Immunity relatively inefficient

Helminths are much adapted

Most helminths extracellular & too large for phagocytosis

Growth is not exponential

Usually mild infections

No division inside host

Do not pose imminent threat

Over-dispersion.

Immunity relatively inefficient

Helminths are much adapted

Most helminths extracellular & too large for phagocytosis

Growth is not exponential

Usually mild infections

No division inside host

Do not pose imminent threat

Over-dispersion.

1.Host:AGE

SEX

Genetic makeup –HbA to HbB : More superior in resistance to H.contortus and O.ostertagii

Enhanced resistance to Cooperia oncophora in Zebu as compared to European cattle

Fasciola gigantica resistance in Indonesian thin tailed sheep (Hansen et al,1999)

Greater production of Th2-like cytokines (IL-4, IL-5, IL-13) in resistant breeds to Haemonchus contortus (Sallé et al 2014)

2.Parasite: Presence of adult worm delays larval development if a new infection takes place

as in E. granulosus in sheep and T saginata in cattle

Interspecific competition between helminths for nutrient and habitat

Humoral:Usually IgE mediated

Cell mediated Immunity can be transferred to naïve animals by transfer of lymphoid

cells of infected animals and infected animals show DTH in Trichinella spiralis (Wakelin, 1978)

Immunity can be transferred to naïve animals by both lymphocytes and serum in Trichostrongylus colubriformes

(J. K. Dineen and B. M. Wagland …1996)

Immunity can be transferred to syngenic sheep by transfer of lymphocytes in Haemonchus contortus. (Smith WD et al 1984)

*Dominance of Th1 or Th2 depends on :

Antigen presenting cell type

Co-stimulatory molecules

Cytokines

Nature and dose of parasite antigen

*Dominance of Th1 or Th2 depends on :

Antigen presenting cell type

Co-stimulatory molecules

Cytokines

Nature and dose of parasite antigen

Type 1 immunity

Usually found in early stages of helminth infection and larval migration.

Few examples are:Dead cysts of Taenia solium (E. Sciutto et al, 2000)

Peri-oval granuloma formation in Schistosoma mansoni (E. J. Pearce et

al….1991)

Th1-like responses might act on migrating larvae of Fasciola spp through the liver parenchyma (E Moreau et al …..2010)

Usually found in early stages of helminth infection and larval migration.

Few examples are:Dead cysts of Taenia solium (E. Sciutto et al, 2000)

Peri-oval granuloma formation in Schistosoma mansoni (E. J. Pearce et

al….1991)

Th1-like responses might act on migrating larvae of Fasciola spp through the liver parenchyma (E Moreau et al …..2010)

Journal of NeuroimmunologyVolume 127, Issues 1–2, June 2002

The Journal of Experimental Medicine " Volume 173 January 1991

Journal of Biomedicine and Biotechnology (2010)

Highly complex multicellular, multifactorial system

Refers to combined immune response, which includes both innate and adaptive components.

Regulated by Th2 cells

Cytokines IL-4,IL-5,IL-9,IL-13.

Characterized by:

Highly complex multicellular, multifactorial system

Refers to combined immune response, which includes both innate and adaptive components.

Regulated by Th2 cells

Cytokines IL-4,IL-5,IL-9,IL-13.

Characterized by:

B cell proliferationAntibody productionClass switchingEosinophilia and Mastocytosis

IL-33

TSLP

IL-25

Source: Secreted by epithelial cells and other cell types (Th2

and mast cells) Functions:

IL-25 induces the production of other cytokines, including IL-4, IL-5 and IL-13  in multiple tissues, which stimulate the expansion of Eosinophils

All three alarmins promote Th2 responses through their ability to induce Th2 cytokine production from ILC2s. (Natural helper cells, Nuocytes )

ILC2s like Th2 cells can produce IL-5, IL-9 and IL-13.

. Nat Rev Immunol 2011;11:375–88.

.

Source: Th2 cells

Mast cells

Eosinophils

NK cells

Functions: Key role in the differentiation, maturation, and survival of eosinophils derived from bone marrow precursors.

IL-5 has been shown to act on mast cell and basophil to release vasoactive mediators

Source: Th2 cells

Mast cells

Eosinophils

NK cells

Functions: Key role in the differentiation, maturation, and survival of eosinophils derived from bone marrow precursors.

IL-5 has been shown to act on mast cell and basophil to release vasoactive mediators

The Journal of ImmunologyMarch 15, 2011

*Sources:*Primarily produced by Monocytes

*To a lesser extent by:

Type 2 T helper cells (TH2),

Mast cells

Treg cells

*Sources:*Primarily produced by Monocytes

*To a lesser extent by:

Type 2 T helper cells (TH2),

Mast cells

Treg cells

Specifically defined macrophages that respond to signalling through the IL-4R alpha.

Have 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

IL-4 strongly induces a non-inflammatory response from AAM..

Specifically defined macrophages that respond to signalling through the IL-4R alpha.

Have 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

IL-4 strongly induces a non-inflammatory response from AAM..

Arginase .Arginase suppresses the NO mediated anti-microbial pathways of classically activated macrophages.

RELM-α ::Stimulation  of  collagen  production  in  myofibroblasts (providing  a  potential  link  between  alternatively  activated macrophages, fibrosis, and tissue repair

RELM β : Intestinal  goblet  cells  up  regulate  and  secrete RELM-β  under the control of IL-13 signalling through the  IL-4 receptor.

Arginase .Arginase suppresses the NO mediated anti-microbial pathways of classically activated macrophages.

