Inflammation introduction😊

Classification of Inflammation

• Inflammation is classified based on two main criteria:

Based on Fluid Type

Acute Inflammation

Blood Report Findings

Location of Acute Inflammation

• Occurs in two places:
1. Blood Vessels (4 events)
2. Cells (7 events)

Four Blood Vessel Events

Carrageenan theory

• Inflammation

1. Vasoconstriction:

• Very first event.

• Temporary

• Reflex to prevent bleeding.

2. Vasodilation:

• Follows vasoconstriction.

• Mediated by histamine and serotonin.

3. Increased Vascular Permeability:

• Most important hallmark event of acute inflammation.

• Everything (cells, plasma, proteins) exits blood vessel → forms exudate.

• Mechanisms:
• Endothelial Cell Contraction or Retraction:
• Most common and important mechanism.
• Gaps form between endothelial cells.
• Mediated by histamine and serotonin.
• Immediate transient response
• (acts fast, stops fast)
• Produced by histamine
• Direct Endothelial Injury:
• Damage from outside/inside.
• Sunburn
• 8-10 hours exposure
• Delayed prolonged response 
• starts late, long recovery
• Mnemonic: Sunbathing with DEEPIKA PADUKON
• (Delayed Prolonged Response)
• Sepsis
• Immediate sustained response 
• damage immediate, recovery prolonged
• Mnemonic: SEPSIS (Immediate Sustained Response)
• Transcytosis:
• Transport through endothelial cell without gaps.
• Via "underground tunnel": 
• Vesicular Vacuolar Organelle (VVO).
• Mediated by VEGF and histamine.
• Angiogenesis:
• Formation of new blood vessels.
• New vessels are immaturE
• have endothelial gaps (leaky channels) 
• Mediated by VEGF and histamine.

Note

• Extravasation
• Happens in Post capillary venules

4. Stasis:

• Outflow of water (exudate) → RBCs concentrated.

• Blood becomes thick/viscous → slows blood flow.

Seven Cellular Events

1. Margination:

• WBCs move from blood vessel center to periphery (margin).

2. Rolling and Weak Adhesion:

• WBCs roll along endothelium, weakly attaching briefly.

• Caused by selectins

Selectin	Location	Binds To
E-selectin: [CD63]	Endothelial cells	Sialyl Lewis X (S-LeX) on leukocytes
P-selectin:	Platelets and endothelial cells	Sialyl Lewis X (S-LeX) on leukocytes
L-selectin:	Leukocytes (WBCs)	GlyCAM, MadCAM, CD34 on endothelium

• Mnemonic:
• Selected (Selectin) for a Role (Roll) in EPL
• EPL (English Premier League) for Selectins (E, P, L)

3. Adhesion (Strong Adhesion):

• WBCs firmly stick to endothelial cells.

• Caused by integrins (on WBCs).
• Mnemonic:
• Add (adhesion) ingredients (integrins)
• we do it in camera → cookey show
• 1st ingredient → together → VCAM
• 2nd ingredient → adich pirinj → alone → ICAM

• Beta 1 integrin: On Leukocytes
• Binds to VCAM-1 on Endothelium
• Mnemonic: We Are One → for Beta 1 and VCAM-1

• Beta 2 integrin: On Leukocytes
• Binds to ICAM on Endothelium
• Also CD11 & CD18, LAFA, MAC.

ICAM Clinical aspects:

• Microbiology: 
• Plasmodium falciparum (cerebral malaria)
• attaches to ICAM

• Virology: 
• Rhinovirus 
• attaches to ICAM.

Types of LAD:

LAD1

• In LFA-1 integrin (CD 18, CD 11 defective) protein defect on phagocytes
• Leads to impaired migration and
• chemotaxis by C5a, IL-8, leukotriene B4 (LIC)

LAD Type	Defect	Clinical Features / Associations
LAD 1	Beta 2 integrin	Delayed umbilical cord shedding, Recurrent infections NO PUS dysfunctional neutrophils
LAD 2	Sialyl Lewis X (S-LeX) (selectin)	Bombay blood group (no H, A, B antigens; anti-H, anti-A, anti-B Abs) + Delayed umbilical cord shedding Bombay blood group = “Oh”
LAD 3	Kindlin-3 (FERMT3 gene)	Bleeding manifestations

• Mnemonic:
• Bombayil (Bombay blood group) kond povan 2 (LAD 2) pere selct (Selectin) cheyth → SaLu (Sialyl Lewis)
• But Salu nte umbilical cord shed ayilla → kond povan patiilann paranju
• Salu ne kude integrate (Integrin) cheyyan umbilical cord valichu uuri (↓ umbilical cord shedding)
• Apo bleed cheyth → 3 (LAD 3) kinder (Kindlin) joyum ferraro roshe (FERMT 3) yum vangi koduth

4. Transmigration (Diapedesis):

• Cell moves out of blood vessel
• Requires basement membrane breakage by 
• Matrix Metalloproteinases (MMPs) (need zinc).
• Mediated by PCAM1 (CD31)
• (Endothelial cells CD34+, CD31 for transmigration).

• Mnemonic: Neutrophil Pee (Pcam) cheyth Matrix (MMP) break aakki on endothelial cell to get out of it

5. Chemotaxis:

• Unidirectional WBC movement towards a target (e.g., bacteria).
• Exogenous Chemotactic Agent:
• Bacterial cell wall produce N formyl methionine
• Endogenous Chemotactic Agents:
• Leukotriene B4
• IL-8
• C5a

6. Opsonization:

• Coating bacteria to make it "tasty" for phagocytosis.
• Most important opsin:
• Fc fragment of IgG 
• (the "garam masala" spice).
• Most important complement opsin:
• C3B 
• (B for Badaa food).
• Mnemonic:
• Opsonins → OOZE (opsonin) CSF (C3B, Serum Protein, Fc fragment)
• (C5A: chemotaxis, C3B: opsonization).

7. Phagocytosis:

• Eating/killing of bacteria.

• Oxygen-Dependent Pathway (Most potent):
• A.k.a. H2O2 MPO Halide system.
• Requires 
• H2O2,
• Myeloperoxidase (MPO),
• chloride,
• Enzyme NADPH oxidase.
• NADPH oxidase
• Made by PHOX gene.

• Oxygen-Independent Pathway:
• No oxygen required.
• Most important example: 
• Major Basic Protein (MBP).
• Made by eosinophils to kill parasitic infections.