Immune Flashcards
Inflammatory Response Mediators
Vasodilation
Histamine, prostaglandin, nitric oxide, bradykinin
Increased vascular permeability
Histamine, complement, bradykinin, leukotrienes, nitric oxide
Leukocyte adhesion
- Cytokines (IL-1, TNF-a), complement, eicosanoids (prostaglandins, leukotrienes), selectins
Chemotaxis
Chemokines, complement, eicosanoids (prostaglandins, leukotrienes),
Fever
• IL-1, TNF-a, prostaglandins
Tissue necrosis
- Neutrophil granules, free radicals
Platelet aggregation
Eicosanoids (prostaglandins, leukotrienes)
Complement crosses the placenta (T/F)
False. They don’t cross
Role of neutrophils
Phagocytic and microbicidal function
Function reduced with premature GN sepsis indomethacin and intrapartum mag
Which molecules allow for cell adhesion rolling?
Decreased L selectin and B 2 integrity
Macrophages present which cells?
T cells and B cells
Macrophages have decreased activation and migration in neonates secondary to?
Poor response to IFN gamma
Adaptive immune system has which type of response?
Antigen specific
Takes 4-7 days to develop
What’s the role of CD8 T cells
- Cytotoxic lymphocytes
- Release perforins, degradative enzymes,
and cytokines - Cytokine production is lower compared with adults
-Cytotoxic activity is limited in neonates
IgG
Crosses the placenta
IgM (pentameter) and IgA (dime)
levels are low at birth as they do
not cross the placenta
Infections with CMV, rubella, and
Toxo can raise levels
Clinical features of immunodeficiency
Delayed umbilical cord separation
Infection - particularly repeated
Failure to thrive
Chronic diarrhea
Symptomatic infection due to live vaccines (eg, rotavirus, Bacille Calmette-Guérin [BCG], oral polio)
Heart or lung disease (low qxygen saturation suggests one of these problems)
Congenital asplenia
Mucosal abnormalities such as thrush, mouth sores, and ulcerations
Petechiae, melena, bleeding
Cutaneous rashes, pigmentary abnormalities
Syndromic appearance (abnormal faces or habits) including facial or craniofacial anomalies
Lymphadenopathy and/or hepatosplenomegaly
Autoimmunity
Absence in NADPh oxidase function. Dx?
Chronic granulomatous disease
Deficiency or absent NADPH oxidase function in
phagocytic cells
80-90% MALE- usually X-linked recessive
Severe, recurrent infections with catalase-positive
bacteria or fungi
Diagnosis made by NBT ->remains colorless
demonstration of absent or severely deficient respiratory
burst activity in phagocytes
Difficult diagnosis in neonates-reduced respiratory burst at baseline
Leukocyte Adhesion Deficiency
• LAD-1 (predominant type)
Deficiency of leukocyte integrins
(very low to absent surface
CD11b/CD18 on PMNs)
• LAD-2
Deficiency of selectin function
(normal CD11b/CD18, decreased
CD15 on PMNs)
Clinical presentation (LAD-1) Recurrent infections Delayed separation of umbilical stump Leukocytosis - NO PUS!!
Disorders of Neutrophil production and function
Myeloperoxidase deficiency
• MC deficiency (1 in 2-4K people), can be clinically silent
• Recurrent candidal infections
Chédiak-Higashi syndrome
• Abnormal degranulation, recurrent infections, albinism, giant intracellular granules
HyperimmunoglobulinE
STAT3 mutation alters PMN chemotaxis
G6PD
Decreased NADPH activity > decreased oxygen dependent killing
Galactosemia
Inhibitory effects of galactose on PMNs
Neutropenia
Glycogen Storage Disease 1B, Shwachman-Diamond syndrome, Kostmann syndrome, Reticular
dysgenesis
Trisomy 21
Depressed chemotactic activity
Not much difference between albumin and total protein. Which immune disorder?
Agammaglobulinemia
Profoundly diminished lg levels of all isotypes
- IgM levels are undetectable
B cell-specific src-associated (Bruton’s) tyrosine
kinase mutation >prevents pre-B cells from
becoming mature B cells/plasma cells
Absence of B cells in the blood and lymphoid tissue
•
Plasma cells are absent in Gl tract
A
• Normal T cell numbers but dysplastic lymph nodes
due to no B cells
Peri rectal abscess and neutropenia in a boy?
