MCM 2-23 Gut Immunity Flashcards Preview

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Flashcards in MCM 2-23 Gut Immunity Deck (39)
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1

lamina propria

directly underneath mucousal layer of intestinal tissue. "thin plate" where most effector responses of mucosal immunity occur

2

skin vs mucosa immunity

SKIN
1. pro inflammatory macrophages and dendrites present
2. infection results in recruitment of inflammatory cells (granulocytes/monocytes)
3. Collateral (immune mediated) damage to tissue. scarring.
4. environment where invading organisms are either destroyed or sealed off (Granuloma)

Muscoca
1.Many immnune cells (lymphocytes, anti-inflammatory macrophages, dendrites) along with immunoglobulin
2. infection results in highly localized inflammation with much less recruitment
3. little to no tissue disruption
4. environment of evolving adaptive immunity where host and microbe co-exist.

3

describe mucus

provides a molecular barrier. glycosylated chains that link end to end, glycosylated allows water to bind

mucus binds to antibodies that bind to corresponding antigens. Traps microorganisms inside, carried along tract and expelled from body

4

describe goblet cells

specialized epithelial cells that produce mucous and sit in epithelium

5

describe the mucus current

deep crevace between villi are a dead pocket, as goblet cells excrete mucus, the mucus flows out and washes these crypts out

6

describe membrane bound mucus

membrane bound mucins expressed on surface of epithelial cells and bound to cells themselves.
-Non goblin epithelial cells
-forms dense layer of mucus, prevents microbes from getting to surface

resists penetration

7

membrane bound vs secreted mucus

membrane bound - thick, dense, protects absorptive epithelium

secreted - excreted by goblet cells, carries bacteria away

8

paneth cells

paneth cells are deep in the crypts of the duodenum (first segment of small intestine).

produces defensins - small peptides that form pores in microbial membranes. leasds to death if concentration high enough. concentration of defensins increases at the bottom of crypts.

9

describe how epithelial cells defect infection and respond

intenstinal absorptive epithelial cells can sense inflammation/bacteria infection with Toll-Like receptors

TLR-5 detect bacteria that have penetrated lamina propria. triggers release of short lived inflammatory cyotkiines

10

special features of intestinal macrophages

still eat and kill microbes
limits collateral damage by not performing respiratory bursts, dont produce cytokines, dont activate T cells

11

important mucus points

functions as barrier to microbial invasion through physical properties and by binding to antibody

intestinal mucus secreted by goblet cells

membrane bound mucus is produced by enterocytes and forms a dense layer, preventing microbes from reaching epithelium

12

intestinal epithelial cells recognize...

microbial invasion and can initiate localized inflammation

13

epithelial cells are turned over...

rapidly, abour every 48 hours, ending inflammatory signaling

14

mucosal macrophages are ________ but not ___________

phagocytotic but not inflammatory signalign

15

2 macroscopic anatomical structures that contribute to mucosal immunity

Waldeyers ring - structures around mouth and throat form a ring of lymphatic tissue. all bacteria entering GI and respiratory can interact with IgA

appendix - collects antigen, has lots of lymphoid follicles, allows for surveillance of large intestine microbiota

16

microscopic structures that contribute to immune response

in the intestine, areas of lymphoid tissue is called peyers patches. provide immune surveillance. Entrance to peyers patches are M cells which are folded to icnrease SA and enhance transcytosis of bacteria from lumen to peyers patch which is filled with dendrites, b cells, and t cells.

17

what do M cells do?

specialize in transporting "transcytosis" microbes and antigens through the epithelium and into underlying lymphoid tissues

18

establishment of pro-active adaptive immunity in mucous tissues

CD103+ dendritic cells found in peyers patches and mucousal lymphoid tissue

-microbes and food antigens get transcytosed through M cell.

