The Immune Response In Time and Space

Question 1

The Immune System at Rest

Answer 1

• barrier establishment and evolution
• Leukocyte proliferation
• lymphocyte development
• complement production and circulation
• lymphocyte recirculation
• pre-emptive immunity at mucosal surfaces(Macs, DC, Mc cells)

Question 2

components of the immediate innate response

Answer 2

antimicrobial peptides

complement

Question 3

components of induced innate response

Answer 3

mac and DC cell activation
acute phase and interferon response
neutrophil infiltration
NK cell response

Question 4

adaptive immunity components

Answer 4

T cell activation and differentiation
B cell activation and differentiation
antibody production by plasma cells
CD8 T cell cytotoxicity

Question 5

what are the barriers that protect internal tissues

Answer 5

mucosal surfaces(GI, UG, respiratory tracts) 
epidermal

Question 6

what are the three compartments of mucosal tissues

Answer 6

1. epithelium
2. lamina propria
3. MALTs

Question 7

what cells are in the epithelial layer of the mucosa

Answer 7

-Intraepithelial lymphocytes:
gamma/delta cells
CD8 alpha/alpha cells
memory CD8 T cells

Question 8

what cells are in the lamina propria?

Answer 8

lymphatic tissue
gamma/delta T cells
CD8
CD4 (Th1 and Th17, T reg)
plasma cells and memory B cells
macs
DCs

Question 9

Mucosal-associated lymphoid tissue

Answer 9

specialized per mucosal tissue

lymph node-like organization

Question 10

barriers produce antimicrobial Peptides to do what?

Answer 10

destroy pathogens
select commensal communities
initiate inflammation

Question 11

what does calprotetin do?

Answer 11

binds and sequesters divalent cations to limit growth of bacteria and fungi

Question 12

what do cathelicidins do?

Answer 12

disrupts membranes of bacteria: additional toxic effects intracellularly killing cells

Question 13

what do surfactant proteins do?

Answer 13

block bacterial surface components and promotes phagocytosis

Question 14

the common myeloid precursor gives rise to what side of the immune system cells?

Answer 14

innate cells

Question 15

the common lymphoid precursor gives rise to what?

Answer 15

B cells, T cells and NK cells

Question 16

lymphocyte circulation allows for what?

Answer 16

maximizes likelihood of antigen encounter

Question 17

how long does it take for a single lymphocyte to completely circulate?

Answer 17

24 hours

Question 18

DCs are probed by how many T cells per hour?

Answer 18

5000

Question 19

once leaving the lymph nodes what percent of lymphocytes enter the lymph and blood?

Answer 19

52% lymph

48% blood

Question 20

why strategy does our body employ for browsing in the immune system?

Answer 20

few specific cells that circulate for a long time rather than making a bunch of cells and wasting energy.
1:100,100 lymphocytes bind a presented antigen

Question 21

where are most infections stopped?

Answer 21

at the epithelium and mucosal surfaces

Question 22

what is the major difference in immunity at mucsoal surfaces compared to epithelium?

Answer 22

recruitment of neutrophils is not immediate

• inflammation is a last resort(chronic infxn, damage, large infxn)
• adaptive response is very local due to resident adaptive immune cells in the lamina propria

Question 23

mucosal immunity is pre-emptive how?

Answer 23

adaptive immunity recruited prior to pathogen entry

• adaptive immune cells located at sites of potential infxn
• mucosal surface is shaped by ongoing immunity due to:
• -antimicrobial peptides
• -IgA secretion
• -Targeted killing
• -Epithelial cell immunity
• -commensal competition

Question 24

initiation of inflammation is done by what?

Answer 24

pattern recognition

• TLRs
• complement
• CD14 (LPS)
• Mannose receptor
• SR-A/B (scavenger receptors)

Question 25

what is exudate

Answer 25

fluid that contains complement, and antimicrobial peptides

Question 26

what is the time line for immediate immune response

Answer 26

0-4 hours

Question 27

what is the time line for induce immune response

Answer 27

4 hour to 4 days

Question 28

what is the time line for adaptive immune response

Answer 28

4 days until pathogen is defeated or truce of chronic disease

Question 29

what are the three compliment pathways

Answer 29

Classical lectin alternative

Question 30

what are the three effector functions of C3b

Answer 30

opsonization MAC a components recruit phagocytic cells to site of infxn

Question 31

what are the five inflammatory cytokines released by Macrophages to promote an inflammatory response?

