Flashcards in Immunodeficiencies Deck (71):
What are immunodeficiencies?
a lack or failure of the immune system
What are primary immunodeficiencies? Secondary?
Primary = congenital
Secondary = acquired
What is the most common cause of immunodeficicencies worldwide?
What type of infections occur more often in a defect humoral immunity?
What type of infections occur more often in a defect cell mediated immunity?
Viruses and intracellular bacteria
What type of infection occur more often when there is a defect in both humoral and cell mediated immunity?
Immunodeficient individuals are more susceptible to developing certain kinds of cancers. What is the etiology of these CA?
Stem from viral infections
What is X-linked agammaglobinemia?
Absence of B cells due to a defect in B cell Tyrosine kinase
What broad class of people usually gets X-linked agammaglobinemia?
What type of infections are pts with X-linked agammaglobinemia susceptible to?
Pyogenic bacteria of extracellular origin
What is diagnostic for x-linked agammaglobinemia?
Absence of circulating B lymphocytes
Why can you not screen infants for x linked agammaglobinemia at 6 months?
Still have mother's antibodies
How do you treat x-linked agammaglobinemia?
Why aren't pts with x-linked agammaglobinemia more susceptible to viruses or fungal infections?
T cells intact.
What is common variable immunodeficiency?
an inability of mature B lymphocytes to differentiate into plasma cells
Does common variable immunodeficiency affect males and females equally?
How do you diagnose common variable immunodeficiency?
normal levels of circulating mature B lymphocytes which can proliferate in response to antigen, but do not differentiate into plasma cells.
Is common variable immunodeficiency acquired or congenital?
What is the etiology of common variable immunodeficiency?
Unknown, but may be d/t intrinsic B cell defects
What is the treatment of common variable immunodeficiency?
monthly gamma globulin shots and antibiotic therapy PRN
What are the comorbidities of common variable immunodeficiency?
Predisposed to autoimmune diseases
What is selective IgA deficiency?
Inability to produce IgA antibodies
Is selective IgA deficiency inherited or acquired?
What are the symptoms of selective IgA deficiency?
usually asymptomatic, but blood transfusions can be problematic
Why are blood transfusions problematic for pts with selective IgA deficiency?
Pts will produce anti-IgA antibodies since they were first exposed to it via breast milk. Causes hyperacute reaction
Why is selective IgA usually asymptomatic?
IgM makes up for it
Why can IgM make up for the lost IgA in selective IgA deficiency?
Has a J chain, and allows it to be transported across mucosal lining
What is the treatment for selective IgA deficiency?
Antibiotics to control infections at mucosal sites
Why can you not give IVIG to pts with IgA deficiency?
They will form hyperacute reaction to the antibodies
How do you diagnose IgA defciency?
Severely decreased levels of IgA.
True or false: pts with IgA deficiency do not express B cells with IgA antibody on their cell surface
False--they do, but not known why these do not differentiate into plasma cells
What are the cytokines that are suspected to play a role in selective IgA deficiency?
IL-5 and TGF-beta.
What are the comorbidities of selective IgA defciencies?
allergies, GI tract, and autoimmune diseases
What is hyper IgM syndrome?
"All IgM, all the time" with NO other antibody types produced
What are the two types of hyper IgM syndrome?
Hyper IgM type II syndrome
What is the cause of X-linked hyper IgM syndrome?
Lack of CD-40 ligand on T cells
What is the cause of hyper IgM type II syndrome?
inherited mutation in the gene activation-induced **cytidine deaminase** which, for unknown reasons, prevents isotype switching.
What is the defective chromosome in Di-george syndrome?
What is the immune problem in Di-george syndrome?
Lack of thymus resulting in lack of T cell production
What are the facial features of Di-George syndrome?
Low set ears and fish mouth
What pharengeal arches does the thymus arise from?
Di-George syndome predisposes pts to what type of infections?
viral and fungal infections
(think cell mediated)
Are immunoglobin levels normal in pts with Di-george syndrome? Why?
Typically yes, because TI antigens still a significant fraction of antibodies
What is the "treatment" for Di-George syndrome?
Thymus transplant, but if pt survives long enough, will generate T cells of unknown origin
What are SCID?
Defects in both B and T lymphocytes
True or false: the spleen, lymph nodes, tonsils, and appendix are not populated by B and T lymphocytes in pts with SCID
Why can you not give immunizations with live, attenuated vaccines to pts with SCID?
Will cause infection and death
What are the four molecular bases of SCID?
1. Lack of adenosine deaminase
2. Lack of purine nucleotide phosphorylase (PNP)
3. RAG1/2 gene defects
4. Mutations for cytokine receptors IL-2,4,7,9,15.
A family h/o early death from infections would be alarming for what disease?
What is the treatment for SCIDs?
Bone marrow transplant (or retroviral therapy)
What is chronic Granulomatous disease?
Recurrent bacterial infections d/t a defect in NADPH oxidase in PMNs
What are the treatments for chronic granulomatous disease?
Bone marrow transplant
What is myeloperoxidase deficiency?
decreased or absent myeloperoxidase enzyme needed to produce HOCl, used by PMNs as a ROS
What type of infections are pts with myeloperoxidase deficiency susceptible to?
There is no increase in susceptibility to infection is seen in these individuals due to compensatory immune mechanisms. However, there can be a decreased ability to ward off certain fungal infections (particularly Candida yeast).
What is Chediak-Higashi syndrome?
Congenital disorder leading to recurrent bacterial infections.
What is the molecular basis of Chediak-Higashi syndrome?
lysosomes of PMNs fuse, reducing their ability to kill microbes
Is T cell and/or NK cell function impaired in pts with Chediak-Higashi syndrome?
What are the signs of Chediak-Higashi syndrome? (4)
1. Silver hair
2. Platelet abnormalities
3. vision impairment
4. PMNs have larger granules
What is the treatment for Chediak-Higashi syndrome?
Bone marrow transplant
What is Leukocyte adhesion deficiency-1 (LAD-1)?
defect in the beta chain of LFA-1 and Mac-1 adhesion molecules renders neutrophils incapable of adhering to endothelial cells for extravasation and suppresses chemotaxis.
What are the symptoms of Leukocyte adhesion deficiency-1 (LAD-1)?
Recurrent bacterial and fungal infection
What is the treatment for Leukocyte adhesion deficiency-1 (LAD-1)? (3)
1. Antibiotics PRN
2. Granulocyte infusions
3. Bone marrow transplant
What is diagnostic for Leukocyte adhesion deficiency-1 (LAD-1)?
Extreme leukocytosis /bc PMNs cannot extravasate
NOT tested but important:
What is severe congenita neutropenia and cyclic neutropenia? Molecular cause?
Either none or cyclical amounts of PMNs. Caused by a defect PMN elastase enzyme
What is Wiskott-Aldrich syndrome?
Poor lymphocyte response to antigens
What is the pattern of inheritance for Wiskott-Aldrich syndrome?
What is the triad of symptoms for Wiskott-Aldrich syndrome?
What are the comorbidities of Wiskott-Aldrich syndrome?
What is the molecular basis of Wiskott-Aldrich syndrome?
defective cytosolic protein (Wiskott-Aldrich Syndrome protein – WASP) that helps regulate the actin cytoskeleton of bone marrow-derived cells
What is the treatment for Wiskott-Aldrich syndrome?
IVIG and abx. Bone marrow transplant