W11 Phagocytosis Flashcards
Phagocytosis: Roles
protection from pathogens
disposal of damaged/dying (apoptotic) cells
processing and presentation of antigens (Ag)
activation of adaptive immune system
links innate and adaptive immunity
Phagocytes`examples + origin
neutrophils, macrophages (M), dendritic cells
origin: myeloid lineage; generated in bone marrow
Other cells (apart from phagocytes)
mast cells, eosinophils, basophils (myeloid lineage)
natural killer (NK) cells (lymphoid lineage; bone marrow)
Phagocytes def.
identify, ingest, destroy pathogens
neutrophils, M, dendritic cells
belong to the innate immune system
Phagocytes have receptors for opsonins
Phagocytes: Neutrophils (PMN)
polymorphonuclear (PMN) leukocytes
most abundant WBCs (circulating in blood)
early response (inflammation)
phagocytosis and killing of microbes
enzymes: lysozyme, collagenase, elastase
Phagocytes: Neutrophils (PMN) - life span
life span = 8-10h/blood; 4-5 days in tissues
Phagocytes: Macrophages (M)
monocytes (blood; 20-40hrs)
efficient phagocytosis
killing of microbes
secrete inflammatory factors (cytokines) => inflammation
Dendritic cells
skin, mucosa, tissues
capture microbes
phagocytosis
not just to eliminate
present Ag to T cells
link innate and adaptive immune response
Dendritic cells and signals for T cell activation
Signal 1 = antigen recognition by MHC:peptide (Major histocompatibility complex) onto TCR
Signal 2 = co-stimulation by CD80/CD86 (cluster of differentiation - protein on Dcells activated by B cells) onto CD28 (proteins on T cells that provide co-stimulatory signals for T cell activation/survival)
Signal 3 = cytokines released by macrophages
Phagocytosis: Steps
Chemotaxis (mobilisation to site of infection/injury)
Recognition and attachment to microbe/dead cells
Engulfment
Killing/digestion of ingested microbe/dead cells
Phagocyte mobilization: Chemotaxis
movement of cells towards site of infection
guided by chemoattractants
chemoattractants released by
bacteria
- N-formyl-methionine-leucine-phenylalanine peptides (fMLP)
- inflammatory cells
chemokines (IL-8) - damaged tissues
Phagocytosis: Recognition of pathogens
Requirements:
react to invading pathogens (foreign)
no reaction to body’s own tissues (self)
PAMPs = structures shared by groups of related microbes
Pathogen-Associated Molecular Patterns (PAMPs)
present on pathogens and not on host cells
invariant structures: shared by an entire class of pathogens
essential for survival of pathogens
prevents pathogen evasion of immune responses
e.g. ds viral RNA=> replication
e.g. lipopolysaccharide (LPS) => bacterial membrane
Pattern recognition receptors (PRRs)
present on phagocytes (and other cells, e.g. epithelia)
recognize PAMPs
detect foreign invaders or aged/damaged host cells
Toll-like receptors (TLRs)
PRR
plasma membrane, endosomal membrane
C-type lectin receptors (CTLRs)
PRR
e.g. mannose receptor
NOD-like receptors (NLRs)
PRR
reside as free proteins in cytoplasm
RIG-like helicase receptors (RLRs)
PRR
cytosolic receptors for viral dsRNA
Scavenger receptors
PRR
various bacterial wall components (CD14 scavenges LPS-LBP)
PRRs: Toll-like receptors (TLRs)
essential roles in innate immunity
conserved during evolution
stimulate production of inflammatory cytokines
human TLRs recognize PAMPs:
lipolysaccharide (gram negative) lipoteichoic acid (gram positive) bacterial DNA sequences (unmethylated CpG) single/double-stranded viral RNA glucans (fungi)
Phagocytosis: Opsonization
facilitates phagocytosis (recognition of microbes)
- Opsonized microbes can be phagocytosed easier
(via receptors for opsonins on phagocytes)
Clinical note!
=> Encapsulated microorganisms require opsonization with antibodies to be effectively phagocytosed!
- coating of microbes with opsonins:
a) proteins of complement system (C3b, C4b) (CR1 recognizes breakdown products of C3)
b) antibodies (immunoglobulin, Ig)