Dendrite sees harmless food antigen (lacking danger molecules) and any t-cells that interact with the harmless food molecule are exposed to IL-10 with no co-stim = causes anergy. Antoher t-cell will be turned into a "food specific" tTreg cell by the dendrite which will express FOXP3


If it is a commensal, even then we want to form a T-cell activation. Dendrite WILL provide a costim.

T-cells actiavtd by dendritic or B cells will cooperate with B-cells, creating antibody excreting plasma cells excreting IgA

19

mucosal immunity is ________

Mucosal immunity is proactive due to the constant presence of secreted Ig’s in the mucous layer as well as well as a greater variety of immune cells (lymphocytes, macrophages, dendritic cells, etc.) in the lamina propria.

20

lymphocytes activated in one mucousal tissue will..

mature to defend all mucousal tissue. Subset of clones will go to other tissues and defend.

as mature lymphocytes leave tissue, roll along BV and come across adhesion molecules. come across moucsal tissue, enters area.

21

where are gut antibodies produced?

1. produced in lamina propria, shuttled to lumen.
2. Polymeric secretory Ig's (IgA and IgM) move through basement membrane and are bound by poly-IG-receptors on epithelial cells
3. this complex moves into the epithelial cell via RME
4. trancytosis moves complex to lumenal face of cell (apical)
5. receptor cleaves, Ig is released

can also be used for retrograde toxin transport
toxins beneath epithelial cells bind to antibodies specific to them, and the complex is moved via transcytosis to the gut lumen to be carried away.

22

M cells

Act as the gatekeeper of the Peyer’s patches (aggregations of lymphoid tissue in the small intestine). They specialize in transporting microbes and antigens through the epithelium and into underlying lymphoid tissues.

23

CD103+ Dendritic Cells

Orchestrate the response to antigens that pass through M cells via transcytosis. They help differentiate between pathogens and harmless antigens. They present antigens to naïve CD4 T cells leading to T cell activation (in response to microbial antigens), or T cell anergy and food antigen-specific Treg development (in response to food antigens). The latter (oral tolerance) is accomplished through IL-10 secretion.

24

Intraepithelial Lymphocytes

Likely poised within the epithelium to respond to viral infection. Most are alpha-beta T cells, which respond to peptides in MHC’s. Fewer are gamma-delta T cells, which are less diverse in specificity and recognize chemical signs of cellular stress as well as peptides in MHC’s; they are generally cytotoxic, but also release growth factors and cytokines that promote rapid repair.

25

CD4+ Effector Cells

Augment antibody production (by pairing with antigen-specific B cells) or activate macrophages in response to invasion. CD4 T cells activated in one Peyer’s patch will move to the other Peyer’s patches to spread the immune response.

26

tregs

Reduce responses to harmless antigens (e.g. food components).

27

what are the two forms of IgA?

IgA1 = 1 looks like L for long. more flexible long arms for better binding. many bacteria have enzymes that cleave Fc off. Found in areas of fewer bacteria (nasal passages)

IgA2 = short hinge. S looks like a 2. Evolved form of IgA that has shorter arms, cannot be cleaved by bacteria proteolysis. Hindered arm movement so does not move as well, but does not get chewed up by bacterial enzymes. Found in areas with LOTS of bacteria, like colon.

28

what allows guides lymphocytes from one mucus to defend all mucus surfaces?

cell receptors and adhesion molecules guide lymphocytes to the correct anatomical locations

29

Effects of invading pathogens vs harmless food particles?

invading pathogens cause t-cell activation, leading to IgA production

Harmless antigens lead naive T-cells to become T-regs and lead to oral tolerance.

30

appropriate T-cell differentiation is important for helminth clearance

helminth - parasitic worm

polarization of t-cells in response to parasitic worms is protective or detrimental

TH2 = produce correct cytokines to give correct response. IgE causes water excretion, pushes parasitic worms off

TH1 - interferon gamma, incorrect. but also activates macrophages which is fine for small paraistes

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