Mike's topics

Question 1

Inflammation

Answer 1

the immune system’s response to harmful stimuli, such as pathogens, damaged cells, toxic compounds, or irradiation

Question 2

Leukocytes

Answer 2

Types of leukocytes are granulocytes (neutrophils, eosinophils, and basophils), monocytes, and lymphocytes (T cells and B cells)

Question 3

Phagocyte types

Answer 3

Neutrophils, macrophages

Question 4

Surface receptors on neutrophils

Answer 4

Fc receptors: CD16, CD32, both binds to IgG -antigen complexes

Complement receptors: C5aR, CD35, CD18

Question 5

What are monocytes

Answer 5

Blood borne precursors of macrophages

Question 6

Opsonization

Answer 6

Process of making a microbe easier to phagocytose

Question 7

What does opsonins include

Answer 7

Complement component C3b and antibody

Question 8

Surface receptor on NK cells

Answer 8

Fc receptors: CD16

Inhibition receptor: KIR
Activation receptor: KAR

Question 9

Mechanism of NK cells being activated and kill virus infected cell?

Answer 9

Infection of cells by some viruses reduces the expression of MHC molecules, thus decreasing the loading of class I peptides in HLA-E, allowing the activation through KARs to induce NK cells killing of the infected cell

Question 10

Which mediators attract neutrophils and eosinophils

Answer 10

TNFa, IL8, IL5

Question 11

What does dendritic cells do

Answer 11

Recognize microbial antigens through innate receptors, and initiate adaptive immune response by presenting peptide antigens to T helper (CD4) cells

Question 12

Role of eosinophils

Answer 12

Mainly responsible for killing large parasites which cannot be phagocytosed

Question 13

What does phagocytes do

Answer 13

Attracted to the site of infection (chemotaxis), bind to the microbe (adhere), ingest (phagocytose), and kill the microbe

Question 14

What does NK cells do

Answer 14

Changes in the surface molecules of cells as the result of virus infection allow NK cells to bind to and kill infected cells by releasing perforins and inducing apoptosis. On binding to virus infected cells, NK cells secrete interferon gamma which protects adjacent cells from being infected

Question 15

What does mast cells and basophils do

Answer 15

When activated, these cells degranulate, releasing a pharmacological mediators which cause vasodilation, increased vascular permeability and leukocyte migration

Question 16

Type I interferon is induced by…

Answer 16

Virus; other cytokines (e.g. IL1, TNFa); intercellular bacteria and protozoans

Question 17

Type I interferon is produced by…

Answer 17

Infected leukocytes; epithelial cells, fibroblasts

Question 18

What does type I IFN do

Answer 18

Inhibit protein synthesis, mRNA translation, and DNA replication -> stop viral replication; stop cell proliferation; increase the lytic activity of NK cells; induce the expression of MHC class I molecules to induce antigen-specific cytolytic T cell response against viral infected cells

Question 19

What does IL-1, IL-6, TNF-a do

Answer 19

Increasing body temp, increase lymphocyte activation, mobilize neutrophils by increasing vascular permeability; induction of acute phase protein release (CRP, MBP) and thus complement and opsonization

Question 20

Which TLRs can recognize virus

Answer 20

TLR 243789

Question 21

Which TLR recognize viral RNA

Answer 21

TLR 378

Question 22

Cell surface TLRs

Answer 22

TLR 1245

Question 23

Endosomal TLRs

Answer 23

TLR3789 13

Question 24

Molecular mechanism of TLR4 recognition of LPS?

Answer 24

Since the interaction between TLR4 and LPS is relatively weak, it needs the help of effector proteins, namely MD-2, LBP, and CD14.
1. MD2 forms stable interactions with the extra cellular domain of TLR4, forming a functional LPS receptor complex
2. soluble LBP in the plasma bind to LPS and transfer it to either the receptor complex or to CD14
3. CD14 transports LPS-LBP to the receptor complex
4. 5/6 acetyl chains of LPS binds to the hydrophobic pocket of MD2. The rest one attach to TLR4. Two phosphate groups of LPS also bind to both TLR4 and MD2

Question 25

Examples of TLR4 recognizing viral components?

Answer 25

Influenza matrix 1 protein
RSV cell surface exposed F protein
HIV tat protein

Question 26

TLR3 is mainly expressed by

Answer 26

DC, fibroblasts, intestinal epithelial cells

Question 27

Physiological ligand for TLR3

Answer 27

RNA species of West Nile virus, encephalomyelitis virus, Zika virus, dsRNA intermediates of DNA virus such as HSV-1

Question 28

PRR

Answer 28

pattern recognition receptor, innate immune receptor that recognizes PAMPs/MAMPs and induces PAMP-trigged immunity

Question 29

PAMP

Answer 29

pathogen-associated molecular pattern, immunogenic conserved molecular motif shared across many pathogens and absent from the host, also referred to as MAMP (microbe associated molecular pattern)

Question 30

DAMP

Answer 30

immunogenic host molecule associated with host tissue damage

Question 31

six overlapping general mechanism of innate sensing

Answer 31

PTI, ETI, sensing of absence of self, sensing of altered self, damage recognition, surveillance

Question 32

examples of sensing of absence of self

Answer 32

1) NK cells and viral infected cells with decreased MHC I expression
2) CD47 being a self recognition signal, sent to macrophage and dendritic cells

Question 33

examples of sensing of altered self

Answer 33

1) cells non-autonomously induce the apoptosis of the virally infected or transformed cells
2) the detection of stressed host cells by NK cells via recognition of MICA and MICB which are induced upon viral infection

Question 35

What happens upon TLR activation

Answer 35

Once activated, TLR undergo a conformational change which leads to recruitment of adaptor proteins to the intracellular signaling domain (TIR). Adaptor proteins include MYD88, TRIF, TIRAP, or TRAM.
Downstream signaling cascade will be activated which eventually leads to the translocation of transcription factors (NF-kB, AP1, IRF3/ITF7) into the cell nucleus, resulting in the expression of key genes of the innate immune system.

Question 36

TLR3 recognize

Answer 36

Viral dsRNA
Small interfering RNA
Self-RNA derived from damaged cells

Question 37

TLR7 recognize

Answer 37

Predominantly expressed in pDCs
Recognize ssRNA from viruses

Question 38

Defining features of SLE

Answer 38

Breakdown of tolerance to nucleic acids
Activation of the interferon system

Question 39

Detailed mechanism of TLR9 activation

Answer 39

1. Upon TLR engagement, MyD88 forms a complex with IRAK protein family members. this complex is called a myddosome
2. During myddosome formation, IRAK4 activate IRAK1, which autophosphorylates and eventually released from MyD88
3. IRAK1 engage with TRAF6
4. TRAF6 catalyze the synthesis of the K-63 linked polyuniquitin chain on TRAF6 itself and the TAK1 complex
5. Activated TAK1 complex can activate 1) the NF-kB pathway: TAK1 will bind to the IKK protein complex, phosphorylate and activate IKKβ. IKK complex will phosphorylate the inhibitory factor of NF-kB -> IKBα, causing its proteosome degradation, and enable NF-kB to be released to the nucleus and start transcription of pro-inflammatory cytokines 2) MAPK pathway: activated TAK1 will also activate MAPK members such as ERK1/2, p38, and JNK, which mediate the activation of AP-1 TF which will activate proinflammatory cytokine production