Innate Immunity I know pornography when I see
- Slides: 33
Innate Immunity I know pornography when I see it. I know a pathogen when I see it.
Definition • Natural ability to fight pathogens. • Acts rapidly. • Does not depend upon previous contact with the pathogen.
Don’t let your competition define you • Textbook definition of innate immunity: non -clonal immune defenses. • It is the adaptive immune response that needs a special definition as it is the most recent addition to our repertoire.
Adaptive immunity is a recent arrival from an evolutionary point of view
Organisms do well without an adaptive immune response Oldest Largest Diverse http: //Bee. Lab. cas. psu. edu
Genetic resistance to disease • Malaria: sickle cell anemia, thalesemia, duffy coat, G 6 PDH • Cholera: cystic fibrosis • AIDS: CCR 5
Glucose 6 -phosphate dehydrogenase (G 6 PDH) • Most polymorphic human gene. • Principal source of reducing power. Glucose-6 -phosphate NADP 6 -phosphogluconate NADPH
Malaria and polymorphisms coincide
G 6 PDH protects against severe malaria infections • Severe malaria sufferers are less likely than control groups to be heterozygous or hemizygous for G 6 PDH. • Female heterozygotes odds ratio: 0. 54 • Male hemizygous odds ratio: 0. 42
The deficiency has some costs • Severe jaundice at birth • Hemolytic anemia • Severe sensitivity to free radical production
Pythagoras: “avoid the bean”
Fava beans and favism • Fava beans can cause hemolytic anemia in G 6 PDH deficient patients • Meals, mothers milk, pollen • Staple food in areas where • G 6 PDH is prevelant
Fava bean active ingredients • Two pro-oxidants: vicine and convicine • Glycosidase releases active compounds which can react to produce H 2 O 2. • Normally these are reduced by glutathione which is reduced by NADPH • All of this happens at a slower rate in G 6 PDH deficiency patients
Results • Normal RBC + vicine: • Hemizygous G 6 PDH • Homozyogous G 6 PDH 1 +/- 0. 053 0. 76 +/- 0. 043 0. 33 +/- 0. 103
Equilibrium is shifted reduction oxidation G 6 PDH Fava beans Plasmodium does poorly under oxidizing conditions
Main points • Genetics of host is critical in defining the disease. • Behavior can modify natural susceptibility.
Flora and Disease • Body ecology can prevent disease • Microorganisms occupy and defend their niche. • This can be use in an applied manner.
Chagas Disease: Trypanosoma cruzi
How do you know it is a symbiont? • Grow the bugs axenically - fail to thrive • Add back bacteria to their food.
What antimicrobial do you use • • Antimicrobial peptide Ecoli 23 u. M Rodococcus rhodnii 500 u. M Trypanosoma cruzi 150 u. M
Transform gut bacteria with cecropin • • • Create a shuttle vector Clone in cecropin Transform bacteria Introduce to insect Stability is an expected problem.
Paratransgenic triatomines cannot vector T. cruzi In hindgut
Triatomines are caprophagic Cruzigard; seeded mock bug frass
Other applications of this model • BT corn: proteinaceous toxin cloned into corn to kill insect pests. • Mosquito expressingle chain antibody against Plasmodium. • Mosquito expressing peptide blocking Plasmodium binding.
Main points • Flora is an important part of an immune system. • Flora can be manipulated.
Parasite defense
Parsitoid wasps lay eggs in insect hosts
Process reconstructed in vitro • Cells purified based upon size and adhesive properties • Plastic bead used as surrogate egg • Monoclonal antibodies raised against different cell types • Factors affecting cell behavior purified
Bead encapsulation
Wasp carries a provirus • • • Polydna virus Poly disperse DNA virus Made only in calyx Injected into larva with egg and toxin Induces apoptosis of granular cells only
How don you demonstrate viral activity • Apoptosis seen in blood cells in natural infection • Add calyx extracts to purified cells and perform tunel assays
Main points • Complex cellular interactions are used to destroy parasites • Apoptosis can be used by the host to prevent the spread of infection. • Apoptosis can also be used by the parasite to destroy the immune system.
- Difference between acquired immunity and innate immunity
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- Cell mediated immunity
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