Immunology

Question 1

What are the order of events in the innate immune response?

Answer 1

(1) Pathogen Recognition;
(2) Complement system activation;
(3) Cytokine and chemokine production;
(4) Recruitment of neutrophil

Question 2

How does the life span and location vary among Neutrophils and Macrophages?

Answer 2

Neutrophils: Short lived, blood stream
Macrophages: Long lived, tissues

Neutrophil life span is 6hrs - few days and the travel throughout the blood stream
Macrophages life span is Months to Years! And they stay resident in the tissues

Question 3

How does the first step of the innate immune response occur?

Answer 3

Pathogen Recognition - through the interaction of PAMPs and TLRs (PRRs)

TLRs are on the surface of cells: Macrophages/Dendritic/fibroblast..

PAMPs: Pathogen associated molecular patterns
TLRs: Toll Like Receptors
PRRs: Pattern Recognition Receptors

Question 4

What happens when PAMPs interact with TLRs

Answer 4

TLR:PAMP binding causes a signal cascade that induces an innate immune response and production of pro-inflammatory cytokines

Question 5

Which TLRs are associated with periodontal disease? What do they recognize specifically?

Answer 5

Upregulartion of TLR 2 (Lipoteichoic acid) and 4 (LPS) on Fibroblasts is associated with periodontal disease (Sarah 2003, Wang 2006)

Question 6

How does P Gingivalis interact with TLRs?

Answer 6

Its Lipid A Moity is a potent inhibitor of TLR 4 when in high iron environments.

Question 7

How can the compliment cascade be activated?

Answer 7

Classical pathway (antigen-antibody)
Lectin Pathway (Lectin binds Mannose on pathogens)
Alternative pathway (Pathogens, injured tissues)

Question 8

Where do the various pathways of the complement cascade converge? What does this result in?

Answer 8

C3 convertase - creates C3a and C3b (C3b is used for opsinization)

Question 9

What does C3b do?

Answer 9

It coats pathogens for recognition (opsinization)

Question 10

What is the final result of the complement cascade?

Answer 10

Formation of a membrane attack complex via C5b, C6, C7, C8, and C9 (C5b-9)

Question 11

How does P. Gingivalis interact with the complement system?

Answer 11

It blocks ALL pathways of the complement system via Gingipains

Degrades C5b (no MAC) but keeps C5a (tissue degredation)

Question 12

What is Autocrine, Paracrine, and Endocrine in relation to cytokines

Answer 12

Where the cytokine takes action
Autocrine - on cells that produce them
Paracrine - on nearby cells
Endocrine - on cells at distant sites

Question 13

What are the functions of cytokines?

Answer 13

4 Rs

Recognition
Recruitment
Removal - either kill the pathogen directly or induce destructive enzymes
Repair - Anti-inflammatory cytokines

Question 14

What are examples of ANTI inflammatory cytokines?

Answer 14

IL-4, IL-10, IL-1ra, TGFb

Question 15

Examples of pro-inflammatory cytokines?

Answer 15

IL-1, IL-6, IL-8, TNFa, INFg, IL-17

Question 16

Main effector of Cell Mediated Immunity?

Answer 16

T Cells

Question 17

Main effector of Humoral Immunity?

Answer 17

B cell

Question 18

Explain the process of Tcell activation

Answer 18

Pathogen phagocytosed by Antigen Presenting Cells
APCs present antigen via Major Histocompatibility Complexes (MHC I or MHC II)
MHCs present antigen to naive T cells

Question 19

Which MHCs interact with which Tcells? What is the result of each?

Answer 19

MHC1 : CD4+ = Thelper cells
MHC2 : CD8+ = cytotoxic T cells - kills infected cells

Question 20

Describe the basic design of an antibody

Answer 20

2 heavy chains
2 light chains
Fab - Vatiable antigen binding site
Fc - constant

Question 21

What are the different classes of antibodies?

Answer 21

IgM, IgG, IgA, IgD, IgE

Question 22

Where is MHC1 expressed?

Answer 22

All nucleated cells

Question 23

Where is MHCII presented?

Answer 23

All Antigen Presenting Cells

Question 24

Explain T-Cell INDEPENDENT B-cell activation

Answer 24

B-Cells have membrane bound antibodies that are Class IgM
Activation of IgM causes release of IgM antibodies
First Immunoglobulin to be released - not very specific

Question 25

Explain T-Cell DEPENDENT B-Cell Activation

Answer 25

B-Cell recognizes antigen with membrane bound antibody
Internalizes antigen
Presents antigen via MHCII (as a mature B-cell)
T-Helper Cell recognizes presented antigen on MHCII
ThCell releases cytokines
Cytokines cause transformation of B-cell to Plasma cell
Plasma cell releases various Ig’s (IgG, IgA, IgM, IgE, IgD)
Also creates memory B cells

Question 26

Which immunoglobulins are MONOMERS?

Answer 26

ALL CELL SURFACE IMMUNOGLOBULINS

Question 27

Which immunoglobulins are NOT monomers? What are they?

Answer 27

Secretory IgM - Pentamer
Secretory IgA - Dimer

Question 28

What do periodontal disease related plasma cells produce?

Answer 28

IgA, IgG, and RANKL

Question 29

What cytokines do Th-17 cells produce? What are they involved in

Answer 29

IL-17
Up regulation of RANKL

Question 30

What cytokines induce the production of Th-17s?

Answer 30

IL-12, IL-23

Question 31

What cytokines do T-regs produce? What are they involved in?

Answer 31

IL-10, TGF-β
Anti-inflammation

Question 32

(Give Citation) What Th Cells are involved in periodontal disease? How is it involved?

Answer 32

Cheng 2014
Th-17
Produces IL-17 which promotes osteoblasts, T-cells, and B-cells to produce RANKL

Question 33

(Give Citation) How is IL-17 involved in periodontal disease?

Answer 33

IL-17 upregulates production of RANKL

ALSO upregulates production of MMPs by fibroblasts (Miossec 2012)

Question 34

What are the stages of neutrophil recruitment? What is this process called?

Answer 34

Called Diapedesis

Tethering - Rolling - Adhesion - Crawling - Transmigration

Question 35

How do neutrophils adhere to endothelial cells?

Answer 35

LFA-1 and Mac-1 on surface of neutrophil
Attach to ICAM 1 and 2 on Endothelial cells

Question 36

What is Leukocyte Adhesion Deficiency type 1? What does it result in? (Pathogenesis)

Answer 36

Gene mutation: defect in LFA-1/Mac-1 : ICAM interaction
Neutrophils cannot migrate to cite of infection

Question 37

What happens if neutrophils can