Deficiency of Adaptive Immunity Flashcards
Primary Immunodeficiency
Congenital
Caused by innate issues with WBC production
Secondary Immunodeficiency
Acquired
When infection or radiation paralyzes immune system development
Measles, malaria, EBV (infectious mononucleosis)
Infections of Pure B cell Deficiency
High grade bacterial pthogens like Staph A, Haemophilus I, and Strep P.
Severe Combined Immunodeficiency (SCID)
Rare, both T and B immunodeficiency. Of the lymphoid stem cell.
DiGeorge Syndrome
Failure of 3/4 pharyngeal pouches to develop into a thymal stroma
No T cell maturation
Also presents with: cardiac defects (tetralogy of flow), parathyroid deficieny (convulsions due to hypocalecemia)
Chromosomal deletion on Chr 22
Fungi and viruses
X-linked Bruton’s hypogammaglobinemia
Failure to b cell differentiation
Pre-B cell arrest, with IgM in cytoplasm
Defect: BTK (Bruton’s Tyrosine Kinase) used for B cell maturation
Can’t make antibody, so that’s the treatment
SCID-X1
X linked, Most common
no production of protein Gamma C, part of IL-2 receptor, shared by 7 known cytokine receptors, including IL-7
IL-7 Critical for development of T and B cell
SCID- ADA Deficiency (Adenosine Deaminase)
Adenosine accumulates in all cells, but it is necessary for developing lymphocytes, so they die
Treatment: give them the missing enzyme, or just blood transfusions, because RBCs are full of Adenosine Deaminase (irradiated to kill T Cells)
V(D)J Recombination Deficiencies
SCID A- highest incidence in athobaskan indians.
Artemis defect- enzyme involved in looping and cutting looping from VDJ recombination
RAG Enzyme- Some mice are rag knockouts
Nude Mice
Fail to make thymic stroma, so no T cells, so they look like DiGeorge Kids
X-linked Hyper IgM syndrome
When T follicular helper or B cell is mutated, and IgM can’t switch to IgG
CD40 mutation on either cell
Immunodeficiency because limitations of IgM
Common Variable Immunodeficiency (CVID)
Can have this and patient can be mostly asymptomatic, and then sudd
enly can’t respond to new challenges
DiGeorge Clinical Manifestations (non immunological)
Fish (arched) mouth, wide spread eyes, low set ears,
T Cell Deficiency Associated Infections
Intracellular pathogens like viruses, certain bacteria, yeast and fungi, especially Candida albicans and Pneumocystis jirovecii
Selective IgA Deficiency
Seems to be able to secrete IgM into mucosa instead, otherwise mostly assymptomatic
Diarrhea and sinoppulmonary infections, or increased allergies
Transplantation Treatment
You can transplant fetal thymi or thymus stromal cells (for DiGeorge), or Bone marrow transplants for SCID
Complications- Graft v host disease
In the thymus, that’s where t cells learn MHC recognition, so matching is crazy imperative
IVIG Treatment
Great for B cell deficiency
Given monthly, 99% IgG, you have to do it in an infusion center, for risk of immunological reaction (sudden inflammatory problem)
Subcutaneous is optional and doesn’t have to be done at a transfusion center
Name two viruses which are immunosuppressive in humans. Discuss a possible mechanism for the immunosuppression caused by one of these viruses.
HIV and Measles, malaria, EBV (infectious mononucleosis)
HIV targets CD4.
B Cell Deficiency Test
Serum electrophoeresis, Ig levels, specific Antibodies
Advanced: antibody response to new antigen, gene sequencing
T Cell Deficiency Tests
Skin tests with recall antigen, or total lymphocyte count
Advanced: CD3,4,8 count, mitogen response
Phagocyte Deficiency Test
WBC Count, diff, smear, NBT test
Advanced: Assay for phagocytosis/chemotaxis, genetics
Complement Deficiency Test
Chem50 test, C1 inhibitor assay
Advanced: Individual complement component evels
