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phagocytosis Flashcards

1
Q

what are the main roles of phagocytosis?

A

β†’to protect the body from pathogens

β†’ to dispose of damaged/dying (apoptotic) cells

β†’ to process and present antigens (Ag) This processing/presenting of antigens activates the adaptive immune system.

β†’links the innate and adaptive immune system.

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2
Q

what are types of phagocytes and what is their origin?

A

β†’lneutrophils
β†’lmacrophages (M)
β†’ldendritic cells

origin: myeloid lineage; generated in bone marrow
function : identify, ingest and destroy pathogens have receptors for opsonins
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3
Q

other cells (apart from phagocytes)

A 
β†’mast cells
β†’ eosinophils
β†’ basophils (myeloid lineage) 
β†’natural killer (NK) cells 
β†’(lymphoid lineage; bone marrow)
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4
Q

what are properties of neutrophils?

A

β†’(polymorphonuclear (PMN)
β†’leukocytes most abundant WBCs (circulating in blood) β†’early response (inflammation)
β†’ phagocytosis and killing of microbes enzymes: lysozyme, collagenase, elastase

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5
Q

what is the lifespan of neutrophils?

A

β†’8-10 hours in blood

β†’4-5 days in tissues

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6
Q

what are properties of macrophages? (include lifespan)

A

β†’monocytes (blood 20-40hrs)
β†’efficient phagocytosis
β†’killing of microbes
β†’secrete inflammatory factors (cytokines) => inflammation

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7
Q

where are dendritic cells found and what is their function?

A

β†’skin
β†’ mucosa
β†’ tissues
β†’capture microbes
β†’phagocytosis
β†’not just to eliminate present Ag to T cells
β†’link innate and adaptive immune response

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8
Q

how do dendritic cells signal for T cell activation?

A

Signal 1
β†’ antigen recognition by MHC:peptide (Major histocompatibility complex) onto TCR

Signal 2
β†’co-stimulation by CD80/CD86 (cluster of differentiation - protein on Dcells activated by B cells)
β†’onto CD28 (proteins on T cells that provide co-stimulatory signals for T cell activation/survival)

Signal 3
β†’ cytokines released by macrophages

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9
Q

what are the steps for phagocytosis?

A

β†’Chemotaxis (mobilisation to site of infection/injury) β†’Recognition and attachment to microbe/dead cells β†’Engulfment
β†’Killing/digestion of ingested microbe/dead cells

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10
Q

what is chemotaxis?

A

β†’ movement of cells towards site of infection

β†’guided by chemoattractants

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11
Q

what are chemoattractants released by?

A

β†’bacteria - N-formyl-methionine-leucine-phenylalanine peptides (fMLP)
β†’inflammatory cells chemokines (IL-8)
β†’ damaged tissues

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12
Q

what are the requirements of recognition of pathogens in phagocytosis?

A

β†’Requirements
β†’react to invading pathogens (foreign)
β†’no reaction to body’s own tissues (self)

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13
Q

definition of PAMPs?

A

β†’PAMPs (pathogen associated molecular patterns) = structures shared by groups of related microbes

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14
Q

what are PAMPs?

A

β†’present on pathogens and not on host cells
β†’invariant structures: shared by an entire class of pathogens
β†’essential for survival of pathogens
β†’prevents pathogen evasion of immune responses
β†’e.g. ds viral RNA=> replication
β†’e.g. lipopolysaccharide (LPS) => bacterial membrane

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15
Q

what are Pattern recognition receptors (PRRs)?

A

β†’present on phagocytes (and other cells, e.g. epithelia) β†’recognize PAMPs
β†’detect foreign invaders or aged/damaged host cells

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16
Q

where are toll like receptors found?

A

β†’ plasma membrane

β†’endosomal membrane

17
Q

C-type lectin receptors (CTLRs)

A

PRR e.g. mannose receptor

18
Q

NOD-like receptors (NLRs)

A

PRR reside as free proteins in cytoplasm

19
Q

RIG-like helicase receptors (RLRs)

A

PRR cytosolic receptors for viral dsRNA

20
Q

Scavenger receptors

A

PRR various bacterial wall components (CD14 scavenges LPS-LBP)

21
Q

what do Toll-like receptors (TLRs) do?

