Inflammation

and Repair - 7

Dr.CSBR.Prasad, M.D.

v3-CSBRP-May-2012

Out comes of Acute Inflammation

May have one of three outcomes:

1. Complete resolution

2. Healing by fibrosis

3. Chronic inflammation

v3-CSBRP-May-2012

Out comes of Acute Inflammation

May have one of three outcomes:

1. Complete resolution

2. Healing by fibrosis

3. Chronic inflammation

This occurs when:

• There is persistence of injurious agent

• There is interference with normal healing

process

Eg: Peptic ulcer, Complicated pneumonia

v3-CSBRP-May-2012

v3-CSBRP-May-2012

Chronic Inflammation

• It’s inflammation of prolonged duration

(weeks or months)

• Here tissue injury, and attempts at repair

coexist

v3-CSBRP-May-2012

Chronic Inflammation

• May follow an acute inflammation or

• May begin insidiously

v3-CSBRP-May-2012

v3-CSBRP-May-2012

Chronic Inflammation

CAUSES:

1. Persistent infections

Mycobacteria, viruses, fungi, & parasites

2. Immune-mediated inflammatory diseases

Autoimmune diseases

Allergic diseases

3. Prolonged exposure to toxic agents

Silicosis (Silica)

Atherosclerosis (Lipid)

v3-CSBRP-May-2012

Chronic Inflammation MORPHOLOGIC FEATURES:

1. Mononuclear infiltrates

2. Tissue destruction

3. Angiogenesis &

4. Fibrosis

In acute inflammation:

1.Vascular changes

2.Edema

3.Neutrophilic infiltration

Vvvvvvvv

v3-CSBRP-May-2012

v3-CSBRP-May-2012

Chronic Inflammation ROLE OF MACROPHAGES

The macrophage is the dominant cellular player in chronic

inflammation

Macrophages are one component of the mononuclear

phagocyte system

The half-life of blood monocytes is about 1 day, whereas

the life span of tissue macrophages is several months

or years

Emigrate into extravascular tissues quite early in acute

inflammation, and within 48 hours

Extravasation is governed by: Adhesion molecules &

chemical mediators

v3-CSBRP-May-2012

Maturation of mononuclear phagocytes v3-CSBRP-May-2012

Chronic Inflammation ROLE OF MACROPHAGES

Macrophages may be activated by a variety of

stimuli:

Microbial products binding with TLRs

Cytokines (e.g., IFN-γ) and

other chemical mediators

v3-CSBRP-May-2012

Chronic Inflammation ROLE OF MACROPHAGES

The products of activated macrophages

1. serve to ELIMINATE injurious agents &

2. to initiate the process of REPAIR

3. responsible for much of the TISSUE INJURY

v3-CSBRP-May-2012

Chronic Inflammation ROLE OF MACROPHAGES

Activation of macrophages results in:

1. increased levels of lysosomal enzymes

2. reactive oxygen and nitrogen species

3. production of cytokines, growth factors

4. other mediators of inflammation

5. Some of these products are toxic to microbes

and host cells

6. Cytokines, chemotactic factors

7. Growth factors – PDGF, Angiogenesis v3-CSBRP-May-2012

v3-CSBRP-May-2012

IFN-ɣ

IL-4

v3-CSBRP-May-2012

Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION

Lymphocytes

Plasma cells

Eosinophils &

Mast cells

v3-CSBRP-May-2012

Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION

Lymphocytes & macrophages interact

biderectionally:

Lymphocytes: IFNɣ arms MØ

Macrophages: IL12 acts on T-cells

v3-CSBRP-May-2012

v3-CSBRP-May-2012

Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION

Plasma cells: • Develop from activated B lymphocytes

• Produce antibodies

• Abs may act against persistent foreign or self

antigens

v3-CSBRP-May-2012

Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION

Eosinophils: • Immune reactions mediated by IgE

• Parasitic infections

• Chemokine that recruits EØ is eotaxin

• Eosinophilic granules that contain major basic protein

• MBP is toxic to parasites

• EØs are of beneficial in controlling parasitic infections, but

they contribute to tissue damage

v3-CSBRP-May-2012

Chronic Inflammation OTHER CELLS IN CHRONIC INFLAMMATION

Mast cells: Widely distributed in connective tissues

Participate in acute and chronic inflammations

Mast cell receptor (FcεRI) binds Fc portion of IgE

Degranulation – releases histamine and prostaglandins

Allergic reactions – sometimes fatal - anaphylactic shock

Secrete a plethora of cytokines

Have the ability to both promote and limit inflammatory

reactions in different situations

v3-CSBRP-May-2012

v3-CSBRP-May-2012

GRANULOMATOUS

INFLAMMATION

• It’s a distinctive pattern of chronic

inflammation

• Seen in some infectious and noninfectious

conditions

• It’s an attempt to contain an offending

agent that is difficult to eradicate

v3-CSBRP-May-2012

GRANULOMATOUS

INFLAMMATION

Infective causes:

• Tuberculosis

• Leprosy

• Cat-scratch disease

• LGV

• Brucellosis

• Syphilis

• Mycotic infections

Non-Infective causes:

• Sarcoidosis

• Berylliosis

• Reactions to irritant

lipids

• Autoimmune diseases

• Crohn’s disease

v3-CSBRP-May-2012

Granuloma

Def: A granuloma is a focus of chronic

inflammation consisting of a microscopic

aggregation of macrophages that are

transformed into epithelium-like cells,

surrounded by a collar of mononuclear

leukocytes, principally lymphocytes and

occasionally plasma cells.

v3-CSBRP-May-2012

Granuloma Components:

Epithelioid cells: have a pale pink granular

cytoplasm with indistinct cell boundaries, often appearing to merge into one another. The nucleus is oval or elongate, and may show folding of the nuclear membrane (boomarang)

Giant cells: Epithelioid cells fuse to form giant cells in the periphery or sometimes in the center of granulomas. - Langhans-type giant cell / foreign body–type giant cell

Older granulomas develop an enclosing rim of fibroblasts and connective tissue

v3-CSBRP-May-2012

Granuloma Types:

There are two types of granulomas, which

differ in their pathogenesis:

1. Foreign body granulomas Eg: Silica

2. Immune granulomas Eg: TB

v3-CSBRP-May-2012

Granuloma

v3-CSBRP-May-2012

Caseating granuloma of TB v3-CSBRP-May-2012

Non-caseating granulomas of sarcoidosis v3-CSBRP-May-2012

Silica granulomas – under polarized light v3-CSBRP-May-2012

Lipid granulomas v3-CSBRP-May-2012

E N D

v3-CSBRP-May-2012

v3-CSBRP-May-2012