Hyper IgM syndrome
Absent thymic tissue, interrupted aortic arch, problems with Ca retention. Dx?
Chromosome 22q11 deletion
Boy with eczema, thrombocytopenia and infections. Dx?
Wiskott-Aldrich Syndrome
Eczema, thrombocytopenia, and susceptibility to
infection (decreased lymphocyte count)
• Platelets are small, defective, and abnormally
shaped
• Lymphocyte numbers are decreased and T cell
function is abnormal
• High IL-4 levels lead to eczema (increases IgE)
• Decreased IgM, Elevated IgA and IgE
• Normal IgG
• X-linked
Lymphadenopathy on vignette. MCC Dx?
HIV
How do you diagnosis SCID?
Absence of TREC
SCID - Deficiency of both antibody and cell-mediated immunity
(low/normal # B cells, decreased T cells/NK cells)
• Diarrhea, pneumonia, otitis, sepsis, cutaneous infections,
eosinophilia
20-30% risk of maternal cell-mediated GVHD (placental transfer of
maternal T cells)
Which pathogen has a 1 reservoir outside of humans and primates
Toxo
Granulomatosis Infectiosum is seen with which disease?
Listeria
Highest sensitivity for maternal chorio
Maternal fever (80%)
What grows in Thayer Martin medium
Gonorrhea
Name single stranded DNA virus
Parvo
Single stranded RNA
Enterovirus
What is associated with
Celery stalking long bone
Salt and pepper retina
Rubella
Infant with infancy with the classic triad of enteropathy, dermatitis, and hyperglycemia. Other siblings died at early age. Dx?
IPEX
Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a systemic autoimmune disease caused by immune dysregulation because of a mutation of FOXP3 affecting control of T-regulatory cells.
Bone marrow and allogeneic hematopoietic stem cell transplantation are the only potential cures presently for IPEX syndrome.
If low TREC on NBS, what is next test?
Flow cytometry of lymphocyte subset
IgG levels not indicated until after 6 mo (bc of maternal antibodies)
Think SCID or Di George or false positive in premie.
What is the MOA of interferon alpha?
Activated in response to infection and act via toll like teceptors.
Limit viral replication
Development of T cell (weeks and location)
8.5 weeks fetal liver
10 weeks thymus becomes lymphoid
11-12 weeks T cells emigrate from thymus to spleen, nodes
16-18 weeks hassall’s bodies in the thymus
B cell development (location and weeks)
8 weeks pre-B cells in fetal liver
8-10 weeks in fetal bone marrow
18-22 weeks in liver lung and kidney
>30 weeks Solely in bone marrow
Natural immune system comprises of?
Neutrophils for chemotaxis, phagocytosis, bacterial killing
Monocytes for chemotaxis, phagocytosis, bacterial killing, wound repair
Complement for opsonization, chemoattraction
Infant with recurrent infections, eczema, coarse facial features and broad nasal bridge. Etiology of this disorder?
Abnormality in neutrophil chemotaxis
Hyperimmunoglobulin E (Jobs syndrome)
Neonate with omphalitis without pus formation and delayed separation of cord. What is the underlying reason for this disorder?
Leukocyte adhesion deficiency
Defective neutrophil adhesion and migration
Mutation in the B2 integrin gene
Infant with partial oculocutaneous albinism, nystagmus, Peripheral neuropathy and recurrent infections. Whats the underlying problem?
Chediak-Higashi
Abnormal neutrophil degranulation (afecta intracellular killing) and monocyte chemotaxis
Infant with recurrent abscesses, poor wound healing and granulomas. What is the underlying cause of this disease?
Chronic granulomatous disease
Dysfunctional NADPH oxidase and abnormal phagocytic microbial ability
X-linked
Test: nitroblue tetrazolium test (neutrophils in pts with CGD cannot produce superoxide and thus test negative(
Pale infant with steatorrhea, failure to thrive, and generalized bone marrow dysfunction. Dx?
Schwachman Diamond Syndrome
AR- decreased neutrophil production
May also have skeletal defects and dysmorphic features
Increased risk for myelodysplastic syndrome
Infant noted with severe neutropenia since 1 month of life with recurrent infections. Dx?
Kostman syndrome
AR
Most neonates reach adult complement levels by what age?
