“Chronic Inflammation”

Assigned by Sir Ayaz ali unar

Presented by group “B”

Nausheen Junejo 22
Raheela Soomro 24
Sajida Mirani 29
Seema Mahoto 32
Aliza Shaikh 50
Chronic Inflammation:
● Chronic inflammation is a response of prolonged duration (weeks or
month) in which inflammation, tissue injury, and attempts at repair
coexists, in varying combinations.
Acute
What is Inflammation?
something severe but short Inflammation is the body’s way
lived, like sudden illness of reacting to injury or
infection, lead to protection
response, bringing in immune
cells and cause redness,
swelling and heat to help heal
the effected area.

Chronic
is for long lasting issues, more
like a persistent condition.
Causes of Chronic Inflammation:
1. Persistent Infection:-
A. Microorganism = Like Mycobacteria , viruses, fungi, & parasites are
difficult to eradicate & cause “DELAYED TYPE HYPERSENSIVITY” .

B. Granulomatous Inflammation = If the infection doesn’t go away , more

immune cells show up to try to kill bacteria / fungi. In time, the extra
immune cells build up and form a hard lump called “GRANULOMA”.

A. Other = Unresolved acute inflammation evolves into chronic

inflammation , Ex: Acute infection of lung into progressive that may
lead to a “CHRONIC LUNG ABSCESS” .
2. Hypersensitivity Disease:-
A. Autoimmune disease =
The body’s defence system gets confused & starts attacking it’s own
cells , thinking they’re invaders , the immune system mistakenly targets &
harm the body’s own tissues
Ex: Rheumatoid arthritis & multiple sclerosis.
B. Allergic disease / reactions =
An allergic reaction triggers the immune system to respond strong to
something usually harmless , like POLLEN or certain FOODS. If this
happens repeatedly or continuously, it can lead to chronic inflammation.

Ex: BRONCHIAL ASTHMA Exposure to allergen like dust mite or

pollen can triggers an allergic reaction
in Asthma
3. Prolonged exposure to potentially toxic agent
, either exogenous or endogenous:-
A. Silicosis = is a lung disease caused by inhaling silica ( exogenous
agent , a non degradable inanimate material) dust over an extended
period.
=> Silica is a mineral found in materials like sand, quartz & granite. When workers in
certain industries like mining or construction , breathe in fine silica dust , it can lead to lung
inflammation & scaring , so prolong exposure to silica leading to chronic lung damage.

B. Atherosclerosis = is like a build up of plaques in artries , overtime ,

substances like fat and cholesterol (endogenous) can stick to artry
walls, forming plaques and make difficult to blood flow smoothly.
Histologic features:-
In contrast to acute inflammation , which is manifested by vascular
changes , edema & predominantly neutrophilic infiltration , chronic
inflammation is characterized by the following :

❑ Infiltration with mononuclear cells includes macrophages ,

lymphocytes , & plasma cells.

❑ Tissue destruction induced by persistent offending agent

(pathogen, toxins) or by inflammatory cells.

❑ Healing damaged tissue attempts to heal through fibrosis and

angiogenesis .
Cells and mediators of chronic inflammation:-

❑ The combination of leukocyte infiltration, tissue damage, and fibrosis

that characterize chronic inflammation is the result of the local
activation of several cell types and the production of mediators.
Role of macrophages:-

● Macrophages are professionally phagocytic cells

● Eliminate microbes in innate and adaptive immunity
● Dominant cells in most chronic inflammatory reactions
● Secret cytokines and growth factors
● Progress inflammation and also role in repair
2 major pathways of macrophage activation:
Classical macrophage Alternative macrophage
activation (M1) activation (M2)
Stimulus : Stimulus :
• Microbial products • IL-4
• IFN-gamma • IL-13
Classically activated M1 Alternatively activated M2
produce produce
• ROS • IL-10
• NO • TGF-beta
• Lysosomal enzymes
Cont:
• Function : • Function :
• all of which enhance their ability • The principle function of
to kill ingested organisms, and alternatively activated
secret cytokines (IL-1,IL-6,IL- macrophages is in tissue repair.
12,TNF) that stimulate Role as anti inflammatory
inflammation.
• These macrophages are
important in host defense
against microbes and in many
inflammatory reactions.
Role of lymphocytes
• Mediators of adaptive immunity
• Provide defense against infectious pathogens
• Microbes and other environmental antigens activate T
and B lymphocytes, which amplify and propagate
chronic inflammation.
• By virtue of their ability to secrete cytokines, CD4+T
lymphocytes promote inflammation and influence the
nature of the inflammatory reaction.
• There are three subsets of CD4+T cells that secrete
different cytokines and elicit different types of
inflammation .
• TH1 cells
• TH2 cells
• TH17 cells
 1) TH1 cells :
● Produce IFN-gamma
○ Activate macrophages by classical pathway

