Immunodeficiencies Flashcards
immunodeficiency:
- impaired _____
- increased _____
- often require _____
- type of infection indicates _____
immune function; susceptibility to infections; IV antibiotics (unusual and severe infections); type of deficiency
immunodeficiency-associated infections:
T-cell deficiencies
viral, fungal, yeast, atypical microorganisms, cancer
immunodeficiency-associated infections:
B-cell and phagocyte deficiencies
microorganisms requiring opsonization (largely bacterial infections)
immunodeficiency-associated infections:
complement deficiencies
resemble B-cell deficiencies
primary immunodeficiency
- congenital
- genetic anomaly
- generally more severe
secondary immunodeficiency
- acquired
- caused by another illness
- more common
- tend to be less severe
primary immunodeficiencies:
- ____ defect, mostly ____
- manifest ____
- between ____ in population
single gene;
sporadic;
early in life;
1:500 and 1:500,000
primary immunodeficiencies:
five groups
- B-lymphocyte deficiencies (most common)
- T-lymphoctye deficiencies
- phagocyte defects
- combined T- and B-cell deficiencies
- complement defects
B-lymphoctye deficiencies
- hypogammaglobulinemia or agammaglobulinemia
- increased susceptibility to Ab-mediated infections (bacterial pneumonia, sinusitis, otitis media)
causes of B-lymphoctye deficiencies
- receptor defects: ineffective intracellular signaling (BCR and cytokine receptors)
- Ab-class switch defect: altered ability to change Ab class (co-stimulatory signal defect)
primary B-cell immundeficiencies
- Bruton’s (X-linked) Agammaglobulinemia
- Common Variable Immunodeficiency
- Selective IgA Deficiency
Bruton’s (X-linked) Agammaglobulinemia
- most severe B-cell deficiency
- receptor defect (BCRs never develop)
- no mature B-cells
- recurrent bacterial infections
- unable to mount any humoral response
Common Variable Immunodeficiency (CVID)
- 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
Selective IgA Deficiency
- unable to produce IgA Abs
- compromised secretory immune system
- severe allergies and recurrent sinus/lung/GI infections
- severe mucopurulent conjunctivitis
primary T-cell immunodeficiencies
-DiGeorge Syndrome/22q11.2 Deletion Syndrome
DiGeorge Syndrome/22q11.2 Deletion Syndrome
- 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
Severe Combined Immunodeficiency (SCID)
-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)
Reticular Dysgenesis
- most severe SCID
- absent/defective stem cell
- no circulating lymphocytes or granulocytes
- usually fatal before or soon after birth
complement deficiencies
- resemble B-lymphocyte deficiencies: bacterial infections
- C3 deficiency: most severe
- terminal complex deficiency (8000x increased risk of Neisseria gonorrhea infection)
phagocytic deficiencies
-often resembles B-lymphocyte deficiencies: bacterial infections
types:
- neutrophil maturation defect
- adhesion molecule defect
- opsonin receptor defect
- pathogen killing defects
-chronic granulomatous disease
chronic granulomatous disease
- pathogen killing defect: absent oxygen-dependent mechanism
- recurrent granulomas in lung, skin, and bones
secondary deficiencies:
- ______ deficiencies
- far more _____ than primary deficiencies
- ____ prognosis
- duration of _____
acquired;
common;
variable;
transient to chronic
number one cause of secondary deficiencies
malnutrition
HIV
- RNA retrovirus
- preferentially infects CD4+ Th1 cells
- HIV also targets other cells in the body
- _____ HIV cases in US
- _____ aren’t aware of their status
- not distributed equally in population:
- ______
- ______
1.2 million;
1 in 7;
men who have sex with men are highest risk group;
AA > Latino > white
HIV:
acute phase
mononucleosis-like syndrome 3 to 6 weeks after infection
HIV:
clinical latency phase
- 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)
HIV:
stage 3- AIDS
- increasing risk of opportunistic infections
- CD4 T-cell count less than 200 cells/mm3 of blood
HIV-related immunologic abnormalities
- 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)
AIDS criteria
- HIV +
- CD4+ T-cell count < 200 cells/mm3
- AIDS-defining condition
most common AIDS-defining infections
- pneumocystis jiroveci pneumonia
- systemic candidiasis
evaluation of immunity
- complete blood count (CBC) with a differential
- quantitative Ig determination
- assay for total complement
- skin tests (tests T-cell immunity)
treatment for immunodeficiencies
- gamma-globulin therapy
- transplantation or transfusion
- treatment with soluble immune mediators
- gene therapy
gamma-globulin therapy
- transient: 3-4 weeks
- effective for B-cell deficiencies
- relatively low risk
transplantation or transfusion
- bone marrow or umbilical cord blood-stem cells
- effective for some primary combined deficiencies
- higher risk of Graft vs Host Disease)