A

β†’ essential roles in innate immunity
β†’ conserved during evolution
β†’ human TLRs recognize PAMPs
β†’ stimulate production of inflammatory cytokines

22
Q

what PAMPs are recognized by TLRs?

A 
β†’ lipolysaccharide (gram negative) 
β†’ lipoteichoic acid (gram positive)
β†’  bacterial DNA sequences (unmethylated CpG)
 β†’ single/double-stranded viral RNA 
β†’ glucans (fungi)
23
Q

what is the role of opsonization?

A

β†’ facilitates phagocytosis (recognition of microbes)
β†’ Opsonized microbes can be phagocytosed easier (via receptors for opsonins on phagocytes)

β†’ Clinical note! => Encapsulated microorganisms require opsonization with antibodies to be effectively phagocytosed because the capsule deflects phagocytes

24
Q

how is opsonization done?

A

β†’coating of microbes with opsonins (such as proteins of the complement system, C3b, C4b, and antibodies, immunoglobulin).

25
how is a phagosome formed and matured?
β†’Microbe makes contact with the membrane β†’actin cytoskeleton rearrangement β†’membrane remodelling occurs to form pseudopods β†’which wrap membrane around microbe = forming phagosome β†’Lysosomes fuse forming phagolysosome β†’Pathogen destruction
26
what are the lysosomes involved in oxygen dependent killing of pathogens?
β†’proteolytic enzymes (cathepsins): degrade microbes β†’lysozyme: breaks bacterial walls β†’lactoferrin: binds iron => not enough left for bacteria β†’defensins: destroy bacterial walls
27
describe the oxygen-dependent killing of pathogens?
β†’resting phagocyte = NADPH + oxidase are not bound β†’activated phagocyte = assembly of NADPH oxidase generation of superoxide anion
28
what are the oxygen-dependent killing equations?
O2 β†’ O2 (superoxide) (OXIDASE) H2O + O2- β†’ H2O2;OH (hydrogen peroxide; hydroxyl radicals) Through DISMUTASE arginine + O2 β†’ NO + citrulline iNOS (inducible NO synthase) NO + H2O2 β†’ peroxynitrite radicals oxidising radicals (ROS and NOS) kill phagocytosed microbes
29
blocking phagocyte attachment
β†’Streptococcus pneumoniae – encapsulated bacteria
30
blocking engulfment
Yersinia
31
blocking destruction
Salmonella – resistant to ROS | Mycobacterium – blocks phagosome-lysosome fusion
32
killing of phagocytes
Staphylococcus aureus – toxin => damages membranes
33
what are other types of prey that phagocytes go after?
β†’Micro-organisms β†’Damaged or dying cells β†’normal turnover of cells = 100-200 billion cells/day apoptosis (programmed cell death) fast, efficient removal by phagocytes β€˜silent removal’: no inflammation phagocytes: discriminate apoptotic vs. viable cells
34
how does phagocytosis of apoptotic cells occur?
eat-me signals apoptotic β†’cell attraction as phosphatidylserine is expressed on apoptotic cell β†’cell binds to phagocytic receptor β†’Rac bound to GDP β†’ Rac bound to GTP β†’which then generates myosin-II and force generation for wrapping by pseudopods β†’Repulsion on viable cell
35
how does discrimination of apoptotic / viable cells happen?
β†’Apoptotic cells β€˜Eat-me’ signals β†’Recognized by phagocytes => promote engulfment β†’Viable cells β€˜Don’t eat-me’ signals β†’ Recognized by phagocytes => no engulfment
36
what happens after phagocytes have taken up apoptotic cells?
``` β†’ secreteβ€˜pro-healing’ cytokines β†’ reduce inflammation (e.g. IL-10) β†’ promote wound healing (e.g. TGB-Ξ²) β†’ presentation of self antigens β†’ role in maintenance of self tolerance ```

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