BIOMED NOTES 24/25

signaling antigen receptors and activation of lymphocytes  1. EC signaling molecule (1st messenger) recognition by transmembrane receptor = signal transmission to effector within cytoplasm = activate second messenger/cytoplasmic domain transformed into recruiting station for signaling proteins = activate target protein = inactivate signaling molecule for cessation  - for transcription, survival, protein synthesis, movement, cell death, metabolic change  2. terminate activation to prevent hyperinflammation phosphatase shutdown (SHP-1/2) - rapidly strip phosphate group from active receptors and kinases  - dephosphorylate ITAM tyrosine on CD3, Iga/b, CD19 - reset signaling machinery back to its unphosphorylated ground state  26S proteasomal degradation (Cbl, K48 polyubiquitin) - ubiquitin ligase Cbl append 附加 small ubiquitin tags to active IC signaling proteins  - K48-linked polyubiquitin chains mark cytosolic kinases (ZAP-70, Lck) for destruction lysosomal de...

1. Immune response non specific  specific  2. Innate  physical & chemical barriers phagocytic cells blood proteins cytokines NK - virus & IC microbes 3. Adaptive  lymphocyte  Ab Ag humoral - EC microbe cellular - T - IC microbe - CD8 direct killing, Th1 + macrophage, Th2 + B cell  4. APC general professional - B, macrophage, DC - outside Ag - MHC 2 - CD4 - endocytosis  5. natural active - Ag enter body - innate & adaptive provide long term protection natural passive - Ab from mom to fetus - short term 6. artificial active - vaccine - long term artificial passive - Ab from individual inject into body - short term 

General principles of transduction signaling & immunological synapses 1. receptor + ligand 2. cytokine - among immune cells 3. chemokine - specialized cytokine - induce chemo attraction 4. monovalent = 1 ligand + 1 receptor 5. multivalent = 2 ligand + 1~2 receptor  - higher affinity due to avidity  - enhanced signal activation - high specificity  - different association & dissociation kinetics 6. Ag binding receptor on T/B increase expression of cytokine receptor on cell surface - higher affinity  7. T + APC = cytokine signals released by T = APC receive  - cytokine secretion facilitated by Ag receptor signaling  - induce redistribution of microtubule organizing center in activated T = Vectorial Redistribution Of The Secretory Apparatus = cytokine enter synapse cleft = between activated T & APC 8. synapse between T & dendritic cell = TCR green, adhesion molecule red, central supramolecular activation complex, peripheral SMAC, distal SMAC cSM...

Mutagenesis - Dr Chau De Ming  1. How homolog study works for a newly discovered gene 有出 Compare unknown gene sequence with known gene sequence in other organism  Use gene seq database  Show similarities   Reveal protein function of new gene  Predict potential roles in cellular processes and pathways  2. How reporter gene works （变gene expression study了 Track timing and location of a protein expression  Green fluorescent protein  Observation of GFP fluorescence when gene of interest is expressed  Enable detection of gene and provide indication of transcriptional activity of the gene  3. Germ line mutation: 有出 First appear in gamete   Passed from parents to offspring  Found in every cell of offspring   Somatic mutation: 无 First appear in somatic cells  Not inherited/passed  Found in specific cells where mutation first originated  4. Point mutation: Affects single ntd base pair  Silent  Missense...

Holobiont = humans are superorganisms composed of human and microbial cells evolving together  Microbes = essential partners  Balance vs imbalance, good vs bad  Microbiome = combined genetic material of microbes in a particular environment  Microbiota = microbes in specific environment  Types of microbes:  Bacteria - firmicutes - Strep Lacto, bacteriodetes, proteobacteria - Klebsiella Enterobacter, actinobacteria  Virus  Fungi - basidomycota, ascomycota  Archaea Protist  Distribution of microbes: ✓ Skin - Actinobacteria - Propionibacterium acnes, Cornyebacterium 1000 21% Mouth 600+ 26% Upper respiratory tract 600+ 14% GIT 25 in stomach 500-1000 in intestine 29% Urogenital tract - Lactobacillus 60sp 9% Functions:  Metabolic contribution  Promote tissue integrity and development  Immune modulation  Protection from pathogens  Roles:  Facilitate nutrients and vitamin acquisition  " Stimulate innate a...

Factors make microbes thrive: GERM SEP Genetic exchange  Ecological interaction  Rapid reproduction  Metabolic versatility  Small size & large surface area  Extreme adaptability  Pervasive environment presence  Factors govern microbial growth:  Resources: carbon, nitrogen, micronutrients SPK Mg, electron receptor sulphate, inorganic electron donors H2 Environmental: temperature, water, pH, oxygen, light, osmotic conditions  Biological: competition for space and resources, predation, symbiosis  Environment reservoir: ✓ 1. Soil CBB Clostridium tetani  Bacillus anthracis  Burkholderia pseudomallei - wet soil, rice paddy, stagnant water  2. Water Freshwater   Vibrio cholera - flood  Leptospira interrogans - rice field, flood  Free living amoeba   Acanthamoeba - granulomatous encephalitis  Naegleria fowleri - warm freshwater - PAM Biofilms in water systems  LP PA Legionella pneumophila - hosp...