursery and school
• Advise patients to acquire a Medic Alert bracelet
• Review patients to ensure that they understand their disease and can use their Epipen
• Utilise patient support groups i.e. AnaphylaxisCampaign

Question 144

Adverse Reactions to Food (3 types)

Answer 144

• Food intolerance: non-immune reactions which include metabolic, pharmacological & unknown mechanisms
  
  • Food poisoning (e.g. bacterial, scromboid toxin)
  • Enzyme deficiencies (e.g. lactose intolerance)
  • Pharmacological (e.g. caffeine, tyramine)
• Food aversion
  
  • Fads, eating disorders
• Food allergy:
  
  • IgE mediated reactions (e.g. anaphylaxis, OAS)
  • Cell mediated (e.g. coeliac)
  • IgE and cell mediated (e.g. atopic dermatitis)

Question 145

3 main management strategies for allergies/anaphylaxis

Answer 145

• Avoidance:
  
  • Education about food labelling, interactions with restaurants & school
  • Nutritional input for dietary balance & growth in children
  • Acknowledge anxiety & potential bullying: mental health support if required
• Emergency mx
  
  • As with anaphylaxis
  • Ensure well-controlled allergic asthma
• Prevention:
  
  • Breast feeding: strong preventer of allergy
  • LEAP study showed that delayed introduction of peanuts in high risk children (atopic dermatitis, egg allergy) reduced development of peanut IgE sensitisation & allergy

Question 146

Question 1: A 18 years old lady with a history extensive eczema who is unable to stop taking anti-histamine medication. What is the most appropriate test to look for IgE sensitisation?

Answer 146

→ RAST - rapid antigen sensitivity blood test

Question 147

Question 2: A 60 year old female with hypotension and skin rash under general anaesthesia. What is the most appropriate test to diagnose anaphylaxis ?

Answer 147

→ Mast cell tryptase

Question 148

Question 3: A 15 year old with a history of asthma and hayfever who notices increasing cough and wheeze shortly after eating peanuts. What is the most appropriate initial diagnostic test ?

Answer 148

→ Skin prick/Serum specific IgE test (RAST)

Question 149

A 55 year old man with a 6 hour history of lip and tongue angioedema involving lips and tongue who is taking an ACE inhibitor and calcium channel blocker for hypertension. Clinical examination show a pulse of 75, blood pressure 150/90, respiratory rate of 18/min and oxygen saturation 98% on air. What is the most likely diagnosis?

Answer 149

→ ACEi angioedema

Question 150

A 35 year old man with a history of spring time hayfever and immediate lip tingling and swelling immediately after eating and apples.

Options:
* IgG4 subclass deficiency
* Cross reactive IgE sensitisation between hay fever and apple allergens
* Apple-hay fever immune complex disease
* Increased Th17 immune response to apple allergen
* Food aversion disorder
What is the most likely explanation for IgE hypersensitivity?

Answer 150

• Cross reactive IgE sensitisation between hay fever and apple allergens

Question 151

DDx of basophilic stripping on blood film

Answer 151

• Basophilic stippling aka Punctate basophilia refers to an observation found when observing a blood smear in which erythrocytes display small dots at the periphery. These dots are the visualization of ribosomes and can often be found in the peripheral blood smear, even in some normal individuals
• Aggregated ribosomal material
• Beta thalassaemia trait
• Lead poisoning
• Alcoholism
• Sideroblastic anaemia

Question 152

DDx of Hypersegmented neutrophil on blood film

Answer 152

• Maximally 5 segments in neutrophils
• Megaloblastic anaemia - reflects impaired DNA synthesis
• Associated with
  
  • B12 deficiency
  • Folate deficiency
  • Drugs

Question 153

Describe target cells on blood film. and DDx

Answer 153

• Codocytes - relatively high surface area: volume ratio
  
  • AKA Sodosopiacytes
• Associated with IDA, thalassaemia, hyposplenism, liver disease
• Should be removed by spleen but if present in blood = abnormal

Question 154

Howell-Jolly bodies

Answer 154

• Nuclear remnant visible in red cells

* This is a sign of hyposplenism

Question 155

• What are the clinical features of anaphylaxis? (10 for complete answer)

