Session 9: The Immunocompromised Host Flashcards
Why is immunodeficiency a clinical problem? Consequences?
Because of the large spectrum of different primary immunodeficiency diseases (PIDs) where there are different phenotypes (>300 diseases) and little knowledge about them. There is also a failure to recognise and diagnose the PIDs where a lot of the diseases might get mixed up as other diseases or just a series of infections. It takes around 8-12.4 years from onset of symptoms for someone to get diagnosed with PID. About 60% or more of the patients will be 18 years old or older when diagnose is made. A consequence of this is that 37% will have permanent tissue/organ damage by this point.
Define immunocompromised host.
State in which the immune system is unable to respond appropriately and effectively to infectious microorganisms. Due to a defect in one or more components of the immune system.
What are the two main categories of immunocompromisation?
Explain them very briefly. (Cause)
Primary immunodeficiency also called congenital.
Due to intrinsic gene defects like missing proteins, missing cells or non-functional components of the immune system.
Secondary immunodeficiency also called acquired. This is due to an underlying disease/treatment like a decreased production/function of immune components or increased loss or catabolism of immune components.
When do you suspect an immunodeficiency?
(What kind of signs are you looking for? (Mnemonic))
Infections defined as SPUR
Severe (infection)
Peristent (infection, won’t go away)
Unusual (infection where the site of infection or type of infection is rather unusual in a healthy individual)
Recurrent (Infection keeps coming back even though it has been cleared)
10 warning signs of PID in children.
4 or more new ear infections within 1 year
2 or more serious sinus infections within 1 year
2 or more months on antibiotic with little effects
Two or more pneumonias within 1 year
Failure* of an infant to *gain weight* or *grow normally
Recurrent, deep skin* or *organ abscesses
Peristent thrush* in *mouth* or *fungal infection* on *skin
Need for intravenous antibiotics to clear infections
Two or more deep-seated infections* including *septicaemia
A family history of PID
10 warnings signs of PID in adults.
2 or more new ear infections within 1 year
2 or more new sinus infections within 1 year in absence of allergy
1 pneumonia per year for more than 1 year
Chronic diarrhoea + weight loss
Recurrent viral infections (colds, herpes, warts and condyloma)
Recurrent need for intravenous antibiotics to clear infections
Recurrent deep abscesses of skin or internal organs
Persistent thrush or fungal infection on skin or elsewhere
Infection with normally harmelss tuberculosis-like bacteria
A family history of PID
Give limitations to the 10 warning signs.
Lack of population-based evidence:
Family history only proven that it is present in 25% of people with PID.
Failure to thrive
Diagnosis of sepsis treated with IV antibiotics
PID patients with different defects may present differently
Infections with a subtle presentation
PID patients with non-infectious manifestations.
Give example of PID patients with non-infectious manifestations.
Autoimmunity
Malignancy
Inflammatory response
Give subgroups of PIDs. (Remember primary)
Which is the most common?
Immunodeficiency due to antibody defects (65%)
Immunodeficiency due to T cell defects (15%)
Immunodeficiency due to phagocytic defects (granulocytic) (10%)
Explain what the problem is in immunodeficiency caused by antibody defects. (Two types)
Give examples.
It can either be a defect in the development of B cells.
E.g. X-linked* agammaglobulinaemia also called *Bruton’s disease
It can also be due to a defect in antibody production
E.g. Common Variable Immunodeficiency CVID, Selective IgA deficiency, IgG subclass deficiency (IgG2), Hyper-IgM syndrome
In the case of the PIDs due to defect in antibody production, what are the most common.
Give a brief description of each.
Common Variable Immunodeficiency is the most common PIDs of this sort that requires treatment.
However Selective IgA deficiency is the most prevalent/common but it is usually asymptomatic and doesn’t require any treatment.
Although if Selective IgA deficiency is associated with IgG subclass deficiency IgG2 patients will require treatment. There is a risk if you have this deficiency that there is a risk of blood transfusion reaction.
Hyper-IgM syndrome has a deficiency in the CD4+ protein that is required from T cells to signal to switch from IgM to IgG. Keeps producing of IgM instead. Requires treatment.
Note that Selective IgA deficiency or IgG subclass deficiency (IgG2) do not need treatment on their own.
Explain what the problem is in immunodeficiency caused by T cell defects. (Two types)
Give examples, explain them very briefly.
Combined B and T cell defects:
Severe combined immunodeficiency (SCID)
Wiskott-Aldrich syndrome
Ataxia telangectasia
T cell defects alone: Di George syndrome (thymus) CD3 deficiency MHC class II deficiencies (not gonna activate CD4+ T cells) Tap-1 or -2 deficiency (MHC class I, not gonna activate CD8+ T cells)
Explain what the problem is in immunodeficiency caused by phagocytic (granulocyte) defects. (3 types)
Example and explain briefly.
Defects in respiratory burst:
Chronic granulomatous disease (CGD)
Defects in fusion of lysosome/phagosomes:
Chediak-Higashi syndrome
Defect in neutrophil production and chemotaxis:
Cyclic neutropenia
LAD protein deficiencies
How could you easily differentiate between types of phagocytic defects PIDs?
By blood test.
CGD and Chediak-Higashi syndrome would have normal neutrophil/granulocyte count.
Cyclic neutropenia and LAD protein deficiencies will have a lowered neutrophil count/other granulocytic count.
How would you by age be able to differentiate between the different subgroups of PIDs and SID?
The onset for T-cell or phagocyte defects are usually < age 6 months.
Onset after 6 months and before 5 years of age suggests a B-cell antibody or phagocyte defect
Onset after 5 years of age or later in life usually suggests a B-cell/antibody/complement or secondary immunodeficiency.
