I know pornography when I see it. Innate Immunity 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 OldestLargestDiverse

Genetic resistance to disease Malaria: sickle cell anemia, thalesemia, duffy coat, G6PDH Cholera: cystic fibrosis AIDS: CCR5

Glucose 6-phosphate dehydrogenase (G6PDH) Most polymorphic human gene. Principal source of reducing power. Glucose-6-phosphate6-phosphogluconate NADPNADPH

Malaria and polymorphisms coincide

G6PDH protects against severe malaria infections Severe malaria sufferers are less likely than control groups to be heterozygous or hemizygous for G6PDH. 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 G6PDH deficient patients Meals, mothers milk, pollen Staple food in areas where G6PDH 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 G6PDH deficiency patients

Results Normal RBC + vicine: 1 +/ Hemizygous G6PDH0.76 +/ Homozyogous G6PDH0.33 +/

Equilibrium is shifted oxidationreduction Plasmodium does poorly under oxidizing conditions G6PDH Fava beans

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 uM Rodococcus rhodnii 500 uM Trypanosoma cruzi 150 uM

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 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 expressing single 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.