Answer 155

• Skin &/or mucosal tissue: hives, itch, swollen lips, tongue, uvula, flushing
• Respiratory compromise: SOB, wheeze (lower airway bronchoconstriction), stridor (upper airway), fall in PEF, hyperaemia, angioedema
• Reduced BP or assoc. symptoms: collapse, syncope, incontinence, MI
• Persistent GIT symptoms: crampy abdominal pain, vomiting, diarrhoea (from increased mucus production in the gut)
• Neuro: impending sense of doom, LOC

Question 156

Immediate management of anaphylaxis

Answer 156

• ABCDEFG
• Patients may require respiratory support
  
  • Intubation may be required for severe bronchoconstriction
  • Tracheostomy if develops upper respiratory tract obstruction (e.g. laryngeal swelling, or severe swelling of the tongue)
• Oxygen by mask
  
  • Improve oxygen delivery
• Adrenaline im (1: 1000 0.5mg for adult and may repeat)
  
  • Acts on B2 adrenergic receptors to constrict arterial smooth muscle
    
    • Increases blood pressure
    • Limits vascular leakage
    • Bronchodilator
  • Repeat if necessary
• Intravenous anti-histamines (10mg Chlorpheniramine)
  
  • Acts to oppose the effects of mast-cell derived histamine
• Nebulized bronchodilators
  
  • Improve oxygen delivery through bronchial dilatation
• Intravenous corticosteroids (Hydrocortisone 200mgs)
  
  • Systemic anti-inflammatory agent.
  • Effect takes about 30 minutes to start, and does not peak for several hours.
  • Important in preventing rebound anaphylaxis (2nd episode)
• Intravenous fluids
  
  • Increase circulating blood volume and therefore increase blood pressure

Question 157

Adults v paeds causes of anaphylaxis

Answer 157

• Causative agent:
  
  • Children: food more common
  • Adults: drugs & venom more common

Question 158

• Frequency of organ involvement: (adults v kids)

Answer 158

• Skin (most frequent): 84% - Almost all patients with anaphylaxis will have skin involvement (itch, erythema, urticaria, angioedema)
• CVS (more often in adults): 72% - (faint, lightheaded, collapse, LOC)
• Respiratory (more often in children): 68% - (asthma, laryngeal oedema)

Question 159

What are some common causes of anaphylaxis

Answer 159

Common causes of anaphylaxis

• Foods
  
  • Peanuts
  • Tree nuts
  • Fish and shellfish
  • Milk
  • Eggs
  • Soy products
• Insect stings
  
  • Bee venom
  • Wasp venom
• Chemicals, drugs and other foreign proteins
  
  • Penicillin and other antibiotics
  • Intravenous anaesthetic agents, eg suxamethonium, propofol
  • Latex
• Only a limited number of foods cause true food allergy
  
  • Distribution of food allergy is different in children compared to adults
  • e.g. wheat is more common in children
  • Shellfish allergy is more common in adults

Question 160

There are two types of latex allergy

Answer 160

• Type I hypersensitivity
  
  • Acute onset of classical allergic symptoms after exposure e.g. wheeze, urticaria, angioedema, anaphylaxis.
  • Spectrum of severity
  • Mucosal route is associated with more severe reactions
  • Different rubber products vary significantly in their allergenic content
• Type IV hypersensitivity
  
  • Contact dermatitis
  • Usually affect hands (glove usage) or feet (due to rubber in footwear)
  • Mainly due to rubber additives eg thiuram rather than latex itself
  • This is T- cell mediated. CD4+ cells activates CD8+ cells to destroy the antigen and release cytokines.
  • Symptoms occur 24-48 hours after exposure (much later than in IgE mediated reactions).
  • Itch ++
  • Rash, well-demarcated, often flaky
  • Not responsive to anti-histamines

Question 161

Why do adults with latex allergy may also have food allergy?

Answer 161

• Type I hypersensitivity to latex; cross reactivity with chitinase containing foods
  
  • Avocado
  • Apricot
  • Banana
  • Chestnut
  • Kiwi
  • Passion fruit
  • Papaya
  • Pear
  • Pineapple

Question 162

What disorders are associated with recurrent meningococcal meningitis?

