microbio notes/terms for final
phagocytic cells plat a critical role in adaptive immunity
-dendritic cells---> one of the more important ones -in bone marrow and migrate to tissues for differentiation -present in most tissues -present in organs except brain, eyes, and testes -function of dendritic cells---> 1st to detect pathogens and activate immune system -dendritic cells in thymus---> help educate T cells -maintain stimulation of B cells during infections
phagocytosis
-detection of pathogens and chemotaxis toward them -mediators of inflammation 1. attachment---> receptors recognize molecules that enhance the binding of phagocytes 2. ingestion -phagosome---> target encircled in membrane -requires ATP, phagocyte shifts to fermentive metabolism -phagolysosome formation---> merges w/lysosome and lysosome explosively discharges toxic substances
innate immunity
-1st line of defense against a pathogen -MAMPs---> microbe associated molecular patterns -bacterial peptidoglycan, lipoprotein, lipoteichoic acid, bacterial flagellin -DAMPs---> danger associated molecular patterns -indicate cell's injured, initiates immune response to non-infectious agents -heat shock proteins, nuclear DNA, ATP
papillomaviruses
-DS circular DNA genome, not enveloped, tissue specific, as cells differentiate replication rate increases (infections can last years) -human papillomavirus (HPV)---> virus acquired by close contact -diagnose---> pap smear to find aberrant cells
dysbiosis
-disease may/may not be a consequence of disruption of normal microbiota -rapid increase in allergic, autoimmune, and inflammatory disease -rapid increase in metabolic diseases -causes---> gut disorders (crohn's), immune disorders (autoimmune), and diabetes & obesity -if you consume things w/ phosphatidylcholine you'll have it in your diet, will be degraded to choline, gut metabolizes, turns TMM and TMAO, and can lead to heart attack, stroke, or death -carnitine is also metabolized into TMAO -TMAO accumulation not seen in vegans
sites of microbial colonization
-dry epithelial (skin) -influenced by sebaceous glands -dry=greater diversity -moist epithelial (mucosa) -respiratory, gastrointestinal, and urogenital tracts
epithelial barriers: skin
-effective 1st barrier -hair stops airborne pathogens -sebaceous glands secrete hydrophobic oils -epithelial cells produce peptide antibiotics
Koch's postulates
-the suspected pathogen must be present in all cases of the disease and absent from healthy animals -the suspected pathogen must be grown in pure culture -cells from a pure culture of the suspected pathogen must cause disease in a healthy animal -the suspected pathogen must be reisolated and shown to be the same as the original
Enterohemorrhagic E. Coli
-transmitted by food and water but also person to person contact -incubation---> 3-4 days -symptoms---> abdominal pain, short lived fever, non bloody diarrhea, vomiting, 1 to 2 days diarrhea turns bloody w/ increased abdominal pain (lasts 4-10 days) -complications---> damage to blood vessels, damage to kidneys and kidney failure, high blood pressure -mechanisms of pathogenesis---> attaches through fimbriae, injects effectors through type III secretion, host cell rearranges and forms pedestals
metabolism is consistent, no microbes
-weight gain---> change in microbiome -after weight loss---> it won't be the same -major impact is on dietary flavonoids
crossing anatomical barriers into host issues: invasion
1). attach to epithelial cells 2a). enter epithelial cells 2b). loosen junction and move between cells 3). transit to deeper tissues
syntrophy
2 different organisms cooperate to degrade a substrate -producer organism can't degrade substrate w/o participation of consumer organism -producer needs consumer to remove products
natural killer cells
-nonphagocytic granular lymphocytes---> in body at lower pops -small amounts of immunoglobin and MHC 1 molecules -behavior similar to cytotoxic T cells
acetyl coA pathway
-take CO2 and reduce one CO2 to methane and the other CO2 to carbonyl group -put the two reduced forms together on an enzyme to synthesize acetate
oral microbiota
-teeth---> non-shedding surface -role in periodontal disease
Danio rero (zebrafish)
-abnormalities can be rescued by microbiota -microbiota involved in -development of immune system -nutrition digestion -regulation of intestinal mucus expression -stimulation of epithelial cell renewal -production of intestinal defensive enzymes
acetogens
-anaerobic bacteria -CO2---> electron acceptor to reduce it to acetate -present in higher nutrient forms than methanogens
methanogenesis
-anaerobic respiration -CO2---> terminal electron acceptor -H---> most common electron donor -electron acceptors---> CO2, formate, alcohols, methylamines, methanol, and acetate
antigens
