What are the 5 different roles of Phagocytosis?
• Destruction of the pathogen via respiratory burst
• Activation of genes leading to cytokine and chemokine release
• Antigen presentation
• Cell recruitment
• Elimination and disposal of dead, apoptotic and damaged cells
What are effector phagocytes?
Effector phagocytes are immune cells involved in defence against pathogens.
Main types include neutrophils and macrophages
Are neutrophils polymorphonuclear?
Yes
What is the most abundant WBC?
Neutrophils
When do Neutrophils act as effectors?
In early antibacterial responses (Inflammation)
What is the lifespan of a neutrophil? (In blood and tissues)
-8-10hrs in blood
-4-5 days in tissues
What enzymes are produced by the neutrophils? (3)
-lysozyme
-Collagenase
-Elastase
Neutrophils perform NETosis; What is NETosis? What are NETs composed of? What is the Purpose?
-Neutrophils release web-like structures known as Neutrophil Extracellular Traps (NETs)
-NETs are composed of DNA, histones, and antimicrobial proteins
-Purpose: To trap and neutralize pathogens, especially bacteria and fungi, in the extracellular environment
Where are phagocytes located?
-Tissue
-Mucosa
-Lymph Nodes
Phagocytes link the....?
Innate and immune responses
What are the 4 general steps 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
What is chemotaxis?
Movement of cells towards site of infection, guided by chemoattractants
Chemoattractants can be released by? (In what form)
- Bacteria
N-formyl-methionine-leucine-phenylalanine peptides(fMLP)
-Inflammatory cells
chemokines (e.g. IL-8)
For phagocytosis to occur, the body either must....?
1)React to Invading Pathogens (Foreign)
2)Regulated Reaction to Body’s Own Tissues (Self)
What are Pathogen Associated Molecular Patterns (PAMPs)?
Structures shared by groups of related microbes
PAMPS are shared by an entire class of...?
Pathogens
PAMPS are essential for the survival of humans because they minimise pathogen evasion of immune responses; what are some examples of PAMPS?
e.g. ds viral RNA=> replicatione.g. lipopolysaccharide (LPS) => bacterial membrane
What are pattern recognition receptors (PRRs)?
Proteins on the surface of immune cells that recognize specific PAMPs
What are Damage-Associated Molecular Patterns (DAMPs)?
Molecules released by damaged or stressed cells
Where are PRRs presented?
Present on phagocytes (and other cells, e.g. epithelia)
What are the 2 main purposes of PRRs?
-Recognize PAMPs and DAMPs (Damage-Associated Molecular Patterns)
-Detect foreign invaders or aged/damaged host cells
Detection and signals through PRRs lead to.....?
Phagocytosis
Can you name the 5 types of PRRs? And can you name some types of these individual PRRs?
-Toll-like receptors (TLRs)
Located on the plasma membrane and 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)
Human TLRs will recognise what? Such as?
PAMPs
Such as:
Lipolysaccharide (gram negative)
Lipoteichoic acid (gram positive)Bacterial DNA sequences (unmethylated CpG)Single/double-stranded viral RNAGlucans (fungi)
TLRs will stimulate the production of what?
Inflammatory cytokines
TLRs have been highly ________ in evolution
What is the missing word?
Conserved
What is opsonisation?
Process where pathogens are marked for phagocytosis (engulfment and destruction) by phagocytic cells
Opsonized microbes can be _______ easier via receptors for ______ on phagocytes.
What are the missing words?
1)Phagocytosed
2)Opsonins
What contributes to the coating of microbes with opsonins (2)? Can you name some examples for each point?
Proteins of Complement System:
Complement proteins, particularly C3b and C4b, can act as opsonins
Antibodies (Immunoglobulin, Ig):
Antibodies, which are produced by B cells as part of the adaptive immune response, can also act as opsonins. Immunoglobulins (Ig), such as IgG, can bind to specific antigens
A picture demonstrating Phagosome formation and maturation:
State the steps of phagosome formation (1-3):
Recognition and Attachment:
Phagocytic cells recognise and attach to the particle, facilitated by receptors
Recognition triggers signalling cascades that lead to actin cytoskeleton rearrangement
Pseudopod Formation:
Actin cytoskeleton rearrangement results in the extension of pseudopodia (membrane projections) around the particle
Engulfment of the particle occurs
Membrane Remodelling:
As the pseudopodia surround the particle, membrane remodeling occurs, leading to the closure of the phagosome
Early phagosome produced
State the steps of phagosome maturation (4-9):
Early Phagosome:
Undergo fusion with endosomes, vesicles derived from the Golgi apparatus
Phagosome Acidification:
Proton pumps actively acidify the phagosome, transforming it into a late phagosome
Acidification is critical for the activation of enzymes
Fusion with Lysosomes:
Late phagosomes undergo fusion with lysosomes, specialized organelles containing various hydrolytic enzymes
Forms a phagolysosome
Enzymatic Digestion:
Enzymes within the phagolysosome, including proteases, nucleases, and lipases
Residual Body Formation:
Forms a residual body within the phagolysosome
Exocytosis or Antigen Presentation:
Processed antigens may be presented on the cell surface, initiating an adaptive immune response
The killing of pathogens by lysosomes is independent of what?
Oxygen
There are 4 components of the lysosome essential for pathogen destruction; can you name them and state their purposes?
-Proteolytic enzymes (cathepsins): degrade microbes-Lysozyme: breaks bacterial walls-Lactoferrin: binds iron, leads to not enough iron left for bacteria-Defensins: destroy bacterial walls
Killing of pathogens can also be oxygen dependent, a picture demonstrating this:
Killing of pathogens leads to the production of oxidising ________
What is the missing word?
Radicals
Phagocytosis dcan be prevented (evaded) by pathogens sadly
There are 4 ways this can occur, state these 4 ways and maybe specific pathogens/bacteria that cause it
-Blocking phagocyte attachment
Streptococcus pneumoniae – encapsulated bacteria
-Blocking engulfment
Yersinia
-Blocking destruction
Salmonella – resistant to ROSMycobacterium – blocks phagosome-lysosome fusion
-Killing of phagocytesStaphylococcus aureus – toxin => damages membranes
What is the normal turnover for cells (for the average human) a day?
100-200 billion cells/day
Phagocytes will discriminate between....?
Apoptotic vs. viable cells
Does apoptosis cause inflammation?
No - Silent removal
Phagocytosis of apoptotic cells is also called what?
Efferocytosis
A picture demonstrating how efferocytosis occurs:
Phagocytes that have taken up apoptotic cells reduce inflammation by what mechanisms? (4)
• Blocking TLR signalling• Blocking proinflammatory cytokine signalling (IFN-• Blocking (TNF- expression)• Promote (IL-10 secretion)
Phagocytes that have taken up apoptotic can change to a 'pro-healing' phenotype by what mechanism? (1)
• Secreting ‘pro-healing’cytokines (e.g. TGB-β)
Phagocytosis allows for antigen processing and presentation and helps to link the innate and adaptive immune responses
A picture outlining this:
A picture overview of phagocytosis:
