5.2. Innate Immune System: Cells

Question 1

Macrophages

Answer 1

Phagocytosis
Inflammation
T-cell activation
Tissue repair

Question 2

Neutrophil

Answer 2

Phagocytosis

Inflammation

Question 3

Eosinophil

Answer 3

Defense against parasites

Question 4

Basophil

Answer 4

Inflammation

Defense against parasites

Question 5

Mast cells

Answer 5

Inflammation

Question 6

Natural killer cell

Answer 6

Killing of infected or tumor cells

Question 7

Dendritic cell

Answer 7

Phagocytosis

Activation of naive T cells

Question 8

Macrophage:

Non activated phagocyte and antigen presenting cell (APC)

Answer 8

Engulfs dead and dying cells

• generally removes debris after barriers penetrated
  1. First cells to respond as it is already present in the tissue under all the barriers
  2. Recognize
• antigen Cos TLR and NLR and mannose receptors
• opsonised antigen Cos CR and Fc receptors

Question 9

Phagocyte

Answer 9

Phagocytose pathogen and degrade in phagolysosome

2. Later in immune response newly synthesized monocytes (live for 1-3 days) leave blood, become macrophages and they predominate cell at 48-96 hrs
3. Long lived cell

Question 10

APC

Answer 10

Antigen presenting cell

• have MHCII
• secrete cytokines and chemokines

Question 11

TNFalpha

Answer 11

Enhance endothelium permeability and expression of adhesion molecules and inflammation

Question 12

IL6

Answer 12

Acts on liver to cause production of acute phase proteins
E.g. C reactive protein, mannose bonding lectin

Cause fever

Question 13

IL1

Answer 13

Fever

Question 14

CXCL8

Answer 14

Recruits neutrophils from bloodstream

Question 15

IL12

Answer 15

Activates NK cells and production of TH1

Question 16

GM CSF

Answer 16

Granulocyte macrophage colony stimulating factor stimulates proliferation of dendritic cell and macrophages

Question 17

Steps of extravasation

Answer 17

1. Rolling adhesion
2. Right adhesion
3. Transmigration
4. Cells now follow chemokine gradient (5)

Question 18

Rolling adhesion

Answer 18

Carbohydrate ligands on the circulating leukocytes bind to P selectin molecules causing it to roll along endothelial surface (1)

Question 19

Tight adhesion

Answer 19

Integrins (activated by chemokine signaling = inside out signaling) on leukocyte surface are now able to bind to integrin receptors (ICAM) on endothelial cells causing cell to bind tightly but transiently and stop rolling (2)

Question 20

Transmigration

Answer 20

Occurs through the gaps between endothelial cells using PECAM proteins present on leukocytes and on junctions between endothelial cells (3)

Leukocyte now produces enzymes which break down the basement membrane (diapodesis) allowing entry into subendothelial tissue (4)

Question 21

Neutrophils

Answer 21

(Phagocyte)

1. Move into tissues because of C3a and C5a and cytokines releases by epithelial cells and macrophages
   - predominant cell you’re enter damaged tissue from the blood in the first 0-48 hrs

Question 22

What do neutrophils recognize?

Answer 22

1. Antigen via TLR

2. Opsonised antigen via CR and Fc receptors

Question 23

How do neutrophils kill pathogens?

Answer 23

1. Phagocytosis
   - phagolysosome formed and antigens inside killed by oxygen dependent and independent mechanism
2. Secretes toxic granules (anti-microbials e.g. defensins, lactoferrin)
   And chromatic (DNA and histones) forming neutrophil extracellular traps (NETs)

Question 24

What cytokines are released by neutrophils?

Answer 24

IFNgamma:

Macrophage activation, increased MHC proteins

Question 25

How long do neutrophils survive?

