Flashcards in Chp. 2 Primary Immunodeficiency Deck (32):
What syndrome is due to maldevelopment of the 3rd and 4th pharyngeal pouches?
DiGeorge Syndrome is due to failure of which structure(s)?
3rd and 4th pharyngeal pouches
What is the 3rd pharyngeal pouch responsible for?
Dorsal Wing: Inferior PTH glands
Ventral Wing: Thymus
Both structures supplied by CN 9
What is the 4th pharyngeal pouch responsible for?
Superior PTH gland
Parafollicular C cells
Cartilage and Laryngeal Muscles
What exact chromosomal deletion is responsible for the failure of the 3 and 4 pharyngeal pouch development?
It is due to 22q11 micro deletion. This means that the deletion is on chromosome 22 on the long arm at spot 11; there are 30-40 genes missing.
What do patients with DiGeorge present with?
DiGeorge presents with T-cell deficiency due to a lack of a thymus
Hypocalcemia due to lack of parathyroid glands
Abnormalities of the great vessels (Tetrology of Fallot)
Facial and Ear deformities
In SCID, what kind of immunity is defective?
Both Humoral AND Cell Mediated Immunity
What are the three etiologies (or 3 different ways a patient can get) of SCID?
1. Cytokine Receptor Defects
2. Adenosine Deaminase Deficiency
3. MHC II Deficiency
What kind of infections would be seen in SCID patients?
These patients are susceptible to fungal, viral, bacterial, protozoal; opportunistic infections and live vaccines (body can't tolerate live vaccine)
What is treatment for SCID patients?
Sterile Isolation (Bubble Baby)
Stem Cell Transplantation
How does cytokine receptor defects lead to SCID?
Because cytokine signaling is necessary for proliferation and maturation of B cells
How does ADA Deficiency lead to SCID?
ADA is necessary for the deamination of adenosine and deoxyadenosine. Deamination is a step in breaking down these molecules. W/o this enzyme, these 2 molecules can't be broken down and instead will accumulate inside the lymphocyte. Not good bc these molecules are CYTOTOXIC TO LYMPHOCYTES
How does MHC II Deficiency lead to SCID?
W/o MHC II, CD4+ T cells cannot recognize Ag. If they never recognize Ag, they can never become activated. Thus many parts of the immune system will never become activated!!!
What is the disorder that is characterized by a complete lack of immunoglobulin?
X-Linked Agammaglobulinemia and is due to disordered B-cell maturation.
Specifically, the Pre and Pro B cells cannot mature. Basically, naive cells cannot become Plasma cells, and its plasma cells that secrete Abs.
What enzyme is deficient in X-Linked Agammaglobulinemia?
Bruton's Tyrosine Kinase. BTK is necessary for a naive B cell to mature into a plasma cell.
When does BTK present?
Presents after first 6 mod of life with RECURRENT BACTERIAL, ENTEROVIRUS, AND GIARDIA LAMBLIA INFECTIONS.
Bacterial, esp extracellular encapsulated
Enterovirus ie polio and cocksackie virus
After first 6 mos of life bc this is when maternal Abs start to wear off. Maternal Abs are present during the first 6 mos of life.
When lacking Ab production, what three types of infection will always be seen?
Bacteria need to be "tagged" by an opsonin to aid in phagocytosis. There are two opsonins - C3b and IgG. If no IgG can be made, then a majority of opsonization is gone, and phagocytic activity will de decreased.
Enteroviral infections target the mucosal GI tract. IgA protects mucosal linings. If no IgA can be made, then the GI tract will constantly be attacked bc its nothing but mucosa down there
These infections for the same reasons as enterovirus
What must be avoided in X-Linked Agammaglobulinemia?
What disease is due to LOW immunoglobulin due to either a B cell or Helper T cell DEFECT (not deficiency)?
Common Variable Immunodeficiency. There is a low amount of Ab production. Usually asymptomatic. Presents late in childhood
What types of infection would be expected in CVID?
Bacterial, Enterovirus, Giardia Lamblia because there is decreased Ab production. Usually late in childhood.
What are CVID patients at risk for developing?
Autoimmune disease and Lymphomas
Describe IgA syndrome
Low SERUM and MUCOSAL IgA.
THIS IS THE MOST COMMON Ab DEFICIENCY!!
What are IgA deficient patients most at risk for developing?
Mucosal Infections, especially viral ones. However most patients are asymptomatic.
Just a heads up: Celiac Disease is due to a IgA deficiency
What primary immunodeficiency is characterized by elevated IgM?
Hyper IgM syndrome
What is responsible for the development of Hyper IgM syndrome?
It is due to a mutated CD40L on CD4+ helper OR defective CD40 receptor on the B cell.
The binding of CD40L to its receptor is the second signal needed for B cell activation. Once the B cell is activated, CD4+ will release IL-4 and IL-5 needed for CLASS TYPE SWITCHING.
Without that second signal, the B cell is stuck as an IgM bc it can't class switch
What Abs are in low number (obvious) and what kind of infections are thus seen?
Low IgA, E, G and result in pyogenic infections due to poor opsonization, especially at mucosal sites.
IgG-->pus infections bc IgG is an opsonin
What is a pyogenic infection?
It is an infection that has severe localized inflammation usually with pus formation and is due to infection with the pyogenic bacteria such as:
Staph, Strep, E. Coli...just any that cause a pus forming infection. pyogenic just means pus forming.
What is Wiskott Aldrich Syndrome
This is a disease where you will see:
No platelets so bleeding could be a problem...AS A MATTER OF FACT, BLEEDING IS A MAJOR CAUSE OF DEATH!!
Recurrent infections due to defective cellular and humoral immunity
What is Wiskott Aldrich Syndrome due to? What is the mode of inheritance?
Mutation in the WASP gene, X-Linked
What are the two complement deficiencies?
Deficiency in C5-C9 (any one of these)
Deficiency in C1 INHIBITOR, not C1 itself...so too much C1
What do patients with a C5-C9 deficiency have an increased risk for?
These people are at increased risk for NEISSERIA INFECTIONS! It is bc C5-C9 make the MAC complex and even tho Neisseria can escape phagocytosis, they are vulnerable to MAC.