Immunocompromised Host

Question 1

What is the most common. Form of antibody deficiency

Answer 1

Cvid

Question 2

Define immunocompromised

Answer 2

– “State in which the immune system is
unable to respond appropriately and effectively to infectious microorganisms”
– Due to defect in one or more components of
the immune system….

Question 3

What is primary immunodeficiency

Answer 3

Primary immunodeficiency: congenital
• Due to intrinsic gene defect (~275 genes)
• Missing protein
• Missing cell - eg no T cells bc certain t proteins lacking, = immune uysstem dead
• Non-functional components

Question 4

What is secondary immunodeficiency

Answer 4

Secondary immunodeficiency: acquired
• Due to an underlying disease/treatment
• ↓ Production/function of immune components
• ↑ Loss or catabolism of immune components
Malnutrition is the most common cause

Question 5

When to suspect an immunodeficiency?

Answer 5

The infection is
– S  severe (death if not treating, life threatening)
– P  persistent (patient does not respond to conventional antimicrobial therapy, or you have to use longer duration to achieve affect)
– U  unusual (unusual site, the of microbe - certain ones should not give infection in certain places, opportunistic microbes)
– R  recurrent (keeps coming back)

Question 6

What are some warning signs of PID in children

Answer 6

-

Question 7

What are some of the warning signs o pid in adults

Answer 7

0

Question 8

What are the limitations of the 10 warning signs?

Answer 8

 General use: Lack of population-based evidence*

• Family history (25% of cases)
• Failure to thrive
• Diagnosis of Sepsis treated with IV antibiotics

 PID patients with different defects/presentations

• T cells/ B cells/ Phagocytes/ complements
• Infections with a subtle presentation

 PID patients with non-infectious manifestations

• Autoimmunity
• Malignancy (4-25% - importance of early diagnosis)
• Inflammatory responses

Question 9

What does the age of onset suggest

Answer 9

• 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.

Question 10

What does the type of microbe suggest

Answer 10

Complement deficiency
• Pyogenic infections (C3)
• Meningitis /Sepsis/Arthritis (C5-C9)
• Angioedema (C1 inhibitor)

Phagocyte defect
• Skin/mucous infections
• Deep seated infections
• Invasive fungal infection (aspergillosis)

Antibody deficiency 
• Sinorespiratory infections (upper resp tract)
• Arthropathies 
• GI infections 
• Malignancies 
• Autoimmunity 

T cell defect - susceptible to almost anything 
• Death if not treated 
• Failure to thrive 
• Deep skin and tissue
abscesses 
• Opportunistic infections

Question 11

Describe the presentation of cod

Answer 11

See slide

Question 12

Describe teh management of primary immunodeficiency diseases

Answer 12

Supportive treatment
• Infection prevention (prophylactic antimicrobials)
• Treat infections promptly and aggressively (passive immunization)
• Nutritional support (Vitamins A/D)
• Use UV-irradiated CMVneg blood 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

Question 13

What is immunoglobulin replacement therapy

Answer 13

Goal
• Serum IgG > 8g/l
• Life long treatment

Different formulations
• IvIg
• ScIg (young patients)

Conditions
• CVID
• XLA (Bruton’s disease)
• Hyper-IgM syndrome

Question 14

What are secondary immune deficiencies

Answer 14

• Decreased production of immune components
– Malnutrition
– Infection (HIV, see group work)
– Liver diseases
– Lymphoproliferative diseases
– Splenectomy
» Causes: infarction (eg sickle cell anaemia), trauma, autoimmune haemolytic disease, infiltration (tumour), coeliac disease, congenital

Question 15

What s the function of the spleen

Answer 15

Immune function - immune reaction against ll microbes in the body
– Bloodborne pathogens
» Encapsulated bacteria!

– Antibody production
» Acute response : IgM production
» Long term protection: IgG production

– Splenic macrophages
» Removal of opsonized microbes
» Removal of immune complexes

Question 16

Describe the presentation and management of asplenic/splenectomised patient

Answer 16

Presentation
• ↑ susceptibility to encapsulated bacteria Haemophilus influenzae,
Streptococcus pneumoniae and Neisseria Meningitidis
• OPSI (overwhelming post-splenectomy infection) ⇒ sepsis and meningitis (1-2% risk of death over 15 years)

Management
• Penicillin prophylaxis (life-long)
• Immunisation against encapsulated bacteria
• Medic Alert bracelet

Question 17

Why might patients with haematological malignancy become immunocompromised and how should they be tratead

Answer 17

Increased susceptibility to infections
• Chemotherapy-induced neutropenia
• Chemotherapy-induced damage to
mucosal barriers
• Vascular catheters
- Treat suspected neutropenic sepsis as an acute medical emergency and offer empiric antibiotic therapy immediately.
- Assess patient’s risk of septic complications

Question 18

What happens to immune components in secondary immune deficiencies

Answer 18

• ↑ loss or catabolism of immune components
– Protein-losing conditions
• Nephropathy
• Enteropathy 
– Burns

Question 19

What should be looked at to recognise IDs

Answer 19

The pattern and type of infections always
reflect the nature of immunological defect
– Age - at presentation
– Sex – Site(s) and frequency of infection(s)
– Type of organism(s)
• Viruses and fungi ⇒ T cell deficiency
• Bacteria and fungi ⇒ B cell/granulocytes deficiency – Sensitivity and type of treatment (surgery)
– Family history

Question 20

What are lab tests for IDs

Answer 20

Look for secondary immunodeficiency General
• Full blood count and differential Tests of humoral (antibody) immunity
• IgG, IgA, IgM (+/- IgE)
• IgG1-4 subclasses
• IgG levels to specific previous vaccines
- tetanus toxoid/HiB/pneumococcus, MMR
- measure antibody in response to test immunisation

Tests for Cell mediated immunity
• Lymphocyte count (FBC)
• Lymphocyte subset analysis (CD4+, CD8+ T, NK & B cells) extended marker panel(s)
• in vitro

tests of T cell function Tests for phagocytic cells
• 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