CHEMICAL MEDIATORS IN INFLAMMATION

 

CHEMICAL MEDIATORS IN INFLAMMATION :-

·         Chemical mediators are special chemical molecules that mediate the process of acute &chronic inflammation.

·         The action of there mediators are tightly regulated.

·         Two main groups of substance acting as chemical mediators of inflammations.

(1)    Release from cells

(2)   Release from plasma ptn.

Chemical mediators substance devided based on structure →

(1)   Vasoactive amines

(2)   Lipid product → (A) prostaglandin

                              (B ) leukotrienes

(3)   cytokines →      (A) chemokines

(4)   product of complement activation .

(5)   coagulation products.

Plasma mediated:-

(A)  factor xii (Hageman factor activation)→kinin system (bradykinin coagulation /fibrin olysin  system)

(B)   complement system activation →(C3a, C5a)→Anaphylotoxins

                                                             C3b

                            ( C5b, C6b ,C7b ,C8b ,C9b)→membrane attack complex

 

Chemical mediators:-

(1)   cell derived (local mediators)

(2)   plasma ptn derived (systemic mediators)

 

(1)            cell derived (local mediators):-

 

(a) preformed mediators in secretory granules

mediators:-

·         Histamin   →  mast cell, basophils ,platelets

·         serotonin  → platelets 

·         lysosomal enzymes → netrophils ,macrophages

 

                    (b ) Newly synthesized

·         prostaglandin →  source →  all lecocytes endothelial cells platelets

·         leuckotrienes  →  source  →  all leukocytes

·         platelets activating factor →  all leukocytes & ECs

·         nitric oxide  →  macrophages

·         cytokines  →  lymphocytes, ECs, macrophages

 

 

 

 

 

 

chronic inflammation:-

chronic inflammation defined as long lasting( weak or month )inflammatory response in which tissue destruction/ injury inflammation , & attempts the healing process simultaneously.

Causes of chronic inflammation:-

(1)   persistant infections

(2)   hypersensitivity disease/ immune mediated inflammatory disease

(3)   prolonged exposer to toxic agent

(4)   chronic inflammation following acute inflammation

(5)   recurrent attack pf acute inflammation

(6)   chronic inflammation starting de nova

general characterstics feature of chronic inflammation :-

(1)   mononuclear cell infiltration.

(2)   Tissue destruction or necrosis.

(3)   Proliferative changes.

 

(1) Mononuclear cell infiltration:-

Chronic inflammatory lesions are infiltrated by mono nuclear inflammatory cell like .

(A)  Phagocytes

(B)   Lymphoids cells

 

(A)Phagocytes:-

its represented by circulating monocytes tissue macrophages ,epithelial cells and some time multinucleated gaint cells macrophages are most imp. Cells in chronic inflammation .

(B) Lymphoid cell:-

It is represented by circulating lymphocytes , plasma cells eosinophils & most cells.

 

 

(2) Tissue destruction:-

·         Tissue destruction is the most imp. Feature of the chronic inflammation .

·         Tissue destruction is performed by activated in macrophages which release a variety of biological active substance

Exp.- protease free radicals & cytokines.

 

        (3)proliferative changes :-

Proliferative changes and attempts to healing by angiogensis & fibrosis.

Cells and mediators in chronic inflammation:-

(1)   Macrophages

(2)   Lymphocytes

(3)   Plasma cells

(4)   Eosinophils

(5)   Mast cells

(6)   Neutrophils

Mechanism of Granuloma / chronic inflammation :-

     cell injury

          ↓                                                                                                     Failure to digest agent

          ↓

Weak acute inflammatory response

          ↓

                                         Engulfment by macrophages

         ↓

                        Persistence of injurious agent

                                             ↓

T cells mediated immune response                           poorly digestible agent

 

                             Activcation of CD4     +   T  cells

(release of lymphokines IL-1,IL-2 growth factor IFN-ϒ (interferon)& TNF- α monocytes chemotactic factors)

↓

Activated macrophages by IFN –ϒ(interferon)

 

Transformation to epithelioid cells gaint cells                secretion of fibroblastic proliferating

Cytokines

Granuloma

 

 

                 

 

Granuloma:-

·         It is the form of chronic inflammation that is characterized by collection of activated macrophages ,T-lymphocytes, &sometime associated with central necrosis.

·         Activated macrophages are called epithelioid cells.

Epithelioid cells :-

·         Epithelioid cells are called because its looks like epithelial cells .

·         Epithelioid cells activated by macrophages with abundant cytoplasm.

·         It may fure with one & other they form multinucleated gaint cells.

Types of granuloma :-

(1)   Foreign body granuloma  eg.- Talc fibers

(2)   Immune granuloma .

Morphology of granuloma:-

·         Activated macrophages with pink granular cytoplasm and indistinct boundaries in H & E stain. Surrounded by lymphocytes .

·         Older granuloma may show rim of fibroblast as well multinucleated gaint cells.

 

 

                                               

                                                                       

 

 

 

 

 

 

  

Disease caused by granulomatus inflammation:-

 Disease                      Caused

Tuberculosis                             →         Mycobacterium tuberculosis

Leprosy                                    →          Mycobacteriumleprai

Cat-scratch disease                →         gram negative bacillus

Syphilles                                   →         Traponema pallidom

Sarcoidosis                                →         unknown causes

Crohn disease                          →          immune reaction