-any type of molecule that causes an immune response in a host by interacting w/ antigen specific receptors on the membrane of host lymphocytes -proteins---> strongest -sugars---> second strongest -lipopolysaccharides---> weak -lipids/DNA---> not good antigens at all -immunology---> big mess and interconnected
Methanogens
-archaea, obligate anaerobes, and produce methane -found in large intestine and mouth (mainly)
function of symbiotic microbes
-assimilation of major nutrients -microbes fix CO2 -measure carbon incorporation into animal tissue -provision of minor but essential nutrients -get essential metabolites from diet/symbiotic microbes -protection -roles in reproduction, physiology, and development (immune system)
avoid host immune system
-avoid/hide---> intracellular growth, invade privleged area (brain) not monitored, avoid/inhibit phagocytosis, and lack MAMPs for detection -actively disrupt immune system---> kill immune cells, interfere w/ effector function
acquired/specific adaptive immunity
-b cells---> antibody mediated immunity (AMI) -t cells---> cell mediated immunity (CMI)
roles of gut microbiota
-barrier/protective---> pathogen displacement, nutrient competition, and production of antimicrobials -metabolic---> feed epithelial cells, degrade plant polysaccharides and mucus, and synthesize vitamins -immune---> educate immune system and induce production of antimicrobials
clostridia
-based on production of toxins -gram positive, strict anaerobe, obligate fermenters, ubiquitous---> normal microbiota, water, soil -types of infections---> skin and soft tissue, food poisoning, diarrhea and colitis -problem bc---> survive adverse conditions, rapid growth, and produce several types of toxins -C. difficile -main cause of infectious diarrhea after hospitalization and antibiotic use -mild to severe diarrhea, bloating, and abdominal pain -complications---> fever, pseudomembranous colitis, toxic megacolon, sepsis shock, and death -actions of toxin---> damages cells by inactivating Rac and Rho GTPase -important cell signaling molecules, cell rounding, apoptosis -prevention/treatment---> hand hygiene, antibiotic prescription (penicillin), mentronidazole/rancomycin, colectomy and fecal microbiome transplantation
antibiotics
-chemicals used to selectively target one type of organism -produces by bacteria, fungi, or plants -selective toxicity and specific cellular target -beta lactam antibiotics---> target cell wall synthesis -fluoroquinolones---> target DNA structure/replication -macrolides---> target protein synthesis -overuse---> inappropriate prescription, use in agriculture, use in animal hobbies, and relaxed regulations -temp resistance---> microbe isn't growing -grow in location not easily accessible or growing in a biofilm -acquired resistance---> horizontal gene transfer and mutations -molecular mechanisms---> reduce permeability of cell to antibiotic, inactivation of antibiotic, alteration of target, and efflux pumps -combat antibiotic resistance---> develop new drugs, prudent antibiotic use, surveillance, infection prevention, infection control
E. Coli
-commensal/mutualistic organism, utility in scientific research, pathogen w/ certain genetic components added -gram negative, non-spore forming, facultative anaerobe, metabolically capable (can make everything it needs) -can ferment lactose to avid and capable of forming indole -fimbriae enhance their intestine-colonizing ability -unique plasmids, pathogenicity islands, each codes for proteins that cause their specific illness
microbial communities
-common for aerobic and anaerobic degradation
Akkermansia muciniphila
-common inhabitant of animal GI tract -specialist in mucus degradation and beneficial to animals (+,0) -advantages for bacterium---> don't compete w/ microbes in lumen and not dependent of food intake -advantages for community---> liberates oligosaccharides -advantages for animals---> mucus barrier's made larger and recycles some mucin as food
termite gut
-contains archaea, bacteria, and sometimes eukarya -acetogens predominate over methanogens
transmission of pathogens
-environment--->inhalation of soil particles, direct contact w/ wound, consumption of contaminated food/water, swimming or bathing in contaminated water -animals---> bites from infected animals, handling dead/live animals, contact w/ animal feces, consumption of animal/plant products, indirect transmission through a vector (mosquitoes) -human restricted -direct transmission (person to person)--->direct skin contact, sexual contact, other bodily fluids -indirect transmission---> airborne droplets, fomites---> inanimate objects capable of transmitting a disease, fecal to oral route
complement
-enzymatic system -produces in macrophages, liver cells, and epithelial cells in gastrointestinal mucosa -circulate in bloodstream until activated
staphylococcus epidermis
