SG14, SG15- Adaptive Immunodeficiencies Flashcards
Ab deficiency will lead to ____ infections
extracellular bacterial infections
T-cell deficiency will lead to ____ infections
viral, fungal, intracellular bacterial infections
compare primary and secondary immunodeficiency
Primary: genetic / developmental defect in immune system, either innate or adaptive
Secondary: acquired (not congenital) defect of immune system
list the 3 possible mechanisms of immunodeficiency (what is lost?)
reduced cell type, cell numbers, or cell function
list the breakdown of Primary Immune Deficiency types
1) Ab deficiency, 65% (B-cells)
2) Cellular, or combined Cellular/Ab deficiency, 25% (T-cells or B and T cells)
3) phagocyte deficiency, 10%
4) complement deficiency, 5%
(1) and (2) are the abnormalities used to diagnose B-cell deficiencies which has the following common infectious consequences: (3)
1- absent/reduced follicles and germinal centers in lymphoid organs
2- reduced serum Ig levels
3- pyogenic bacterial infections, enteric bacterial and viral infections
(1), (2), (3) are the abnormalities used to diagnose T-cell deficiencies which has the following common infectious consequences: (3)
1- reduced T-cell zones in secondary lymphoid organs
2- reduced DTH rxs to common Ags
3- defective T cell proliferation in response to mitogens (in vitro)
4- viral, fungal, intracellular bacterial infections + viral associated malignancies
Innate immune deficiencies leads to the following common infectious consequences…
variable, but commonly pyogenic bacterial and viral infections
about 50% of SCID cases are inherited in a (1) fashion causing a defect in (2) and leading to (3) not being able to proliferate
1- X-linked recessive
2- γ chain subunit of several CK receptors, IL-2Rαβγ particuarly (affects IL-2, IL-4, IL-7, IL-9, IL-15, IL-21)
3- immature lymphocytes
about half of the autosomal SCID cases are caused by mutation of (1) which functions to (2) and its defects leads to accumulation of (3) and affects (4) cells most
1- ADA (adenosine deaminase)
2- breakdown of adenosine
3- toxic metabolites during proliferation
4- Th cells
the most common clinical syndrome associated with B-Cell maturation is (1) with there is a defect in (2) which results in (3)
1- X-linked Agammglobulinemia (Bruton’s)
2- Bruton Tyrosine Kinase (BTK) mutation
3- B cell maturation halts at pre-B cell phase
the most common defect in T cell maturation is (1) inherited in (2) fashion
1- DiGeorge Syndrome (CATCH-22)
2- autosomal dominant
no thymus –> no T cells –> repeated viral, fungal, intracellular bacterial infections
Ig(1) deficiency is most common and leads to (2)
Ig(3) deficiency is rare and is easily treated with IV Ig
1- IgA
2- recurrent respiratory and urinary tract infections + intestinal issues
3- IgG
(1) is where there is defective isotype switching and cell-mediated immunity due to a mutation in (2); people are highly susceptible to (3)
1- X-linked Hyper-IgM Syndrome
2- CD40L (costimulatory on T-cells)
3- Pneumocystis jiroveci (intracellular fungus)
list the management of the following primary immunodeficiencies: SCID, cell-mediated defect, B-cell defect, complement defects
ALL- possibly gene therapy, prophylactic antibiotics
- SCID- none or HSC transplantation
- Cell Mediated: stem-cell transplant
- B-cell: passive immunity via healthy donors
- Complement (+ neutropenia): aggressive antimicrobial therapy when infection occurs
(1) is a disease due to a mutation in the WAS gene through (2) inheritance. WAS gene is responsible for (3) and its deficiency leads to (4) which characterize its diagnosis
1- Wishkott-Aldrish Syndrome
2- X-linked recessive
3- cellular skeleton component => small, frail platelets & leukocytes + fail to migrate
4- eczema, reduced platelets, immunodeficiency
Ataxia-Telangiectasia results from a mutation in (1) leading to (2) and (3); it is characterized by the following three abnormalities: (4)
1- DNA repair gene
2- abnormal DNA repair during recombination of Ag receptor gene segments
3- defective lymphocyte maturation
4- gait abnormality, spider veins (vascular malformation), immunodeficiency
list the common causes of secondary immune deficiencies
- malnutrition
- disease
- malignancies: myelomas, lymphomas, leukemia (tumors are commonly immuno-suppressive)
- steroids + other drugs + radiation = latrogenic causes
- AIDS
describe basic components of HIV
- retrovirus (lentavirus genus)
- 2 copies of ssRNA
- enveloped: derived from host, with class I or II MHC
- recognizes CD4 Ag on Th cell
list the 2 common drugs that cause secondary immune deficiencies (include mechanism)
- Corticosteroids: depletes CD4 cells, dec eosinophils/basophils, inhibits T/B cell maturation and CK synthesis
- Cycolosporin: inhibits IL-2 dependent signaling
Duncan Syndrome, aka (1), is a defect in (2) [include function] and once person is exposed to (3), (4) will result and (5) are symptoms [treat with (6)]
1- X-linked lymphoproliferative syndrome
2- SAP (adaptor protein involved in lymphocytic signaling)
3- EBV
4- uncontrolled B cell proliferation, CTL activation => defective NK cell/CTL function and Ab responsed
5- lymphomas, irreversible hepatitis, bone marrow failure
6- anti-CD20
