Primary Immunodeficiency Flashcards
What are the potential consequences of immunodeficiency?
Susceptibility to infection
Susceptibility to certain types of cancer
Increased incidence of autoimmunity
Where may the defect lie in primary immunodeficiency?
Components of the innate immune system
Stages of lymphocyte development – adaptive immune system
Responses of mature lymphocytes to antigenic stimulation
(the earlier the effected element in the immune process, the greater the problem)
How might a defect in B cells and/or in complement system present?
Repeated infection with encapsulated bacteria
How might a defect in IgG and IgA system present?
Recurrent respiratory infection by pneumococcus or Haemophilus spp.
How may a defect in macrophages present?
Infections with staphylococci, gram-negative bacteria and fungi
How may a defect in T cells or macrophages present?
Intracellular organisms such as protozoa, viruses, and intracellular bacteria, including mycobacteria
What may reactivation of latent herpes represent?
T-cell deficiency
What may neisseria meningitides represent?
Complement defects
Describe the relationship between T-cell deficiency and mycobacterium infection
The severity of T-cell immunodeficiency is also reflected in patterns of mycobacterial infection
Mycobacterium tuberculosis is a virulent organism that causes lung infection in immunocompetent people
In mild T-cell immunodeficiency, the same organism is able to invade the body outside the lungs
More severe immunodeficiency predisposes to widespread infection with mycobacteria of low virulence normally found in the environment (e.g., M. avium intracellulare complex)
What are the causes of primary immunodeficiency?
- Mutations
- Polymorphisms
- Polygenic disorders
What is a polymorphism?
- Polymorphism involves one of two or more variants of a particular DNA sequence
- The most common type of polymorphism involves variation at a single base pair
- Polymorphisms can also be much larger in size and involve long stretches of DNA
What part of the immune system do polygenic disorders usually affect?
Antibodies
Some of these polygenic conditions may be caused by autoimmunity
What is severe combined immunodeficiency (SCID)?
A group of disorders that affect both T and B cells
Multiple mutations
- Some are autosomally inherited and there may be a history of consanguinity
- Other types are X-linked and there may be a history of early deaths in maternal uncles
Infants with SCID die in the first few months of life unless treatment is given
- Stem cell transplant can cure SCID but it has to be done quickly
- Many countries screen for SCID in new-borns
Give two examples of how polymorphism cause immunodeficiency?
Human leukocyte antigen (HLA) alleles are polymorphic and affect the outcome of infections
-Individuals with HLA alleles that are unable to bind viral peptides have a worse outcome
Mannan-binding lectin (MBL) is a collagen-like protein that binds sugars in bacterial cell walls and activates the classic complement pathway
-Polymorphisms in MBL and complement affect the risk for infections
What are some examples of polygenic disorders affecting immunity?
Common variable immunodeficiency (CVID)
IgA deficiency
Specific antibody deficiency
