Inflammation cellular events

 cellular events :-

·         cellular phase of the acute inflammation

·         leucocytes are recruited to the site of infection.

·         Then leucocytes ingent and destroy the injurious agents (microbes/ necrotic tissue/ foreign bodies)

·         Leucocytes also secrete growth factor for the repair of injured cells

·         Here two thing we should be know of

1)      Leucocytes recruitment

2)      Leucocytes activation

1)Leucocytes recruitment:-   

* Journey of leukocytes from vessels lumen to site of infection.

* Leucocytes in the lumen of blood vessels

·         Margination

·         Rolling

·         Adhesion

*Migration across the endotheliam.

1) Margination:-

In the early stage of inflammation the rate of flow of blood is increased due to vasodilation.

·         RBCs move faster and leukocytes pushed out of the central cellular column.

·         As a result ,leucocytes accumulate at the  periphery of the vessels and the process is called margination.

2)Rolling :-

There leukocytes move on the endothelial surface by stickying transiently along the way is called as rolling .

3)Adhesion :-

This weak transient adhesion is mediated via molecules

·         Here two molicules are present

1)selection

2)integrins

1)selection:-

Selection molecules present in both leucocytes &ECs.

Selection also K/a Adhesion receptors

P- selection –present on ECs& platelets

E-selection –present on ECs

L- selection – present on leucocytes.

2)Integrins :-Integrins used in adhesion.

·         Integrins are WBC; means they are present on the surface of WBC

·         Integrins role are molecule k/a inter cellular adhesion molecules (ICAM)

·         There molecule sticking on the surface of wbc ECs, and it not move forword.

·         More gapping present on the surface of endothelial wall for this its perform  transmigration.

Transmigration ( migration across the endothelial wall)

·         After adhesion, means – leucocytes- endothelium adhesion

·         Leucocytes mights into interstitium, bymoving in between the endothelial cells called transmigration or diapedsis

Chemotoxis:-

·         Chemotaxis is movement of leucocytes towards the site of infection or injury along with chemical molecules

·         Thin process in k/a chemotoxin

·         Transmigration of leucocytes after crossing several barriers (endothelium ,basement membrane, perivascular myofibroblast &matrix.)

·         Main chemotactic agents are:-

·         Soluble bacterial products (formylated peptide )

·         Leukotriene B4(LT-B4) product of lipooxygen are (LOX), pathwayof arachidonic acid metabolites

·         Components of complement system (C5a in particular)

·         Chemokines/ cytokines (1L-B,MCP-1,M1P-α, eotoxin etc.

·         Kallikerin (end product of the kinin system)

·         Mediated through G-protein coupled receptors

·         Leukocytes move by extending pseudopods.

After the recruitment of leukocytes:-

1)      To recognize the microbes / necrotic cells/foreign bodies

2)      Once if recognize the leucocytes killing & phagocytosis

1)To recognize the microbes / necrotic cells/foreign bodies:-

All there stimuli are recognize by receptors on the phagocytes they are known as phagocytic receptors

There are different kinds of receptors on phagocytes:-

1) mannore receptors

2)Scavenger receptors-present on WBC

3)opsonin receptors- bacterial surface

Phagocytosis:-

·       Phagocytosis is the killing & degradation of the foreign particles

·       Phagocytosis is the process of cellular engulfment of a solid particulates material (eg. Microbes, foreign particular material

·       Phagocytosis is k/a cell eating

·       Pinocytosis is k/a cell drinking

·       Processes of phagocytosis is performed by the three steps

1)      Recognition & Attachment

2)      Engulfment

3)      Killing & degradation

1)   Recognition & attachment :-

·         Cell surface express the receptors those who are recognize micro organism.

·         Wbc cell receptors are mannore & scavenger receptors.

·         Process of the micro organism are coated with specific protein is k/a opsonins.

 

IgG protein

                                                                                                                      Receptor for C3b

           receptoer for IgG

   Opsonisation:-      

Some molecules are joint with the surface of bacteria .there molecules are antibody; IgG antibody, C3b compliments & collection particles.

2)   Engulfment :-

·         The opsonised particle bound to the surface of phagocytes is ready to be engulfed

·         Then after ,pseudopods are formed around the attached particles due to activation of action filaments beneath cell wall

·         Pseudopods enveloping in a phagocytic vacuole.

·         Then the phagosomal & lysosomal membrane fuses to from phagolysosome.

Fig.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Killing & degradation:- 

Neutrophils → oxygen independent →bacteria kill by lysozyme                                                    +                                                                                                                                  monocytes                    oxygen dependent – mast cell→produce by ROS & its more effective

 

a)      by ROS & lysosomes enzymes

b)      the ROS is produced by oxidative burst in leukocytes.

Fig.

 

 

 

 

 

 

 

 

   2O2+ NADPH  →  NADP +  H+       

Superoxide is then coverted by spontaneous dismutation to hydrogen peroxide.

+                                                                                                                                                                                        HOCl +  

HOCL                                    OCl (hypochloroun free radical )