5 - Cells of the Innate Immune System - Angyal

Question 1

Draw a diagram highlighting all the cells of the innate immune system.

Answer 1

311 - 5 word Q1.

Question 2

Name the 3 professional phagocytes

Answer 2

Neutrophils, monocytes, macrophages

Question 3

Describe the process of phagocytosis

Answer 3

1) phagocyte binds to the bacteria, helps if Abs bound to pathogen (opsonisation)
2) pseudopods extend around the pathogen
3) invagination of phagocyte membrane leading to phagosome formation
4) fusion of lysosome w/ phagosome -> phagolysosome. here enzymes eg lysozyme break down macromolecules. ROS/RNS are also produced
5) release of microbial products
6) if it is an APC then the peptides are presented on the surface of the cell on the MHC-II molecules to present to other T cells

Question 4

Name the 3 types of polymorphonuclear granulocytes and list them according to their abundance (most abundant being first)

Answer 4

neutrophils, eosinophils, basophils

Question 5

Describe eosinophils and basophils in terms of their…

i) % in blood & any other locations
ii) their granules and contents
iii) their activity and organisms they’re effective against
iv) any receptors?
v) what they release
vi) any similarities?

Answer 5

EOSINOPHILS;

i) 6%, also found in connective tissue under mucous surfaces
ii) granules contains enzymes harmful to opsonised parasites
iii) phagocytic activity. also can cause damage to host tissue. effective against multicellular organisms eg parasites
iv) receptors for C3b, IgG, IgE
v) release histamine, cytokines (IL4), prostaglandin

BASOPHILS;

i) <1% in blood
ii) preformed granules similar to mast cells
iii) Effective against parasites
iv) Fc receptors, C3a,C5a, IgE
v) release histamine, cytokines (IL4/13)

vi) both effective at targeting pathogens and both play role in allergy, bth have IgE receptors and release histamine

Question 6

what is the % composition of neutrophils in the blood?

Answer 6

50-60%

Question 7

Under what conditions are neutrophils activated and where can they be released from if needed in high numbers?

Answer 7

upon infection -> hypoxic conditions -> activation and release into tissue. vast quantities can be released from the bone marrow if necessary.

Question 8

What is the lifespan of a neutrophil?

Answer 8

6h - 1/2 days. if reaches the tissue they can persist for much longer when dealing with infection

Question 9

What are the 2 types of granules present in a neutrophil?

Answer 9

specific - lysozyme, elastase, collagenase

auzrophillic - microbicidal substances eg defensins

Question 10

What happens to the neutrophil once the bacteria has been pahogcytosed/infection has been dealt with?

Answer 10

death by apoptosis

Question 11

What are the functions of neutrophils?

Answer 11

• phagocytosis
• release of granular contents eg lysozyme, defensins
• netosis. once neutrophil is dying can release neutrophil extracellular traps (NETs). DNA, proteins expelled which traps microbes
• cytokine production
• production of ROS/RNS

Question 12

What is the process of neutrophil movement into tissues called?

Answer 12

diapedesis - extravasation of neutrophils into surrounding tissue

Question 13

Describe the structure of mast cells

Answer 13

ovoid nucleus with cells that look elongated

Question 14

Where are mast cells predominantly located?

Answer 14

mature cells are tissue-resident that protect mucosal surfaces

Question 15

What do mast cells preformed granules contain?

Answer 15

ser proteases, histamine (therefore allergy response)

Question 16

What do mast cells newly synthesised granules contain?

Answer 16

prostagalndins/leukotriens

Question 17

Describe the sensitisation process/allergy response brought about by mast cells.

Answer 17

• peanut antigen in body
• taken up by APC and presented to T cell. the Th2 cell then releases cytokines (IL4/5/13) which causes B cells to response by making antigen specific IgE
• IgE binds to Fc receptors on mast cells
• when same peanut antigen in body again, cross links to IgE bound on mast cells. stimulatory signal for mast cell to release granule contents etc (degranulation)

Question 18

How does the release of mediators against parasites by the mast cells kill them eventually?

