Immunodeficiency disorders Flashcards
What results in a primary immunodeficiency?
genetic or developmental defect in the immune system
What is a secondary/acquired immunodeficiency?
loss of immune function due to exposure to an external agent
primary immunodeficiencies affect either __ or__ immune functions
adaptive or innate
What is reticular dysgenesis?
occurs when stem cells fail to differentiate = total lack of leukocytes
What cells can lymphoid immunodeficiencies affect?
T, B, NK cells
What is the range of effects of a B cell specific immunodeficiency?
range from a complete absence of B cells, plasma cells, and immunoglobulin to a selective loss of certain immunoglobulin classes
What do serious B cell defects usually result in?
frequent bacterial infections
T cell defects result in frequent…
viral and fungal infections
What is SCID? what does it include?
severe combined immunodeficiency disorder
refers to a family of disorders affecting both B and T cells or T cells
- Bare-lymphocyte syndrome
- DiGeorge syndrome
What 2 SCID defects affect both T, B and NK cells?
- Adenosine deaminase deficiency
2. X linked IL-2Rγ chain deficiency
How does ADA deficiency affect lymphoid cells?
results in the accumulation of adenosine which is toxic for all lymphocytes
How does a defect in the IL-2Rγ chain cause SCID?
impedes signalling through the IL-2 receptors (and other cytokines) which are critical for T, B, and NK cell activation
What 2 defects affect both B and T cells?
- RAG1 or RAG2
2. Artemis deficiency
What is the result of a RAG1 or RAG2 deficiency ?
failure of the T and B cell precursors to differentiate because there is no recombinase enzyme
What is the result of an Artemis deficiency?
Failure to cleave the hairpin loop during variable region recombination
What defect affects T cells only?
- CD3 zeta (ζ) chain deficiency
What is the result of the zeta (ζ) chain deficiency?
T cell signalling is impeded as well as humoral responses to T-dependent antigens
What defect results in bare lymphocyte syndrome?
defective expression of class II MHC - fail to transcribe genes that encode class II MHC
What lymphocytes are impacted by bare lymphocyte syndrome?
B, T, cells
- APCs are mainly the ones that can’t express the MHC
what are the symptoms of SCID?
Severe and recurrent infections
- bacterial, viral, fungal
Tend to be fatal
What treatments are available for SCID?
- Bone marrow transplant form HLA matched donor
2. Gene therapy (experimental)
T cell immunodeficiencies mainly result in?
susceptibility to viral, fungal, and protozoal infections
What is DiGeorge syndrome?
Children born with no (or almost no) thymus or parathyroids
What is the result of having no thymus ?
Few functional T cells are preset
- no cell mediated immunity
Are there B cells present in DiGeoge syndrome?
Yes but they can’t make specific antibody without Th cells
What’s a potential treatment for DiGeorge syndrome?
transplantation of a fetal thymus
How common is X-linked agammaglobulinemia?
occurs in 1 in 103 to 106 males
- relatively common
What is the cause of X-linked agammaglobulinemia?
Defect in Brunton’s tyrosine kinase disrupts B cell signalling
As a result Pre-B cells in the BM fail to differentiate into mature ones
- don’t undergo light chain rearrangement
What do individuals have in X-linked agammaglobulinemia?
little to no circulating antibody
How can you treat X-linked agammaglobulinemia?
injections of pooled human IgG
What infections are X-linked agammaglobulinemia patients susceptible to? why?
sinopulmonary infections due to a continued lack of secretory IgA
What causes X-linked hyper-IgM syndrome?
Defect in the gene coding for the CD40 ligand
What kind of antigens do people with X-linked hyper-IgM syndrome fail to respond to? Why?
T dependent antigens because the CD40 on the B cell needs to interact with CD40L on the T cell in order to produce specific antibody
What is the response to T-independent antigens like in X-linked hyper-IgM syndrome?
normal
Why are there high levels of IgM in X-linked hyper-IgM syndrome?