Answer 25

Short lived cells: | A couple of days

Question 26

Eosinophils

Answer 26

1. Kill extracellular parasites too large to engulf (E.g. helminths) by releasing highly toxic granules and ROS 2. Synthesize prostaglandins & cytokines which amplify the immune response - inflammation 3. Levels increase when Th2 cells secrete IL5 4. Can act as phagocytes 5. Involved in allergic responses

Question 27

Basophils

Answer 27

1. Have receptors for IgE 2. Release histamine, IL4 when activated 3. Promote Th2 development 4. Involved in allergic responses and inflammation

Question 28

Mast cell

Answer 28

1. Sentinel cells present in the skin, mucosal epithelium, and connective tissues that rapidly secrete proinflammatory cytokines & lipid mediators in response to infections and other stimuli 2. Express receptors for IgE antibodies (Fc receptors) and TLR 3. When activated they release histamine (cause vasodilation and increase capillary permeability) and lipid mediators e.g. prostaglandins 4. Promote acute inflammation and provide defense against helminths 5. Plays a role in allergic reactions

Question 29

Life span of mast cell

Answer 29

Weeks to months

Question 30

Helminths

Answer 30

Worms

Question 31

Natural killer cells

Answer 31

Lymphoid lineage cell important for killing cells infected with cytoplasmic pathogens and cancer cells

Question 32

How do natural killer cells recognize cells?

Answer 32

1. Receptors for stress receptors (MICA) on infected cells 2. Receptors which bind MHCl in cells e.g. KIRS 3. Receptors for antibodies (FcR)

Question 33

How are natural killer cells activated?

Answer 33

1. By IFNalpha (dendritic cells) 2. IFNbeta (fibroblasts) 3. IL12 (macrophages)

Question 34

How do natural killer cells kill infected cells?

Answer 34

1. Apoptosis induction by perforin & granzyme - increase stress receptors on infected cells together with lack of MHCl on infected cells - infect cells coated in antibody (ADCC)

Question 35

Cytokines secreted by natural killer cells

Answer 35

IFNgamma: Activates macrophages Increase MHC expression and antigen processing Suppresses TH2

Question 36

Lifespan of natural killer cells

Answer 36

2 weeks

Question 37

Dendritic cells

Answer 37

[Phagocytes and antigen presenting cells (APC)] 1. Most important cell in activating naive T cells - link between innate and adaptive immune system 2. Recognize pathogens via TLRs and mannose receptor & opsonised pathogen via CR 3. Phagocytose pathogen and degrade in phagolysosome 4. This activates dendritic cell to produce co-stimulatory proteins and chemokine receptors 5. Further activated by IFNalpha and IFNbeta 6. Moves via chemokine gradient in lymph to nearest lymph node 7. Present antigen to naive T cells

Question 38

Cytokines produced by dendritic cells

Answer 38

1. TNFalpha - enhances endothelium permeability & expression of adhesion molecules & inflammation 2. IL6 - acts on liver to cause production of acute phase proteins E.g. C reactive protein, mannose binding lectin and cause fever 3. IL1 - fever 4. IL12 - activates NK cells and production of Th1 cells 5. IFNalpha - antiviral - increased MHCl

Question 39

Dendritic cell lifespan

Answer 39

Days to weeks

Question 40

Definition of Inflammation

Answer 40

``` Calor (heat) Dolor (pain) Rubor (red) Tumor (swelling) Loss of function (immobility) ```

Question 41

Inflammation

Answer 41

1. Initiated by injury to or infection in tissue 2. Chemokines and cytokines releases by macrophages, Mast cells and damaged cells cause vasodilation resulting in increased local blood flow & permeability of endothelial cells resulting in increased leakage of fluids into tissues accounting for heat, redness and swelling - accumulation of complement and MBL in tissues which aid in host defence 3. Increased neutrophils and monocytes move to the area 4. Induces local blood clotting which provides a barrier to spread or infection 5. Released mediators such as TNFalpha, bradykinin & histamine stimulate nerve endings, give rise to pain 6. The loss of function due to swelling and pain 7. Inflammation prevents spread of damaging agents, removes cell debris and pathogens, alerts adaptive immune system and sets the stage for repair