Inherited Immunodeficiencies Flashcards
What is asplenia ?
A genetic or acquired deficiency that renders the spleen inactive. This will place you at a high risk for infection by encapsulated bacteria and septic infections. The spleen is a blood filter and macrophages take up pathogens from the blood.
How can you acquire asplenia ?
Have your spleen removed after a traumatic injury.
How do you treat your patients that have asplenia ?
Give them prophalactic antibiotics when performing any procedure (even dental work) and vaccinate them against capsulated bacteria.
What will a phagocyte defect result in ?
It will result in a defect in the recruitment of phagocytes to the sites of extravascular infection and will result in severe immunodeficiency. This is a process that is mediated by cell surface adhesion molecules.
What is CD-18 deficiency ?
Leukocyte adhesion deficiency which will result in defective migration into infected tissues.
What happens in chronic granulamatous disease?
Phagocytes cannot produce reactive oxygen species resulting in an impaired ability to kill bacteria (autosomal recessive ) Patients with this condition will have chronic bacterial infections.
What is myloperoxidase deficiency ?
In this condition the patients macrophages are unable to efficiently kill phagocytosed microbes because they have impaired ability to produce hypochlorus acid and toxic oxygen species and therefore will have an impaired respiratory burst.
What is chediak - Higashi syndrome ?
Partial albinism abnormal platelet function and severe immunodeficency
What are neutropenias ?
Neutropenias are characterized by low numbers of granulocytes usually defined as a neutrophil count below 500 cells / uL /
Describe severe congenital neutropenia
Characterized by low numbers of granulocytes usually defined as neutrophil could less than 500 cells/uL.
What is Kostmann syndrome ?
Severe congenital neutropenia. This is an autosomal recessive condition that is associated with a gene abnormality of granulocyte colony stimulating factor.
What is a common name for ( X-Linked Hypohydrotic ectodermal dysplasia and immunodeficiency) and what does it do ?
NEMO (I love that Fiiish- entourage quote) A genetic condition where PRR are intact but transcription of genes that should be expressed after binding are not.
What do toll like receptors stimulate ?
NFkB which controls cytokine and chemokine expression.
How do you treat NEMO ?
2x daily injections of Gamma Globulin
What will a defect in properdin P cause ?
Properdin P enhances the activity of the alternative complement pathway will lead to heightened sensitivity to Niceria
What problems will a patient have that is deficient with C-1 Inhibitor defects?
Patients with C1 inhibitor defects fail to control the inappropriate activation of the classical complement cascade. The uncontrolled cleavege of C2 will result in the production of the C2b vasoactive fragment. This will cause fluid accumulation in tissues and epiglottic swelling that can lead to death
**HANE
What will happen to patients who lack the decay acceleration factor and CD59 ?
These protect the host cell surfaces against the complement cascade. Without them the complement cascade will degrade the RBC’s
What will a defect in C3 cause ?
Susceptibility to encapsulated bacteria. This will show you the emphasis of C3b in opsonization.
What is the main concern with a defect in antibody production ?
Defective antibody production will creat an inability for a cell to clear its self from extracellular pathogens and viruses that are sensitive to neutralizing antibodies.
What will a defect in C5-C9 cause ?
Susceptibility to niceria. You will not be susceptible to every pathogen because you will still be able to opsonize bacteria
What is X-Linked agammaglobulinemia (XLA)
Absence of immunoglobins in the serum. The defective gene codes for a protein tyrosine kinase which is expressed on b cells and neutrophils. The disease will display a profound B cell deficiency making the host susceptible to both extracellular and intracellular pathogens
What will pre-B cell deficiency result in
This is a result of a mutation in the Delta 5 gene. This is a component of the surrogare light chain that paris with the my heavy chain during somatic recombination of light chain genes. This will result in a profound B cell deficiency
What will selective IgA do to the host ?
IgM can be transported across the mucosal epithelium and do the job of IgA. When you have low levels of IgA the body will produce more of the other copies of the other isotype.
What is X-linked Hyper IgM syndrome ?
A disease that is characterized by high levels of IgM but low concentrations of the other isotypes. The most common defect will be that T cells can not interact with CD-40 on T cells.
What will a TAP transporter have a deficiency with ?
This will result in very low levels of MHC class 1 molecules and defective responses to intracellular pathogens due to CD8+ T deficiency
What will a CD-8 alpha chain defect result in ?
This will have the same presentation as the TAP transport defect
Define Severe Combined Immune Deficiency
This is when patients have T cell deficits in both CD4 and CD8 T cells.
What is adenosine deaminase deficiency?
A deficiency in purine nucleotide phosphorylase deficiency. This will result in the SCID phenotype which leads to the accumulation of nucleotide catabolites that are particularly toxic to developing T and B cells
What is bare lymphocyte syndrome
Lack of expression of all MHC II molecules which results in inability of CD4 T cells to be positively selected in the thymus.
What is DiGeorge syndrome ?
This disease results from a small deletion on chromosome 22 that results in congenital heart disease, palatal abnormalities, learning disabilities and hypocalcemia
What is complete digeorge syndrome ?
Liek normal digeorge syndrome but the patients also have an underdeveloped or nonexistent thymus
What is common gamma chain deficiency ?
The common gamma chain is the signaling component of a numner of cytokine receptors. This protein interacts with JAK-3 to initiate signaling once the cytokine receptor has been engaged by tytokine ginding. If you do not produce a functional form of this protein you can not initiate signaling of any of the cytokine receptors.
What is Omenn syndrome?
A mis-sence mutation that result in partially active RAG enzymes. Lack of RAg activity results in an absence of B cells and lower number of oligocolnial auto-reactive T Cells
What is Zap 70 Deficiency ?
A deficiency in Zap-70 which is a tyrosine kinase that associates with phospholipid ITAMS during signaling via the T cell receptor complex. These patients will have abscence of CD8 T cells but normal numbers of CD4 T cells. The result is SCID. This is treated with Bone marrow transplant.
What is AIRE ?
A transcroption factor that regulates expression of several hundred host-tissue specific genes by epithelial cells in the thymic medulla. The host specific proteins sere as a source of self-proteins
