1.2 Innate Immune System

Question 1

What are the sites of infection on the extracellular part of cell?

Answer 1

Interstitial spaces, blood, and lymph

Epithelial surfaces

Question 2

What are the sites of infection in intracellular parts of the cell?

Answer 2

Cytoplasmic and vesicular

Question 3

What are the pathogenic mechanisms of tissue damage?

Answer 3

Exotoxin release
Endotoxin release
Direct cytopathic effect

Question 4

How is lymph created?

Answer 4

Interstitial fluid leaks out of capillaries and into the tissues, washing cells of body with the liquid, and now that it’s out of capillaries it’s called lymph

Question 5

Steps of the alternative pathway

Answer 5

C3 is cleaved into C3b and C3a
- Cleavage of it exposes the thioester bond and nucleophilic attack occurs at the bond
- The attack can be facilitated by water and results in soluble C3b
OR
- The attack can be facilitated by an R group and results in C3b bound to pathogen surface

Question 6

What does the C3b bound to bacteria trigger?

Answer 6

Opsonization (C3b is tagged as foreign object) which enhances phagocytosis

• C3b is englufed by endocytosis, creates a phagosome, and lysosomes kill the pathogen

Question 7

The C3b complex can also activate ___

Answer 7

C5

Question 8

What happens when C5 is activated?

Answer 8

C5 attaches to C3b complex –> splits C5 into C5b and C5a –> C5b forms a pore on the surface of the pathogen

• It forms a membrane attack complex

Question 9

Does the membrane attack complex (MAC) affect host cells?

Answer 9

No

• Protects from C9 pore forming

Question 10

Complement compounds increase ___ ___

Answer 10

Vascular permeability

• Complements flow out of blood vessels

Question 11

Defensis are what?

Answer 11

Antimicrobial peptides

• they’re secreted on mucosal surfaces to kill invaders

Question 12

What’s cell is the main source of defensis in the intestine?

Answer 12

Paneth cells

• They produce antimicrobial peptides

Question 13

What brings the defensin into the lipid bilayer?

Answer 13

Electrostatic attraction and the transmembrane electric field

• all defensins poke a hole in the membrane and form a pore

Question 14

What are TLRs?

Answer 14

• Recognize conserved pathogen molecules
• Type of pattern recognition receptor (PRR) that recognize molecules that are broadly shared by pathogens
• allows the immune system to recognize and attack non-self molecules

Question 15

Innate immune receptors recognize ___ ___

Answer 15

Microbial structures

Question 16

Recognition of microbial products through what?

Answer 16

Toll-like receptors

Question 17

TLR binding stimulates ___ production

Answer 17

Cytokine

Question 18

Describe cytokines

Answer 18

• Small secreted proteins released by host cells that act on other host cells
• Act over short distances and short time span and at low concentration

Question 19

Define chemokines

Answer 19

They’re cytokines that attract leukocytes to infection cites

Question 20

Define interferons

Answer 20

They’re cytokines that have antiviral activity

Question 21

Localization of ___ production is important

Answer 21

Cytokine

• local infection is good
• systemic infection is bad

Question 22

Describe the process of cytokine recruitment of neutrophils:

Answer 22

Neutrophils roll along the surface and binds to various ligands and interacts with LFA-1 and ICAM-1, causing tight binding

If there’s an IL8 receptor that interacts with IL8, it triggers diapedesis

• Attracts neutrophils from bone marrow to tissues where IL8 is being produced by macrophage eating bacteria

Question 23

What is IL6 effect on the liver?

Answer 23

Induces the liver to make mannose-binding lectin, fibrinogen, C-reactive protein

Question 24

What does C-reactive protein do?

Answer 24

It binds phosphocholine on bacterial surfaces and acts as an opsonin and as a complement activator

Question 25

What does mannose-binding lectin do?

Answer 25

it binds to carbohydrates on bacterial surfaces, acting as an opsonin and as a complement activator

Question 26

Process for mannose binding lectin activating complement

Answer 26

Mannose activating serine protein (MASP-2) cleaves C4 to C4a and C4b Activated MASP-2 cleaves C2 to C2a and C2b C2a binds to C4b forming C4b2a C4b2a binds C3 and cleaves it to C3a and C3b C3b binds covalently to microbial surface

Question 27

Antibody specific for a microbe can stimulate ___ to break down ___ and ___

Answer 27

C1 C4 C2

Question 28

Natural Killer cell receptors recognize what

Answer 28

Virally infected cells and kill them

Question 29

What's the process for innate viral protection?

Answer 29

Once a virus infects a cell, it induces a transcription factor that's called IRF3 Transcription factor's activated Comes in and binds DNA and induces NF(delta)B and makes interferons which can have a paracrine effect on other cells or autocrine effect on itself on IRF7 which would produce IFN-2

Question 30

Process for NK cells to eliminate infected cells

Answer 30

Virus infection of cells triggers interferon response Interferons drive the proliferation of NK cells NK cells activate NK cells induce apoptosis of infected cells

Question 31

What's the process for innate NK activation?

Answer 31

Macrophages produce cytokines that recruit and stimulate NK cells NK cell and macrophage form a pair with a synpase and IL-12 and IL-15 activate the NK cell NK cell is stimulated to divide and macrophages are stimulated to be activated NK cells secrete interferons Interferons bind to its receptors on macrophages and activates them to increase phagocytosis and secretion of inflammatory cytokines

Question 32

Process for phagocytic killing of microbes

Answer 32

Neutrophils bind bacteria, engluf them and destroy them with the toxic contents of the neutrophil granules

Question 33

What raises and lowers the pH in the phagocytic killing of microbes?

Answer 33

NADPH = raises 2H+ = lowers

Question 34

What are the cells of adaptive immunity?

Answer 34

``` NK/T cell precursor B cell T cell Plasma cell Effector cell NK cell ```

Question 35

What are the cells of innate immunity?

Answer 35

``` Neutrophil Basophil Eosinophil Monocyte Dendritic cell Macrophage Mast cell NK cell ```

Question 36

Function of dendritic cells

Answer 36

Process antigen material and present it on the cell surface to T cells