Phagocytosis

Question 1

What is a phagocyte?

Answer 1

A self-eating microorganism that forms part of the innate immune system, whilst also linking to the adaptive immune system.

Question 2

What are the different roles of phagocytes?

Answer 2

• 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

Question 3

Describe the origins of phagocytes and there initial response to infection

Answer 3

• Frequently originate from monocytes and differentiate into specialised tissues-specific macrophages
• Kick start immune responses by secreting inflammatory factors (cytokines) => inflammation
General points

Question 4

Describe some general points about phagocytes

Answer 4

• Life span = 8-10h/blood; 4-5 days in tissues
• Phagocytosis and killing of microbes using Enzymes produced: lysozyme, collagenase and elastase
• Preform NETosis

Question 5

Describe THE 3 FUNCTIONS of phagocytes

Answer 5

• Capture microbes and antigens
• Phagocytosis for antigen processing and presentation to T cells
• Link the innate and adaptive immune responses

Question 6

What are the four steps in phagocytosis?

Answer 6

1. Chemotaxis (mobilisation towards pathogens or site of infection/injury)
2. Recognition and attachment to microbe/dead cells or Recognition and attachment of a different kind
3. Engulfment
4. Killing/digestion of ingested microbe/dead cells

Question 7

Describe Chemotaxis (mobilisation towards pathogens or site of infection/injury)

Answer 7

• Guided by chemoattractants
• Released by:
• Bacteria - N-formyl-methionine-leucine-phenylalanine peptides (fMLP)
• Inflammatory cells - chemokines (e.g. IL-8)

Question 8

What are the requirements for recognition and attachment to microbe?

Answer 8

• React to invading pathogens (foreign)
• Regulated reaction to body’s own tissues (self)
• Pathogen Associated Molecular Patterns (PAMPs)
• Structures shared by groups of related microbes

Question 9

What PAMPS do TLRs respond to in humans?

Answer 9

Human TLRs recognize PAMPs:
 	Lipolysaccharide (gram negative)
 	Lipoteichoic acid (gram positive)
 	Bacterial DNA sequences (unmethylated CpG)
 	Single/double-stranded viral RNA
 	Glucans (fungi)

Question 10

Describe the recognition and attachment of a different kind

Answer 10

Opsinisation: pathogen is coated in proteins from complement system e.g C3B AND C4B

antibodies bind to pathogen (Ig)

Question 11

Describe engulfment

Answer 11

1. Actin polymers form protrusions from the membrane
2. Pathogen is contained inside a phagosome where is starts digesting the pathogen
3. Transported to a lysosome where is gets digested, breaking down lipids, proteins ect. Forming a Lysophagosome
4. Cell excretes the waste products by exocytosis

Question 12

What chemicals do lysosomes contain?

Answer 12

• Proteolytic enzymes (cathepsins): degrade microbes
• Lysozyme: breaks bacterial walls
• Lactoferrin: binds iron => not enough left for bacteria
• Defensins: destroy bacterial walls

Question 13

Describe the production of Peroxynitrite radicals and what do these radicals do?

Answer 13

Equations and these radicals degrade the pathogen whilst in the lysophagosome

Question 14

How can pathogens resist getting phagocytosed

Answer 14

Block phagocyte attachment - SP - encapsulated bacteria

Block engulfment - Yersinia

Blocking destruction - salmonella is resistant to ROS and mycobacterium blocks lysosome-phagosome fusion

The killing of phagocytes S.aureus producing toxins damaging membrane

Question 15

What other 2 processes are phagocytosis involved in?

Answer 15

Damage or dying cells and apoptosis

Question 16

What are the consequences of the apoptotic process?

Answer 16

1. Change to a ‘prohealing’ phenotype
2. Secrete ‘prohealing’ phenotype to

these reduce inflammation and promote wound healing

3. Presentation of self-antigens - role in maintenance of cell tolerance