Answer 162

• Immunological
  
  • Complement deficiency
    
    • Recurrent infection with encapsulated organisms
      
      • Neisseria meningitis,
      • Gonococcus, H influenza B, pneumococcus
  • Antibody deficiency
    
    • Recurrent bacterial infections, especially of upper and lower respiratory tract
• Neurological
  
  • Any disruption of blood brain barrier
    
    • Occult skull fracture
    • Hydrocephalus
• Generally suggested that adults with sporadic meningococcal disease should be screened for complement deficiency

Question 163

How would you manage a patient with complete C7 deficiency

Answer 163

• Meningovax, pneumovax and HIB vaccines
• Daily prophylactic penicillin
• High level of suspicion for infection
  
  • Can’t just give him C7, it is highly labile and would just get degraded.
• Ideal is gene therapy but not possible as of yet

Question 164

How does SLE causes complement deficiency?

Answer 164

• Immune complexes bind to C1q and activate classical pathway
• Complement is consumed
  
  • Low levels of C4 and C3 complement suggest SLE is active
• ESR and dsDNA titre also reflect activity of disease

Question 165

histologically SLE kidneys

Answer 165

• Renal biopsy
  
  • Diffuse proliferative nephritis
  • Immune complex and complement deposition
    
    • Lumpy bumpy deposition

Question 166

1 immune suppression drug that makes SLE worse

Answer 166

NB: sulphasalazine is known to make lupus worse.

Question 167

Diagnosing SLE

Answer 167

Diagnosis
SLICC criteria (2012)
* Patient must have biopsy proven lupus nephritis with positive ANA or dsDNA OR
* patient must have four criteria including at least one clinical + one immunological criteria
3 best tests
1. Anti-dsDNA antibodies
2. Complement: Low C3 and C4 (SLE consumes complement)
3. ESR (high) but CRP normal. If CRP is high think infection, serositis or arthritis
Also do
* BP
* urine for casts or protein (lupus nephritis)
* FBC, U&E, LFT
* Skin or renal biopsies may be diagnostic

Question 168

Management for SLE

Answer 168

Management

• treat whatever organs that are affected
• mild: PRN anlagesia, hydroxychloroquine (first line)
• Moderate: pred, hydroxychloroquine (DMARD), AZA/metho/mycophenolate mofetil (anti-T cells)
• Severe: DMARD =/- steroids, biological agents (esp rituximab to deplete B cells and reduce auto-antibodies)
• life-threatening: cyclophosphamide (non-specific toxic immunosuppressant), plasmapheresis

Question 169

New therapy for SLE

Answer 169

• Low dose interleukin-2 therapy (IL-2)

* IL-2 promotes T-cell growth. At low dose, it helps to expand T-reg because they have highest affinity for IL-2

Question 170

The two most common clinical manifestations of anaphylaxis?

Answer 170

angioedema and urticaria

Question 171

Why do you give IV corticosteroids to prevent in cases of anaphylaxis

Answer 171

rebound anaphylaxis

Question 172

Adults with recurrent meningococcal disease should be screened for defects in which immune system pathway

Answer 172

complement especially alternative and final pathway

Question 173

What is serum sickness

Answer 173

Common reaction of pencillin

• Mechanism
  
  • Penicillin can bind to cell surface proteins
  • Acts as a neo-antigen: stimulates a very strong IgG antibody response
  • Individual is sensitised to penicillin.
  • This is not anaphylaxis because it is IgG and NOT IgE
• Subsequent exposure to penicillin stimulates
  
  • Formation of immune complexes with circulating penicillin
  • The production of more IgG antibodies.
• Immune complexes are deposited in small vessels, affect the glomerulus and lead to infiltration of macrophages and neutrophils.

Question 174

What further investigations would you do to confirm the diagnosis of serum sickness in response to pencillin? (share some similarities with SLE)

Answer 174

• Low serum C3 and C4
  
  • Indicative of classical complement pathway activation
  • (Immune complex measurements unreliable)
• Specific IgG to penicillin
  
  • Can be performed if specifically indicated, but takes time
• Characteristic biopsy features (skin, kidney)
  
  • Infiltration of macrophages and neutrophils
  • Deposition of IgG, IgM and complement

Question 175

Managing a patient with serum sickness

Answer 175

• Discontinue penicillin immediately → self-limiting after
  
  • THIS IS THE MOST IMPT BIT
• Decrease systemic inflammation with corticosteroids
• Ensure appropriate fluid balance

Question 176

Management of Bruton’s

Answer 176

• Immunoglobulin replacement therapy
  
  • Pooled serum IG
  • Administered every 3 weeks
• Indefinite treatment
  
  • Stem cell/bone marrow transplantation would be a more permanent treatment

No point vaccinating

Question 177

• 64 yr old lady is seen in A+E after slipping and injuring her left hip when getting out of the bath.
• Other problems
  
  • Persistent back pain and generalised lethargy for 12 months
  • Three episodes of pneumococcal pneumonia in last 2 years
  • Post-menopausal – on HRT
• Physical examination
  
  • Swollen, tender hip with marked limitation of movement
  • Clinically anaemic
    X-ray show pepper pot skull with decreased bone density

Bloods show normal ALP, with normocytic anaemia

What is your DDX?