-everyone has -benefits -produces bacteriocins, inhibits S. aureus biofilm formation, induces production of host cell anti-microbial peptides (AMP), and inhibits excessive inflammation post injury
traits of pathogens
-excel @ -attaching to specific sites -many cross barriers -many adopted to growth in the host -some produce toxins---> secretion systems and pathogenicity islands -some have the ability to evoke very strong inflammatory responses
anaerobic degradation
-fermentation -produced partially oxidized products -used by acetogens, methanogens, and syntrophs
crossing the cellular barrier
-few pathogens stay put, many are facultive intracellular pathogens, some are obligate intracellular pathogens -entry---> active microbe directed process
toxins
-function varies but is always specific -properties---> exo=secreted and AB (active and binding) toxin=structure -host cell type/tissue -enterotoxin=GI tract -neurotoxin=nervous system -hepatotoxin=liver -leukocidin=leukocytes
SARS-CoV-2 (covid)
-genome---> large for RNA virus, large RNA replicase (doesn't change as fast as others) -replication -entry---> receptor, found in upper and lower respiratory epithelial cells, heart, kidney, and gut, entry through endocytic pathway, and fusion dependent on acidification of endosome, and involves S protein cleavage -translated at ribosome, polyprotein made 1st then degraded by viral proteases, replicase makes genomic and sub genomic RNAs, translated into structural proteins and genome fuses to vesicles containing envelope proteins -symptoms---> 2-14 days post exposure, loss of smell, fever, cough, shortness of breath, fatigue and body aches -treatment---> onoclonal antibodies but no longer effective and there are steroids to mitigate immune response, protease inhibitor, RNA-dependent replicase -paxlovid---> reduce risk of hospitalization, nirmatrelvir and ritonavir -molnupiravir---> attack the enzyme that copies virus genome and trick it into using drug in its genome to cause mutations -vaccines---> RNA/DNA vaccines, virus vector vaccines -mRNA vaccines---> pfizer, moderna, etc -nasal vaccine---> live attenuated virus uses poor codons to weaken virus translation
growth and colonization
-growth and replicate---> acquire nutrients and appropriate environment condition---> temp, pH, and oxygen -extracellular pathogens---> secreted hydrolytic enzymes -intracellular pathogens---> nutrients from host cell cytoplasm -sense and respond to environment---> regulation of virulence factors is response to host environment -quorum sensing
dietary flavonoids
-high fat diets---> lacks dietary flavonoids -dietary flavonoids increase w/ healthy diet -higher flavonoids---> decrease food intake, and increase activity and energy expenditure -lower flavonoids---> increase food intake, and decrease activity and energy expenditure
indentification of self
-immune system differentiates self from non-self---> difficult at molecular lvl -immune system creates lymphocytes that responds to macromolecules -self---> proteins, sugars, and lipids floating around that're part of our body and accessible to immune system
rhinoviruses
-infection of the nose and most frequent cause of common cold -course---> symptoms 2-3 days post infection, nasal discharge, headache -pathogenesis---> protein capsid, positive strand, ssRNA virus, polyprotein, small and simple -symptoms easily recognizable -treatment---> over counter meds, vaccine impossible due to rapid variation
prions
-infection proteins (PrP) -made by a single gene -functions in cell signaling and neuron development -infectious PrP---> folds it differently/incorrectly -aberrant version---> refolding of normal protein -pathogenesis---> protein protein interactions -PrPsc binds to normal PrPc---> changes confirmation -accumulation in lysosomes=cell death -moves from cell to cell using transport systems
damage
-invasion of tissues and growth, production of hydrolytic enzymes, formation or dissolution of blood clots, disrupt normal immune response, damage facilitates transmission to new host/reservoir -production of toxins -exotoxin---> secreted toxin -endotoxin---> lipopolysaccharide -infection of protein effectors into host cells---> secretion systems deliver effectors
microbes abundant in lower gastrointestinal tract (GUT)
-large #'s of immune cells and tissues -single layer epithelial cells -uptake nutrients and water, mucus secretion, antimicrobials and enteric hormones produced, and rapid cell turnover
vaccines
-live attenuated strains---> replicating strain w/ defects -won't cause disease but it'll raise immune response -dead virus/bacteria---> if cell mediated immunity response needed, requires more doses and becomes less effective -component vaccines---> subunit-protein subunits of virus/bacterium, toxoid-modified/inactivated toxin, polysaccharide-capsular polysaccharides, boost immunogenicity and effectiveness
adaptive immunity occurs