3-6 months
Early (C1-4) components vs late (C5-9) component deficiencies of the complement system are associated with which infections?
Early C1-4 pneumococcal
Late C5-9 neiserria
IL 1 and TNF alpha role
Cytokines involved in leukocyte adhesions and mediating fever response
Infant with h/o pneumonia, multiple bouts of itits, diarrhea, sinusitis between 4-12 months of life. Dx?
X linked agammaglobulinemia
Severe deficiency of B cells leading to hypogamma-globulinemia
Infant with episodic fever triggered by immunizations with athralgias, rash, diarrhea, vomiting, oral ulcers. Dx?
Hyperimmunoglobulin D Syndrome
Mutation in mevalonate kinase gene
Treatment with 3 hydroxy 3 methylglutaryl co enzyme A reductase inhibitors or TNF inhibitors or IL 1 inhibitors
Severe form is mevalonic aciduria
Alloimmune neonatal neutropenia are mediated by antibodies that bind to human neutrophil antigen (HNA)
HNA 1a
Neonate born to a mother w lupus and now 7 days old w renal vein thrombosis. Mother with prior pregnancy losses. Which is the most common autoantibody associated with neonate’s condition?
Antiphospholipid syndrome
Neonate without other findings of SLE and 30% of mother’s w SLE have antiphospholipid antibodies which increases risk for clots and pregnancy loss.
Most common thoracic duct anatomy involves a
Single duct
When does the stratum corneum keratinization begin?
32-34 weeks gestation and matures within 2 weeks after birth
Skin keratinization is delayed is delayed in premies because of this
Difference between preterm and term immunity
Decreased complement
Lower neutrophils stores and adhesion
Decreased activity CD4 and CD8
Decreased maternal transfer of IgG that happens in 3rd trimester
Most common manifestation of primary infantile systemic lupus erythematosus?
Glomerulonephritis, then pneumonitis
What marker is used to diagnose SCID with low TREC present?
Beta actin levels
Term
Low TREC + normal beta actin = abnormal result —> obtain flow cytometry
Preemie
Low TREC + normal beta actin = abnormal result —> repeat TREC by 40 weeks
What is the initial event in pathogenesis of congenital heart block in neonatal lupus syndrome?
Cardiocyte apoptosis
Most common cause of neutropenia in early neonatal period is
Pregnancy-induced hypertension
What amino acid is essential for disulfide covalent bonding in chemokines?
Cysteine
The most common manifestation of neonatal SLE is?
Thrombocytopenia (MC)
then rash and direct hyperbilirubinemia
MCC of apnea after immunizations in preemies
Having apneic episodes before immunization
How can phagocytosis be more effective?
By complement component 3 and IgG coating
Role of follicular B 2 cells
Provide adaptive immune response against thymus dependent antigens
High affinity Ab - highly specific to Ag
B1 cells are part of the ___ immune response
Innate
Found primarily in the peritoneal and pleural cavities
Low affinity antibodies with broad antigen specificity
Role of Marginal zone B cells
Found in spleen
Innate immune response against thymus independent Ag
Create low affinity Ab with briad Ag specificity
Patients with X linked agammaglobulinemia is characterized by mutation in which enzyme?
Beuton tyrosine kinase
Near abscence of all immunoglobulins
Present after 2 months as maternal IgG is still present in newborn period
CD 40 ligand mutations lead to ______.
X linked Hyper IgM
High to normal IgM
Low IgG, IgA, IgE
This mutation leads to abnormalities in IG class switch recombination
What decreases neutrophil chemotaxis?
GCSF
Granulocyte macrophage colony stimulating factor
What decreases neutrophil chemotaxis?
Mag sulfate (intrapartum) Excessive theophylline [ ] Indomethacin administration
By what postnatal age does maternal IgG typically disappear in neonatal circulation?
9 months
Neutrophils of term neonates compared to adults
Decreased migration
Poor adherence to endothelium
Decreased chemotactic response
Comparable phagocytosis and de granulation
Most common complement decifiency
C2
Where do the classical and alternative pathways converge ?
C3
Differences between classical and alternative pathways?
Classical complement pathway requires Ag-Ab reaction (immune complex formation)
Alternative pathway may be Ab independent
Patients with splenic dysfunction show a peripheral blood smear with
Howell jolly bodies
Name 4 collectins
Surfactant protein A, SP-D, conglutinin, mannose binding lectin
