Session 9 Flashcards
(41 cards)
What is an “immunocompromised” host?
State in which the immune system is unable to respond appropriately and effectively to infectious microorganisms
• Due to defectin one or morecomponents of the immune system
What are the two types of reason as to thy somone is immunocompromised?
Primary immunodeficiency: congenital • Due to intrinsic gene defect (~275 genes) •Missing protein •Missing cell •Non-functional components
Secondary immunodeficiency: acquired
•Due to an underlying disease/treatment
•↓Production/function of immune components
•↑Loss or catabolism of immune components
When should you suspect an immunodeficiency?
Infections defined as “SPUR” o Severe o Persistent o Unusual o Recurrent
What are the limitations of the 10 warning signs of immunodeficiency?
General use: Lack of population-based evidence e.g doesn’t use likelihood of patient history.
PID patients with different defects/presentations
PID patients with non-infectious manifestations e.g malignancies, autoimmunity, inflammatory responses.
What kinds Immunodeficiency are caused by antibody defects?
~65% of all PIDs due to antibody deficiency
Defect in B cell development
• X-linked agammaglobulinaemia(Bruton’s disease)
Defect in antibody production • Common Variable Immunodeficiency (most common that requires treatment - treated with IV immunoglobulin) • Selective IgA deficiency (most prevalent but most don't require treatment, only unless they have IgG subclass deficiency (IgG2) too) • IgG subclass deficiency (IgG2) • Hyper-IgM syndrome (defect in CD40 protein so cant switch from Igm to IgG)
What do you need to know that’s important with selective IgA deficiency?
Autoimmune so don’t give IgA
What kinds of Immunodeficiency is caused by T cell defects?
~15% of all PIDs
Combined B and T cell defects
• Severe combined immunodeficiency (SCID) (mutation that stops T and B cells maturing and when there’s an issue with T helper cells it affects antibody production too)
T cell defects • Di George syndrome (thymus) • CD3 deficiency (important in activating T cells) • MHC class II deficiencies (Cant activate CD4+) • TAP-1 or -2 deficiency (MHC class I) (These are the transporters that take the peptide antigen through the cytoplasm to MHC class I molecules)
What kinds of immunodeficiency is caused by phagocytic defects
~10% of all PIDs
Defects in respiratory burst
• Chronic granulomatous disease (CGD)
Defect in fusion of lysosome/phagosomes
• Chediak-Higashi syndrome
Defect in neutrophil production and chemotaxis
• Cyclic neutropenia
• LAD protein deficiencies (Leukocyte adhesion protein deficiency so leukocytes cant attach to endothelium and enter infected area)
How age of patient when symptoms present to diagnose immunodeficiency disease?
Age of symptom onset:
• Onset < age 6 months highly suggests a T-cell or phagocyte defect.
• Onset > 6 months and <5 years old often suggests a B-cell antibody or phagocyte defect.
• Onset >5 years old and later in life usually suggests a B-cell/antibody/complement or secondary immunodeficiency.
What is the diagnosis for this clinical case?
• 6 month-old boy who was born at term (40 weeks) physically normal and apparently healthy.
• In last 3 months, he has been plagued with recurrent fungal(diaper rash, oral candidiasis), viral(upper respiratory tract infections), and bacterial(otitis media) infections, all of which resolved with appropriate pharmacologic intervention.
• Below the 50% percentile for weight.
• Routine childhood immunization OK.
• Weak IgG response to vaccines
• Both sexes of the family have been affected by these infections.
Boy is 6 months old when symptoms present and only in the last 3 months. Microbes present indicate issue with T cell development of granulocyte issue
failure to thrive
IgG response bad so issue with B cells possibly due to T cell problem
There’s is a family history so genetic
Diagnosis: Severe combined immunodeficiency (SCID)
What is the diagnosis for this clinical case?
• 12-month-old boy with 4 episodes of severe gram-positive bacterial pneumonia in the last 6 months
• He has had recurrent diarrhoea (Giardia lamblia) and his tonsils are barely detectable.
• Below the norm for height and weight
• Recommended paediatric immunizations (low IgG, undetectable IgE, IgA and IgM and no B cells)
• Patient has three healthy sisters aged 3, 5, and 7 years. The family lost a boy at 10 months of age to bacterial pneumonia 8 years ago.
Boy is 12 months old, repetitive bacterial pneumonia in last 6 monthsso b cell or granulocyte deficiency
mostly bacteria, no viral of fungal infections
failure to thrive
No B cells and very low antibodies so B cell issue.
Only boys affected in family so x-linked.
Diagnosis: Bruton’s disease
What is the diagnosis for this clinical case?
• A young patient who developed since the age of 4 weeks multiple staphylococcal abscesses in the chest, skin, face and buttock requiring surgical incision and a course of systemic antibiotics for 10 days.
• By the age of 2 he was admitted to the hospital 5 times for staphylococcal infections and pulmonary aspergillosis.
• Height and weight below the average
• Three elder brothers had died of infections at an early age but sisters healthy
• Neutrophils failed to produce oxygen radicals (respiratory burst)
Below 6 months so issue with granulocytes Bacterial and fungal infections X-linked Neutrophils can't produce oxygen burst Diagnosis: chronic granulomatous disease
What is the diagnosis for this clinical case?
• 40 year-old women is referred to the Allergy & Immunology clinic after suffering throughout her life recurrent bacterial respiratory (sinusitis, otitis, tonsillitis) and gastrointestinal infections (intermittent diarrhoea).
