1) Chronic inflammation is a prolonged response lasting weeks or months where inflammation, tissue injury, and repair occur simultaneously in varying combinations. 2) Macrophages play a dominant role by destroying pathogens and activating other cells like lymphocytes. Lymphocytes also amplify and prolong the inflammatory response. 3) Different immune cells contribute to chronic inflammation, including eosinophils which help fight parasites and mast cells which promote allergic reactions through IgE. Neutrophils can also persist in some chronic bacterial infections.

1. CHRONIC
INFLAMMATION
Syed Arshad Ullah
Lecturer CMT-BKMC
Introduction
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Mast
Cells
Eosinophils
Lymphocytes
Neutrophils
3/15/2022 1

2. CHRONIC INFLAMMATION
(Robbins Basic Pathology 10th E)
Chronic inflammation is a response of prolonged
duration (weeks or months) in which inflammation,
tissue injury, and attempts at repair coexist, in
varying combinations.
Role
of
Lymphocytes
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Mast
Cells
Eosinophils
Lymphocytes
3/15/2022 2

3. Causes
3
2
1
Persistent
Infection
•By
microorganisms
i. Mycobacteria
ii. Certain viruses
iii. Fungi
iv. Parasites
Hypersensitivity
diseases
•Autoimmune
Disease
1. Rheumatoid
Arthritis
2. Multiple sclerosis
•Allergic diseases
1. Bronchial Asthma
2. Allergic reaction
Prolong Exposure
to Exogenous and
endogenous toxic
agents
Exogenous agent:
Silica Silicosis
Endogenous:
Cholesterol &
other lipids
Atherosclerosis
Cells
&
Mediators
Lymphocytes
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Mast
Cells
Eosinophils
Lymphocytes
3/15/2022 3

4. Cells
&
Mediators
Causes
Morphology
Infiltration with
mononuclear cells
 Macrophages
 Lymphocytes and
 Plasma cells
Tissue Destruction
 Induced by persistent
offending agent i.e.,
 Microorganism or
 Inflammatory cells
like Macrophages
Attempts at healing
 By connective tissue
replacement or
deposition at the site
of damaged tissue
 There is Angiogenesis
and fibrosis
Cells
&
Mediators
Cells
&
Mediators
Role
of
Macrophages
Eosinophils
Lymphocytes
3/15/2022 4

5. 01 02
Causes
Morphology
Cells
&
Mediators
03 05
04
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
3/15/2022 5

6. Dominant cells in Chronic
Inflammatory reaction
Secreting cytokines and
growth factors
 Act on various cells
 By destroying foreign invaders
and tissues, and
 By activating other cells, notably
T lymphocytes
Professional phagocytes
Act as filters for particulate
matter, microbes, and
senescent cells.
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Effector cells
Eliminate microbes
in cellular and
humoral immune
responses
3/15/2022 6

7. • Macrophages are tissue cells derived
 From hematopoietic stem cells in the bone
marrow and
 From progenitors in the embryonic yolk sac
and fetal liver during early development
• In circulation they are known as monocytes.
• Macrophages are normally diffusely
scattered in most connective tissues.
Macrophages Distribution
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
3/15/2022 7

8. • Found in specific locations in organs i.e,
 Liver (Kupffer cells)
 Spleen and lymph nodes (sinus histiocytes)
 Central nervous system (microglial cells)
 Lungs (alveolar macrophages)
• Together these cells comprise the
mononuclear phagocyte system
Macrophages Distribution
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
3/15/2022 8

9. Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes Maturation of mononuclear phagocytes
(A) During inflammatory reactions, the majority of tissue macrophages are derived
from hematopoietic precursors. Some long-lived resident tissue macrophages
are derived from embryonic precursors that populate the tissues early in
development.
(B) The morphology of a monocyte and activated macrophage
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes Maturation of mononuclear phagocytes
(A) During inflammatory reactions, the majority of tissue macrophages are derived
from hematopoietic precursors. Some long-lived resident tissue macrophages
are derived from embryonic precursors that populate the tissues early in
development.
(B) The morphology of a monocyte and activated macrophage
Role
of
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
3/15/2022 9

10. Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes Maturation of mononuclear phagocytes
(A) During inflammatory reactions, the majority of tissue macrophages are derived
from hematopoietic precursors. Some long-lived resident tissue macrophages
are derived from embryonic precursors that populate the tissues early in
development.
(B) The morphology of a monocyte and activated macrophage
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Macrophage activation
2
1
Classical
Pathway
Also Called
M1
Alternative
Pathway
Also Called
M2
3/15/2022 10

11. Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes Maturation of mononuclear phagocytes
(A) During inflammatory reactions, the majority of tissue macrophages are derived
from hematopoietic precursors. Some long-lived resident tissue macrophages
are derived from embryonic precursors that populate the tissues early in
development.
(B) The morphology of a monocyte and activated macrophage
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Role
of
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Role
of
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Macrophage activation
1
Classical
Pathway
Also Called
M1
Induced
• By microbial products
 Endotoxin and other sensors
• By T cell–derived signals
 The cytokine IFN-γ,
in immune responses
Produce NO and ROS and
upregulate lysosomal enzymes
Kill ingested organisms and secrete
cytokines that stimulate inflammation
(TNF, IL-1, chemokines, and others)
3/15/2022 11

12. Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes Maturation of mononuclear phagocytes
(A) During inflammatory reactions, the majority of tissue macrophages are derived
from hematopoietic precursors. Some long-lived resident tissue macrophages
are derived from embryonic precursors that populate the tissues early in
development.
(B) The morphology of a monocyte and activated macrophage
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Role
of
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Role
of
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Not actively microbicidal
• They secrete growth factors that promote
angiogenesis, activate fibroblasts, and
stimulate collagen synthesis.
Macrophage activation
Induced
• Cytokines other than IFN-γ, such as
IL-4 and IL-13, produced by T
lymphocytes and other cells.
2
Alternative
Pathway
Also Called
M2 Function : tissue repair
3/15/2022 12

13. Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes Maturation of mononuclear phagocytes
(A) During inflammatory reactions, the majority of tissue macrophages are derived
from hematopoietic precursors. Some long-lived resident tissue macrophages
are derived from embryonic precursors that populate the tissues early in
development.
(B) The morphology of a monocyte and activated macrophage
Causes
Morphology
Cells
&
Mediators
Role
of
Macrophages
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Role
of
Lymphocytes
Mast
Cells
Eosinophils
Role
of
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Macrophage activation
• In response to most injurious stimuli
• First activation pathway is the
classical one  destroy the
offending agents
• Followed by alternative
activation initiates tissue
repair.
3/15/2022 13

14. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Eosinophils
Lymphocytes Macrophage activation
Role
of
Macrophages
Different stimuli activate monocytes/macrophages to develop into functionally distinct populations. Classically activated
macrophages are induced by microbial products and cytokines, particularly IFN-γ. They phagocytose and destroy microbes
and dead tissues and can potentiate inflammatory reactions. Alternatively, activated macrophages are induced by other
cytokines and are important in tissue repair and the resolution of inflammation.
14

15. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Mast
Cells
Eosinophils
Role
of
Lymphocytes
Macrophages
Microbes and other environmental antigens
activate T and B lymphocytes, which amplify
and propagate chronic inflammation
Some of the strongest chronic inflammatory
reactions, such as granulomatous inflammation
are dependent on lymphocyte responses.
Lymphocytes may be the dominant population
in the chronic inflammation seen in autoimmune
and other hypersensitivity diseases
2. Role of Lymphocytes in
Chronic Inflammation
3/15/2022 15

16. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Mast
Cells
Eosinophils
Role
of
Lymphocytes
Macrophages
CD4+ T lymphocytes promote inflammation
by secreting cytokines, hence promote
inflammation
There are three subsets of CD4+ T cells that
secrete different cytokines
TH1
cells
Cytokine
IFN-γ
Activates
Macrophages
by M1
pathway.
TH2
cells
IL-4, IL-5,
and IL-13
Recruit and activate
eosinophils
TH17
cells
IL-17 & other
cytokines
Induce the
secretion of
Chemokines
responsible for
Recruiting
neutrophils
M2 pathway of
macrophage
activation.
3/15/2022 16

17. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Mast
Cells
Eosinophils
Role
of
Lymphocytes
Macrophages
Both TH1 and TH17 cells are involved in
defense against many types of bacteria
and viruses and in autoimmune
diseases.
TH2 cells are important in defense
against helminthic parasites and in
allergic inflammation
3/15/2022 17

18. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Mast
Cells
Eosinophils
Role
of
Lymphocytes
Macrophages
Lymphocytes and macrophages interact in a
bidirectional way
Macrophages display
• Antigens to T cells
• Express membrane
molecules (called
costimulators)
 activate T cells
• Produce cytokines (IL-12
and others) that also
stimulate T cell responses
Activated T lymphocytes
• Produce cytokines
• Recruit and activate
macrophages
• Promoting more
antigen presentation
and cytokine secretion.
• The result is a cycle of
cellular reactions that
fuel and sustain chronic
inflammation
3/15/2022 18

19. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Mast
Cells
Eosinophils
Role
of
Lymphocytes
Macrophages
Macrophage–lymphocyte interactions in chronic inflammation. Activated T cells
produce cytokines that recruit macrophages (TNF, IL-17, chemokines) and
others that activate macrophages (IFN-γ). Activated macrophages in turn
stimulate T cells by presenting antigens and via cytokines such as IL-12.
3/15/2022 19

20. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Mast
Cells
Role
of
Eosinophils
Lymphocytes
Macrophages
• Eosinophils are abundant in immune reactions
mediated by IgE and in parasitic infections
• Their recruitment is driven by adhesion molecules
and by specific chemokines (e.g., eotaxin)
derived from leukocytes and epithelial cells.
• Eosinophils have granules that contain major
basic protein, a highly cationic protein that is
toxic to parasites but also injures host epithelial
cells.
• This is why eosinophils are of benefit in
controlling parasitic infections, yet also
contribute to tissue damage in immune reactions
such as allergies.
3. Role of Eosinophils in Chronic I nflammation
3/15/2022 20

21. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Role
of
Mast
Cells
Eosinophils
Lymphocytes
Macrophages
• Mast cells are widely distributed in connective
tissues
• Participate in both acute and chronic
inflammatory reactions
• Mast cells arise from precursors in the bone
marrow
• Mast cells (and basophils) express on their
surface the receptor FcεRI (Fc epsilon RI), which
binds the Fc portion of IgE antibody.
4. Role of Mast Cells in Chronic Inflammation
3/15/2022 21

22. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Role
of
Mast
Cells
Eosinophils
Lymphocytes
Neutrophils
Macrophages
• In immediate hypersensitivity reactions, IgE bound
to the mast cells’ Fc receptors specifically
recognizes antigen, and in response the cells
degranulate and release mediators, such as
histamine and prostaglandins
• This type of response occurs during allergic
reactions to foods, insect venom, or drugs,
sometimes with anaphylactic shock.
• Mast cells also are present in chronic
inflammatory reactions, and because they secrete
cytokines, they can promote inflammatory
reactions.
3/15/2022 22

23. Causes
Morphology
Cells
&
Mediators
Lymphocytes
Mast
Cells
Eosinophils
Lymphocytes
Role
of
Neutrophils
Macrophages
• Induced either by persistent microbes or by
cytokines and other mediators produced by
activated macrophages and T lymphocytes.
• In chronic bacterial infection of bone
(osteomyelitis), a neutrophilic exudate can persist
for many months.
• Neutrophils also are important in the chronic
damage induced in lungs by smoking and other
irritant stimuli.
• This pattern of inflammation has been called
acute on chronic.
5. Role of Neutrophils in Chronic Inflammation
23

24. 3/15/2022 24

25. 3/15/2022 25