Answer 177

• Multiple myeloma
• Osteoporosis and Sjogren’s syndrome
• Osteoporosis and SLE

Question 178

Symptoms of multiple myeloma

Answer 178

CRAB 
Calcium - high 
Renal - bence jones proteins in urine 
Anaemia - from overcrowding of bone marrow with monoclonal plasma cells 
Bone pain - Lytic lesions of bone

A Bence Jones protein is a monoclonal globulin protein or immunoglobulin light chain found in the urine,

Also freq. infection due to production of ‘useless’ malignant clone - immune paresis

Question 179

Why is ESR elevated in multiple myeloma

Answer 179

Rouleaux formation in multiple myeloma

• ESR: measures the rate of fall of erythrocytes through plasma
• Rises if protein constituents of plasma increase or change
  
  • Increases attractant charge
  • Causes erythrocytes to clump together
  • Clumped erythrocytes fall more quickly through plasma

Dengue also causes rouleaux formation

Question 180

Investigations for ?MM

Answer 180

• Igs and electrophoretic strip, Urinary BJP, skeletal survey

Question 181

Management of multiple myeloma

Answer 181

• Refer to haematologist for specialist management
• TX: corticosteroids, thalidomide, cyclophosphamide
• Usually 3-5yr survival.

Question 182

Relationship with RA and pregnancy

Answer 182

• Post-partum presentation frequently described - possibly related to changes in Th cell profiles during/after pregnancy; Th2 cells tend to dominate during pregnancy with switch back to Th1 postpartum
  
  • And as we discussed in the allergy lecture, Th1 is generally pro-inflammatory.

Question 183

Rheumatoid arthritis - genetic predisposition

Answer 183

• HLA DR
  
  • HLA DR4 present in 60-70% patients cf 20-35% controls (caucasian)
  • Only specific DR4 subtypes, ie Dw4, Dw14, Dw15, are RA associated
  • HLA DR1 also predisposes to RA
  • Predisposing HLA class II molecules share common sequence at positions 70-74, an area predicted to lie within the alpha helix forming the wall of the peptide-binding groove
  • Peptide presentation by disease associated HLA class II molecules may be involved in disease pathogenesis
• PAD type 2 and 4
  
  • Peptidylarginine deiminase polymorphisms increase citrullination of proteins
  • Suggests increased load of citrullinated proteins may increase likelihood of developing rheumatoid arthritis. Note the loss of B cell tolerance to citrullinated proteins in patients who develop rheumatoid arthritis
• PTPN 22
  
  • Protein tyrosine phosphatase non-receptor 22 is a lymphocyte specific tyrosine phosphatase which suppresses T cell activation. 1858T allele increases susceptibility to rheumatoid arthritis, SLE, type 1 diabetes
  • Suggests T cell activation is involved in pathogenesis of rheumatoid arthritis

Question 184

Before starting a RA pt on biologics - what needs to be considered

Answer 184

• Consider risk of infection especially prior to use of ‘biologic’ agents
  
  • Screen for exposure to TB using CXR and TB ELISPOT
  • Screen for exposure to Hepatitis B
  • Screen for exposure to Hepatitis C
  • Consider possibility of HIV infection
  • Prior history of septic arthritis/infected joint prosthesis
  • Educate patient to stop drug and seek advice if acute infection
  • Consider need for vaccinations
• Consider risk of malignancy
  
  • Prior history of malignancy
  • Advise re sun exposure/skin protection

Question 185

Biologics in RA

Answer 185

• TNFa antagonist. Inhibits downstream events in inflammation. (etanercept, adalimumab)
• Rituximab. Antibody specific for CD20. Depletes B cells (not plasma cells).
• Tocilizumab. Antibody specific for IL-6 receptor – widespread effects
• Disruption of T cell function e.g. abatacept. Infrequent use if severe active RA that failed all three above. Abatacept. CTLA-4 – Ig fusion protein. Binds to ligands of CD28 (CD80 and CD86) and thereby inhibits T cell activation.

