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Immunology > Lec 8: Granulocytes and Secretion Pathways > Flashcards

Lec 8: Granulocytes and Secretion Pathways Flashcards

1
Q

What is a granule

A

It depends, but generally, it is a vesicle within a granulocyte

contains immune mediators

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2
Q

Purpose of FcR

A

binds Antibodies can activate granulocytes

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3
Q

What are the 4 types of granulocytes

A

Mast cells
Neutrophils
Eosinophils
Basophils

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4
Q

Which activators cause granulocytes to release their granules

A

FcR
Cytokines
Inflammation
PRR activation

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5
Q

How are granules formed

A

Granules are formed by vesicles budded from the Golgi complex during cell differentiation

Secretory granules are different for they are formed during the course of development, and have a different set of immune mediators from regular granules

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6
Q

How are granules classified

A

Classification is based on:

Production during granulopoiesis
Distinct protein markers

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7
Q

What are the three types of graules in NEUTROPHILS, and their mediators

A

Primary/ azurophilic
Secondary/ specific
Tertiary/ gelatinase

These are in order of production, and release from th= cell is coordinatinated and the reverse of synthesis

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8
Q

Markers of Primary/ azurophilic granules and their mediator

A

myleoperoxidase/ CD63

Myleoperoxidase = Production of HOCl

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9
Q

Markers of Secondary/ specific granules and their mediator

A

Lipocalin–2/ CD66b

Lactoferrin = Up-regulation of neutrophil adhesion molecules and deayed apoptosis

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10
Q

Markers of tertiary/ gelatinase granuels and their mediator

A

Gelatinase/ CD11b

Gelantianse = degradation of the cartilage matrix

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11
Q

Neutrophil produced Secratory vessicles

A

Markers = albumin, CD45, Cd16b and CD13

formed by endocytosis and can secreted extracellular vesicles “exosomes”

Secratory granules can contain newly-synthesized mediators like cytokines and chemokines

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12
Q

Classical secratory pathways (w/ granules)

A

regulated exocytosis
Piecemeal degranulation
consitutive exocytosis

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13
Q

Nonclassical secratory pathways (w/ granules)

A

membrane transporter
exosome release
microvesicle shedding
cell lysis

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14
Q

Piecemeal degranulation

A

small vesicles shuttling large granule contents

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15
Q

Regulated granule secreation

A

Engagement of PRRs or Fc receptors can initiate granule discharge

note PRR and FcRs are DIFFERENT triggers

During activation, not all granules are released simultaneously -> first formed, last released
-> controller release of granules by type based on initiating stimuli

Granules can also be released upon death

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16
Q

Snare System (brief overview)

A

Vsnares and Tsnares allow specificity of granule secreation to target a specific plasma membrane

Snare proteins make SNAREpin structures with lipid membranes

17
Q

V-Snares

A

V for Vesicle

found on the synaptic vesicle membrane

also called (synaptobrevin/ VAMP)

18
Q

T-Snares

A

T for Target

found on the plasma membrane

SNAP-23 and Syntaxin-4

19
Q

Purpose of SNARE proteins// mechanism

A

bindng of snare proteins triggers a conformational change and brings plasma membranes close together and releases contents of the granule

Note, this process is reversible, and thus the granul;e membrane may be recycled and refilled after release from the target membrane

20
Q

Regulated Exocytosis

A

see diagram

21
Q

Constitutive Exocytosis

A

see diagram

22
Q

Regulated death of granulocytes

(4 types) and are they pro or non-inflammatory

A

Apoptosis (less inflammatory)

NETosis, Necroptosis and pyrotosis (deez are inflammatory)

23
Q

Neutrophil death

A

once a neutrophil is activated it will die (by PAMPS, DAMPS and immune complexes)

phagocytosis -> apoptotic blebbing -> and or autophagy to kill an intracelluar pathogen if present

cellular content released which is highly inflammatory ie/ cellar explosion

Disruption of neutrophil function is associated with tissue injury, chronic inflammation dn autoimmunity

24
Q

NADPH oxidase complex

A

generates high levels of Reative Oxygen Species,

important in phagosome in which a microbe may be transported into. ROS busts open the micobe cell membrane nd then granules with pre-stored mediators may fuse with the phagosome

25
Q

Neutrophil Extracellular Traps (NETs)

A

Netosis is the process of secreting NETs
-> basically just barfed out DNA

Traps for pathogens

  • > localization of antigens
  • > increased effectiveness of granulocytes
  • > Increased concentration of cytokines

slows diffusion and allows for better enzymatic antimirobial activity

26
Q

NETosis and Neutrophil Activation

A

leads to:

Activity of phagosome NADPH oxidase

generation of ROS

Breakdown of intracellular membranes

Neutrophil elastase (NE) and myeloperozidase (MPO) 
enter the nucleus and modify histones, thus chromatin dencondenses

Plasma membrane ruptrues and releases cell contents

Cell dies form NETosis

27
Q

Problems associated with NETosis

A

XS antigen presentation from self DNA which leads to antibodies generated against self DNA

=clinical conditions like lupus, and other autoimmune dieases

28
Q

What are in NETs

A

Granule proteins

Elastase and cathepsin -> proteinases with broad substrate specificty

MPO -> myeloperoxidase has antimicrobial activity

DNA and Histones -> Promotion of Thrombosis

29
Q

NETs as drivers of adaptive immunity

A

Traps pathogena nd keeps it in one area

Easier to bind antigen in a closed area
-> concentrated area
Drives inflammation 
-> more APCs
-> more activaton
30
Q

How can microbes evates NETs

A

directly inhibiting NET formation
Coating themselves in a capsule// slime layer
secreting endonucleases that degrade NETs

Pathogens can also secrete enzymes that convert NET compounds into toxic molecules that kill immune cells
-> production of deosyadenosine (dAdo) triggers apoptosis in nearly macrophages

31
Q

What is a granule? What types of mediators are found in granules

A

?

32
Q

How are granules produced aand secreated

A

?

33
Q

Name a functiohnof a secreted mediator from neutrophiles

A

elastase

34
Q

Name a functiohnof a secreted mediator from Basophils

A

Histamine increases the permeability of the capillaries to white blood cells and some proteins, to allow them to engage pathogens in the infected tissues.

35
Q

Name a functiohnof a secreted mediator from Eosionophils

A

eosinophil peroxidase, ribonuclease (RNase), deoxyribonucleases (DNase) and lipase

36
Q

Name a functiohnof a secreted mediator from Mast cells

A

Histamine

37
Q

Explain how FcRs can facilitate granule secreation. Give an example

A

?

Antibodies -> bind -> activate

38
Q

What is the function of a neutrophil NET, and explain the risk/ benefit ratio

A

?

Immunology (23 decks)

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