HP Lecture 3

• tolerance

  maintenance of host health (fitness) at a given parasite burden (# of parasites in the host)
• virulence: the ability of a pathogen to cause disease in a host
• premunition: parasite under control as persistent latent infection; malaria, chagas
• concomitant immunity

  current parasite infection makes host resistant to related species; schistomoasis
• Immunity

  • self and nonself recognition
• hematopoietic stem cells (HSCs):

  can self renew and differentiate into terminally differentiated cell types of innate and adaptive immunity
• innate immunity- already had it (any antigens), 1st line of defense, min and hours
• adaptive immunity: found in jawed vertebrates; aquired (sp. antigen); builds up overtime; weeks and months
• memory in adaptive immunity:

  allowing it to remember a previous encounter w/ the pathogen
• Innate immunity: physical/chem barriers

  • epithelial barrier, phagocytes, natural killer cells, ILC 1,2,3 (innate lymphoid cell)
• defensins

  salt from sweat and antimicrobial peptides active against parasite and pathogens
• TLR and PAMPS (pathogen-associated molecular patterns)

  • innate immune cell receptors bind to common and essential molec. on pathogens
• inflammation- vascularized tissues response to injury/infection
• cytokines- small prtn exhibiting sp. effects on interactions, communication, and behavior btwn cells
• ILS (interleukins); IL-1

  cytokine notations, act on leukocytes
• CDS (cluster of differentiation): CD4, CD8
• CAMs( classically activated macrophages) AAMS (alternatively) : 2 major subsets
• NFKB (nuclear factor kappa B)

  pro inflammatory regulator
• PPAR (peroxisomal proliferator-activated receptor gamma

  major anti inflammatory regulator
• B cells: bursa, bone marrow

  T: thymus
• BCR: B cell receptor- mmbr-bound antibody
• IgM- complement fixation

  IgD

  IgG- major antibody

  IgA- secretory form

  IgE- worms and allergy

  immunoglobulin isotypes
• humoral immunity (b cell)- against extracellular pathogens
• gene segments- somatic recombination for Igs, vast number of diff. BCRs and TCR
• Ag (antigen)- can elicit an immune response
• clonal selection theory- initial availability of various immature lymphocytes
• T cell subsets: Th1, 2, 17, Tc: cytotoxic
• Treg- regulate immune response
• Tfh (follicular helper)

  help B cells in lymphoid follicles (w/in lymph node) to improve antibody
• MHC: restriction (major histocompatibility complex)
• Ag Presentation

  • intracellular and extracellular antigens
  • MHC
  • HLA (human leukocyte antigen)
  • Class 1: proteasome; Tc (internal), on surface
  • class 2: lysosomal cathepsins; Th (external) only APC
• APC:

  B, DC, M (B cell), dendritic cell, macrophage
• polymorphism of immune genes: product diversity against diff. (novel) pathogens
• Granulomas

  organized and compact struct

  host can't destroy parasite

  wall off parasite

  granuloma (parasite w/in host immune and other cells)

  found in parasitic protozoa and helminth infection
• Hygiene hypo

  • coevolution btwn human and parasitic worms (and other pathogens)
  • old friends hypo (worms help immune maturation, IM, immunomodulation)
  • 2 hygiene hypo (young and adult)
  • autoimmunity and allergy (due to absence of parasitic input in an clean environment(
• dysbiosis (abnormal microbiome)
• helminth therapy: add back worm/worm products

  coming of age
• IGE- worms and allergy

  • IGE and eosinophils target worms
  • metazoans parasite immunogens as IgE targets
  • prtn w/ over 63% seq identity w/ human homologs aren't allergenic
  • molec. mimicry
• Tfh13- anaphylaxis by high affinity IgE (allergens induce IGE leading to anaphylaxis

  Tfh2- worms induce low affinity IgE (worm products don't lead to anaphylaxis)
• epitopes: european white birch and ascaris prtn profilin