2)TH2 cells :
● Secrete IL-4, IL-5, and IL-13
○ Activate eosinophils and are responsible for macrophage
activation by alternative pathway

3)TH17 cells :
● Secrete IL-17
○ Responsible for recruiting neutrophils into the reaction
Macrophages and lymphocytes interact in bidirectional way,
and these interactions play an important role in propagating
chronic inflammation.
Macrophages display antigen to T cells which activate it,
and produce cytokines (IL-12) that also stimulate T cell
responses.
Activated T cells, in turn, produce cytokines which activate
macrophages, promoting more antigen presentation and
cytokine secretion.
The result is a cycle of cellular reactions that fuel and
sustain chronic inflammation.
Other cells in chronic inflammation:-
➢ Types of White blood cells (Granulocytes) including:
Eosinophils, Mast cells , & Neutrophils may be prominent in chronic
inflammation.
1. Eosinophils:
• These are abundant in immune reactions mediated by
immunoglobulin E (IgE) in parasitic infections.
• Eosinophils have granules that contain major basic protein, highly
cationic protein that is toxic to parasites, this is why eosinophils are
benefit in controlling parasitic infection.
● The granules of eosinophils also contain Leukotriene & peroxidase
which can damage tissue and cause inflammation.

● Eosinophils also involve in Allergic diseases.

● Eosinophil count is elevated in parasite diseases & hypersensitivity

diseases.
2. Mast cells :
• These are widely distributed in connected tissues & participate in both
acute & chronic inflammatory reactions.
• Mast cells arise from precursors in bone marrow. They have many
similarities with basophil but do not arise from basophil.
• Mast cells & basophil express on their surface the receptor FcERI,
which bind the fc portion of IgE antibody.
• In immediate hypersensitivity reactions IgE bound to the mast cell, fc
receptor specifically recognizes antigen & in response the cells
degranulate & release inflammatory mediators like Histamine and
prostaglandin.
• This type of response occurs during allergic reactions to food, insect
venome or even drugs.
3. Neutrophil:
• Neutrophils are the most abundant immune cell in blood.
• Neutrophils are characteristic of acute inflammation, may forms of
chronic inflammation , lasting for months.
• The abundant neutrophils adhere to capillaries, increasing vascular
resistance, & produce inflammatory cytokines that induces vascular
injury & promote chronic inflammatory conditions.
Granulomatous inflammation:-

• Granulomatous inflammation is a form of chronic inflammation

characterized by collection of activated macrophages often with T-
lymphocytes and sometimes, associated with central necrosis.
OR
• Granulomatous inflammation is the morphologically specific pattern of
chronic inflammation induced by T-cells and macrophages activation
in response to an agents that is resistant to eradication.
• Granuloma:
➢ These are the langhans giant cells consisting of large mass of
cytoplasm and many nuclei.
➢ Granulomas formation is cellular attempt to contain an offending
agent that is difficult to eradicate.
▪ There are two types of Granulomas-
1. Caseating granular, cheesy appearance of necrosis ex:
Mycobacterium tuberclosis.
2. Non- caseating, no necrosis centres ex: Sarcoidosis crohn
disease.
● On the basis of different pathogenesis, granulomas are of two
types :

1. Immune granuloma:
➢ These are caused by variety of agents that are capable of inducing
persistent T-cell mediated immune response, this type of immune
response produces granulomas usually when inciting agent can not
be readily eradicate such as persistent microbe or self antigen in such
responses, macrophages activated T-cells to produce cytokines, such
as IL-2 which activates other t-cells, perpetuating the response and
IFN-Y, which activates macrophages.
2. Foreign body granuloma:

➢ These are seen in response to relatively inert foreign bodies, in

absence of T- cells mediated immune responses typically, foreign
body granulomas form around materials such as Talc (associated with
intravenous drug abuse), sutures, or other fibres large enough to
preclude phagocytosis by a macrophages but are not immunogenic
epithelial cells and giant cells are opposed to surface of foreign body.
● Reference:
✓ Robbins basic pathology
✓ Google “Search images”