Things to Know from Review Questions Flashcards
What are the 5 clinical hallmarks of LAD?
delayed separation of umbilical cord
omphalitis (infection of umbilical stump)
severe recurrent infections w/ no pus formation
high WBC count
skin ulcers and gingivitis
What is the most frequently diagnosed primary phagocytic immunodeficiency?
Chronic granulomatous disease
What makes up the C3 convertase in the alternative complement pathway?
C3b+Bb
What would you see in a B cell-related deficit?
low B cells - if serum immunoglobulins are normal –> probably an innate immune problem
Which Ig has the shortest half life?
IgE
In what disease discussed in the CIS would there be 2x normal levels of neutrophils?
LAD
What is LAD-III caused by?
defective activation-dependent signaling of beta2 integrins –> similar defects as in LAD-1
What is NK cell killing described as?
extracellular
What is used to positively check TCRs in t cell development?
Tissue specific antigens on MHC I and II
What is activated in the lectin complement pathway?
MASP 1 and 2
In the MHC class I path of Ag presentation, how do cytokines affect proteosomes?
Enhances their ability to cleave viral proteins into the size and shape necessary for MHC I
Which Ig is in the smallest concentration in serum?
IgD
What bacteria often cause LAD I?
staphylococcus aureus and gram-negative bacilli
What is immune tolerance?
What cells does it occur in?
failure to mount a response to an antigen - only occurs in lymphocytes w/ Ag-specific receptors
What would you see in T cell-related deficit?
infection and even death due to live vaccinations
in addition to frequent infections, etc
What makes up the C3 convertase in the classical pathway?
C2a+C4b
What innate immune cell is involved in hypersensitivity reactions?
What happens with this?
mast cells
cross-link high affinity IgE receptor –> MC releases histamine, serotonin, etc
What cells undertake positive selection of T cells?
medullary thymic epithelial cells
What does the severity of LAD depend on?
degree of CD18 deficiency
severe = <2% normal CD18
mild to moderate = 2-30% normal CD18
What is the biochemical cause of CGD?
enzymatic deficiency of NADPH oxidase in phagocytes –> can’t make superoxide anion and O2 radicals –> can’t phagocytose
What is the first and only Ab made produced in a fetus?
IgM
What happens to IL-23 and IL-17 axis in LAD I?
neutrophils never get to infection so IL23 and IL17 never decrease –> chronic inflammation
Which Ig is involved in helminth parasitic defense?
IgE
also involved in allergies
What are the adaptive immunodeficiencies?
combined cellular and Ab = 15%
Cellular = 5%
Ab = 65%
What 2 membrane-bound Abs and cell marker does a mature B cell express?
IgM, IgD, and CD19
What is the idiotype of an Ab?
antigen-binding site = Vh + VL
In LAD, where do the recurrent infections generally occur?
oral and genital mucosa
skin
GI
respiratory tracts
What is a granuloma?
build-up of unregulated inflammation - often see at wound sites in CGD
What complements induce vasodilation and smooth muscle contraction?
C3a, C4a, C5a
Of the 3 tonsil types (palatine, pharyngeal, and lingual), which one has no definitive capsule?
lingual tonsils
What type of lymphoid nodule has a germinal center and mantle/corona?
secondary lymphoid nodule
primary lymphoid nodules don’t have this yet
What are the two major types of CGD?
X linked = most common form
Autosomal recessive CGD
What are the two Igs on naive B cells?
IgM and IgD
What is a J chain?
the part that connects the two parts of an IgA dimer
Which immunoglobulin mediates the release of mediators from mast cells and basophils when exposed to an allergen?
IgE
Why does CGD cause granulomas?
thought to be due to failure to degrade chemoattractants and antigens –> persistent neutrophil accumulation
impaired killing of microbes –> persistent cell-mediated immune activation
What do pts with lad NOT have increase susceptibility to?
viral infections
What complements induce solubilization and clearance of immunocomplexes?
C3a, C3b
What complements induce opsonization?
C3b, C3bi
Which Ig is a pentamer?
IgM
What is first in innate immune response, TLR activations, or NK cell activation?
TLR activation
What are warning signs of an immunodeficiency disorder?
8+ ear infections in one year a bunch of other infections deep-seated or recurrent infections need for IV antibiotics to clear infections family history of ID
What test do you use to check for chronic CGD?
What does a positive test look like?
nitroblue tetrazolium (NBT) test
cells w/ CGD won’t stain blue; carriers will be half and half
What do both activated NK cells and CD4+ T cells release to enhance MHC class II expression?
