Mumbai Call Girls Service 9910780858 Real Russian Girls Looking Models
chronic inflamation
1. Topic : Cells and Mediators of chronic inflammation with
special reference to phagocytosis
Moderator: Dr Amrit Sarmah
Assistant Professor, Dept of Pathology
Tezpur medical college and Hospital
Presented by : Dr Lekhraaj Gautam
PGT , Dept of Pathology
Tezpur Medical College and Hospital
3. Definition:
Chronic inflammation is a response of prolonged duration
(weeks or months) in which inflammation, tissue injury, and
attempts at repair coexist, in varying combinations.
Causes:
Persistent Infection
Hypersensitivity reactions
Prolonged exposure to toxic agents: Exogenous
Endogenous
5. Cell mediators of Chronic Inflammation
Mononuclear – phagocyte system
Lymphocytes
Plasma cells
Eosinophils
Mast cells
Neutrophils
6. Role of Macrophages:
Most dominant cell and professional phagocytes.
Derived from hematopoietic stem cells in the bone marrow
and from progenitors in the embryonic yolk sac and fetal
liver during early development.
Circulating cells of this lineage: Monocytes
Mononuclear phagocyte system (sometimes called
reticuloendothelial system)
7.
8.
9. Activation of Macrophages:
M1: Main role of these
macrophages in host defence is
to destroy microbes and
promote inflammatory response.
M2: These macrophages are not
actively microbicidal ; instead,
their principal function is to
terminate inflammation and
promote tissue repair.
12. Chemokines:
They are a family of small (8–10 kD) proteins that act
primarily as chemoattractants for specific types of
leukocytes. They are classified into four major groups,
according to the arrangement of cysteine (C) residues in
the proteins:
C-X-C chemokines – IL 8 ( CXCL8)
C-C chemokine – eotaxin , MIP-1α
C chemokines – XCL1
CX3C chemokines – CXC3CL1
13. Role of Lymphocytes:
Generation of long lived memory cells.
Bidirectional Lymphocyte – Macrophage interactions.
Formation of granulomas.
14. Eosinophils:
Abundant in immune reactions mediated by Ig E and in parasitic
infections.
Recruitment is driven by especial chemokines e.g., eotaxin
They have granules that contain major basic protein, a highly
cationic protein that is toxic to helminths but also may injure host
epithelial cells.
15. Mast cells:
Participate in both acute and chronic inflammatory
reactions.
Express on their surface the receptor that binds the Fc
portion of Ig E antibody.
Neutrophils:
Seen in many forms of chronic inflammation as well.
Osteomyelitis
COPD
17. Granulomatous Inflammation:
Granulomatous inflammation is a form of chronic
inflammation characterized by collections of activated
macrophages, often with T lymphocytes, and
sometimes associated with central necrosis.
Epithelioid cells
Giant cells
18. Epithelioid cells:
The activated macrophages , differentiated as a result of
prolong antigenic stimulation, having pink granular
cytoplasm with indistinct cell borders having elongated
slipper shaped nuclei.
Further differentiation or fusion of epithelioid cells leads to
development of multinucleated giant cells.
21. Immune granulomas:
Caused by agents that are capable of inducing a
persistent T cell mediated response.
In such responses, activated Th1 cells produce cytokines
such as IFN- γ , which activates macrophages.
22.
23.
24. Phagocytosis
• Phagein = "to devour", kytos = "cell“,
osis = “process” (from Ancient Greek)
• Phagocytosis is the process of
engulfment and destruction of solid
particles such as bacteria, dead tissue and
foreign particles by the cells.
• Neutrophils
• Monocytes
• Macrophages
30. Opsonization → Attachment stage
• Opsonization refers to the process of coating of bacteria by
the opsonins.
• The opsonin coated bacteria gets attached to the surface of
phagocyte through the opsonin receptors.
• The principal opsonins :
IgG opsonin
C3b opsonin.
mannose binding lectin
35. Oxygen derived radicals may be
released extracellularly from leucocytes
implicating tissue damage
accompanying inflammation.
Antioxidants:
Superoxide dismutase
Catalase
Glutathione peroxidase
Ceruloplasmin
Plasma transferin
36.
37. Lysosomal Enzymes:
Neutrophils and macrophages contain lysosomal enzymes that
contribute to oxygen independent microbial killing.
Neutrophils have two main types of granules:
• The smaller specific (or secondary) granules-collagenase,
gelatinase, lactoferrin, plasminogen activator, histaminase, and
alkaline phosphatase.
• The larger azurophil (or primary) granules-MPO, bactericidal factors
factors (such as defensins), acid hydrolases, and a variety of neutral
proteases (elastase, cathepsin G, nonspecific collagenases,
proteinase 3.
38. Frustrated Phagocytosis:
It is a phenomenon where the lysosomal granules fused
with phagocytic vacuoles containing engulfed material
releases its contents into the extracellular space.
Usually seen when the neutrophil tries to eat something
too big , such as huge immune complex.
39. α 1-antitrypsin neutrophil elastase
Def leads to increase risk of emphysema due to destruction of elastic
support fibres of lung , because of uncontrolled elastase activity.
40. Neutrophil extracellular trap:
Neutrophil extracellular traps (NETs) are extracellular fibrillar
networks that concentrate anti-microbial substances at sites of
infection and prevent the spread of the microbes by trapping them
in the fibrils
NETs provide an additional mechanism of killing microbes that
does not involve phagocytosis.
In the process of NET formation, the nuclei of the neutrophils are
lost, leading to the death of the cells, sometimes called NETosis,
representing a distinctive form of cell death affecting neutrophils.
NETs also have been detected in the blood during sepsis.
41. Activated neutrophil in response to pathogenic stimulation
ROS dependent activation of arginine deaminase
Conversion of arginine to citrulline
MPO and Elastase
Chromatin decondensation
Rupture of nuclear envelope and release of chromatin
42. A. Healthy neutrophils with
nuclei stained red and
cytoplasm stained green.
B. Release of nuclear material
from neutrophils forming
extracellular trap.
45. IL-16
Doxorubicin which was widely used a chemotherapeutic agent has slowly
been withdrawn as a frontline treatment due to severe cardiotoxicity.
Anti-IL-16 antibody : inhibits DOX induced M1 macrophage differentiation
reduces the inflammatory response
elevated cardiac function
Therefore it was concluded that anti-IL-6 antibody is beneficial in
preventing cardiac toxicity induced by chemotherapy drug DOX.