Immunology Flashcards
Clinical features of neonatal lupus
Neonatal myasthenia gravis
neonates born to mother’s with MG have a 10-20% chance of being affected
most newborns have normal muscle tone and activity
Transient neonatal myasthenia gravis:
- transplacental passage of IgG autoantibodies
- no sxs in first few days: transplacental passage of maternal meds and maternal concentration of alpha-fetoprotein (inhibits autoantibody binding to acetylcholine receptors)
- symptoms: hypotonia, dec spont movements, poor feeding, respiratory insufficiency
- Dx: high concentrations of acetylcholine receptor antibodies
- prognosis is good- recovery by ~ 2 months
Good Morning America
IgG
IgM
IgA (colostrum)
Function of the spleen
-synthesis of antibodies against carbohydrate antigens
- clears microorganisms from bloodstream
Effect of splenectomy:
- increased susceptibility to infection: E.coli, H flu, Staph, strep pyogenes, malaria, viruses
- usually rapid onset of infection- more likely to be fatal
most important feature for immunologic function = malpighian bodies (secondary follicle)
Describe T cell lymphopoiesis
8.5 wks: percursors in fetal liver
10 wks: thymus becomes lyphoid
11-12 wks: T cells emigrate from thymus to spleen, nodes
16-18 wks: Hassall’s bodies in thymus
Describe B cell lymphopoiesis
~ 8 wks: Pre-B cells in fetal liver
8-10 wks: in fetal bone marrow
18-22 wks: liver, lung, kidney
>30 wks: B cell production solely in bone marrow
Natural immune system
First-line defense
non-specific
Rapid availability
Does not rely on T/B cell
Does not require prior epxosure to organism or antigen to function
Components:
- neutrophils: chemotaxis, phagocytosis, bacterial killing
- monocytes: chemotaxis phagocytosis, bacterial killing, wound repair
- complement: opsonization, chemoattraction, inflammation
Neutrophil function in neonate
- decreased migration
- normal bacterial killing if healthy, decreased if ill
- majority of neutrophils in bone marrow
- neonates < 1500g have lower total neutrophil concentration
- longer period of neutrophilia following infection
- higher baseline proliferationrate (doesnt increase much with infection)
Disorders of neutrophil FUNCTION
- abnormalities of chemotaxis: hyperimmunoglobulin E (hyper-IgE, Job’s syndrome)
- adhesions abnormalities: Leukocyte adhesion deficiency
- intracellular killing: myeloperoxidate deficiency, Chediak-Higashi, chronic granulomatous disase
Disorders of neutrophil PRODUCTION
- decreased production: Shwachmann-Diamond syndrome, Kostmann syndrome, Reticular dysgenesis
- excessive margination: pseudoneutropenia, endotoxemia
- accelerated usage or destruction: autoimmune/alloimmune neutropenia, Chediak Higasi
Hyperimmunoglobulin E
Job’s syndrome
Hyper IgE
abnormal neutrophil chemotaxis
STAT 3 mutation
recurrent infections- especially of skin
coarse facial features
broad nasal bridge
eczema
Early complement vs later complement deficiencies associated with which infections
- Early: C1-4 = pneumococcal
- Late: C5-9 = neiserria
Leukocyte adhesion deficiency
Type 1: issue with integrin
- very low/absent CD11/CD18
- delayed separation of umbilical stump (beyond 21 days), leukocytosis
Type 2: issue with selectin
- normal CD11/CD18, low CD15
NO PUS
When do you reach adult levels of complement
3-6 months
chronic granulomatous disease
ABSENCE of NADPh oxidase function
X-linked recessive (M»>F)
Severe, recurrent infections with CATALASE POSITIVE bacteria/fungi (ex. staph, pseudomonas, aspergillus, candida, enterobacter)
Dx: Nitroblue tetrazolium test (NBT)
- remains colorless = absent/deficiency respiratory burst in phagocytes
myeloperoxidase deficiency
recurrent candidal infections
Chediak-Higashi
Abnormal degranulation = giant intracellular granules
- recurrent infections
- albinism
- nystagmus
- peripheral neuropathy
Wiskott Aldrich
Triad: eczema, thrombocytopenia, susceptibility to infection (dec lymphocyte count)
Eczema: caused by high IL-4 levels –> incr IgE
NORMAL IgG
DEC IgM
INCR IgA, IgE
X-linked
Hyper-IgM syndrome
X-linked- CD40 ligand mutations
- abnormal T helper cell regulation of B cell Ig isotype switching
Symptoms start ~6 mo as maternal IgG decreases
peri-rectal/oral abscesses
Sinopulmonary infections, chronic diarrhea
neutropenia
Pneumocystic carinii pneumonia, encapsulated organisms (H flu, Strep pneumo)
High rate of malignancy- lymphomas, GI adenomas
LOW IgG, IgA, IgE
NORMAL/INC IgM
Which immunoglobulin crosses the placenta?
IgG!
provides passive protection to the neonate
What produces the immunoglobulins?
B-cells!
Describe the different immunoglobulins
IgA: secretory; main component in colostrum, resp/GI secretions
IgG: binds and activates complement, binds Fc receptor to facilitate action
IgM: binds and activates complement, FIRST antibody expressed after infection
IgE: ALLERGIC reaction- binds to basophils/mast cells leading to histamine/leukotriene release
IgD: ? antigen receptor, importnat in regulating B-cell development
Agammaglobulinemia
X-linked
severe deficiency of B cells leading to hypogamma-globulinemia
recurrent infections 4-12 mo
- pneumonia, otitis, sepsis, meningitis
- ENCAPSULATED bacteria: H flu, Strep pneumo
total protein - albumin = immunoglobulins
- if this number is low, think agammaglobulinemia
Could be due to mutation in Bruton tyrosine kinase
Absent TRECs on newborn screen- next step?
Flow cytometry- lymphocyte subset eval
Could be SCID, DiGeorge