IFN gamma
What is LAD-II caused by?
impaired adhesive functions of P-selectin glycoprotein ligand 1 (PSGL-1)
mutation in a fucose transporter –> defective fucosylation of PSGL-1
What are the innate immunodeficiencies?
phagocytic cell = 10%
complement = 5%
Why do pts with lad I have elevated C-reactive protein and erythrocyte sedimentation rate?
hyperinflammation –> cytokines go to liver –> APPs and Ce-reactive protein and fibrinogen increase in production
What would you test for if you suspected a complement or phagocytic cell deficit?
total complement assay
CBC+diff
assessment of respiratory burst = NBT test, flow cytometry, chemiluminecence
assessment of phagocytosis, chemotaxis, bactericidal activity
In the first checkpoint of lymphocyte selection, what type of genetic rearrangements are selected for and saved from apoptosis?
in frame rearrangements that make a good protein
Which immunoglobulin has the highest serum concentration and the longest half life?
IgG
What do T helper 2 cells do?
release IL4 –> b cells proliferated to make Abs and kill extracellular microbes
What complement induce B cells to go to lymph nodes?
C3d
Where do granulomas develop?
in skin, GI tract, and genitourinary tract
What types of infections are pts with CGD susceptible to?
Why?
recurrent pyogenic infection w/ catalase-positive organisms
in catalase-neg organisms, the H2O2 that is produced by all aerobic bacteria can be used to kill it in a phagosome; catalase + bacteria can inactivate H2O2 and pts with CGD have nothing else to kill them with
What complements make up the MAC complex?
C5b, C6, C7, C8, C9
What type of cell produces cathelicidins?
neutrophills
What are the 3 professional APCs?
What type of MCH do they have?
dendritic cells, macrophages, B cells MHC class II
What types of microbes are T helper 1 cells involved in?
intracellular
What is LAD-I caused by?
mutations in gene for beta2 integrins (CD11/CD18) –> decreased levels on leukocytes
What are the regions on a MHC that are most variable?
the parts that bind TCR and Ag = N terminus of alpha and beta
What is the normal IL-23 and IL-17 axis?
microbes enter –> IL-23 increases –> neutrophils come in and kill microbes and apoptose –> phagocytosed by macrophages –> IL-23 decreases and downstream IL-17 decreases –> turn off inflammation
What cells do CD8+ T cells kill?
any nucleated cell w/ MHC class I - Ag complex that is non-self
What type of response do T-independent antigens induce in the body?
not a protein, so can’t break down for MHC
innate response and IgM antibodies produced
What are the 5 types of possible primary immunodeficiencies?
combined cellular and Ab = 15% cellular = 5% phagocytic cell = 10% complement = 5% antibody = 65%
What do T helper 1 cells do?
release INF gamma –> activate macrophages to kill intracellular microbes and helps dev. of CD8 T cells
What are the types of leukocyte adhesion deficiency?
LAD I
LAD II
LAD III
What makes up the C5 convertase in the alternate pathway?
C3b + Bb + C3b
How do cytotoxic T cells kill infected cells?
with perforins and granzymes like natural killer cells
What happens to change a pro-B cell to a pre B cell?
heavy chain of BCR is finished recombining and forms a complete protein –> binds to surface w/ surrogate L chain
What happens at the pre B cell stage?
check for intracellular signaling of heavy chain –> have a good heavy chain of BCR –> proliferate to make a lot of them
allelic exclusion of other genes for heavy chain
start VJC recombo of light chain
What characterizes an immature B cell?
recombo of light and heavy chains are done and passed checkpoint by binding loosely to a self Ag
only contains IgM
Located in the bone marrow (then migrates to spleen)
What is CD19?
cluster differentiating factor
found on mature T cells and B cells
What is central tolerance?
checking receptor against self Ag
in BCR and TCR
What is promiscuous gene expression?
when complete representation of self Ags must be present on mTECs to negatively select TCRs
What is the sequence of B cell maturity from stem cell to mature B cell?
HSC –> pro b cell –> pre b cell –> immature b cell –> mature b cell
What cell markers are on a pro b cell?
cd43
cd19
cd10
What cell markers are on a pre b cell?
cd43
cd220
What cell markers are on an immature b cell?
IgM
cd43
What cytokine is the most important in getting neutrophils to cross the blood vessels and enter tissue?
IL-8
What is the antibody made in a primary response?
what is the antibody made in a secondary response?
IgM = primary
IgG = secondary
What CD is on RBCs?
CD47
What CD is on mast cells?
CD23
What CD is on scavenger cells?
CD36
What CD is on monocytes?
CD14
What CDs are on neutrophils?
CD15 and 16
What CD is on dendritic cells?
CD80