RELM-α ::Stimulation  of  collagen  production  in  myofibroblasts (providing  a  potential  link  between  alternatively  activated macrophages, fibrosis, and tissue repair

RELM β : Intestinal  goblet  cells  up  regulate  and  secrete RELM-β  under the control of IL-13 signalling through the  IL-4 receptor.

.

*The factors involved in the activation of eosinophils

*Granulocyte-macrophage colony-stimulating factor (GM-CSF) 

*EAF ; Eosinophil Activating Factor

*PAF ; Platelet-Activation Factor

Text book of veterinary immunology 9th edition Ian R Tizzard

Cellular and Molecular Immunology 7th edition

.

Text book of veterinary immunology 9th edition Ian R Tizzard

EPO: oxidants and NOECP,ENT: Ribonucleases

Potent inflammatory cells that are distributed throughout mucosal barrier tissues

Mucosal mast cell proteinases are secreted in serum and local intestinal secretions during expulsion of GI nematodes

(Woodbury et al., 1984)

MCs play an important role as late-stage effectors

Mastocytosis controlled by IL3, IL9 and other stem cell factors

Potent inflammatory cells that are distributed throughout mucosal barrier tissues

Mucosal mast cell proteinases are secreted in serum and local intestinal secretions during expulsion of GI nematodes

(Woodbury et al., 1984)

MCs play an important role as late-stage effectors

Mastocytosis controlled by IL3, IL9 and other stem cell factors

.

Mast cells

Histamine 5HT Proteinases Prostaglandins Leucotrienes

Increased mucosal permeability/SM contraction

Immunity against helminths differs from bacterial and viral immunity

Helminths typically induce Type 2 immune response through the production of cytokines IL-4,IL-5,IL-9,IL-10, and IL-13.

Th1 responses are found only in early stages like larval migration.

Type 2 response is non inflammatory response.

Interleukins act on both innate effector cells and adaptive effector cells.

AAM plays main role in tissue repair through IL-4 and IL-13.

Eosinophils play role in parasite killing

Interleukins hence lead parasite killing, expulsion and tissue repair

Immunity against helminths differs from bacterial and viral immunity

Helminths typically induce Type 2 immune response through the production of cytokines IL-4,IL-5,IL-9,IL-10, and IL-13.

Th1 responses are found only in early stages like larval migration.

Type 2 response is non inflammatory response.

Interleukins act on both innate effector cells and adaptive effector cells.

AAM plays main role in tissue repair through IL-4 and IL-13.

Eosinophils play role in parasite killing

Interleukins hence lead parasite killing, expulsion and tissue repair

[1] Immunology of Parasitic Helminth Infections :Andrew S. MacDonald, MariaIlma Araujo, and Edward J. Pearce INFECTION AND IMMUNITY, Feb. 2002, p. 427–433[2] Protective immune mechanisms in helminth infection Robert M. Anthony, Laura I. Rutitzky, Joseph F. Urban Jr, Miguel J. Stadecker‡, and William C. Gause|| Eur J Immunol. 2003 Sep;33(9):2382-90[3] Anthony RM, Rutitzky LI, Urban JF, Stadecker MJ, Gause WC. Protective immune mechanisms in helminth infection. Nat Rev Immunol 2007;7:975–87. [4] Licona-Limón P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 2013;14:536–42.[5] Saenz SA, Taylor BC, Artis D. Welcome to the neighbourhood: epithelial cell derived cytokines license innate and adaptive immune responses at mucosal sites. Immunol Rev 2008;226:172–90.[6] 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. (7) Allen JE, Maizels RM. Diversity and dialogue in immunity to helminths. Nat Rev Immunol 2011;11:375–88. (8) Tom N. McNeilly,and Alasdair J. Nisbet Immune modulation by helminth parasites of ruminants: implications for vaccine development and host immune competence Tom N. McNeilly, and Alasdair J. Nisbet Parasite 2014, 21, 51(9) Ian R Tizzard Textbook of veterinary immunology 9th edition

[1] Immunology of Parasitic Helminth Infections :Andrew S. MacDonald, MariaIlma Araujo, and Edward J. Pearce INFECTION AND IMMUNITY, Feb. 2002, p. 427–433[2] Protective immune mechanisms in helminth infection Robert M. Anthony, Laura I. Rutitzky, Joseph F. Urban Jr, Miguel J. Stadecker‡, and William C. Gause|| Eur J Immunol. 2003 Sep;33(9):2382-90[3] Anthony RM, Rutitzky LI, Urban JF, Stadecker MJ, Gause WC. Protective immune mechanisms in helminth infection. Nat Rev Immunol 2007;7:975–87. [4] Licona-Limón P, Kim LK, Palm NW, Flavell RA. TH2, allergy and group 2 innate lymphoid cells. Nat Immunol 2013;14:536–42.[5] Saenz SA, Taylor BC, Artis D. Welcome to the neighbourhood: epithelial cell derived cytokines license innate and adaptive immune responses at mucosal sites. Immunol Rev 2008;226:172–90.[6] 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. (7) Allen JE, Maizels RM. Diversity and dialogue in immunity to helminths. Nat Rev Immunol 2011;11:375–88. (8) Tom N. McNeilly,and Alasdair J. Nisbet Immune modulation by helminth parasites of ruminants: implications for vaccine development and host immune competence Tom N. McNeilly, and Alasdair J. Nisbet Parasite 2014, 21, 51(9) Ian R Tizzard Textbook of veterinary immunology 9th edition