10. Immunocompromised Host Flashcards
What is primary immunodeficiency (PID)?
Congenital immunodeficiency due to an intrinsic gene defect.
Could be missing protein missing cell or non-functional components.
What is secondary immunodeficiency?
Acquired immunodeficiency due to an underlying disease or treatment.
Could be due to decreased production or increased loss of immune components.
What acronym is used to identify when to suspect an immunodeficiency?
"SPUR" Severe Persistant Unusual - site or microorganism Recurrent
How many warning sites must be demonstrated to be diagnosed with PID?
2
What are some common causes of PID?
- Antibody deficiency
- Common variable immunodeficiencies (CVID)
- Combined T and T cell
- Phagocytic defects
Which PID is caused by phagocytic defects?
Chronic granulomatous disease - defective NADH oxidase
What information can be useful when trying to diagnose a PID?
Age of onset
Type of microbes and sites of infection
Presentation <6 months is likely to be defect in what?
T cell or phagocytic defect
Presentation 6 months- 5 years is likely to be a defect in what?
B cell/Antibody or phagocyte
What do antibody defects usually only present after around 6 months?
Maternal IgG antibodies are in the circulation for the first 6 months
Presentation >5 years is likely to be a defect in what?
B cell/antibody
Complement
or Secondary immune deficiency
What type of infections are characteristic of complement deficiency?
Meningitis, sepsis, arthritis (C5-C9) Pyogenic infections (C3)
What type of infections are characteristic of phagocyte defects?
Skin/mucous infections
Deep seated infections
Invasive fungal infections
Which fungal infection is associated with phagocyte defects?
Aspergillosis
What inheritance pattern does chronic granulomatous disease show?
Autosomal recessive
What infections are associated with antibody deficiency?
Sinorespiratory infections Arthopathies GI infections Malignancies Autoimmunity
Which type of PID is giardia lambia associated with?
Antibody
What X-linked disease causes defects in B cell development?
Bruton’s disease
What are the signs of T cell defects?
Failure to thrive
Deep skin and tissue accesses
Opportunistic infections
Death if not treated
What other immune cell will be affected by T cell defects?
B cells - T cells provide cytokine signals that stimulate isotype switching to IgG, so IgG levels will decrease.
Are viral and fungal infections associated with T or B cell deficiency?
T cell
Are bacterial and fungal infections associated with T or B cell deficiency?
B cell and granulocytes
What supportive treatment can you give to patients with PID?
- Prophylactic microbials
- Nutritional support - Vitamins A+D
- Avoid live attenuated vaccines
- Treat infections promptly and aggressively
What specific treatment can you give to patients with PID?
Regular immunoglobulin therapy (IVIG or SCIG)
What type of PID is HSCT used for?
Severe combined immunodeficiency (SCID)
What comorbidies are patients with PID at an increased risk of developing?
Malignancies - avoid non-essential exposure to radiation
Autoimmune diseases
Organ damage
Which PID conditions is immunoglobulin replacement therapy used for?
CVID
Bruton’s disease
Hyper-IgM syndrome
What can cause secondary immunodeficiency due to decreased production of immune components?
Liver diseases Malnutrition Splenectomy Infection (HIV) Lymphoproliferative diseases
What is the immune function of the spleen?
- Antibody production from B cells
- Splenic macrophages remove opsonised microbes
- Removal of blood borne pathogens and encapsulated bacteria
Which bacteria are asplenic patients at a higher risk of infection by?
Encapsulated -
Haemophilus influenzae
Strep. pneuomia
Neisseria meningitidis
How can asplenic patients be managed to avoid overwhelming infection?
- Life-long penicillin prophylaxis
- Immunisation against encapsulated bacteria
What is an OPSI?
Overwhelming post-splenectomy infection
- Sepsis or meningitis usually
How does chemotherapy alter a patients susceptibility to infections?
Increased risk of infections:
- Neutropenia
- Damage to mucosal barriers
- Vascular catheters
What can cause secondary immunodeficiency due to increased loss or catabolism of immune components?
Protein-losing conditions:
Nephropathy
Enteropathy
Burns
Where is aspergillus usually found?
Ubiquitous in dust, soil and the air
When can aspergillus become pathogenic?
Rarely in normal hosts, but can cause disease in immunodeficient hosts.
What is the most common site of infection of aspergillus?
Lung
What type of infection is aspergillus?
Fungal
How is aspergillus infection treated?
Amphotericin
Why might aspergillus not be detected on a blood culture?
Tend to remain isolated and form cavities rather than entering the blood stream
What group of viruses does Varicella-zoster belong to?
Herpes-simplex
What primary infection does varicella-zoster cause?
Chicken pox
What is the structure of varicella zoster?
dsDNA
Enveloped
How is varicella zoster transmitted?
Via respiratory droplets
Outline how varicella zoster virus invades and multiplies within hosts.
Initial infection in respiratory mucos
Spreads to lymph nodes, where it replicated
Progeny spread to liver and spleen where multiply further.
Explain how varicella zoster viruses causes characteristic vesicular rashes?
Endothelial and skin epithelial cells become infected, causing virus-containing vesicular rashes
How long is the incubation period of varicella zoster?
15 days - while multiplying in the liver and spleen
How long after initial exposure does the characteristic rash appear?
14-21 days
When is a person infected with varicella zoster most infectious?
1-2 days before rash appears
Can it be caught by contact with vesicular fluid in rashes?
No, respiratory droplet transmission, cells must re-infect mucosa at the end of incubation period
How does varicella zoster cause shingles later in life?
Viruses enter cutaneous neurones and migrate to ganglia, where they remain in latent state.
They can become reactivated to cause shingles.
What is characteristic of shingles?
Dermatomal rash
How can shingles be treated? Which patients are likely to need treatment?
Acyclovir in immunocompromised patients as infection can be severe
