Innate Immunity

Question 1

What Ig would be found in the urinary tract, vagina tears, saliva

Answer 1

IgA

Question 2

List 4 potent vasodilators

Answer 2

Prostaglandins, leukotrienes, histamine, bradykinin

Question 3

What are potent inducers of fever

Answer 3

TNF, IL-1, IL-6

Question 4

How do innate immune cells distinguish self from non self Ags

Answer 4

Pathogen associated molecular patterns (PAMPs) are recognized by specialized receptors (PRRs, TLRs)

Question 5

Mannose receptors

Answer 5

Recognizes glycans with terminal mannose, which are not found on human cells

Question 6

Innate cells have a nonclonal distribution of receptors, what does this mean

Answer 6

All cells have receptors with identical specificities

Question 7

Which TLRs recognize extracellular pathogens (bacteria)

Answer 7

1, 2, 4, 5, 6

Question 8

What TLR recognizes dsRNA

Answer 8

3

Question 9

What TLR recognizes ssRNA

Answer 9

7, 8

Question 10

What TLR recognizes CpG DNA

Answer 10

9

Question 11

What are two important transcription factors activated by TLRs

Answer 11

NF-kB- promotes expression of cytokines and endothelial adhesion molecules (most important TF for inflammation)
Interferon regulatory factors IRFs- stimulate production of antiviral cytokines IFN-a/b (type I interferons)

Question 12

Which TLRs recognize fungi

Answer 12

2, 6

Question 13

MyD88 and IRAK4 deficiency

Answer 13

TLR disorders that lead to increased susceptibility to infection by bacteria or viruses

Question 14

PAMPs and inflammasomes

Answer 14

PAMPs activate inflammasomes which contain NLR. NLRs trigger activation of NF-kB and MAPK, which activates caspase-1
Caspase 1 processes precursor forms of IL-1B and IL-18 to active forms (IL-1B and IL-18 are potent proinflammatory cytokines)

Question 15

DAMPs

Answer 15

Endogenous danger molecules released from damaged or necrotic cells. Induce potent inflammatory responses by activating innate immune system during non-infections inflammation

Question 16

List 3 DAMPs released by necrotic cells

Answer 16

HMGB1
Uric Acid
Heat shock proteins

Question 17

DAMPs and autoimmunity

Answer 17

DAMPs instigate innate immune pathways that promote adaptive autoimmune responses against self-Ags which manifest as severe clinical symptoms

Question 18

List some inflammatory mediators that macrophages produce

Answer 18

Cytokines/chemokines
ROSs
NO
Prostaglandins
Defensins

Question 19

What preformed mediators are released by mast cells

Answer 19

Proteases

Histamine

Question 20

Which type of signaling can cytokines participate

Answer 20

Endocrine, paracrine, autocrine

Question 21

Macrophages may secrete which anti-inflammatory cytokines

Answer 21

IL-10, TGF-b

Question 22

What is the function of IL-8

Answer 22

Chemotactic factor for neutrophils, basophils, T cells

Question 23

What is the function of IL-12

Answer 23

Activate NK cells

Induce T cell differentiation of CD4–>Th1 cells

Question 24

Classical pathway is initiated by what

Answer 24

Binding of IgM or two IgG on a molecules surface

Question 25

Explain classical pathway steps

Answer 25

C1 binds to IgM or 2x IgG on microbe
C1 cleaves C2 and C4
C4b attaches to microbe, C2a attaches to C4b forming C3 convertase– C4bC2a
C3 convertase cleaves C3–> C3a, C3b
C3b binds microbe and C3 convertase forming C5 convertase C4bC2aC3b
C5 convertase cleaves C5 into C5a/C5b
C5b initiates MAC formation consisting of C5b, C6-C9 (multiple C9 molecules)

Question 26

What induces the secretion of acute phase proteins

Answer 26

TNF-a, IL-1, IL-6

Question 27

High blood concentrations of ___ and ____ allow more accurate laboratory detection of inflammation

Answer 27

CRP and SAA

Question 28

Where do neutrophils/monocytes enter tissue

Answer 28

Through post-capillary venules, except parenchymal tissues (liver, lung, kidneys- all blood enters through capillaries)

Question 29

TNF-a and IL-1 have what effect on endothelial cells

Answer 29

They active them, increasing surface expression of P-selectin and E-selectin, which bind PSGL-1 and ESL-1, respectively. These are constitutively expressed on neutrophils

Question 30

LFA-1 and VLA-4 method of action

Answer 30

Both are expressed in low affinity state on neutrophils. Once rolling of neutrophil on endothelium occurs, chemokines bind receptors on neutrophil and activate LFA-1/VLA-4 which bind with high affinity to ICAM-1 and VCAM-1 on endothelial cells

Question 31

Rolling is ____ dependent, while adhesion, crawling and transmigration are ____ dependent

Answer 31

Rolling- Selectin dependent

Adhesion/crawling/transmigration- Integrin dependent

Question 32

What is the most important chemokine that regulates migration/infiltration of monocytes into tissues

Answer 32

Monocyte chemoattractant protein 1 MCP-1

Question 33

M1 vs M2 macrophages

Answer 33

M1 are classically activate macrophages, induced by microbial products binding TLRs, and cytokines like IFN-y
M2 are alternatively activated Macrophages, induced by IL-4, IL-13 and involved in tissue repair/fibrosis

Question 34

Interferons trigger the killing of viruses by what methods

Answer 34

Inhibition of protein synthesis
Degradation of viral RNA
Inhibition of viral gene expression
Activation of NK cells

Question 35

NK cell activating receptors

Answer 35

KIRs, recognize stress associated molecules such as MICA and MICB

Question 36

NK cell inhibiting receptors

Answer 36

Recognize Class I MHC and inhibit the activation signal

Question 37

How do NK cells kill

Answer 37

Release perforins, then granzymes from NK cell enter hole and activate apoptosis
Macrophage then digests dying cells