Because t-independent antigen stimulation is the only kind occurring and there is no class switching
What are Selective immunoglobulin deficiencies?
When one antibody class or subclass is missing
What is the most common selective immunoglobulin deficiency?
IgA deficiency
What causes an IgA deficiency?
Failure of IgA committed B cells to differentiate into plasma cells
What do patients with IgA deficiency often suffer from?
frequent bacterial and vial sinopulmonary infections as well as increasde allergies due to excessive IgE production
What is the treatment for IgA deficiency?
Broad spectrum antibiotics
What do myeloid immunodeficiencies affect?
innate immune function, particularly phagocytosis
What are the 3 myeloid cell immunodeficiencies ?
- Congenital neutropenia
- Chronic granulomatous disease
- Leukocyte adhesion deficiency (LAD)
What causes congenital neutropenia?
Decreased production of granulocyte-colony stimulating factor (G-CSF)
What is the result of decrease in granulocyte-colony stimulating factor (G-CSF)?
Myeloid stem cells fail to differentiate into neutrophils
What is the result of congenital neutropenia?
frequent bacterial infections
What causes chronic granulomatous disease?
defect in the oxidative pathway used by phagocytes to generate hydrogen peroxide?
What is the result of chronic granulomatous disease? What is there an excess of? what are people susceptible to?
Phagocytes are unable to kill many types of bacteria
Excessige inflammatory responses
susceptibility to bacterial and fungal infections
What is also impaired with chronic granulomatous disease?
Antigen processing and presentation
- and T cell activation indirectly
What causes leukocyte adhesion deficiency? (LAD)
failure to express the ß subunit of the adhesion molecules LFA-1, MAC-1 (CR3), and gp150,90 (CR4)
What are the three pathologies (in terms of cells) that result from LAD?
- impaired extravasation of neutrophils, monocytes, and lymphocytes
- impaired ability of CTL and NK cells to adhere to target cells
- impaired conjugate formation between Th and B cells
What are 2 major problems for people with LAD?
Frequent bacterial infections and impaired wound healing
What happens if there are defects in any of the early components of the classical complement pathway?
prevents generation of classical c3 convertase
What else is not produced if there are defects in early classical complement pathway components? what is the result
C3b opsonin
frequent bacterial infections and immune complex disease
What are the most severe type of complement deficiencies?
C3 deficiencies
What do C3 deficiencies cause? (3 things)
frequent bacterial infections, failure to form MAC, and immune complex disease
What is the result of a C5-C9 deficiency?
Few health problems except for an increase in infection by Neisseria species
Why is immune complex disease rare with C5-C9 deficiencies?
likely because enough C3b is produced for immune complex clearance
What is the result in a defect in Factor D or properdin?
Susceptibility to infection by Neisseria species
What are Factor D and properdin essential for?
proper functioning of the alternative complement pathway
What is the cause of Acquired Immunodeficiency Syndrome (AIDS)? what is the result?
HIV-1 virus cuases progressive destruction of CD4+ Th cells
results in progressive loss of immune resposiveness
What other 2 cell types are also infected by HIV-1
Macrophages and DCs
Why does AIDS result in death?
opportunistic pulmonary infections, rare cancers, and central nervous system complications
How is HIV1 spread?
Sexual contact, infected blood, and from mother to infant during birth or breastfeeding
What co-receptor is the one used by HIV-1 to infect T cells?
CXCR4
What co-receptor is the one used by HIV-1 to infect macrophages?
CCR5
What is another means of causing a secondary immunodeficiency?
by immunosuppressive drugs
What is the effect of anticancer drugs like cisplatin? How do they impact the immune response?
target rapidly proliferating cancer cells
also toxic to proliferating bone marrow stem cells, T cells and B cells
What are 2 immunosuppressive drugs that are used to prevent organ graft rejection?
cyclosporin A and rapamycin
What do graft rejection drugs do to the immune response?
interfere with normal T cell responses
- makes them unresponsive
What are 2 side effects from anti graft rejection drugs?
infections and certain cancers
