Phagocytosis

• endocytosis

• defense role

• profesional phagocytes

elimination- clearing -

Phagocytosis

Phagocytosis

activationother cells

secretionenzymes, cytokines

presentationAg

killing

regulation

Inflammation

Phagocytosis

• Professional Effective phagocytosis and secretion:

» macrophages» neutrophil granulocytes

• Non- Professional Secretion

» eosinophils» basophils» mast cells

Professional phagocytes

• macrophages (monocytes), neutrophils

• elimination of microbs, partiles

• membrane receptors– complement R: CR1, CR2– receptors for Ab: Fc receptors

Mechanism

• 1) adhesion - endotel• 2) diapedesis• 3) chemotaxis• 4) adhesion – bacteria, ... (+ opsonisation)• 5) ingestion• 6) digestion (killing and degradation)

Adhesion endothelium - neutrophils

Neutrophil Endothelial cell Function

Lex (CD15)sialyl-Lewis x

antigen

P-selectin (CD62P) rolling

Integrins: CD11a (LFA-1) CD18

ICAM-1, 2 (CD54, CD102)

adhézia

CD11b (Mac-1)CD18

ICAM-1 adhézia

Adhesion endothelium - monocytes

Monocytes Endothelial cell

Function

Integrins 1 (CD29)

VCAM-1 rolling

CD11a (LFA-1) CD18

ICAM-1, 2(CD54, CD102)

adhézia

CD11b (Mac-1)CD18

ICAM-1 adhézia

Diapedesis and chemotaxis

• Diapedesis

• Chemotaxis - chemotaxins – exogenous: bacterial oligopeptides (FMLP), LPS, lipids

– endogenous: C5a, Ba, fibrinopeptides, kalikrein, plasminogen activator, metabolites of arachidonic acid (LTB 4,...)

Stimulation of chemotexis, but also adherence, endocytosis and sekretion of lysosomal enzymes.

Adhesion

• 1) surface molecules of particle

• 2) opsonins

Opsonins – immune phagocytosis

• Opsonisation:

– opsonins (specific molecules)– facilitation of adhesion– principle – opsonins represent ligands for receptors

of phagocytes

Phagocytosis

Phagocytosis

Immuneopsonins

Non-immune

Opsonins – immune phagocytosis

Receptor

Opsonin(ligand)

Cells

CR1 C3b, C4b neutrophils, monocytes, B cells, some T cells

CR2 C3b neutrophils, monocytes, macrophages, B cells

FcR Ab: IgG, IgM

monocytes, macrophages, neutrophils

Opsonins

C3b

Ab

Phagocytes - receptors Bactetia + opsonins

CR3

FcR

Ingestion - digestion

• Ingestion >>> pseudopodia – phagozómu.

• Digestion >>> lysosom –phagolyzozóm.

• Lysosoms >>> enzymes

• Role > killing and destruction.

Microbicidal mechanisms

1) Oxygen dependent

2) Oxygen independent

Microbicidal mechanisms

Oxygen dependent

• Myeloperoxidase independent- hydrogenperoxide

- superoxide anion- hydroxyl radical- singlet oxygen

2) Myeloperoxidase (MPO) dependent- MPO + hydrogenperoxide + I-

- MPO + hydrogenperoxide + Cl-

Respiratory burst

• Antimicrobial molecules

• Process:- stimulation of phagocytes (mikroorganizmy, C5a,

Ag+Ab,...)

- oxygen consuption- anaerob. metabolism- superoxide

Respiratory burst

MPO mechanisms

Oxygen independent mechanism

- low pH in phagolysosome- cationic proteins- defensines- bactericidal proteins- lysozyme- neutral proteinases- lactoferin- phospholipase A2- histones (leukin)

Deficiences

1.1. Low number of phagocytesLow number of phagocytes

a. Kostmann syndrom – inherited agranulocytosis –infections of skin and mucosa

b. Cyklic neutropenia – every 3rd week 2. Failure of functionFailure of function

a. CGD (Chronic granulomatous disease) - defect of NADPH-oxidase - X chromosome – linked decreased bactericidal activity - recurent pyogenic infections staphylococcal infections - pneumonia

Deficiences

b. LAD (Leukocyte Adhesion Deficiency)

- failure of adhesins on phagocyte - ↓ expresion of β2 subunit of integrins (CD18)

Phagocytes: - do not adhere to endothelial cells - absent in the site of inflammation

- recurent skin infections- wound healing- candidiasis