Quiz 1 Flashcards
Isolated congenital asplenia
- due to ribosomal protein SA and laminin mutations
- increased susceptibility to encapsulated bacteria
- immunizations are important
Properdin deficiency
recurrent infections
Factor H or I deficiency
- unchecked complement activation
- renal disease and recurrent infections
C5-9 deficiency
Neisseria infections susceptibility
-meningitis and gonorrhea
Paroxysmal Nocturnal Hemoglobinuria
- PIGA gene mutation impairs HRF, protectin, and DAF function
- complement mediated RBC lysis, hemoglobinuria, symptomatic anemia, thrombosis
- Tx: eculizumab (anti-C5)
C3 deficiency
recurrent bad infections, Ag-Ab complex (lupus like) disease
Inappropriate complement activation
C5a, C3a, C4a mediated anaphylaxis
MBL deficiency
recurrent infections
C4A or C4B gene deficiency
propensity to develop SLE
genes located in MHC Class III area
C1INH deficiency
- Hereditary angioedema
- increases C2 kinin and bradykinin levles
- painless swelling that does not respond to antihistamines
C1INH treatment
- C1INH: Berinert, Cinryse, Ruconest
- bradykinin B2 receptor antagonist: icatibant
- Kallikrein inhibitor: Ecallantide
- 2nd line is fresh frozen plasma
C1INH Types
1: less C1INH
2: less functional C1INH
3: level and function are normal, females Facton XII gain of function triggers kallikrein-kinin system
acquired: anti-C1INH Ab, excessive C1 activation
IRAK4 or MyD88 deficiency
strep, staph, gram negative susceptibility in children
typically by age 14 adaptive immune system takes over
NEMO deficiency
aka IKK-gamma subunit deficiency
incontinentia pigmenti (worsening skin condition)
anhidrotic ectodermal dysplasia (conical teeth, skin, hair)
impaired Ab class switching
recurrent infections
Septic shock
due to systemic bacterial infection and TNF-alpha release
increased susceptibility with TLR4 mutation
UNC-93B deficiency
needed for TLR3, TLR7-9
increased susceptibility to HSV
Familial cold autoinflammatory syndrome 1
gain of function NLRP3 mutation (cryopyrin)
rash, fever, arthralgias following cold exposure
Tx: canakinumab (antiIL-1beta), rilanocept (IL1 inhibitor)
Chediak-Higashi syndrome
large cytoplasmic granules in neutrophils impede diapedisis
Chronic Granulomatous Disease (CGD)
deficiency in NADPH oxidase subunit impairs H2O2 production in neutrophils, prevents respiratory burst
- Sx: boils, abscesses, pneumonia, osteomyelitis
- typically X-linked recessive
- Susceptibility to: Staphyloccocus aureus, Aspergillus fumigatus, Serratia marcescens, Nocardia asteroides, Burkholderia cepacia
CH50
screens classical pathway defect
near 0 in C1-C8 deficiency
half normal in C9 deficiency
low in factor I or H deficiency
AH50
screen for alternative pathway defect
C3d
marker for classical pathway activation
Ba
marker for alternative pathway activation
C1q
detects immune complexes
IRAK4
test for TLR deficiency
DHR (dihyrorhodamine)
tests for respiratory burst
Properdin
stabilizes C3bBb
DAF and MCP
kicks C3b off of C3b2Bb
-MCP also recruits factors I
Factors H and I
inactivate C3b to iC3b
C3b2Bb
alternative C5 convertase
S protein, clusterin, factor J
prevent C5b67 from inserting into membrane
HRF and protectin
prevent C9 polymerization
anaphylatoxins
C5a>C3a>C4a
inflammatory response
alpha2-macroglobulin
inactivates bacterial proteases
defensins
family of antimicrobial peptides
pentraxis
circulating proteins bind pathogen and immune cell
C4b2b3b
classical C5 convertase
C1INH
binds to C1r and C1s and dissociate from C1q, also inhibits clotting and kinin systems
lectins
recognize carbohydrates
scavenger receptors
SR-A, SR-B, MARCO
recognize negatively charged microbial ligands
CR1
recognizes C3b
CR3 and CR4
recognize iC3b and LPS
TLR4
recognizes LPS
TLR3
recognizes dsRNA including HSV
TLR9
recognizes unmethylated CpG
TLR pathway
TLR activation - intracellular TIR domain - MyD88 - IRAK4 - TRAF6 - phosphorylation of IKK - degradation of IkB from NFkB - NFkB increases transcription of cytokines and adhesion proteins
Pyrogens
IL1beta, IL-6, TNF-alpha
IL-12
activates NK cells and IFN-gamma production
CXCL8
chemokine recruits basophils and neutrophils
NLRs (NOD-like receptors)
recognize intracellular PAMPs
NLRP3
recognizes intracellular PAMP and forms inflammasome to activate pro-IL-1beta –> inflammation
Sialyl-Lewis-x
on neutrophils, interaction with endothelial selectin to slow
LFA-1
on neutrophil, binds ICAM-1 on endothelium for extravasation
lipofuscin
age-related pigment associated with atrophy
nuclear changes with cell death
- pyknosis: chromatin condensation
- karyorrhexis: nuclear fragmentation
- karyolysis: fading of nucleus
Coagulative necrosis
architecture remains, greater protein denaturation than enzymatic digestion
Liquefactive necrosis
architecture is lost early, greater enzymatic digestion than protein denaturation