Immunodeficiencies

Question 1

immunodeficiency:

• impaired _____
• increased _____
• often require _____
• type of infection indicates _____

Answer 1

immune function;
susceptibility to infections;
IV antibiotics (unusual and severe infections);
type of deficiency

Question 2

immunodeficiency-associated infections:

T-cell deficiencies

Answer 2

viral, fungal, yeast, atypical microorganisms, cancer

Question 3

immunodeficiency-associated infections:

B-cell and phagocyte deficiencies

Answer 3

microorganisms requiring opsonization (largely bacterial infections)

Question 4

immunodeficiency-associated infections:

complement deficiencies

Answer 4

resemble B-cell deficiencies

Question 5

primary immunodeficiency

Answer 5

• congenital
• genetic anomaly
• generally more severe

Question 6

secondary immunodeficiency

Answer 6

• acquired
• caused by another illness
• more common
• tend to be less severe

Question 7

primary immunodeficiencies:

• ____ defect, mostly ____
• manifest ____
• between ____ in population

Answer 7

single gene;
sporadic;
early in life;
1:500 and 1:500,000

Question 8

primary immunodeficiencies:

five groups

Answer 8

• B-lymphocyte deficiencies (most common)
• T-lymphoctye deficiencies
• phagocyte defects
• combined T- and B-cell deficiencies
• complement defects

Question 9

B-lymphoctye deficiencies

Answer 9

• hypogammaglobulinemia or agammaglobulinemia

- increased susceptibility to Ab-mediated infections (bacterial pneumonia, sinusitis, otitis media)

Question 10

causes of B-lymphoctye deficiencies

Answer 10

• receptor defects: ineffective intracellular signaling (BCR and cytokine receptors)
• Ab-class switch defect: altered ability to change Ab class (co-stimulatory signal defect)

Question 11

primary B-cell immundeficiencies

Answer 11

• Bruton’s (X-linked) Agammaglobulinemia
• Common Variable Immunodeficiency
• Selective IgA Deficiency

Question 12

Bruton’s (X-linked) Agammaglobulinemia

Answer 12

• most severe B-cell deficiency
• receptor defect (BCRs never develop)
• no mature B-cells
• recurrent bacterial infections
• unable to mount any humoral response

Question 13

Common Variable Immunodeficiency (CVID)

Answer 13

• most common primary immune deficiency
• 90% of cases are sporadic (no family hx)
• class-switch defect: lacking IgG, IgA, and IgM
• onset of symptoms is delayed until late 20s
• recurrent bacterial respiratory infections
• increased cancer risk

Question 14

Selective IgA Deficiency

Answer 14

• unable to produce IgA Abs
• compromised secretory immune system
• severe allergies and recurrent sinus/lung/GI infections
• severe mucopurulent conjunctivitis

Question 15

primary T-cell immunodeficiencies

Answer 15

-DiGeorge Syndrome/22q11.2 Deletion Syndrome

Question 16

DiGeorge Syndrome/22q11.2 Deletion Syndrome

Answer 16

• partial or complete absence of T-cell immunity (CD4+ and CD8+)
• thymic aplasia or hypoplasia (little or no circulating T-cells)
• endocrine, vascular, and facial abnormalities
• viral, fungal, and intracellular bacterial infections
• higher incidence of autoimmune disease
• 90% of cases are sporadic

Question 17

Severe Combined Immunodeficiency (SCID)

Answer 17

-combined T- and B-cell deficiencies (some NK)

possible causes:

• toxic metabolic by-products
• cytokine receptor defects
• V(D)J recombination defects
• TCR defects: bare lymphocytes (class I: no Tc/CD8; class II: no Th/CD4)

Question 18

Reticular Dysgenesis

Answer 18

• most severe SCID
• absent/defective stem cell
• no circulating lymphocytes or granulocytes
• usually fatal before or soon after birth

Question 19

complement deficiencies

Answer 19

• resemble B-lymphocyte deficiencies: bacterial infections
• C3 deficiency: most severe
• terminal complex deficiency (8000x increased risk of Neisseria gonorrhea infection)

Question 20

phagocytic deficiencies

Answer 20

-often resembles B-lymphocyte deficiencies: bacterial infections

types:

• neutrophil maturation defect
• adhesion molecule defect
• opsonin receptor defect
• pathogen killing defects

-chronic granulomatous disease

Question 21

chronic granulomatous disease

Answer 21

• pathogen killing defect: absent oxygen-dependent mechanism

- recurrent granulomas in lung, skin, and bones

Question 22

secondary deficiencies:

• ______ deficiencies
• far more _____ than primary deficiencies
• ____ prognosis
• duration of _____

Answer 22

acquired;
common;
variable;
transient to chronic

Question 23

number one cause of secondary deficiencies

Answer 23

malnutrition

Question 24

HIV

Answer 24

• RNA retrovirus
• preferentially infects CD4+ Th1 cells
• HIV also targets other cells in the body

Question 25

- _____ HIV cases in US - _____ aren't aware of their status - not distributed equally in population: - ______ - ______

Answer 25

1.2 million; 1 in 7; men who have sex with men are highest risk group; AA > Latino > white

Question 26

HIV: | acute phase

Answer 26

mononucleosis-like syndrome 3 to 6 weeks after infection

Question 27

HIV: | clinical latency phase

Answer 27

- asymptomatic period 2-10 years after infection (w/o Tx) | - CD4 T-cell count greater than 500 cells/mm3 of blood (normally between 500-1500 cells/mm3)

Question 28

HIV: | stage 3- AIDS

Answer 28

- increasing risk of opportunistic infections | - CD4 T-cell count less than 200 cells/mm3 of blood

Question 29

HIV-related immunologic abnormalities

Answer 29

- lymphopenia (low CD4+ T-cell count) - cutaneous anergy (defect in cell-mediated immunity) - hypergammaglobulinemia (polyclonal B-cell stimulation by Epstein-Barr virus) - CD4:CD8 ratio <1 (normally between 1 and 4)

Question 30

AIDS criteria

Answer 30

- HIV + - CD4+ T-cell count < 200 cells/mm3 - AIDS-defining condition

Question 31

most common AIDS-defining infections

Answer 31

- pneumocystis jiroveci pneumonia | - systemic candidiasis

Question 32

evaluation of immunity

Answer 32

- complete blood count (CBC) with a differential - quantitative Ig determination - assay for total complement - skin tests (tests T-cell immunity)

Question 33

treatment for immunodeficiencies

Answer 33

- gamma-globulin therapy - transplantation or transfusion - treatment with soluble immune mediators - gene therapy

Question 34

gamma-globulin therapy

Answer 34

- transient: 3-4 weeks - effective for B-cell deficiencies - relatively low risk

Question 35

transplantation or transfusion

Answer 35

- bone marrow or umbilical cord blood-stem cells - effective for some primary combined deficiencies - higher risk of Graft vs Host Disease)