Question 186

new (2018) oral drug for RA

Answer 186

• Oral biologics - tofacitinib, baricitnib (data suggest just as good as conventional DMARDs)
  JAK inhibitors

Question 187

What type of hypersensitivity reaction - serum sickness

Answer 187

Type 3 because it forms antibody-penicillin complexes, vasculitis, renal

Question 188

What is rheumatoid factor

Answer 188

IgM antibody against Fc potion of IgG

Question 189

Polymorphisms in peptide arginine deaminase (PADI) enzymes are associated with which disease

Answer 189

Rheumatoid arthritis

Question 190

Transplant drugs

1. Steroids
2. Cyclosporin
3. Tacrolimus
4. Sirolimus
5. OKT3
6. IL-2 receptor antibody
7. Anti-lymphocyte antibody

45M undergoes heart transplant. 72hours after, pt shows signs of organ rejection which is resistance to steroids. A mouse monoclonal antibody is administered to save the transplant

Answer 190

OKT3

Mouse monoclonal antibody targeting the human CD3, used to treat rejection episodes. The antibody efficiently clears T cells from the recipient’s circulation. T cell is the major mediator of acute organ rejection

CAUTION: may cause anaphylaxis due to murine protein stimulation immune system → potentially cytokine storm and death

Question 191

Autoimmune antibodies

1. Anti-smooth muscle
2. p-ANCA
3. c-ANCA
4. Anti-Jo1
5. anti-CCP
6. Anti-centromere
7. Anti-topoisomerase
8. Anti-dsDNA
9. Anti-parietal cell
10. anti-TSH

45F with proximal myopathy. Rash surrounding both eyes. High resolution CT shows pulmonary fibrosis

Answer 191

Dermatomyositis

4. Anti-Jo1

Helitrope rash around the eyes
Gottron’s papules
Non-nasolabial sparing malar rash (sparing think SLE)

Presence of anti-Jo1 typically suggest interstitial pulmonary involvement with raised ESR and raised CK levels

Assoc with SLE and scleroderma

Question 192

Autoimmune antibodies

1. Anti-smooth muscle
2. p-ANCA
3. c-ANCA
4. Anti-Jo1
5. anti-CCP
6. Anti-centromere
7. Anti-topoisomerase
8. Anti-dsDNA
9. Anti-parietal cell
10. anti-TSH

43M with planes of fingers especially after cold weather + recent onset of difficulty in swallowing

Answer 192

6. Anti-centromere

Limited systemic scleroderma 
CREST syndrome 
_calcinosis 
_raynauds 
_ oesophageal dysmotility 
_ sclerodactylyl 
_ Telangiectasia  

Anti-topoisomerase is for diffuse systemic scleroderma
- involvement of kidneys, heart and lungs (pulmonary fibrosis)

Question 193

Autoimmune antibodies

1. Anti-mitochondrial muscle
2. p-ANCA
3. c-ANCA
4. Anti-Jo1
5. anti-CCP
6. Anti-centromere
7. Anti-topoisomerase
8. Anti-dsDNA
9. Anti-parietal cell
10. anti-TSH

52M referred to gastro with itchy skin and malaise. Also bruising on arms and leg

Answer 193

1. anti-mitochondrial

PBC!!!!

itching due to pruritis (increased bile acid in circulation)
Brusing due to poor absorption of fat soluble vitamins including Vit K, but also D - osteomalacia, A - blindness)

Question 194

Dry eyes, dry mouth + joint pain

Diagnosis?
What other Sx
How to diagnose

Answer 194

Sjogren’s

Other Sx - Schirmer’s test for dry eyes, parotid swelling

Blood test show raised ESR and mild anaemia
Also ANA+
Diagnostic with salivary gland biopsy showing infiltrate of T and B cells, CD4+ T cell most prominent

Question 195

Autoimmune antibodies

1. Anti-mitochondrial muscle
2. p-ANCA
3. c-ANCA
4. Anti-Jo1
5. anti-CCP
6. Anti-centromere
7. Anti-topoisomerase
8. Anti-dsDNA
9. Anti-parietal cell
10. anti-TSH

saddle shaped nose, frequent nose bleeds and haempytsis

Answer 195

3. c-ANCA - GPA/Wegeners

Granulomatosus with polyangiitis

Saddle nose deformity due to perforated septum
Lungs (pulmonary haemorrhage)
Kidneys (glomerulonephritis)

Question 196

Anti-ribonucleoprotein

Answer 196

Associated with mixed connective tissue disease

Question 197

35F presents toGP with blurry vision and weakness in legs. CSF show oligoclonal bands of IgG on electrophoresis

Diagnosis?
What is the antigen?

