BSCI422 Immunology January 26, 2010
Introduction to the class Went over syllabus Student expectations
BSCI422 Immunology January 27, 2010
Innate Immunity, the signal transduction and cytokine production When you’re exposed to a microbe, your body has innate immune responses that can kill the microbe right away, there is no recovery or memory period. It is the very first response. If you amount an affective innate immune response, you don't need to develop an adaptive immune response. In reality, most cases, you get infected and the innate immune responses deal with some of the microbe and those that survive go on to cause an infection and so immunological memory kicks in. You need innate immunity first. Innate immunity does two things: Kills the microbe right off the bat. Prevents any infection Or helps to generate an adaptive immune response
Characteristics: Recognize specific molecular patterns associated with pathogens, Pathogen associated molecular patterns (PAMPS). So the innate immune response is less specific than the adaptive immune response. It just recognizes general molecular patterns. This immunity is encoded in our germ line. The way we make T cell receptors by rearranging out DNA to have an infinite number of different antigenic specificity. We can recognize essentially anything. We all have the same receptors, they are wired to our genome. Example: Gram Negative Bacteria They have lipopolysaccaride on outer cleave and it is recognized by our innate immune response.
Where it all started: 1996 A fruit fly was killed by a fungi because it had no innate immunity. The molecule that fruit fly was lacking was called TOLL. This was the first evidence that the gene that contributed to the innate immune response was similar to a molecule in our own genes. In our bodies, they are referred to as TOLL Like Receptors (TLR). The signal transduction pathway was then developed in 2000. There are 11 TLRs. Each binds to different molecular patterns upon recognition. The most important is TLR4 which binds to an adapter molecule which then signals a kinase cascade. A kinase phoysphorylates substrates. So there is phosphorylation of downstream substrates that activate them.
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When you activate this pathway, you turn on a set of transcription factors that induce the immune response genes. One of these transcription factors is NF-kB. NF-kB: A set of transcription factors which will sit on the promoter of an immune response gene and induce the transcription of the genes. Long story short: TLR are encoded in the genome and they recognize molecular patterns and therefore pathogens associated with patterns and they activate a set of transcription factors called NF-kB. NF-kB turns on two general classes of immune molecules: *Cytokines *Co-stimulatory molecules Some TLReceptors are located on outside of the cell. Some of them are located in the inside of the cell in vacules or endosomal compartments. They are sitting in the cytosol so foreign proteins can be recognized outside the cell or inside the cell. MEMORIZE ALL 11 OF THE TLR, but stress TLR4, TLR2, TLR9 TLR4 recognizes lipopolysaccarides, which is on negative gram bacteria. TLR2 recognizes peptidoglycan from bacteria. We don't have these substances so we can know something is wrong if we encounter them.
TLR 5 recognizes bacterial flagella and we do not have flagella.
Some TLR recognize single stranded RNA and double stranded RNA. Our bodies have single stranded RNA (messenger RNA) so the single stranded RNA can sometimes be exposed to these TLR and we amount an immune response. But they don't only recognize foreign substances but also self but usually self is sequestered away from it in a healthy cell.
Structure: All of 11 of these TLreceptors have leucine rich repeat motifs and can recognize different ligands. Their backbone looks like...
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