Innate Immune System

Question 1

3 main components of innate immune system

Answer 1

1. Physical Barriers
2. Cells
3. Soluble Mediators

Question 2

What are the physical barriers?

Answer 2

Skin and mucosa

Question 3

How does the skin act as a physical barrier?

Answer 3

Physical barrier, physiological conditions, Glands

Question 4

How do mucosal surfaces act as barriers?

Answer 4

Mucus and Cilia

Question 5

What are the cells of the innate immune system?

Answer 5

Granulocytes (Neutrophils, basophils, mast cells, eosinophils), Monocytes→macrophages, Dendritic cells, NK cells

Question 6

Granulocytes and their function

Answer 6

Neutrophils - Phagocytosis,
Basophils and Mast cells histamine,
Eosinophils - parasites

Question 7

Monocytes/macrophage function

Answer 7

Monocytes → migrate to tissue → macrophages → phagocytosis and antigen presentation to T cells

Question 8

Dendritic cells, their function and what do they express

Answer 8

Antigen presentation
After phagocytosis → migrate to lymph nodes → activate CD4+ and CD8+ T cells
Fc - complexes
Cytokines - regulation

Question 9

NK cells and their function

Answer 9

Kill malignant/viral cells
inhibition - self-HLA
activation - heparan sulphate proteoglycans

Question 10

What soluble mediators are in the innate response

Answer 10

Cytokines and complement

Question 11

Key cytokines and their roles

Answer 11

TNF-alpha, IL-1(fever) - main, initiators
Chemokines - leukocyte recruitment
IFNs - viruses

Question 12

Complement and their role

Answer 12

Tightly regulated soluble factors inactive in blood
Once activated: Opsonisation, Vasodilation + increased vasc permeability, Chemo attraction, activation of leukocytes, MAC

Question 13

How is C3 activated?

Answer 13

Classical: Antigen binds antibody → C1 activated →C2, C4 activated which activate C3 convertase
MBL: MBL binds carbs on bacterial surface → C2, C4 activated which activate C3 convertase
Alt: C3 binds to bacterial cell wall components (LPS) → C3 autoactivation

Question 14

C3 activation to MAC formation to bacterial killing

Answer 14

C3 activation → final common pathway C5-9 → MAC formation → MAC makes pores in bacteria

Question 15

Steps of innate immunity before pathogen killing

Answer 15

1. Phagocyte recruitment
2. Microorganism recognition
3. Opsonisation → endocytosis
4. Phagolysosome

Question 16

Phagocyte recruitment process

Answer 16

Cellular damage and bacterial products → local cyto/chemokines production
Cytokines → increased vascular permeability
Chemokines → attract phagocytes

Question 17

Microorganism recognition process

Answer 17

TLR and MR - recognise PAMPs
FcR - immune complexes

Question 18

Opsonin examples

Answer 18

Antibodies binding to FcR
Complement components binding to CR1
Acute phase proteins

Question 19

Microbial Killing mechanisms

Answer 19

1. Oxidative
   NADPHo → ROS (superoxide and H2O2)
   MPO - H2O2 + Cl- → HOCl
   HOCl kills
2. Non-oxidative
   lysozyme and lactoferrin in different specific granules → broad coverage

Question 20

Phagocyte death process and abscess formation

Answer 20

Neutrophil glycogen depleted → cell death → release of residual enzymes → liquefaction → pus formation (dead neutrophil accumulation) → abscess formation