Type 2 immunity against helminths

1. Dr. Aquil Mohmad
M-5527
Host protective roles of type2 immunity :
Parasite killing and tissue repair, flip sides of
the same coin.
Minor credit seminar
Topic

2. Alerting of immune system .
Macrophages.
Eosinophils.
The effector molecules.
Adaptive immune repair.
Conclusion

3. Type2 immunity is highly complex multicellular,
multifactorial system characterized by
cytokines Il-4,IL-5,IL-9,IL-13.
T helper cells differentiate into sub
populations Th1 cells and Th2 cells.
They can be distinguished by mixture of
cytokines that they secrete.

4. Contd…

5. Contd…
TH2 type response refers
to combined immune
response, which include
both innate and adaptive
components.
This response is
produced against
helminth parasites.

6. Interleukin-33:
IL-33 is a member of the IL-1 family and its receptor ST2
is expressed on mast cells, Th2 cells and ILC2s.
 IL-33 is released in a bioactive form by dying cells and a
key mechanism by which mast cells respond to injury is
via recognition of IL-33 .

8. IL-33 promote IL-13 production by both
ILCs and CD4+ T cells, which in turn
increases production of the antiworm
effector molecule RELM by intestinal
epithelial cells.

9. TSLP is expressed predominantly by epithelial
cell.
 Expression of TSLP is constitive in lungs and
gut and promote type2 responses.

10.  TSLP receptors are expressed on dendritic
cells.
 TSLP amplifies type 2 effector responses by
enhancing the polarizing effects of IL-13 on
macrophages.
 TSLP cause suppresion of inflammatory
response.

11. Role of th2 cells in parasitic expulsion

12. Type 2 immunity in repair of
parasitic damage

13.  All three alarmins promote Th2 responses through their
ability to induce IL-5 and IL-13 production from ILC2s.
 ILC2s like Th2 cells can produce IL-5, IL-9 and IL-13.
IL-13 producing ILC2s promotes goblet cell mucus
secretion and smooth muscle contraction processes that
mediate the expulsion of helminth parasites.

14.  IL-9 and IL-5 released from ILCs increases
eosinophils and mast cells.

16.  Alternatively activated macrophages (AAM ) are
specifically defined cells that respond to signaling through
the IL-4R alpha.
Macrophages express receptors for both IL-4 and IL-13 and
their receptors share the common IL-4R chain, which is
central to most type 2 effector responses.

17. IL-4 strongly induces a
non-inflammatory response
from AAM.
AAM are important
sources of down regulatory
cytokines including TGF- ,
PGF and the IL-1 receptor
antagonist .

20. Eosinophil accumulate following
parasitic infection largely in
response to IL-5, a cytokine not
only critical for recruitment but
also eosinophil differentiation from
the bone marrow.
Eosinophil can attach to the
cuticular surface of larvae, release
damaging mediators and kill
worms in antibody and
complement dependent fashion.

22. The effector molecules
Arginase: Arginase 1 is produced by alternative
macrophage activation.
Arginase suppresses the NO mediated anti-
microbial pathways of classically activated
macrophages.

23. *
The IL-4R dependent production of arginase
contributes to tissue remodeling and repair.

24. Role of inate effector cells in repair

26. IgE immunoglobin is secreted of B-cell class switching in
response to Th2 cytokines .
The strong association of IgE with helminth infection
neutralizes proteins that cause damage such as the
parasite proteases used to migrate through the tissue.

28. Role of Th2 cells in tissue repair

31. Metazoan parasites typically induce Type 2 immune
response through the production of cytokines IL-4,IL-5
and IL-13.
Type 2 response is non inflammatory response.
Type 2 response involves both innate effector cells
and adaptive effector cells.
AAM plays main role in tissue repair through IL-4 and
IL-13.

32. References
[1] Allen JE, Maizels RM. Diversity and dialogue in immunity to helminths.
Nat Rev Immunol 2011;11:375–88.
[2] Anthony RM, Rutitzky LI, Urban JF, Stadecker MJ, Gause WC. Protective
immune mechanisms in helminth infection. Nat Rev Immunol 2007;7:975–
87.
[3] Licona-Limón P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2
innate lymphoid cells. Nat Immunol 2013;14:536–42.
[4] Saenz SA, Taylor BC, Artis D. Welcome to the neighborhood: epithelial
cellderived cytokines license innate and adaptive immune responses at
mucosal sites. Immunol Rev 2008;226:172–90.
[5] Gause WC, Wynn TA, Allen JE. Type 2 immunity and wound healing:
evolutionary refinement of adaptive immunity by helminths. Nat Rev
Immunol 2013;13:607–14.