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Acute Inflammation

Leukocyte Emigration

Name Details Endothelium Leukocyte


Margination ▪ Vasodilation— slows blood flow in
postcapillary venules
▪ ↑ Vascular Permeability ➔
hemoconcentration
▪ Cells marginate from center of flow to
the periphery

Rolling Selectin "speed bumps" are upregulated on P/E-Selectins ▪ Sialyl Lewis X


endothelial cells. glycoprotein
1. histamine ➔ ⊕ Weibel Palade ▪ L-selectin
Bodies in Endothelial Cells ➔
P-selectin
2. TNF and IL-1 ➔ ⊕ E-selectin

Adhesion ▪ TNF and IL-1 ➔ Cellular adhesion ICAM and VCAM Integrins (CD18)
molecules (ICAM and VCAM)

▪ C5a ➔ Integrins

Transmigration ▪ Leukocytes transmigrate across the PECAM-1 (CD31)


and Chemotaxis endothelium of postcapillary venules

▪ move toward chemical attractants


(chemotaxis) – attracted by
1. IL-8
2. C5a
3. LTB4
Leukocyte adhesion deficiency (LAD-1)
Characters ▪ autosomal recessive defect of LFA-1 integrins (CD18 subunit)

S/s ▪ delayed separation of the umbilical cord (> 30 days)


▪ recurrent bacterial infections that lack pus formation

Ix ▪ Increased neutrophils in serum (neutrophilia)


▪ Absence of neutrophils at infection sites

Leukocyte adhesion deficiency (LAD-3)


Characters ▪ Defect in β-integrins

S/s ▪ delayed separation of the umbilical cord (> 30 days)


▪ recurrent bacterial infections that lack pus formation
▪ bleeding (β-integrins in platelets)
Phagocytic Killing

opsonization phagocytosis is enhanced by opsonins


▪ IgG
▪ C3b

Phagocytosis Pseudopods extend from leukocytes to form phagosomes ➔ which are


internalized and merge with lysosomes to produce phagolysosomes.

Phagolysosome O2 dependent killing is the most effective mechanism


Killing ▪ O2 is converted to O2- by NADPH oxidase (oxidative burst)
▪ HOCl- generated by MPO in phagolysosomes ➔ destroys phagocytosed
microbes

Lysosome contents O2 independent killing


▪ Lysozyme ➔ digests bacterial cell walls by cleaving peptidoglycan
▪ Defensins ➔ form channels in bacterial cell membranes
▪ Lactoferrin ➔ chelates iron
▪ Hydrolytic enzymes

Resolution Neutrophils undergo apoptosis and disappear within 24 hours after resolution of
the inflammatory stimulus
Chediak-Higashi syndrome

Characters ▪ defect in lysosomal trafficking regulator gene (LYST) ➔ microtubule dysfunction in


phagosome-lysosome fusion
▪ characterized by impaired phagolysosome formation
▪ autosomal recessive

S/s ▪ Increased risk of pyogenic infections


▪ Pancytopenia/neutropenia (due to intramedullary death of neutrophils)
▪ Defective primary hemostasis (due to abnormal dense granules in platelets)
▪ Albinism (abnormal storage of melanin within melanocytes)
▪ Peripheral neuropathy

Ix ▪ Giant granules in leukocytes – (due to failure of these granules to degranulate to


phagosome ➔ and then fusion of granules arising from the Golgi apparatus)
Chronic Granulomatous Disease

Introduction/Epidemiology

▪ characterized by poor O2 dependent killing.


▪ Due to NADPH oxidase defect (X-linked)

Signs and Symptoms

➔ Leads to recurrent infection and granuloma formation with

▪ Catalase + organisms (All bacteria produce H2O2. Catalase- can’t degrade accumulated
H2O2 which is used by host cells to generate HOCl- even in absence of NAPH Oxidase.
Catalase + can degrade H2O2 produced by themselves)
a) Staphylococcus aureus
b) Burkholderia Cepacia
c) Pseudomonas cepacia
d) Serratia marcescens
e) Nocardia

▪ Aspergillus (fungal infections)

*State Bank Pakistan Selling Notes


Investigations
Nitroblue tetrazolium ▪ is used to screen for CCD
test (NBT) ▪ Neutrophils are incubated with NBT dye ➔ which turns blue if NADPH
oxidase can convert O2 to O-
▪ but remains colorless if NADPH oxidase is defective.

Dihydrorhodamine ▪ preferred test


Flow Cytometry 1. DHR ➔ Rhodamine (if NADPH Oxidase is present)
(DHR) 2. Rhodamine ➔ green fluorescence