2. Intestinal Immune System

mLN = mesentic lymph nodes

GALT = gut associated lympoid tissue

• Immunantwort wird hier gestartet

Isolated lymphoid follicles

• respiratory (lungs, nasopharyngeal …)

• genito-urinary tract (uterus, bladder …)

• gastrointestinal tract (stoamach …)

• ocular mucosa (eye, conjunctiva)

• skin 2m^2

• respiratory 100m^2

darm

• mucosa (schleimhaut)

• submucosa

• muscularis

1. inductive -> immunse response is initiated

2. effector -> immune repsonses acts

• epithelium

• laminate propria (inside)

• muscularis mucosa

• villus (typical illeum (small intestine))

• crypt (typical colon (large intestine))

1. Epithelia

2. Stromal cells

3. Immune cells

Epithelium: Epithelial and Immune Cells

Lamina Proprialisiertes: Stromal and Immune Cells

• provides a barrier towards outside - tight junctions keep microbes out while allowing transport/diffusion of nutrients/air across epithelium

• renewed every 3-5 days

1. enterocyte -> major cell in surface

2. goblet cells -> major mucous producing cell

3. tuft cells -> chemosensory, very rare, morphologically unique (molucelary very similar to taste cells in oral cavity)

4. Paneth cells -> produces antimicrobielles Peptides and stem cell differentiation factors

1. Barrier formation

   • produce AMP

   • transport of IgA

   • tight junctions seal the luminal contents from microbiota spilling in

2. innate immunity

   • IEC ecpress PRR (pattern recognition receptors) and sense viral and bacterial products initiating innate immune responses

3. immunoregulatory

   • in response to both commensals and infections, IECs can produce various cytokines that impact on immune cells homeostasis or their activation during nfection and inflammation

1. tuft cells sense infections & produce the cytokine IL-25 in the intestinal mucosa

2. IL-25 promotes ILC2 expansion and release of IL-13

3. IL-13 expands tuft cells and induces mucous production by goblet cells leadting to helminth explusion

Sitting on layer of stromal cells

• fibroblasts

• myofibroblasts

• pericytes

• smooth muscle cells

• provide structure/scaffold and ECM (Extracellular Matrix, the structural and signaling network outside cells that supports tissues, stores cytokines, and regulates immune responses and repair.) (we assume this)

• present antigen

• sense infection and commensal trhough TLR (toll like receptor, special angeborenen PRR )

• maintain the intestinal stem cell niche

• establish the BMP/WNT gradient (of stemm cells)

• nurturing vessels

• important during morphogenesis

• express chemokines and ctokines receptors

• express prr and cytokines

• altered in IBD/DSS

• most nummerous cell type in LP

• support epihelial and immune cells by growth factors and structure

• necessary for galt

• cricle (adentitial cells -> smc -> endothelia)

• submucosa arround bigger vessels

• nurture the vessels with growth factors

• express several immune relevant genes

• contractile (smaller vessels) and non-contractile (larger vessels)

• surround blood vessels

• support and growth/survival factors for vessels

• found surrounding larger vessels

• providing central structure in the villus

• in gut wall performing peristalsis

Presence of a large number of leukoytes in the normal intestine

• intraepithelial lymphocytes (IEL)

• lamina propria

• almost all t cells >85% cd8+ t cells

• largest population of tcells in a body

1. induced IELs (t-cells (CD8/CD4) -> signal -> IEL)

   1. requier Ag for respond

   2. considered one of the first lines of defense

   3. CDab and sometimes develop to CDaa

   4. memory is mostly associated with rapid activations and inante like properties

2. natural IELs (out of thymus)

   1. many aß (CD8+) reacht to self Ag but most yd t cells

   2. cytotocix

   3. CDaa

   4. respond to tissue stress

• lymphocytes: Tcells, Bcells, innate lymphoid cells, nk cells

• phagocytes: dendritic cells and macrophages

• granulocytes: neutrophils, eosinophils, basophils, mast cells

ab T cells:

• major pathogenic role in inflammation

• antigen specific

yd T cells:

• can have innate and adaptive roles

• 
  

• mostly IgA producing plasma cells

• 3-4 g IgA daily - 75% total Ig production

• important in non invasive or locally invasive infections and in preventin reinfection

• innate protection, critical for innfection

• critical for tissue homeostasis

NK cells:

• key cytotoxic role in infection and cancer

NKT cells:

• invariant TCR recognizes glycolipids in the context of CD1d

• can respon to cytokines independent of TCR

MAIT cells:

• mucosal associated invariant T cells

• semi-invariant TCR recognizes pyrimidine-like derivative of the riboflavin biosynthesis in the context of MR1

• can respon to cytokines independent of TCR

1. Conventional Dendritic Cells

   • prof. antigen presenting cells

   • migrate to draining lmyph nodes ot initiate adaptive immune responses

1. Macrophages

   • innate protection, critical for infection

   • pathogenic role in inflammation (overaktive etc)

   • critical for tissue homeostasis, protective during inflammation

   • APCs

• neutrophils, eosinophils, basophils, mast cells

task:

-> recruited in response to infection/inflammation

-> release cytotoxic granules evolved to kill pathogens

1. Segmented Filamentous Bacteris reuire for gut Th17

2. Microbiota reuired to supress Th2 responses

3. Clostridia required for gut IL 10 producing Treg

• mesentric lymph nodes

• GALT - Gut associated Lymphoid Tissue

  • Peyer´s Patches

  • Cryptopatches

  • Isolated lymphoid follicles

1:

• tyhmus

• bone marrow

2:

• lymph nodes

• spleen

• GALT ( Peyersches patches +ILF)

1. resident DC

   • permanetly in mLN

   • sample Antigen (AG) trapped in mLN

2. migratory DC

   • in gut Lamina Propria

   • sample Ag from tissue

   • transport Ag to mLN

1. cDC1 present to naive Tcell that develop into Th1 and spread IFNy also they develop to CD8 which spread IFNy/gzB

2. cDC2 present naive T cell that develop into Th2 that spread IL13/4/5 and naive T cell can also develop into Th17 (mainly) that spread IL17/22

1. Microfold cells transport antigen from the gut lumen to the subepithelial dome

2. DCs in SED capture Ag and present to T calls and B cells

• develop after brith during neontal life

• CP: mostly LTi (lymphoid tissue induced) cells and some DCs

• ILF: monstly B cells, T cells and DCs