GI Immunity

Question 1

Entry into body for pathogens?

Answer 1

mucosal lining of GI tract is GREAT ENTRY POINT

- immune system puts forth a great effort into defending that area

Question 2

Central Immune System

Answer 2

Th1 response

- IgG is most common AB (75%)

Question 3

Surface Immune System

Answer 3

Th2 response

• IgA 1 and 2 are most common AB
• they are secreted into extracellular space to find and neutralize the pathogens

Question 4

Tolerance?

Answer 4

mucosal immune system is more tolerant than central because we need to get nutrients into our system!!!

Question 5

The changing ecosystem of GI tract

Answer 5

different areas of GI tract have differing pH to help protect us from pathogens
- nutrients spend most time in colon –> plenty of time for the bacteria to replicate

Question 6

GALT

Answer 6

primary site for antigen entry!!!

- GI and resp tracts harbor largest reservoirs of lymphocytes

Question 7

Layers of Defense

Answer 7

1. Intraepithelial Barrier
2. Lamina propria
3. Peyer’s Patch
4. Mesenteric Lymph Nodes

Question 8

Intraepithelial lymphocytes

Answer 8

contains effector cells –> don’t need an antigen to be presented to them

Question 9

Lamina propria

Answer 9

immune cells need to have antigen presentation

Question 10

Peyer’s Patches

Answer 10

• found in distal ileum
• allows antigens to cross so immune system can recognize them and build immunity
• M cells is specialized cell responsible for allowing antigens in which come in contact with numerous follicles enriched by B and T cells
• germinal centers are absent at birth -> develop once antigens are present

Question 11

of lymphocytes as you travel down GI tract?

Answer 11

they increase!

Question 12

Lymphocyte migration

Answer 12

itinerate –> constantly on the move

• Selectins and Integrins direct movement
• beta-7 integrin is common on mucosal lymphocytes
• extravasation controlled by chemokines, adhesions, integrins

Question 13

Role of vitamins?

Answer 13

Vitamins and metabolites can provide homing cues

• Vit D specifically for skin
• Vit A specifically for gut

Question 14

Inductor and Effector Sites

Answer 14

Inductor –> in mucosa of GI tract -> M-cells allow antigens to enter and begin selecting and activating B/T cells -> immune cells then travel to lymph nodes and get further educated -> enter blood -> travel to effector site
Effector Site –> B/T cells enter through endothelium and perform immune functions on antigens

Question 15

Isolated Lymphoid Follicles

Answer 15

• collection of lymphocytes in lamina propria

- density increases distally in GI tract

Question 16

GI defense strategies

Answer 16

1. Block entry into organism -> most pathogens
2. Block entry into cell -> bacteria/virus
3. Prohibit spreading -> most
4. Direct killing -> most
5. Kill infected cell -> virus, intracellular bacteria, protozoa
6. Expulsion -> multicellular parasites
7. Nutrient deprivation -> bacteria, protozoa

Question 17

1. Block entry into organism

Answer 17

• epithelial and mechanical barriers –> tight junctions, trefoil factors (rapid repair or perforations
• cilia-mediate expulsion -> mucins from goblet cells
• Neutralizing antibodies -> natural (IgM, IgG) or sIgA
• Antimicrobial peptide -> perforates bacterial cell walls
• Enzymes -> lysozyme and PLA2

Question 18

Penetration into host cell

Answer 18

some bacteria and viruses cross epithelium via M-cells through transcytosis

• macrophages on basolateral side engulf microbes
• strong route for vaccination

Question 19

Molecular Harbingers

Answer 19

PAMPs -> recognized by TLRs
TLR -> drive production of cytokines that cause inflammation (NFkB)
TF -> transcription factors cause nausea, fever, aches (inflammation)

Question 20

Intraepithelial Barrier

Answer 20

intraepithelial lymphocytes promote barrier repair and are rapidly recruited
- express CD8 and recognize MHC class I
2 types of TCR
1. alpha-beta (thymus derived)
2. gamma-delta (non-thymic derived)

Question 21

Lamina propria

Answer 21

Reservoir to 70-80% of total lymphocytes, predominantly CD4 recognized by MHC II

Question 22

2. Block entry into cell

Answer 22

Neutralizing Antibodies –> sterically block the pathogen adherence to host cells precluding invasion
- bacteria agglutinate

Question 23

IgA Synthesis

Answer 23

1. Normal/regular way we already learned (APCCD4 T-cellIgM –> secretes AB
2. isolated lymphoid follicles (DC presents to B-cell with BAFF)
3. Stromal cell presents to B-cell (T-cell independent)

Question 24

3. Prohibit Spreading

Answer 24

Coagulation, vaso-constriction –> vascular responses
Neutralizing ABs
Interferons Type 1 –> increase MHC I –> Cell-mediated cytotoxicity

Question 25

4. Direct Killing

Answer 25

``` Antimicrobial Peptides --> punch holes Bacterial permeability proteins --> similar to AMP Lysosomes and Stomach Environment Complement ROS, RNS --> neutrophils and macrophages ```

Question 26

Defensins

Answer 26

alpha -> neutrophils, NK cells, Paneth cells | beta -> leukocytes and epithelial cells

Question 27

5. Kill infected host cell

Answer 27

Type 1 Interferons -> induce MHC I expression | -> NK cells, NKT cells, CTL, Antibody dependent cytotoxicity

Question 28

6. Expulsion

Answer 28

``` IgE -> drives secretion of mast cells and eosinophils -> lots of mucous Vasoactive substances - LKT, PGE, Hist Mucous Smooth muscle contraction Cilia-mediated expulsion ```

Question 29

7. Nutrient Deprivation

Answer 29

Take away any of these -> shut down metabolism of pathogen - Lactoferrin --> takes away iron - Natural resistance-associated macrophage protein -> manganese - ZIP/ZnT -> Zinc - Calprotectin -> broad spectrum scavenger of divalent cations - Lipocalin -> lipids - Indoleamine 2,3-dioxygenase -> tryptophan

Question 30

Acute Inflammation mediators

Answer 30

``` Th1 Lymphocytes IFN-gamma M-1 macrophages IgG and sIgA CTL cells NK cells ```

Question 31

Chronic Inflammation mediators

Answer 31

``` Th2/Th17 lymphocytes IL-4 and IL-17 M-2 macrophages IgE Eosinophils Basophils ```

Question 32

Salmonella infection

Answer 32

1. Contacts cells with Type II secretion system (delivers toxins for step 2) 2. Subverts host cell cycle 3. Restructures cytoskeleton 4. Pronounced ruffling --> entry 5. Recovers