• As a child she was hospitalized for pneumonias and GI infections (Giardia lamblia)
• Both IgG, IgM, IgA below normal. Poor IgG response to pneumococcal vaccines. Number of B cells and T cells were normal.
• Mother and sister had also poor response to polysaccharide vaccines and died from haemolytic anaemia and non-Hodgkin’s lymphoma.
40 years old with long history of bacterial infections in mucosal membranes.
Low antibody count and poor IgG response to vaccines.
Normal number of B and T cells.
Cancer association
Diagnosis: Common Variable Immunodeficiency
Explain the management of PIDs
Supportive treatment
• Infection prevention (prophylactic antimicrobials)
• Treat infections promptly and aggressively (passive immunization)
• Nutritional support (Vitamins A/D)
• Use UV-irradiated CMVnegblood products only
• Avoid live attenuated vaccines in patients with severe PIDs (SCID)
Specific treatment
• Regular Immunoglobulin therapy (IVIG or SCIG)
• SCID: Hematopoietic Stem Cell therapy (HSCT, 90% success)
Comorbidities
• Autoimmunity and malignancies
• Organ damages (lung function assessment)
• Avoid non essential exposure to radiation
Explain the management of PIDs
Supportive treatment
• Infection prevention (prophylactic antimicrobials)
• Treat infections promptly and aggressively (passive immunization)
• Nutritional support (Vitamins A/D)
• Use UV-irradiated CMVnegblood products only
• Avoid live attenuated vaccines in patients with severe PIDs (SCID)
Specific treatment
• Regular Immunoglobulin therapy (IVIG or SCIG)
• SCID: Hematopoietic Stem Cell therapy (HSCT, 90% success)
Comorbidities
• Autoimmunity and malignancies
• Organ damages (lung function assessment)
• Avoid non essential exposure to radiation due to malignancy tendencies
What is immunoglobulin replacement therapy?
• Goal
o Serum IgG> 8g/l
o Life long treatment
• Different formulations
o IVIg
o ScIg (young patients) (weekly)
• Conditions
o CVID
o XLA (Bruton’sdisease)
o Hyper-IgM syndrome
What could cause a secondary immune deficiency?
Decreased production of immune components:
• Malnutrition
• Infection (HIV, see group work)
• Liver diseases (liver produces CRP)
• Haematological malignancies
• Therapeutic treatment (corticosteroids, cytotoxic drugs)
• Splenectomy
Increased loss of immune components:
• Protein-losing conditions (Nephropathy, Enteropathy)
• Burns
What must be considered with patients with haematological malignancies?
Increased susceptibility to infections
• Chemotherapy-induced neutropenia
• Chemotherapy-induced damage to mucosal barriers
• Vascular catheters
- Treat suspected febrile neutropenia as an acute medical emergency and offer empiric antibiotic therapy immediately.
- Assess patient’s risk of septic complications
What are key points to remember about Immunodeficiencies? (important flashcard to learn)
Recognition and diagnosis of IDs
• When to suspect an immunodeficiency
o SPURinfections (10 warning signs)
o Age-at presentation (sex) o Site(s)of infection(s)
o Type of microorganism(s) o Sensitivity and type of treatment (surgery)
o Secondary causes of immunodeficiency
o Family history
Laboratory investigation of IDS
Suspicion of antibody/B cell deficiency :
• IgG, IgA, IgM (+/-IgE)
• IgG1-4 subclasses
• IgG levels to specific previous vaccines
• Measure antibody in response to “test” immunization Suspicion of T cell deficiency
• Lymphocyte count (FBC)
• Lymphocyte subset analysis (CD4+, CD8+ T, NK & B cells)
• In vitro tests of T cell function Suspicion of phagocyte deficiency
• Neutrophil count (FBC)
• Neutrophil function tests (eg oxidative burst for CGD)
• Adhesion molecule expression (for LAD) Tests for Complement
• Individual components
• Tests of complement function (CH50 /AP50)
Definitive tests –molecular testing and gene mutations
Why is travel history important?
Recognise imported diseases (rare / unknown in UK)
Different strains of pathogen
•Antigenically different
•Impacts on protection/ detection
•Antibiotic resistance
Infection prevention
•On the ward
•In the lab
What must you consider when taking a travel history?
WHERE have they gone?
Sub-Saharan Africa,
S.E .Asia, S / C America tend to have more prevalent travel infections.
WHEN did symptoms begin?
< 10 days
10-21 days
>21 days
WHAT (are the symptom/sign Resp (SOB/cough) GI (diarrhoea) Skin (rash) Jaundice CNS (headache / meningism) Haematological (lymphadenopathy / splenomegaly / haemorrhage) Eosinophilia can indicate parasite
HOW (did they acquire it) Food/water Insect/tick bite Swimming Sexual contact Animal contact (bite/safari) Recreational activities
Other aspects?
Any unwell travel companions or contacts?
Pre-travel vaccinations/preventative measures?
Healthcare exposure?
What are the 5 main species of plasmodium (malaria causing virus)? What is the vector?
- falciparum
- vivax
- ovale
- malariae
- knowlesii
•Vector - female Anopheles mosquito
Who is most at risk of malaria?
Young, old, pregnant
What is the most deadly form of malaria?
Plasmodium falciparum, also most common and should assume falciparum first