Answer 197

Myelin basic protein are implicated in pathogenesis of multiple sclerosis.

MS is a demyelinating disease associate with antigenic stimulation of CD4+ T cells which activates CD8+ cytotoxic T cell directed against oliogdendrocyte proteins

Other clinics features

• optic neuritis
• urinary/bowel incontinence
• weakness of arm/legs
• dysphagia

Question 198

34M known IVDU presents with 1 week history of fever, fatigue and abdo pain + joint pain. Angiogram reveals multiple aneurysm

1. Stony fruit
2. HBsAg
3. Myelin basic protein
4. Rhesus antigens
5. Peanuts
6. Anti-Serum
7. Synovial membrane antigens
8. Poison ivy

Answer 198

2. HBsAg

Pt has polyarteritis nodosa (PAN) associated with pANCA. HepA is associated with PAN

Immune complexes deposited within vessels leading to fibrosis and vessel wall weakening → aneurysm

Corticosteroids and cytotoxic agents required to control disease progression

Anti-serum disease is when patient becomes sick after non-human nail source f serum is injected IV resulting in immune complex hypersensitivity type 3

Question 199

45M with SLE presents to GP with nosebleed and gum bleeding when he brushes teeth. BT show v low platelet count

1. Stony fruit
2. HBsAg
3. Myelin basic protein
4. Rhesus antigens
5. Glycoprotein IIb,IIIa
6. Anti-Serum
7. Synovial membrane antigens
8. Poison ivy

Answer 199

5. Glycoprotein IIb,IIIa

Pt has autoimmune ITP! IgG directed at platelets make them more susceptible to destruction and hence thrombocytopenia and bleeding

Secondary causes include SLE and antiphospholipid syndrome

Question 200

39M MSM with PCP. What test to confirm underlying diagnosis?

1. Histocompatibility
2. Immunofluoresence
3. Latex fixation
4. Patch test
5. Skin prick test
6. Western blot
7. DAT

Answer 200

6. Western blot

Dude has HIV

Question 201

Kveim test

Answer 201

Sarcoidosis

Not done in UK. Sample of spleen from known sarcoid injected into patient. Presence of non-caseating granule formation on biopsy of site 4-6 weeks after = pt has sarcoid

Question 202

5 year old boy with purpura on legs and buttock, joint pain and abdo pain. Mother states child has suffered from sore throat approx 1 week before. Doctor like to perform an investigation to confirm diagnosis

1. Histocompatibility
2. Immunofluoresence
3. Latex fixation
4. Patch test
5. Skin prick test
6. Western blot
7. DAT

Answer 202

2. Immunofluoresence

Testing for anti-IgA antibody in HSP

Question 203

Complement tests CD50 and AP50. What does each test

how does RA, SLE, membraoproliferative glomerulonpehritis affect complement levels?

Answer 203

CH50 is a marker for the classical complement activating pathway. AP50 is for the alternative pathway

Complements are also acute phase proteins. hence when there is chronic inflammation e.g .RA, there is increase in CH50

SLE there is complement consumption aka deficieny in C3 and C4, hence LOW C3 and C4 are markers of SLE activity

In membranoproliferative glomerulonephritis, there is nephritic factors (which are IgG against C3). Hence they will also have low C3. but v SLE, they have normal C4

if there is reduced AP50, means C3, B, D or P factors must be low. This predisposes pt to encapsulated bacteria

Question 204

C1 inhibitor deficiency

Answer 204

hereditary angioedema, characterised by facial swelling

may lead to airway compromise and respiratory distress

Question 205

DiGeorge CATCH 22

Answer 205

Cardiac abnormalities 
atresia Oesophageal 
Thymic hypoplasia 
Cleft lip
HypoCa 
22q11.2 mutation

Question 206

what is the AIDS defining illness in HIV?

