16. Primary Immunodeficiency Flashcards
What antibodies protect babies in the first few months of life?
IgG
What are the classifications of immunodeficiency?
Primary (congenital)
Secondary (acquired)
What causes primary immune deficiency?
Part of the immunity is missing of does not work properly
Mainly chased by mutation do can also be caused by autoimmunity
Where may the abnormality responsible for primary immunodeficiency be?
Components of the innante immune system
Stages of lymphocyte development
Response of mature lymphocytes to antigenic stimulation
What disorder affect the innate immune system?
Chronic granulomatous disease Leukocyte adhesion type 1,2 and 3 NK cell deficiencies Toll like receptor defects Mendelian susceptibility to mycobacterium
What diseases affect the B cells (defects in antibodies)
Agammagkobulinemias
Hypogammaglobukinemias- selective IgA/Ig2 deficiency, ICF syndrome, common variable immunodeficiency,
Hyper IgM syndromes
Defective T cell signaling- proximal TCR signalling defects, hyper IgE syndromes
Familial hemophagocytic lymphohistiocytoses
What are the features of B cell deficiency?
Succeptibility to pyogenic bacteria, pneumonia, meningitis, enteric bacteria, viruses and some parasites
Reduced serum IgG
Normal DTH reactions to common antigens
Absent or reduced germinal follicles and germinal centres
What are the features of T cell deficiency?
Pneumocystis jiroveci, many viruses, atypical mycobacteria, fungi
Serum Ig levels normal or reduced
DTH reduced
What should you suspect with neisseria infection?
Complement defects
What should you suspect with invasive candida infections?
TH17 defect
What happens if you are deficient to IgG and IgA?
Recurrent respiratory infections with pneumococcus or haemophilus spp
Infections with staph, gram -ve and fungi are associated with what?
Reduced phagocytes
What happens if latent herpes is reactivated or shingles?
T cell deficiency
What does kaposi sarcoma, burski sarcoma and EBV suggest?
T cell deficiency
What is a mutation
Permenant alterations the a part of the DNA. This can lead to an abnormal protein or complete loss of the protein. Can lead to severe disease
What is a polymorphism?
Not necessary pathological. One of two base pairs are normal but typically doesn’t cause problems. However can cause some mild disease
What is a polygenic disorder?
More than one gene is involved in the disease. Pretty common, if they affect immune system they affect antibodies
What is SCID?
Severe combined immunodeficiency
Severe effect on B cells and T cells. Severity varies depending on how quickly they are treated after birth. Treatment is stem cell transplant. Will die in first few months unless treatment is given
What are the different types of SCID?
Defective thymic development.
Defects in nucleoside pathways
Defects in cytokine signalling
What are the most common change in the immune gene due to polymorphism?
HLA gene that codes for MHC. This leads to defective antigen presentation.
What is the most common polygenic disorder?
Common variable immunodeficiency (CVID) IgA deficiency and specific antibody deficiency. Patients have low levels of IgG, levels of IgA and IgM, B and T cells are variable
causes recurrent respiratory tract infection
What primary immunodeficiency are caused by autoimmunity?
Autoimmune polyendocrinpoathy candidiasis ectodermal dysplasia
(APECED)
Frequenlty encounter severe recurrent candida infections
produce autoantibodies against interleukin 17
How do you diagnose primary immune deficiencies?
Recurrent infections, unusual infections, infections that are hard to treat, always have diarrhoea, rashes without cause,
Low lymphocytes count (<1x10^9/L) (measured by flow cytometry)
How can you lose antibodies?
Kindney disease, gut disease
How do you treat primary immunodeficiency?
Prophylaxis with antibiotics
Immunoglobulin replacement therapy
Antibodies against a wide range of latnlfems
Ig pooled fro, thousands of normal donors
If replacement can be given IV or sub cut
Plasma screened for HIV and hep B and C antibodies
How do you treat SCID?
Avoid live vaccines
Prophylaxis against opportunistic infections such as pneumocystis jiroveci
Stem cell transplantation can be applied and are the most successful if done a few weeks after birth. If that doesn’t work you can use gene therapy
How do you treat primary immunodeficiency with gene therapy?
Using recombiant technology to correct the genetic defect in the patients own stem cells which can reconstitute the immune system.
Used in patients with SCID for whom no suitable stem cell donor was available
What criteria must be met before gene therapy is successful?
Genetic mutation for each patient must be identified and evidence showed that correcting mutation will improve condition
The transfected gene must confer a proliferation or survival advantage
Gene therapy must not cause malignancy
