Immunology 2 Flashcards
Major consequence of immunodeficiency
Increased susceptibility to infection
Susceptible to cancer
Increased risk of autoimmunity
Define primary immunodeficiency
Genetic, congenital disorders
When part of the immune system is either missing or functioning abnormally
Can be caused by mutations or autoimmunity
For primary immunodeficiency where can the abnormality occur?
- components of the innate immune system eg Chronic granulomatous disease affects the phagocytes
- stages of lymphocyte development
-responses of mature lymphocytes to antigenic stimulation
Eg hyper-IgM syndromes
If you are B cell deficient what kind of infection are you susceptible to?
Pyogenic bacteria (eg otitis, pneumonia, meningitis, osteomyelitis),
Enteric bacteria
Viruses
Parasites
If you are T cell deficient what kind of infection are you susceptible to?
Pneumocystis jiroveci,
Viruses,
Atypical mycobacteria,
Fungi
If disease presents with encapsulated bacteria what is the likely immunodeficiency
B-cell defects
Complement defects
If disease presents with neisseria what is the likely immunodeficiency
Complement defects
If disease presents with:
-Invasive fungi
Staphylococcus,
Gram negative bacteria
what is the likely immunodeficiency
phagocyte defects
If disease presents with:
- low-virulence mycobacteria
- cytomegalovirus
- EBV/ lymphoma
- HHV8/ Kaposi sarcoma
- pneumocystis
- TB
- Candida
- Reactivation of herpes simplex and herpes zoster
what is the likely immunodeficiency
T-cell defects
More intracellular pathogens
Causes of primary immunodeficiency?
Mutations (permanent alteration in the DNA sequence) Polymorphism (involves one of two variants of a DNA sequence) Polygenic disorders (disorders caused by the combined action of more than one gene)
What is a SCID
Severe Combined ImmunoDefiency
Group of disorders that affect both T and B cells
Can be autosomally inherited or X-linked
Treatment for SCID
Immediate Stem cell transplant
Or gene therapy
Avoid live vaccines until treatemtn
Prophylaxis against pneumocystis jiroveci
Example of a SCID
DiGeorge Syndrome (22q11 deletion)
Bare lymphocyte syndrome (defects in transcription factors)
MHC class I deficiency (mutations in TAP1, TAP2 and TAPASIN)
Common polygenic disorders that affect antibody production
Common Variable Immunodeficiency (CVID),
IgA deficiency,
Specific antibody deficiency
Describe CVID
Common Variable ImmunoDeficiency
Most common primary immunodeficiency requiring treatment
Patients have low levels of total IgG
IgA, IgM and B and T cell levels are variable
Causes recurrent respiratory tract infection
Can also cause infections of the gut, skin, nervous system
Suggestive autosomal-recessive inheritance
Name an example of primary immunodeficiencies caused by autoimmunity
Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dysplasia (APCED)
Have a defect in central tolerance and experience many types of autoimmunity
normally frequently experience severe recurrent Canadia infection
(Can’t fight as body produces autoantibodies against IL-17)
Some produce autoantibodies against IFN-y (these patients have problems with mycobacteria please infection)
Clinical presentation and history of SCID
Develop infection in first week of life,
Unusual or recurrent infection,
Diarrhoea,
Unusual rashes
Low lymphocyte count
History:
- FH of neonatal death
- FH of consanguinity
Treatment of primary immunodeficiency
Prophylactic antibiotics
Immunoglobulin replacement therapy
In primary immunodeficiency what criteria must be met for gene therapy
Genetic mutation must be identified,
Transferred gene must confer a proliferation or survival advantage
Must not cause malignancy
What is secondary immunodeficiency
Synthesis of key components is suppressed (eg bone marrow infiltration or infection) or their loss is accelerated