Answer 206

Candidiasis of the esophagus, bronchi, trachea, or lungs [(but NOT the mouth (thrush)]
Cervical cancer, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (greater than one month’s duration)
Cytomegalovirus disease (other than liver, spleen, or nodes)
Cytomegalovirus retinitis (with loss of vision)
Encephalopathy, HIV related
Herpes simplex: chronic ulcer(s) (more than 1 month in duration); or bronchitis, pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal (more than 1 month in duration)
Kaposi sarcoma
Lymphoma, Burkitt’s (or equivalent term)
Lymphoma, immunoblastic (or equivalent term)
Lymphoma, primary, of brain
Mycobacterium avium complex or M kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis, any site (pulmonary or extrapulmonary)
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jiroveci pneumonia
Pneumonia, recurrent
Progressive multifocal leukoencephalopathy
Salmonella septicemia, recurrent
Toxoplasmosis of brain
Wasting syndrome due to HIV

CD4 <200cells/ul

Question 207

34F presents with itchy and desquamating, erythematous rash on the wrist approx 3 days after wearing new bracelet. which cytokine is first to be released during the initial exposure?

1. IL10
2. IFNy
3. IL2
4. TNFa
5. IL12

Answer 207

5. IL12

This is a Type 4 hypersensitivity reaction - long lag time, contact dermatitis

During first encounter, APC such as macrophage engulf allergen and presents to CD4. CD4 and macrophage communication to release IL12

During second exposure, the memory CD4 Th1 from first encounter now release IFNy, IL2 nad IL3 activating macrophages to release TNFa which causes the symptoms

IL10 is produced by Th2 cells which inhibits Th1 cells

Question 208

56F with blurry vision and bilateral weakness. Vision worse after bath. what is most likely target in this disease process?

1. pancreatic b-cell
2. nickel
3. proteolipid protein
4. synovial membrnae
5. tuberculin

Answer 208

3. proteolipid protein

this woman has MS. MS also against myelin basic protein

pancreatic b-cell is for T1DM
nickel for contact dermatitis
synovial mmebrane protein is for RA
tuberculin for TB

Question 209

How does HIV kill CD4 T cells

Answer 209

1. Infected CD4 killed by CD8
2. budding of HIV from CD4 causes rupture
3. infected CD4 may fuse with uninfected CD4 to form syncytia giant cells thta ballooon and die

Question 210

HIV and macrophages

Answer 210

HIV engulfed by macrophgae for APC are not destoryed

macrophages are also replicating reservoirs. Macrophage can enter BBB and this is how HIV can cross BBB

Question 211

ANA staining patterns for the following conditions

• SLE
• Sjogrens
• Dermatomyositis
• mixed connective tissue disease
• drug induced SLE
• systemic sclerosis

Answer 211

SLE - speckled, anti-Smith
SLE - peripheral, anti-dsDNA
Sjogren - speckled, anti-Ro
Dermatomyositic - speckled, anti-Jo1
Mixed connective tissue disease - speckled, anti-RNP
Drug induced SLE - homogenous, anti-histone
Systemic sclerosis - nucleolar pattern, anti-RNA polymerase `

Question 212

Autoimmun hepatitis autoantibodies type 1 v type 2

Answer 212

Type 1 - anti-smooth muscle and anti-nuclear

Type 2 - anti-liver kidney microsomal

Type 2 is more common in children (presents earlier) and poor steroid response type 1 is diagnosed aged 10 and up, good response to steroids

Question 213

Dx caused by autoantibodies against

1. Ganglioside LM1
2. Ganglioside GM1
3. Hu
4. Myelin-associated glycoprotein
5. Purkingje cells

Answer 213

1. GBS
2. ALS
3. hu is part of peripheral nerves (PNS dx)
4. MS
5. CNS

GBS v ALS

• GBS symmetrical inflammatory polyneuropathy that begin sin the legs and ascends, finally affecting the muscles of respiratory
• ALS (amyotrophic lateral sclerorsis) subtype of motor neurone disease characterized by loss of neurons in the motor cortex as well as anterior horn of the spinal cord, therefore associated with upper rand lower motor neuron signs

Question 214

35F referred to ophthalmologist after seeing floaters in right eye and lost of accommodation. 3 weeks ago, she had trauma to her left eye. Steroids were given to prevent potential loss of vision

1. Keratoconjunctivitis sicca
2. Sympathetic opthalmia
3. Uveitis
4. Keratitis
5. Scleritis

Answer 214

2. Sympathetic opthalmia

Her recent trauma to the eye has caused break in immuno privillege. eyes are immunoprivilleged sites.

