Immunodeficiency Syndromes - Monteleone 4/14/16 Flashcards
primary immunodeficiency
definition
4 types
conds characterized by intrinsic immune system defects : inherited or de novo genetic defects
- immune system that is either hampered or absent
- show increased susceptibility to infection, autoimmune diseases, malignancies!
four types:
- B cell defects
- T cell defects
- complement defects
- phagocytic system defects
*most common?
antibody > combined > phagocytic > cellular > complement
50>20>18>10>2
components of immune system
- innate vs adaptive
- cellular vs humoral
innate
- cellular: monocytes/macrophages/DCs, NK cells
-
humoral: complement
- fx (either solo or with abs): kill microbes, lyse cells, opsonization, effect chemotaxis
- contributes to post-tissue damage infl
adaptive
-
cellular: T cells
- fx: cytotoxicity; help activate B cells to produce antibodies; cytokine secretion
-
humoral: B cells → antibodies
- bind and form immune complexes
- neutralize
- opsonize for phagocytosis, often with complement
- targets cells for NK cell ADCC
- bind and form immune complexes
types of immunoglobulins
- fraction
- major fx
IgG (75% of serum Ig; major in extravascular spaces)
- half life: 23 days
- main ab that controls infection (not first)
IgM
- first Ig produced
- good at lysing microorganisms
IgA
- important in mucosal immunity
IgE
- binds to basophils and mast cells
- parasitic infection and allergy
warning signs of immune deficiency
infections (more than normal number)
- 4+ ear
- 2+ serious sinus
- persistent thrush, skin fungal infection
- 2+ deepseated infections (ex. septicemia)
abnormal antibiotic req
- need for IV antibiotics to clear infection
- 2 or more months on antibiotics with little effect
- recurrent/deep skin/organ abscesses
index of suspicion
- frequency/severity of infection
- duration of infection
- susceptibility to abnormal infectious agents
- response to antibiotics
index of suspicion for diff components of immune response
[types of orgs]
T cells → mucocutaneous candidiadis, persistent resp infection, diarrhea, failure to thrive
- fungal, herpes virus infections
B cells → sinopulmonary
- bacterial, parasitic, enterovirus infections
phagocytes → skin infections, visceral abscesses
- bacterial, fungal infections
- nontuberculous mycobacteria, Salmonella
complement → Neisseria bacteria (meningitis, gonorrhea)
SCID
severe combined immunodeficiency
virtually complete lack of immune fx
- diminished or absent T cells
- specific gene defects determine impact on B cells and complement
without treatment, prognosis is death by infection/failure to thrive in first year
DiGeorge Syndrome
defect impacting organs derived from 3rd and 4th pharyngeal arches
- cardiac: tetralogy of Fallot
- face: low set ears, cleft palate
- parathyroid: hypocalcemia
- thymus: atresia = low/absent T cells
tx: thymus or bone marrow transplant
ataxia telangiectasia
- variable T cell defect: low CD3/CD4
- defects in B cells → IgA, IgE deficiency
- neurologic defects → loss in motor skills, unsteady gait
- telangiectasias (tiny spider veins) appearing in later childhood
- increased susceptibility to infection
due to gene mutation
Wiskott Aldrich syndrome
- progressive T cell syndrome
- also affects B cells
- small platelets, thrombocytopenia with petechiae/bruising/bleeding
- eczema
- infections: upper resp and opportunistic
- high incidence of autoimmunity and lymphoid malignancy
X linked (mostly boys)
B cell (antibody deficiencies)
- agammaglobulinemia
- IgA deficiency: most common primary immunodef!
- hyperIgM syndrome
- common variable immunodef (CVA)
- X-linked lymphoprolif syndrome (Duncan’s)
- transient hypogammaglobulinemia of infancy
selective IgA deficiency
- most common primary immunodef
- only IgA deficient/absent
- usually asymptomatic, sometimes get recurrent infections/allergies/autoimmune disease
- sometimes progress to Common Variable Immunodef
sometimes coincident with IgG2 deficiency
what’s special about IgA?
- secretory IgA = 2-4 IgA monomers linked by two addtl chains (J chain and another; formed in IgA-producing plasma cells) + secretory component (polypep that prevents proteolytic degradation in intestine)
no treatment:
agammaglobulinemia
intrinsic B cell disorder : defect in Bruton Tyr kinase → maturation arrest of preB cells → all Igs decreased or absent
- also B cells nearly absent in blood/periph
X linked or (rare) autosomal
tx: IV or subcut Igs
common variable immunodef
low levels of serum Igs
- usually normal levels of B cells..something else is off → either lack of CD4 fx or too many CD8s
- often dont develop recurrent infection until 2nd/3rd decade of life
unclear genetic/inheritance pattern
tx: IV, subcutaneous Ig replacement
phagocytic disorders
- chronic granulomatous disease
- neutropenia: chronic or cyclic
- Chediak-Higashi syndrome
- leukocyte adhesion deficiency
- hyperIgE syndrome (Job’s)
