An introduction to innate immunity

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1 An introduction to innate immunity Hans-Peter Duerr Department of Medical Biometry University of Tübingen, Germany Tübingen, 27. April / 17

2 Motive: superinfection with helminths Parasite establishment rate (PER) [ established parasites ] year O. v. incidence (<=40ys) "Proportional" immune response (PER = 10-3 IR) Protective immune 0.0 response ATP Infection rate (IR) ["offered" parasites per year] Proportional but decreasing immune response The problem with a proportionally acting immune response: IR = 100, PER = parasites are eliminated by the immune response IR = 1000, PER = parasites are eliminated by the immune response 2 / 17

3 Program Part I: Biology of (innate) immunity Part II: Observations & Hypotheses Miscellaneous: Immunosenscence Immunouppression 3 / 17

4 Relevance for modeling immunity publications "innate immunity" 3365 publications immun* & math* & model 488 publications innate & immun* & math* & model 13 publications 4 / 17

5 Pathogens Bacteria Viruses Parasites, Protozoa Fungi Proteins, Prions Cancer cells 5 / 17

6 Innate & adaptive immunity Innate Immunity is fast (hours) is genetically based and inheritable is nonspecific: All antigens are attacked pretty much equally no memory evolutionary "old" Adaptive Immunity is slow, delayed (days) receptors are somatically encoded is highly specific via antibodies memory, can last life-long evolutionary "young" 6 / 17

7 First-line defense: Physical and chemical barriers Saliva, tears, nasal secretions: contain lysozyme, destroys Gram positive bacterial cell walls. Lactoperoxidase: enzyme found in mother's milk. Lungs: ciliary action; coughing and sneezing. Hair follicles secrete sebum ("Talg") that contains lactic acid and fatty acids: inhibit the growth of some pathogenic bacteria and fungi. Skin: mechanical barrier, secretions inhibit growth of organisms. Stomach: hydrochloric acid (0.9 < ph < 3.0) and proteindigesting enzymes Sticky mucus in respiratory and gastrointestinal tracts. 7 / 17

8 Second-line defense: Phagocytic cells & CK's Granulocytes (polymorphonuclear leukocytes, PML) Natural killer cells Makrophages Cytokines (Interleukines, IFN, TNF): messenger substances of the immune system 8 / 17

9 Interaction between innate and adaptive immune system Dendritic cells e.g. Macrophages APCs (antigen-presenting cells) Lymphocytes become interact with T B Innate immune system Adaptive immune system 9 / 17

10 Hypotheses & observations Infection rate Infection dose Evolutionary "old" pathogens: viruses protozoa Infection rate Evolutionary "young" pathogens: metazoa ("parasites") Infection dose 10 / 17

11 Hypothesis on controlled superinfection A Protection Susceptibility threshold Time B Protection Susceptibility threshold Time C Protection Susceptibility threshold Time Infection rate A B C Legend Host protected against superinfection Host susceptible due to loss of immunity "Unsuccessful" parasite (becomes neutralised) Infection pressure "Successful" parasite (leads to infection) 11 / 17

12 Modifications of controlled superinfection Magnitude of the immunological response diminishes over time due to influences of suppressing or degenerating immunity (infection, age) Protection Susceptibility threshold Time Threshold of susceptibility decreases with time due to influences of suppressing or degenerating immunity (infection, age) Protection Susceptibility threshold Time Legend Host protected against superinfection Host susceptible due to loss of immunity "Unsuccessful" parasite (becomes neutralised) "Successful" parasite (leads to infection) 12 / 17

13 Hypotheses & observations Infection rate Infection dose Multiple (instable) equilibriae? 13 / 17

14 Outlook DFG-Projekt: Mathematische Modelle zum Infektionsprozess bei Filariosen und seine Bedeutung für die großen Bekämpfungsprogramme APOC und GPELF days 14 / 17

15 Hans-Peter Duerr Universität Tübingen Institut für Medizinische Biometrie 15 / 17

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