Answer 18

mediators are constantly released which creates an unfavourable environment for the parasite. because the parasite poses no IMMEDIATE danger, release of these mediators over time result in parasite eventually being cleared

Question 19

Briefly describe the professional APCs

Answer 19

monocytes/macrophages

• mononuclear cells that can circulate in the bloodstream or exist in tissues.
• can exist as resident cells in tissues eg microglial cells in brain / alveolar macrophages in the lungs

Question 20

Describe the composition of monocytes in the blood.

Answer 20

90%;
classical subset (CD14++/CD16-). Have the potential to migrate into tissue and become inflammatory monocytes.
intermediate (CD14++/CD16+)
non - classical (CD14+/CD16+)
10%;
Patrolling monocytes which move along endothelial walls

Question 21

Where do monocytes differentiate into macrophages?

Answer 21

when they move into the tissue

Question 22

What do CD16/14 receptors allow the monocytes/macrophages to do?

Answer 22

CD16 - Fc receptor. allows for opsonised phagocytosis.

CD14 - recognises LPS

Question 23

In the tissue, how do APCs help fight infection?

Answer 23

phagocytosis, opsonised phagocytosis (CD16),secrete cytokines to recruit other effector cells (eg IL8 -> neutrophils), produce RNS/ROS, present antigen on surface via MHC-II

Question 24

How are macrophages involved in the innate response?

Answer 24

• express wide variety of PRRs
• high phagocytic activity (100 bacteria/cell) that is driven by scavenger, mannose or complement receptors
• production of pro-inflammatory cytokines (eg TNF, IL1B)

Question 25

How are macrophages involved in the adaptive response?

Answer 25

• MHC - II expression allows antigens to be presented to lymphocytes
• express IFNy
• Fc receptors for receptor mediated phagocytosis eg IgG
• antibody dependent cell mediated cytotoxicity (ADCC)

Question 26

Draw a table highlighting the phagocyte bactericidal agents that are contained within the phagosome of both macrophages and neutrophils (5 categories)

Answer 26

311 - 5

Question 27

How is NO and other RNS produced?

Answer 27

arginine + O2 -> citrulline + NO through inducible nitric oxide synthase (iNOS2).
NO can then be converted to other more reactive species eg nitrite (NO2-)

Question 28

Describe the process of O2 dependent killing

Answer 28

• activation of TLRs, chemotactic receptors (fMLF stimulus) and other cytokine receptors causes a respiratory burst through activation of phagolysosome membrane bound NADPH oxidase
• phagocytosis results in phagosome then fusion with primary and 2ndry granule and NADPH oxidase becomes functional
• increase in O2 and conversion -> O2- by NADPH oxidase
• influx of ions releases other proteases found in granule matrix eg superoxide dismutase (SOD) which converts 02- superoxide -> H202
• other peroxidases then convert -> OH- hydroxyl radicals etc

Question 29

Which are more long-lived monocytes/neutrophils

Answer 29

monocytes > stable. neutrophils die after a few pathogen killings (after producing RNS etc) and monocytes are much more effective especially when migrating into the tissue

Question 30

Draw a diagram highlighting how NK cells are activated/inhibited

Answer 30

311 - 5 word

Question 31

how do NK cells kill their target cells and what are these target cells?

Answer 31

secrete perforin or granzyme B -> spontaneous killing . perforin creates inserts into membrane, creating holes, granzyme B enters the cytoplasm and induces apoptosis.
Fas/FasL receptor triggering induces apoptosis in target cells
targets; virally infected/intracellular bacteria, tumour cells with altered MHC-I

Question 32

Describe how dendritic cells link the innate and adaptive immune system

Answer 32

important APCs

• when drained to lymph nodes, they present antigens to naive CD4+ T cells
• release of certain cytokines then determines which Th subset that T cell will differentiate into

Question 33

Describe how DCs can help viral infections

Answer 33

many TLRs on endosomes (TLR3/7/8/9) Which result in release of IFNa/B upon activation. IFNs effective against viral infections