Chronic Inflammation

Prolonged response that initiates after 48 hrs. and may last for very long time and even years.
Due to the radical oxygen species there is damage to the tissues.

Mycobacteria – most prolonged bacteria that causes tuberculosis.

Autoimmune diseases – amplified allergic reaction response.
When the body is not able to eliminate the foreign particles by lysosomes the particles seats in
the tissues causes chronic inflammation. Ex. Silicosis.

Acute: Neutrophilic and vascular changes

Chronic : tissue destruction, attempts healing and infiltration by mononuclear cells
(macrophages, dendric cells) and lymphocytes B and T.

Cells and Mediators of Chronic Inflammation:

1. leukocyte infiltration
2. tissue damage
3. healing process by fibrosis

Macrophages

These cells have different names depending on their location and function.

Resident macrophages
Forms precursors in the bone marrow, and then travels in the blood stream to reach the
tissues. Cell in the tissues are called resident macrophages.

Activate macrophages - performs different functions than non-activated.

Inflammation reactions begins with the infiltration of monocytes that emigrate within 48 hours.

Classical pathway = activation occurs by induction from endotoxin, interferon gamma and Th1.
These are known as Macrophages M1. The lysosomal enzymes will enhance the cell to kill the
bacteria and stats the inflammation.
Alternative = No function of microbicidal. Function is tissue repair by IL-4 and IL -13. Formation
of fibroblast. These cells are known as M2.

IL 13 and IL 4 will participate in endogenies for tissue repair.

Macrophages present antigens to T cells and the T cells will produce Th17 and Th1 to recruit
more T cells.
Role of lymphocytes:

Main function is to work as mediators.

selectin and integrins and their chemokines migrates by this regulation.

Th1 cells produce IFN gamma and activate macrophages in the classical pathway.
TH2 cells secrete IL 4, IL 5,and IL 13 for recruitment of eosinophils.
Th17 cells secrete Il 17 and other cytokines does activation of neutrophils.

Th1, Th17 = bacteria and viruses.

Th2 = activate alternative pathway to get rid of parasites and allergic inflammation . Also IL5
plays same role.

Eosinophils – cells shown in high amounts when there is a parasite infection or an allergic
reaction.

Mast cell – contains FceRI receptors located in the surface and the other receptor is called Fc.

Patterns of chronic inflammation :

1. Granulomas inflammation = accumulation of macrophages in the epithelial cells called
epithelioid cells and some macrophages that becomes larger called giant cells.

Foreign body is surrounded by the giant cell and in the periphery the cell epithelioid cells.

Characteristics caused by granulomas are central necrosis and caseous necrosis.

Epithelial cells are made of macrophages with large plasma amount.

Systemic effects of inflammation:

Fever = caused by bacterial infections such as pyrogens

Exogenous pyrogens – caused increased in the prostaglandins which increases the temperature.

Acute phase proteins = plasma proteins that act as opsonins ( makes the microbes easier to be
digestible by macrophages) to kill microbes and maintain homeostasis.
Fibrinogen – used to exam for rouleaux (stacks of red blood cells by fibrinogen). These
fibrinogen do form scabs.
Serum amyloid when located in the heart muscle makes the muscle to toughen in the heart.
C-reactive protein – used for searching for markers to identify if patient will have a heart
attack.

Leukocytosis = bacterial infections causes leukocytes to raise to 15,000-20,000.

Leukemoid – occurs in the bone marrow cell becomes affected.

Eosinophilia = increase of eosinophils.
Leukopenia = decrease of WBCs.

Sepsis = severe bacterial infections causes high amounts of production of cytokines TNF and IL-
1 will cause an impairment of different tissues. Causes septic shock .

Tissue Repair

Eliminates offending agents

- Cell and Tissue Regeneration:

Proliferation of new tissues and formation of scar (fibroblast).

Ability of tissues to repairs location = mouth, tissues, and visceral.

Stable Tissues

G0 cell cyle
Liver is the organ that is most capable of renewing.

Permanent Tissues
Does not have capacity to renew. Permanent muscle damage occurs in the brain in muscle.

Cell Proliferation

Tissues will remain in the kinesis state prior entering in the cell cycle to proliferate.

Mechanism of tissue regeneration

Proliferation of residual and differentiation of stem cells.

Liver regeneration
Occurs in three stages
1. Kuppfer cells produces IL 6 cytokines which enter the hepatocyte to stimulate cell
metabolism to cause the cell to enter again into the cell cycle. Once the cells is proliferated it
goes back into the G0 phase.

Repair connective tissue deposition

When heart muscle cells are damaged it is replaced by thick connective tissues.

Steps of scar formation

1. endothethelial junctions are separated and blood vessels become to increase causing edema.
2. migration of fibroblast. when it reach the site with the new blood vessels forms the
granulation tissue.
3. remodeling is the maturation of the collagen fibers and formation of the scar.

Summary:
M2 macrophages – promotes healing process.
M1 macrophages – promotes inflammation.

Angiogensis

This is the process of formation of new blood vessels during healing.

TGF Beta – mostly important for the activation of fibrinogen for healing.

TIMPs = causes formation of scar and is regulated by metalloids

Collagen Fibers are stained in BLUE .

Factors that inhibit healing:

Repair by scarring :
Occurs when there is damage only to the surface of the skin ( epithelial layer).

Abnormalities in tissue repair

- Wound
- Ulcers in lower limbs. Very common to diabetic patients.

Excessive scarring

Keloid scarring (right) and hypertrophy scarring (left) . Genetic factor mutated causing extreme
scarring to above the normal amount.