Answer 31

``` IL-1B TNF-alpha IL-6 CXCL8 IL-12 (up regulates receptors, IFNs, proliferation in NK) ```

Question 32

Inflammatory cytokines stimulate the liver to do what? | think of IL-6

Answer 32

make acute phase response - CRP - MBLs - Complement components - Clotting factors - Lipopolysaccharide binding proteins - inflammatory products like phospholipase A2

Question 33

what does CXCL8 do and what is the receptor?

Answer 33

it is the primary neutrophil chemokine | neutrophil CXCL8 receptor is CXCL1/2 and causes the LFA-1 to be expressed

Question 34

what are the three effector mechanisms of neutrophils?

Answer 34

phagocytosis degranulation NETs

Question 35

where does the interferon response come from?

Answer 35

immune cells or infected cells

Question 36

what are the 3 things IFNs do?

Answer 36

- induce resistance to viral replication in all cells - increase expression of ligands(stress) for receptors on NK cells - activate NK cells to kill virus infected cells

Question 37

what are the two cells that release perforin and granzyme?

Answer 37

CD8 T cells and NK cells

Question 38

what are the 3 ways NK cells kill cells?

Answer 38

granule exocytosis release death-receptors IFN gamma and NO

Question 39

what are the 3 classic antigen presenting cells?

Answer 39

DCs Macs B cells

Question 40

what T cells can act as a antigen presenting cell?

Answer 40

gamma/delta T cell

Question 41

what cells activate T cells

Answer 41

DCs

Question 42

what cells can activate B cells

Answer 42

FDCs and Macs

Question 43

what is the time line for T cell activation in a lymph node

Answer 43

min-24 hrs- Ag enters 1-24 hrs-T cell/APC interactions 24-96 hrs- T cell proliferation and differentiation 72-96 hrs: Egress of effector cells

Question 44

what is the time line for B cell activation in a lymph node?

Answer 44

minutes: Ag enters min-6 hrs- B cell/Ag interaction 6hrs- B cell migration to T cell zone 24-48 hrs-B cell prolif. and migrate to outer follicle zone 48-96 hrs- development of germinal center 72-96 hr: egress of effector cells

Question 45

what are the 3 signals for T cell activation

Answer 45

MHC with TCR and co-receptor (activation) B7 on APC with CD28 on T cell(survival) cytokine signal (differentiation)

Question 46

cytokinesis of activated T cells is how long

Answer 46

every 20 min

Question 47

T cell differentiation is dependent upon what?

Answer 47

the pathogen that activated the APC

Question 48

cytokines that induce the formation of Th1 cells

Answer 48

IL-12 | IFN-gamma

Question 49

cytokines that induce the formation of Th17

Answer 49

TGF-beta IL-16 IL-23

Question 50

cytokines that induce the formation of Th2

Answer 50

IL-4

Question 51

cytokines that induce the formation of Tfh cells

Answer 51

IL-6 | IL-21

Question 52

cytokines that induce the formation of T reg cells

Answer 52

TGF beta | lack of inflammatory cytokines

Question 53

what cells do B cells capture antigen from in lymph nodes

Answer 53

Macs and FDCs

Question 54

B and Tfh cells form cognate pairs at what location in the lymph node

Answer 54

follicle boundary

Question 55

how do Tfh cells aid in B cell activation?

Answer 55

stimulate proliferation induce centroblast formation induce class switching and SMH provide survival signals to FDC selected centroblasts induce plasma or memory cell differentiation

Question 56

what is the primary focus?

Answer 56

proliferation of IgM secreting B cells for several days driven by IL-5 and IL-6

Question 57

what is the secondary focus(germinal center)

Answer 57

B cells rapidly divide every 6 hours to form centroblasts and germinal centers driven by IL-6, IL-15 and BAFF

Question 58

what are the four effector functions of antibodies

Answer 58

virus and toxin neutralization opsonization complement fixation (classical pathway) antibody dependent cell-mediated cytotoxicity (NK and CD8 cells)

Question 59

once a CD8 T cells is activate does it need a secondary signal to kill cells?

Answer 59

nope

Question 60

cytokines released by Th1 cells?

Answer 60

``` IFN-gamma GM-CSF TNF-alpha LT IL-2 ```

Question 61

cytokines released by Th2

Answer 61

``` IL-4 IL-5 IL-10 IL-13 TGF-beta ```

Question 62

cytokines released by Tfh

Answer 62

IL-21 IL-4 IFN-gamma

Question 63

cytokines released by Th17

Answer 63

IL-17 IL-21 IL-22 IL-26

Question 64

cytokines released by T reg

Answer 64

TGF-beta IL-10 IL-35

Question 65

Routes to cell death, there are 2

Answer 65

necrosis, induces inflammation(DAMPs) and PMN recruitment -direct toxic effect -indirect toxic effect apoptosis, suppresses inflammation

Question 66

The adaptive immune system improves with time how?

Answer 66

``` B cells: -increased Ab concentration -improved Ab affinity T cells: -memory T cells -population expansion -persistence ```

Question 67

Immune resolution and repair process and cells involved

Answer 67

- inflammatory cytokine reduction - anti-inflammatory cytokines produced - T reg cell signaling and development - T cell CTLA4 expression(bind B7 on DC to inhibit T cell activation)

Question 68

inhibition of Th17 cells induces what type of T cell development?

Answer 68

T regulatory cells which release TGF-beta

Question 69

the release of TGF-beta from T reg cells does what?

Answer 69

- Th1 secrete IFN-gamma which inhibit Th2 cells | - Th2 secrete TGF-beta and IL-10 to inhibit Th1 and Macs