Features and activation of phagocytes Flashcards
define Phagocyte
eating cell
define Phagocytosis
The uptake of large solid particles by the process of endocytosis
define Endocytosis
The uptake of extracellular material by invagination of the
plasma membrane to form vesicles enclosing the material
who discovered endocytes?
Ilya Ilyich Mechnikov’s
Importance of phagocytes in innate immune system
- Engulf pathogens and apoptotic or necrotic cells,
2. Release cytokines, e.g. to induce the Acute Phase Response in Macrophages
Importance of phagocytes in the Acquired immune system
- Present antigens from these ingested particles to T cells (Macrophages and Dendritic cells only)
name 3 phagocytic cells?
Neutrophils, monocytes / macrophages,
and dendritic cells
whats the function of macrohphages?
phagocytosis and antigen presentation
whats the function of a dendritic cell?
antigen uptake in peripheral site and antigen presentation in lymph nodes
whats the function of a neutrophil?
phagocytosis and activation of bactericidal mechanisms.
whats the action of neutrophils?
- Most important cellular component in bacterial destruction
- 60% to 70% of circulating white blood cells (WBCs)
- Max 24 hours (1/2 life = 7 hours)
- response to inflammatory stimulus
- Lobed nucleus and cytoplasmic granules (lysosomes)
what are Mononuclear phagocytes?
monocytes/macrophages
whats the prevalence of Mononuclear phagocytes?
- 3 to 8% of circulating WBCs
- Monocytes spend 1-2 days in blood, then go to tissues and become macrophages
- Secrete biologically active compounds that regulate the immune system (e.g. cytokines)
- Present antigens to T-lymphocytes
what are the key differences between neutrophils and macrophages?
- N- hrs M- years
- N- 1st new arrivals at inflamed sites M-Arrive later
- N- Not present in healthy tissue
recruited to sites of inflammation M- Present in healthy - N- Dedicated phagocytes
M-Phagocytosis, Antigen presentation,Secrete proteins
where does a Monocyte differentiate into a Macrophage?
in tissue
name 4 types of macrophage
Alveolar Macrophage (Lungs) Microglial Cell (Brain) Kupffer Cell (Liver) Langerhans Cell (Skin)
what happens to Phagocytes at sites of infection?
- Initially PMNs most prevalent form of phagocyte
- Monocytes move in and differentiate to macrophages
- Both eventually die (PMNs die rapidly) due to ingestion of microbes and damaged tissue, forming pus
- Pus formation especially notable with PYOGENIC bacteria (Greek, Pyon = Pus), e.g. Staphylococcus, Streptococcus, Neisseria
what the affect of Salmonella on neutrophils?
induces infiltration of neutrophils into the gut lumen
what are the Stages of Phagocytosis?
- CHEMOTAXIS- phagocytic cell attracted to infection - microbial products, components of WBC or damaged tissues, complement
- ADHERENCE- attachment of phagocyte to organism, may require OPSONISATION
- INGESTION- involves pseudopods, fusion of pseudopods results in internalization in a specialized vacuole - PHAGOSOME
- DIGESTION- phagosome fuses with lysosome, creating PHAGOLYSOSOME. Produce lytic enzymes to digest bacteria (lysozyme, proteases, nucleases, lipases), also superoxide anion, OH -, and H2O2
- Undigestible material forms RESIDUAL BODY, migrates to plasma membrane Fusion releases waste materials, recruits other phagocytes
How do phagocytes recognise microbes
in order to phagocytose them?
- Microbes recognised directly by characteristic surface components.
- Microbes recognised indirectly if opsonised
how do phagocytes Directly recognise microbes?
- via Pattern Recognition Receptors (PRR) on phagocyte e.g. Mannose-receptor, scavenger receptors, also certain Toll-like receptors
- These PRR recognise conserved chemical components termed Pathogen Associated Molecular Patterns (PAMPs) on surface of microbes and trigger activation and phagocytosis
define OPSONISATION
a process that facilitates phagocytosis by coating antigens with an opsonin
who discovered Opsonin?
George Bernard Shaw 1856-1950
what are Opsonins?
- Opsonins are soluble Pattern Recognition Receptors (PRR)
- They bind a variety of microbial surface molecules which are important in microbial viability conserved during evolution
- Lipopolysaccharide (LPS), Liptoteichoic acid (LTA), Mannose (a microbial sugar molecule)
what are the most important opsonins?
1) IgG antibodies
2) Complement factor C3b
3) Acute phase proteins:
e. g. C-Reactive protein (CRP), Mannose-Binding Lectin (MBL), Collectins (SP-A, SP-D)
how do IgG Receptors work?
- Fab-region reacts with organism
2. Fc domain reacts with Fc R on phagocyte
how do Complement receptors work?
- CR3 and CR4 Found on both monocytes/macrophages and neutrophils
- Both integrins, dimers of CD18 and CD11b = CR3 or CD18 and CD11c = CR4
- Both bind C3b
what does CR3 (Mac-1) also recognise?
- The extracellular matrix - promotes adhesion
- ICAM-1 (CD54) on endothelial cells (CD18 required for phagocyte movement into tissues)
- Some surface structures on microorganisms - ie CR3 can sometimes bind in ABSENCE of opsonin
what are Acute Phase proteins?
c- reactive protein, MBL
what affect does C-reactive and MBL proteins have?
binds phosphorylcholine on bacterial surfaces acting as a opsonin activating compliment.
What effect does activation have on phagocytes?
Macs and neutrophils:
Increased phagocytosis + killing of phagocytosed microbes
Macs only:
Increased cytokine release, antigen presentation, expression of co-stimulatory molecules
What activates macrophages?
require two stimuli for full activation Cytokines e.g. IFN (from TH1 cells) - important TNF Chemokines e.g. CCL2 (MCP-1)
Microbial compounds recognised by
Pattern Recognition Receptors
e.g. TLRs, Mannose Receptor etc
T cells (via CD40 L)
Surface molecules on monocytes- Involved in activation
- CD14 (receptor for lipopolysaccharide (LPS) binding protein)
- CD40
- IFNg Receptor
- Mannose receptor (mediates phagocytosis of microbes)
- Scavenger receptors (bind bacterial and yeast cell wall carbohydrates or lipids)
- TLRs (1-10)
- Chemokine receptors
what are the responses of activated macrophages?
- increased expression of co-stimulators
- Killing of phagocytosised microbes
- secretion of cytokines
- increased expression of MHC
whats the role of Production of reactive oxygen intermediates nitric oxide; increased lysosomal enzymes?
Killing of microbes in phagolysomes (effector function of macrophages)
whats the roles of secretion of cytokines by macrophages?
TNF-a, IL-1: leukocyte recruitment (Inflammation)
IL-12: TH-1 differentiation,
IFN-g production (induction of response)
what the immunological role of Increased expression of:
CD80, CD86 (B7)
Class I, Class II MHC
Increased T cell activation (amplification)
