Innate Immune Protection

Question 1

Define Innate Immunity

Answer 1

A non-specific defence mechanism that a host uses immediately or within several hours after exposure to antigen.

Question 2

True or False: Repeated exposure to the same antigen increases the strength and speed of the innate immune response

Answer 2

False

Innate immunity responds the eaxct same way each time as it does not confer immunological memory.

Question 3

What are some of the innate barriers to pathogen entry?

Answer 3

Skin - Thick physical barrier makes it difficult for pathogens to penetrate. Also the secretion of sebum (fatty acids) can inhibit survival of microbes on the skin.

Cilia and Mucus in the Respiratory tract.

HCL/Low pH and Acid Hydrolases in the Stomach.

Tears, sweat and saliva - Contain lysozymes which cleave between sugars of the peptidoglycan layer within bacterial cell walls

Commensal Microbiota - Outcompete harmful pathogens for adhesion space and nutrients

Question 4

What is the key protein in the complement cascade and what activates it?

Answer 4

C3 - activated by C3 convertase to produce C3a and C3b

Question 5

What are the effector fates of C3a and C3b?

Answer 5

C3a stimulates a pro-inflammatory response with C5a by stimulating Mast cells to release Histamine, which increases vascular permeability enhancing chemotaxis

C3b along with other complement proteins (C5b,C6,C7,C8,C9) forms the Membrane Attack Complex (MAC) which causes cell lysis

C3b can also form thioester bonds with the surface of pathogens. Complement receptor CR1 on macrophages can recognise the C3b proteins and bind to them, leading to phagocytosis - Opsonisation

Question 6

How do cells of the innate recognise pathogens?

Answer 6

They express Pathogen Recognition Receptors (PRRs) which can recognise Pathogen Associated Molecular Patterns (PAMPs)

PAMPs are found exclusively on non-host cells and thus provides the innate immune system with broad recognition specificity

Question 7

Give examples of common PAMPs

Answer 7

LPS on Gram -ve bacteria

Lipoteichoic acid on Gram +ve bacteria

Question 8

Give examples of common PRRs

Answer 8

Toll-like receptors - Membrane

Nod-like receptors - Cytoplasm

Collectins - Serum

Question 9

How does the structure of Collectins aid their function?

Answer 9

Collectins are made up of a collagen-like region, which interacts with effector parts of the immune system, and a lectin region, which binds to sugar molecules on the pathogen’s surface

Question 10

How many mammalian TLR homologues exist?

Answer 10

At least .10

Question 11

Which TLRs function as dimers?

Answer 11

TLR-1,2,4,6

Question 12

What do NOD 1 receptors sense?

Answer 12

Gamma-glutamyl diaminoprimelic acid in peptidoglycan only in Gram -ve bacteria.

Question 13

What do NOD 2 receptors sense?

Answer 13

Muramyl dipeptide in peptidoglycan (Both Gram bacteria)

Question 14

True or False: Macrophages are short lived and Neutrophils are long lived cells

Answer 14

False

Neutrophils are short lived

Macrophages are relatively long lived

Question 15

Describe the process of phagocytosis.

Answer 15

PRR on phagocyte recognises PAMP on pathogen.

Phagocyte extend psedopodia and engulfs the pathogen, forming a phagosome.

Lysosome fuses with phagosome to form a phagolysosome.

Digestive enzymes degrade the pathogen.

Peptide loaded onto MHC class II molecule and expressed on cell surface.

Indigestible remnants and waste materials are released from the cell by exocytosis.

Question 16

What are some non-phagocytic oxygen-dependent killing mechanisms displayed by Macrophages and Neutrophils?

Answer 16

Generation of Reactive Oxygen Species (ROS):

Post-phagocytosis, there is an increase in O2 uptake - “Respiratory Burst”.

Oxygen is reduced by NADPH oxidase to form Hydroxyl radicals and Hypochlorite.

Question 17

What protects the immune cells from the ROS that they produce?

Answer 17

They have enzymes that catalyse the converion of ROS into less harmful intermediates.

Myeloperoxidase

Superoxide dismutase

Catalase

Question 18

Describe an oxygen-independent killing mechanism used by Neutrophils and Macrophages.

Answer 18

Production of Reactive Nitrogen intermediates

O2 + L-arginine –> NO + L-citrulline

This reaction is catalysed by the enzyme NO Synthetase (iNOS), which is induced by cytokines IFN-gamma and TNF, as well as bacterial components.

Cofactor used is tetrahydrobiopterin.

Question 19

Name 2 pro-inflammatory cytokines.

Answer 19

IL-1 and IL-6

Question 20

Name the cytokine involved in the activation of macrophages.

Answer 20

TNF-alpha

Question 21

Name the cytokine involved in the activation and differentiation of CD4 T cells.

Answer 21

IL-12

Question 22

Name the other cytokine (not TNF-alpha) that activates macrophages.

Answer 22

IFN-gamma

Question 23

Name 2 chemokine produced by macrophages and endothelial cells to stimulate chemotaxis.

Answer 23

IL-8

Monocyte chemotactic protein (MCP)

Question 24

Which interferons are involved in the response to virally infected cells and what immune cell responds to these interferons?

Answer 24

Type 1 interferons - IFN-alpha & IFN-gamma

NK cells respond by killing the infected cells and producing IFN-gamma, to activate macrophages, upregulate MHC expression and together with IL-12, stimulate differentiation of CD4 Th1 cells.

Question 25

Which innate immune cells can undergo respiratory burst?

Answer 25

Neutrophils

Macrophages

Dendritic cells

NOT NK cells

Question 26

What are the activation signals required to stimulate inactive/naive T cells?

Answer 26

Signal 1 - TCR recognises antigen/peptide on MHC class II on APC.

Signal 2 - CD80/CD86 on APC recognises CD28 on T cell provides co-stimulation.