Phagocytosis

Question 1

Describe the chemotaxis stage of phagocytosis

Answer 1

Chemotaxis is the movement of cells towards the infection site guided by chemoattractants released by
- Bacteria : N-formyl-methionine-leucine-phenylalanine
peptides (fMLP)
- Inflammatory cells: chemokines IL-8
- Damaged tissues

Question 2

Why is pathogen killing oxygen dependent?

Answer 2

When activated, phagocytes assemble NAPH oxidase to generate a superoxide anion O2-
Oxidising radicals NOS and ROS kill phagocytosed microbes

Question 3

What are the roles of phagocytosis?

Answer 3

• protection from pathogens
• disposal of damaged/dying cells
• processing and presentation of antigens (Ag)
• activation of adaptive immunity - links innate & adaptive

Question 4

Describe how PAMPs enable pathogen recognition

Answer 4

Pathogens recognised by PAMPs which are structures shared by groups of related pathogens
PAMPs are present on pathogens and not on the host cells
They are essential for pathogen survival

Question 5

Which innate immunity cells are phagocytes?

Answer 5

Phagocytes are specialised cells belonging to innate immune system
Neutrophils, macrophages and dendritic cells are able to identify, ingest and destroy pathogens
Phagocytes originate from myeloid lineage, generated in bone marrow

Question 6

Which lysosomes are involved in pathogen killing?

Answer 6

Proteolytic enzymes (cathepsins) degrade microbes
Lysozyme breaks bacterial walls
Lactoferrin binds iron so lesss available for bacterial metabolism
Defensins destroy bacterial walls

Question 7

How do certain pathogens sabotage Phagocytosis?

Answer 7

Streptococcus pneumoniae blocks phagocyte attachment

Verisnia blocks engulfment

Salmonella is ROS resistant and is a myobacterium which blocks destruction

Straphylococcus aureus is - toxin which damages membranes, blocking the killing of pathogens

Question 8

Apart from phagocytes, what other cells are involved in innate immunity ?

Answer 8

Mast cells, eosinophils, basophils (myeloid lineage)
NK cells (lymphoid lineage generated in bone marrow)

Question 9

Give examples of PAMPs

Answer 9

Viral dsRNA during viral replication

Lipoproteins (LPs) in the bacterial membrane

Question 10

What are the 4 stages of the phagocytosis process?

Answer 10

1. Chemotaxis - mobilisation to injury site
2. Recognition & Attachment to microbe
3. Englufment
4. Killing / digestion

Question 11

Describe apoptosis (dying cells) phagocytosis

Answer 11

Apoptosis is the efficient removal of dying cells via phagocytosis which doesn’t cause inflammation
Apoptosis is able to discriminate between apoptic and viable cells

Question 12

How does pathogen recognition occur?

Answer 12

PAMPs recognised by PRRs

Encapsulated microbes are opsonised making them easier to phagocytose

Question 13

Describe the features of Neutrophils (PMNs)

Answer 13

• polymorphonucelar PMN leukocytes
• most abundant WBCs circulating in the blood
• provide an early inflammatory response
• life span = 8-10hrs in blood, 4-5days in tissues
• phagocytose and kill microbes using lysozyme,
  collagenase & elastase enzymes

Question 14

Name some examples of PRRs (Pathogen recognition receptors)

Answer 14

TLRs (toll like receptors)
CTLRs (C-type lectin receptors) - mannose receptors
NLRs (NOD like receptors) free proteins in cytoplasm
RLRs (RIG like helicase receptors) cytosolic receptors for viral dsRNA
Scavenger receptors for various bacterial wall components (CD14 scavenges LPS-LPB)

Question 15

What 3 signals do dendritic cells send for T cell activation?

Answer 15

Signal 1: antigen recognition MHC-TCR
Signal 2: co-stimulation via CD80/86 ligation to CD26
Signal 3: Modulation via cytokine production

Question 16

How is apoptis process able to differentiate between apoptic and viable cells?

Answer 16

Apoptic cells sen d ‘eat me’ signals recognised by phagocytes promoting engulfment

Viable cells send ‘don’t eat me signals’ recognised by phagocytes ensuring no engulfment occurs

Question 17

What are the essential features of monocytes & macrophages?

Answer 17

Monocytes survive in the blood for 20-40hrs
Macrophages are found in tissues
Both cause efficient phagocytosis
kill microbes by secreting inflammatory factors (cytokines) causing inflammation

Question 18

Describe and explain the function of TLRs

Answer 18

TLRs (toll like receptors)
found on plasma and endosomal membranes
They are conserved during evolution and human TLRs recognise PAMPs
stimulating inflammatory cytokine production

Question 19

Explain what is meant by opsonisation

Answer 19

Molecular mechanisms to chemically modify apoptic cells to have stronger interactions with NK and phagocyte receptors
Opsonisation facilitates phagocytosis recognition by coating microbes with opsonins which are:
- proteins of the complement system (C3b, C4b)
- antibodies (Ig)

Question 20

How are Phagosomes fomed and matured?

Answer 20

1. Phagocyte membrane reorganised via actin
   cytoskeleton rearrangement
2. Pseudopods formed around microbe via membrane
   remodelling
3. Once pathogen has been completely surrounded by
   phagocyte its engulfed into cytosol
   => phagosome
4. Phagosome fuses with lysosomes => phagolysosome
5. pathogen destruction occurs

Question 21

What is phagocytosis?

Answer 21

Ingestion of microorganisms, other cells and nutrients by phagocytes
It is a mechanism of innate immunity

Question 22

Outline the features of dendritic cells

Answer 22

Found in skin and mucosal tissues
Capture microbes and phagocytose them not just to eliminate but also present antigens to T cells linking innate and adaptive immunity

Question 23

What is the outcome of apoptosis?

Answer 23

Phagocytes that take up apoptc cells secrete 'prohealing' cytokines 
reducing inflammation (IL-10) and promote wound healing (TGB-β)
They also present self antigens to maintain self tolerance