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
SCID
Failure of T lymphocytes to develop
B lymphocytes compromised/absent
Acquired immune system
specific response that relies on T and B lymphocytes
Type and function of T lymphocytes
CD4 T cells: cytokine secreting helper cells
- present antigen with MACROPHAGES to B-lymphocytes
CD8 T cells: cytotoxic killer cells
Function of T lymphocytes
MUST travel to thymus to complete development
activate macrophages
cell-mediated
present antigen to B-lymphocytes (CD4 T helper with macrophages)
T = THYMUS
Function of B lymphocytes
Mature with bone marrow
Humoral-mediated
Produce immunoglobulins!
Preterm infants with poor antibody response to infection
B = BONE MARROW
Triad: enteropathy, dermatitis, hyperglycemia
Family history of other siblings dying at early age
IPEX
Immune dysregulation
Polyendocrinopathy
Enteropathy
X-linked
FOXP3 mutation affecting control of T-regulatory cells
Tx: bone marrow or allogeneic hematopoietic stem cell transplantation
Shwachman-Diamond
AR
- generalized bone marrow dysfunction
- dysmorphic features
- malabsorption–> steatorrhea–> failure to thrive
- skeletal defects
Increased risk of myelodysplastic syndromes
Kostmann syndrome
Severe congenital neutropenia
AR
frequent infections beginning in first months of age
severe neutropenia, low ANC since birth
HIGH RISK for AML or myelodysplasia
Development from the blood stem cell
Classical vs alternative complement pathway
Preterm vs term immunity
Decreased complement
Lower neutrophil stores/adhesion
Decreased CD4/CD8 activity
Decreased maternal IgG transfer (most 3rd tri)
Immature B cells produce which type of immunoglobulin
IgM
Mature B cells switch from IgM to other isotypes
Switch is antigen driven and requires signaling between CD40 on B cell with CD40 ligand on T cell
Make up of Ig molecule
Heavy chain: determines class/sub-class
Light chain:
Fab (fragment antigen binding): binds antigens
Fc: primary effector domain, changes here after antigen binding cause host response
Synagis targets which part of the RSV virus?
F protein
Part of the lung most affected by RSV
Bronchiole
think: RSV causes bronchiolitis
triad of watery diarrhea, endocrinopathy (hypothyroidism, neonatal insulin dependent DM), eczematous dermatitis
IPEX
X-linked
BMT or suppress autoimmunity is the only treatment
