SG14, SG15- Adaptive Immunodeficiencies

Question 1

Ab deficiency will lead to ____ infections

Answer 1

extracellular bacterial infections

Question 2

T-cell deficiency will lead to ____ infections

Answer 2

viral, fungal, intracellular bacterial infections

Question 3

compare primary and secondary immunodeficiency

Answer 3

Primary: genetic / developmental defect in immune system, either innate or adaptive

Secondary: acquired (not congenital) defect of immune system

Question 4

list the 3 possible mechanisms of immunodeficiency (what is lost?)

Answer 4

reduced cell type, cell numbers, or cell function

Question 5

list the breakdown of Primary Immune Deficiency types

Answer 5

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%

Question 6

(1) and (2) are the abnormalities used to diagnose B-cell deficiencies which has the following common infectious consequences: (3)

Answer 6

1- absent/reduced follicles and germinal centers in lymphoid organs
2- reduced serum Ig levels
3- pyogenic bacterial infections, enteric bacterial and viral infections

Question 7

(1), (2), (3) are the abnormalities used to diagnose T-cell deficiencies which has the following common infectious consequences: (3)

Answer 7

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

Question 8

Innate immune deficiencies leads to the following common infectious consequences…

Answer 8

variable, but commonly pyogenic bacterial and viral infections

Question 9

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

Answer 9

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

Question 10

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

Answer 10

1- ADA (adenosine deaminase)
2- breakdown of adenosine
3- toxic metabolites during proliferation
4- Th cells

Question 11

the most common clinical syndrome associated with B-Cell maturation is (1) with there is a defect in (2) which results in (3)

Answer 11

1- X-linked Agammglobulinemia (Bruton’s)
2- Bruton Tyrosine Kinase (BTK) mutation
3- B cell maturation halts at pre-B cell phase

Question 12

the most common defect in T cell maturation is (1) inherited in (2) fashion

Answer 12

1- DiGeorge Syndrome (CATCH-22)
2- autosomal dominant

no thymus –> no T cells –> repeated viral, fungal, intracellular bacterial infections

Question 13

Ig(1) deficiency is most common and leads to (2)

Ig(3) deficiency is rare and is easily treated with IV Ig

Answer 13

1- IgA
2- recurrent respiratory and urinary tract infections + intestinal issues

3- IgG

Question 14

(1) is where there is defective isotype switching and cell-mediated immunity due to a mutation in (2); people are highly susceptible to (3)

Answer 14

1- X-linked Hyper-IgM Syndrome
2- CD40L (costimulatory on T-cells)
3- Pneumocystis jiroveci (intracellular fungus)

Question 15

list the management of the following primary immunodeficiencies: SCID, cell-mediated defect, B-cell defect, complement defects

Answer 15

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

Question 16

(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

Answer 16

1- Wishkott-Aldrish Syndrome
2- X-linked recessive
3- cellular skeleton component => small, frail platelets & leukocytes + fail to migrate
4- eczema, reduced platelets, immunodeficiency

Question 17

Ataxia-Telangiectasia results from a mutation in (1) leading to (2) and (3); it is characterized by the following three abnormalities: (4)

Answer 17

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

Question 18

list the common causes of secondary immune deficiencies

Answer 18

• malnutrition
• disease
• malignancies: myelomas, lymphomas, leukemia (tumors are commonly immuno-suppressive)
• steroids + other drugs + radiation = latrogenic causes
• AIDS

Question 19

describe basic components of HIV

Answer 19

• retrovirus (lentavirus genus)
• 2 copies of ssRNA
• enveloped: derived from host, with class I or II MHC
• recognizes CD4 Ag on Th cell

Question 20

list the 2 common drugs that cause secondary immune deficiencies (include mechanism)

Answer 20

• Corticosteroids: depletes CD4 cells, dec eosinophils/basophils, inhibits T/B cell maturation and CK synthesis
• Cycolosporin: inhibits IL-2 dependent signaling

Question 21

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)]

Answer 21

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