Phagocytosis Flashcards
What is phagocytosis?
Phagocytosis- cell eating
We could say it is an effector function that is part of the innate immune response but also a mechanism that links the innate with the adaptive immune response
What are the different roles of phagocytosis?
Destructions of the pathogen via respiratory burst
Activation of genes leading to cytokine and chemokine release
Antigen presentation for presentation to other cells like T-cells
Cell recruitment e.g. chemokines
Elimination and disposal of dead, apoptotic and damaged cells
What are active tissue macrophages and what do they do?
Blood monocyte can give rise to an active tissue macrophage (TEM)
Frequently originate from monocytes and differentiate into specialised tissue-specific macrophages
Very efficient phagocytes
Very efficient at detecting and killing of microbes
Eliminate dead or dying cells
Kick start immune responses by secreting inflammatory factors (cytokines)
What are dendritic cells? (location and function)
Located in tissue, mucosa, lymph nodes
Capture microbes and antigens through phagocytosis
Phagocytosis for antigen processing and presentation to T cells
Link the innate and adaptive immune responses
What are the different stages of phagocytosis?
Chemotaxis (mobilisation towards pathogens or site of infection/injury)
Recognition and attachment to microbe/dead cells
Engulfment
Killing/digestion of ingested microbe/dead cells ( with dead cells its called efferocytosis)
What is the phagocyte mobilisation- chemotaxis stage?
Movement of cells towards site of infection
Guided by chemoattractant
Released by:
Bacteria- N-formyl-methionine-leucine-phenylalanine peptides (fMLP)
Inflammatory- chemokines (e.g. IL-8)
Epithelial cells that have been damaged
What are the requirements for the recognition stage of phagocytosis?
Requirements:
Reacts to invading pathogens (foreign)
Regulated reaction to the body’s own tissues (self)
Pathogen-Associated Molecular Patterns (PAMPs)
Structures shared by groups of related microbes
What are pattern recognition receptors (PRRs)?
Present on phagocytes (and other cells e.g. epithelia)
Recognise PAMPs and DAMPs (Damage-Associated Molecular Patterns)
Detect foreign invaders or aged/damaged host cells
Detection and signals through PRRs lead onto phagocytosis (among other things)
Examples include:
Toll-like receptors (TLRs)-plasma membrane, endosomal membrane
C-type lectin receptors (CTLRs)- e.g. mannose receptor
NOD-like receptors (NLRs)- reside as free proteins in cytoplasm
RIG-like helicase receptors (RLRs)- Cytosolic receptors for viral dsRNA
Scavenger receptors- various bacterial wall components (CD14 scavenges LPS-LBP)
What do toll-like receptors (TLRs) do?
Essential roles in innate immunity Conserved during evolution Human TLRs recognise PAMPs: Lipopolysaccharide (gram-negative) Lipoteichoic acid (gram-positive) Bacterial DNA sequences (unmethylated CpG) Single/double-stranded viral RNA Glucans (fungi) Stimulate production of inflammatory cytokines
What is opsonisation?
Phagocytosis: Opsonisation
Facilitates phagocytosis (recognition of microbes)
Opsonised microbes can be phagocytosed easier (via receptors for opsonins on phagocytes)
Coating of microbes with opsonins:
A) Proteins of complement system (C3b, C4b)
B) Antibodies (immunoglobulin, Ig)
How does NADPH oxidase destroy bacteria?
Elements of the NADPH oxidase in its resting state will be inactive but then once a pathogen is inside the phagolysosome, the elements and subunits of the NADPH oxidase will come together to mediate a reaction to produce the generation of superoxide anions
These are very aggressive radicals that will also destroy bacteria
What are some of the ways pathogens avoid destruction?
Blocking phagocyte attachment- Streptococcus pneumoniae- encapsulated bacteria
Blocking engulfment- Yersinia
Blocking destruction- Salmonella; resistant to ROS (reactive oxygen species)
Mycobacterium; blocks phagosome-lysosome fusion
Killing of phagocytes- Staphylococcus aureus - toxin —> damages membranes
How do phagocytes discriminate between viable and apoptotic cells?
There are specific signals that lead to either attraction or repulsion between the cells and the phagocyte
Apoptotic cells:
‘Eat-me’ signals
Recognised by phagocytes–> promote engulfment
Viable cells
‘Don’t eat-me’ signals
Recognised by phagocytes —> no engulfment
What are the consequences of efferocytosis?
Phagocytes that have taken apoptotic cells:
-Reduce inflammation by:
Blocking TLR signalling
Blocking proinflammatory cytokine signalling (IFN-alpha)
Blocking (TNF-alpha expression (a strong inflammation cytokine))
Promote (IL-10 secretion)
-Can change to a ‘pro-healing’ phenotype
E.g. Secrete ‘pro-healing’ cytokines (e.g. TGB-beta)
-Presentation of self antigens
Role in maintenance of self tolerance
