1. summary
 Inflammation-acute and chronic
 Acute - cardinal sign
stimuli
changes -vascular & cellular
•vascular- vasodilation;
increased vascular permeability
transcytosis

2. ACUTE INFLAMMATION-
CELLULAR EVENTS
“AIM IS TO DELIVER LEUCOCYTES TO THE
SITE OF INJURY”
 LUMINAL
 MARGINATION
 ROLLING
 ADHESION
 TRANSMIGRATION ACROSS ENDOTHELIUM
 MIGRATION IN INTERSTITIAL TISSUES

4. STEPS OF EXTRAVASATION OF INFLAMMATORY CELLS

5. ACUTE INFLAMMATION-
CELLULAR EVENTS
 MARGINATION- Increased No. Of WBCs In The
Periphery Adjacent To Endothelium
 ROLLING- Slow Tumbling And Transient
Adhesion
 PAVEMENTING- Complete Lining Of
Endothelium By WBCs

6. LEUCOCYTE ADHESION AND
TRANSMIGRATION-MECHASINMS
 DUE TO ADHESION MOLECULES
 4 CLASSES OF ADHESION
MOLECULES
Selectins
Immunoglobulin class
Integrins
Mucin like glycoproteins

7. ADHESION MOLECULES
SELECTINS
 ADHESION OF LEUCOCYTES TO ENDOTHELIAL CELLS
 E-SELECTINS
 On endothelial cells
 Bind to CHO groups on granulocytes,monocytes.Memory T cells
 P-SELECTINS
 Endo And Platelets
 Bind Neutro,T-Lymphos, monos
 L-SELECTINS
 impt in homing

8. ADHESION MOLECULES
IMMUNOGLOBULIN CLASS
 EXPRESSED ON ENDOTHELIAL CELLS
 ICAM-1:INTERCELLULAR ADHESION MOLECULE
 VCAM-1:VASCULAR CELL ADHESION MOLECULE
 ACT AS LIGANDS TO INTEGRINS

9. ADHESION MOLECULES
INTEGRINS
 HETERODIMERIC CELL SURFACE PROTEINS
 + ON MANY CELLS
 CELL-CELL AND CELL-MATRIX
INTERACTIONS

10. ENDOTHELILI LEUKOCYTE MOLECULE ROLE
AL MOLECULE
GLYCAM1 L-selectin ROLLING
P- SELECTIN Sialyl-Lewis X–modified proteins ROLLING
E-SELECTIN Sialyl-Lewis X–modified proteins ROLLING+
ADHESION
V CAM 1 CD11/CD18 (β2) integrins (LFA-1, ADHESION
Mac-1)
I CAM 1 VLA-4 (β1) integrin ADHESION+
TRINSMIGRATIO
N

11. Innflammation induces redistribution of
adhesion molecules

13.  leukocyte adhesion deficiency type 1:
defective biosynthesis of the β2 chain shared by the
LFA-1 and Mac-1 integrins.
 Leukocyte adhesion deficiency type 2: d/t
absence of sialyl-Lewis X,

14. Stages of Phagocytosis: Chemotaxis:
DEFINITION- Process Of Directed Cell Migration
Along A Chemical Gradient
Responsible for emigration of leucocytes towards the
site of injury

15. CHEMOTAXIS-AGENTS
 EXOGENOUS
 BACTERIAL PRODUCTS-COMMONEST
 PEPTIDES OR LIPIDS
 ENDOGENOUS
 COMPLEMENT COMPONENTS-C5a
 LEUKOTRIENE B4
 CYTOKINES-IL-8

16. CHEMOTAXIS-MECHANISM
 Bind to specific receptors on leucocytes
 Effector molecules produced-phospholipase,
tyrosinase etc
 Second messengers-finally leading to polymerization
of actin
 Leucocyte moves by extending filopodia

17. Neutrophil Crawling on a Glass
Slide
It is going that way:

18. RECRUITMENT OF LEUCOCYTES
TO SITE OF INJURY
 INITIAL 6-24 HOURS– NEUTROPHILS
 LATER-- MONOCYTES

19. Recognition of Microbes and Dead Tissues

20. Phagocytes are Attracted to Site
of Infection by Chemotaxis

21. Stages of Phagocytosis: Adherence:
Phagocyte plasma membrane attaches to surface of
pathogen or foreign material.
 Adherence can be inhibited by capsules (S.
pneumoniae) or M protein (S. pyogenes).
 Opsonization: Coating process with opsonins that
facilitates attachment.
 Opsonins include antibodies and complement
proteins.

22. Stages of Phagocytosis (Cont…)
3. Ingestion: pseudopods formation:
lead to engulfment of the microbe
4. Digestion: phagolysosome formation.
Lysosomal enzymes includes:
Lysozyme: Destroys cell wall peptidoglycan
Lipases and Proteases
RNAses and DNAses
After digestion, residual body with
undigestable material is discharged.

23. Process of Phagocytosis

24. KILLING AND DEGRADATION
 O2 DEPENDENT-MORE IMPORTANT
 O2 INDEPENDENT

26. O2 DEPENDENT MECHANISMS
 Phagocytosis stimulates burst of oxygen
consumption
 Production of ROS
 Superoxide produced during oxidation of
NADPH
 Superoxide converted to H2O2
 Further reduced to hydroxyl radical

27. O2 DEPENDENT MECHANISMS
 Hydrogen peroxide not very effective by itself
 Converted by MPO in presence of Cl to form HOCl
(hypochlorite)

28. O2 INDEPENDENT
MECHANISMS
 Bacterial permeability increasing protein-
phospholipase activation
 Lysozyme
 Lactoferrin
 Major basic protein-for parasites
 Elastase

29. DEGRADATION
After killing microbes are degraded in lysosomes by
acid hydrolases

30. LEUCOCYTE INDUCED TISSUE INJURY
 Protector becoming offender
 Release of microbicidal products into EC space
 Endothelial injury and tissue necrosis
 Amplify inflammation
 Eg.-ARDS, acute transplant rejection,
glomerulonephritis

31. INFLAMMATION: REGULATION

32. DEFECTS IN LEUCOCYTE FUNCTION
GENETIC
 ADHESION DEFECTS-
 LAD1, LAD2
 INTEGRINS AND SELECTIN RECEPTORS DEFECTIVE
 REC BACTERIAL INFECTIONS AND IMPAIRED HEALING
 DEFECTS IN PHAGOLYSOSOME FUNCTION
 CHEDIAK HIGASHI SYN
 AR
 DEFECTIVE TRANSFER OF LYSOSOMAL ENZYMES

33. DEFECTS IN LEUCOCYTE FUNCTION
 DEFECT IN MICROBICIDAL ACTIVITY
 CGD-DEFECTS IN NADPH OXIDASE
 REC BACTERIAL INFECTIONS
 MPO DEF
ACQUIRED-VARIOUS ASPECTS LIKE
PHAGO,CHEMO ETC AFFECTED
 DM
 MALIGNANCY
 MALNUTRITION
 ANEMIA