Presentation of photoreceptor antigento immune cells now have caused the body’s own immune cells to target the eyes which may lead to blindness

1. keratoconjunctivitis sicca is related to Sjogren. Tested by Schirmer’s test

Question 215

Clinical diagnostic criteria for anaphylaxis (3 ways)

Answer 215

1. Known allergen + low BP
2. Likely allergen + >2 of following:
   - skin signs
   - resp signs
   - low BP
   - GI signs e.g. crampy abdo pain, vomiting
3. No/unknown allergen + acute onset of skin signs (urticaria, angio-oedema) + 1 of the following:
   - respiratory signs
   - decreased BP, collapse, syncope, incontinence

Question 216

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

vs

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.

Answer 216

Top 26M is acute urticaria
Bottome 35F is urticaria vasculitis

Acute urticaria is defined being present for less than 6 weeks, whereas chronic urticaria persists
for more than 6 weeks. In both cases the urticarial rash is intermittent, comes and goes and normally
persists in a single site for less than 24 hours.

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. In this instance a skin biopsy of the urticarial
lesion is useful to confirm/repute presence of a vasculitis.

Question 217

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.

All Answer Choices
A. C1 inhibitor deficiency
B. Extrinsic allergic alveolitis
C. Allergic asthma
D. Urticarial vasculitis
E. Idiopathic angioedema
F. IgE mediated anaphylaxis
G. Coeliac disease
H. Chronic urticaria
I. Panic attack
J. Acute urticaria
K. Mast cell degranulation

Answer 217

Correct K. Mast cell degranulation

NOT F. IgE mediated anaphylaxis

Because the tablet for angina that he took was aspirin. And aspirin related allergies are mast cell mediated not IgE

Question 218

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.

C1 inhibitor deficiency or panic attack?

Answer 218

Correct A. C1 inhibitor deficiency

this is not panic attack because there is usually no ACTUAL SWELLING in panic attacks

CI inhibitor def = classically ANGIO-OEDEMA + itch + abdo pain (just like allergies BUT there is no IMMUNOLOGICAL BASIS!

Question 219

A 35 year old woman presents with a two day history of a red itchy skin rash which started soon after her first scuba-diving lesson. She is otherwise well.

All Answer Choices
A. Contact hypersensitivity
B. Allergic bronchopulmonary aspergillosis
C. Anaphylaxis
D. Allergic rhinitis
E. Hereditary angioedema
F. Allergic asthma
G. Acute angioedema
H. Acute urticaria
I. Allergic conjunctivitis
J. Chronic urticaria

Answer 219

Correct H. Acute urticaria

THIS IS NOT CONTACT HYPERSENSTIVITY!!
because the rash appeared too quickly after her scuba diving. This is LATEX allergy which is acute urticaria!

For contact derm, you need DAYS to develop becasue it is T cell mediated and you usually NEED an sensitisation event first

Tx with PO antihistamines

Question 220

A 22 year old woman presents with an intermittently itchy and desquamating skin rash on her abdomen which is unresponsive to antihistamines

A. Contact hypersensitivity
B. Allergic bronchopulmonary aspergillosis
C. Anaphylaxis
D. Allergic rhinitis
E. Hereditary angioedema
F. Allergic asthma
G. Acute angioedema
H. Acute urticaria
I. Allergic conjunctivitis
J. Chronic urticaria

Answer 220

Correct A. Contact hypersensitivity

THIS IS NOT CHRONIC URTICARIA because this is NOT histamine driven because it was UNRESPONSIVE TO HISTAMINE!

urticaria = histamine, mast cells
contact hypersensitivity is T cell mediated hence NOT HISTAMINE

Question 221

This 45 year old woman presents to A&E 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.

What is the cause of her symptoms?

Answer 221

SPOT THE ACEi

IN ALL ALLERGY QUESTIONS, SPOT THE ACEi and stop it.

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!

Question 222

MHC associated with Th1 and Th2 cells

Answer 222

Major histocompatability complex class 2

Question 223

MHC associated with cytotoxic T cells

Answer 223

Major histocompatability complex class 1

Question 224

Which complement factor is an important chemotaxic agent?

Answer 224

C3a

C3 is cleaved into C3a and C3b. C3a is chemotaxis and C3b is the activates C5-C9.