II.

Granulocyte Immunology
Yudy Tjahjono, B.Sc., M.Sc.Biol.
Anatomy
Anatomy-Cell Surface
Anatomy-Granules
 Neutrophils Special aspects
• Rolling, Trans- and Paracellular Migration
• Complement Fc Receptors
• Killing (3 Ways)
• Autoimmunity and Alloimmunity
Neutrophils Function: Killing
Phagocyte response to infection
• The SOS signals
– N-formyl methionine-
containing peptides
– Clotting system peptides
– Complement products
– Cytokines released by
tissue macrophages
• Phagocyte response
– Vascular adherence
– Diapedesis
– Chemotaxis
– Activation
– Phagocytosis and killing

SOM PathMicro online textbook

 Phagocytosis
A. Attachment via receptors
A
– FcR, complement R, scavenger
R, Toll-like R

B. Pseudopod extension B

C. Phagosome formation

D. Granule fusion and

Phagolysosome formation
D
Neutrophils Degranulation

• ROS
• Associated
with
Pathogen
• activated by
fMLP, IL-8
NOX / NOXA: NADPH Oxidase SodA: Superoxide dismutase
GopA: Glutathion Peroxidase AhpC: Alkylhydroperoxide Reductase
MPO: Myeloperoxidase
Neutrophils Extracellular Traps
(NET)
 NETosis
SUICIDAL NETosis VITAL NETosis
Neutrophils as APC
Granulocyte Antigens
 Allo vs Autoimmunity
• Autoimmunity: Immunological reaction
caused by immunological components
(antigen, cells, Ig’s, etc.) inside the body

• Alloimmunity: Immunological reactions

caused by immunological components
from other individuals with the same
species.
 Neutrophils
Alloantigens (and –antibodies)
Neutrophil alloimmunity associated
pathogens

• Alloimmune neonatal neutropenia (NIN)

• Severe Congenital Neutropenia
(Kostmann’s Syndrome)
• Autoimmune neutropenia
(Granulocytopenia)
• TRALI
New Neutrophils Autoantigens
 Neutrophils Immunological Assay
• GIFT
• GAT
• MAIGA
• PCR-Typing
• FACS
GAT and GIFT
MAIGA
PCR-Typing

 Internal controls
 Antigens (cDNA)
FACS
Hematology Analyzer
 Neonatal Alloimmune neutropenia

occurs when a mother becomes sensitized to a foreign antigen that is present on

fetal granulocytes. These fetal granulocyte antigens sensitize the mother and
provoke antibody production.
Immunoglobulin G (IgG) antibody readily crosses the placenta and destroys fetal
granulocytes by providing opsonic assistance to splenic macrophages

Symptom: delayed separation of the umbilical cord, skin infections, otitis, or

pneumonia within the first 2 weeks of life.
 Severe Congenital Neutropenia
(Kostmann Syndrome)

•Rare 1:100.000
•Hereditary, Autosomal Dominant
•Accumulation of Granulocyte
Precursor in Bone Marrow
•Granulocytopenia, WBC Count
Normal
•Splenomegaly
•Increased risk of developing
Leukemia
 Autoimmune Neutropenia

• In Infants and young

children, where the
body identifies the
neutrophils as enemies
and makes antibody to
destroy them
TRALI