-lymph nodes---> gets antigens from connective tissue -spleen---> gets antigens from blood -B cells---> recognize/capture antigens directly -T cells---> can't get antigens on their own
players of adaptive immunity
-lymphocytes---> b and t cells -antigen presenting cells---> macrophages, dendritic cells, B cells
ways to study symbiotic microbes
-manipulate host animals -germ free -gnotobiotic---> add known species -micro analysis---> sequence and analyze all genomes of all members of microbiota
egestion and antigen presentation
-neutrophils---> accumulate junk then die -macrophages and monocytes lives much longer
Chlamydia
-obligate intracellular parasites of eukaryotes, no cell wall peptidoglycan, extremely temperature sensitive -complication---> pelvic inflammatory disease which causes sterility in women, eye infections, respiratory disease, and joint infections -pathogenesis---> infect epithelial cells of cervix, bacteria ascend in endometrium and fallopian tubes, strong inflammatory response by neutrophils, adaptive response in submucosa, scarring occlusion -C. pneumoniae -healthy people may get it and may have a role in heart disease -growth cycle---> metabolically inert, has a number of adhesions on outer surface, sticks to host, stimulates own uptake, once inside endosome vesicles they interfere lysosome fusion and acidification, entry---> actively modify vesicle and prevent fusion -differentiates into RB -RB---> begins genome replication, growth, and division -two options 1.turn into EBs, leave cell and find other host cells to infect 2.adpot a non-infectious, non-replicating persistent form which is done when immune system is active -treatment---> antibiotics
plasmodium-Malaria
-only reservoir---> humans -vector---> female mosquito -takes blood meal, gametocytes go out, undergo fertilization, swim to salivary gland and mature, become infective, and bite another human -once in humans---> 7-30 days -liver stage---> divide for awhile then go dormant -blood stage---> stick to red blood cells, feed of RBC lyse, when many lyse at once=crisis -symptoms---> fever, chills, sweating, headache, abdominal pain -treatment---> artemisinin-based drugs, chloroquine, lumefantrine, or amodiaquine -resistance---> sickle cell gene (Hbs) or when people don't have duffy antigen
aerobic degradation
-oxidizes products produced -ex: CO2, nitrate, and sulfate -oxygen consumed quickly
Shiga toxin integrates into E. Coli genome
-produced by some shigella -no mechanism for secretion from cell -phage induction induces expression of toxin -phage-mediated lysis releases toxin -AB toxin---> B subunit binds host globotriasylceramide (GB3) glycolipids -subunit enters cell, cleaves rRNA and kills cells -diagnosis---> culturing the microorganism and serological test to identify the strain -toxin producing strains---> detected in stools using serological assays -rapid detection---> lessens chances of progression to hemolytic uremic syndrome -treatment---> no antibiotics because it'd release more shiga toxin
probiotics
-pure cultures of microbial strains that yield a health benefit enhance function of epithelial barrier and modulate a host immune response
T lymphocytes
-regulates immune system -response to antigen only when associated w/another host cell -MHC 1---> status monitors for cells -functions---> immune system reacts and method of signaling that the cell is healthy -MHC II---> found only on antigen presenting cells (Macrophages, dendritic cells, and B cells) -function---> vessels to present foreign antigens to T cells, bind to antigens that originate from an exogenous source -CD4+ cells--> recruit and regulate immune system -TH1---> recruit and regulate other cells -TH2 antibody production---> regulate B cells and antibody production and antibody mediated immunity -T suppressor cells---> turn down immune response after a pathogen's dealt w/ -CD8+ cells---> T cytotoxic cells, activation by antigen cause these cells to attack -Clonal energy---> t cell reacts w/antigen in MHC1 molecule but not MHC2 molecule -T suppressor cells---> shuts off normal immune response -sequestering---> where no immune system is -activity of cytotoxic T cells---> recognize infected cells via MHC1 display on infected cells and kills them
influenza A
-replication---> enter when acidification of endosome, negative strands to nucleus, assembly and membrane and budding -airborne droplets, local upper respiratory tract infection, damages ciliated apithelium of URT -symptoms---> fever, malaise, head ache, and body ache -complications---> secondary bacterial infections -treatment---> antivirals if given soon post infection, annual vaccination
Staphylococcus aureus
-skin and eye infections, food borne illness, toxic shock syndrome, nosocomial infections -MRSA and vancomycin---> resistant to antibiotics -gram positive, catalyze positive, common inhabitants of skin, facultative w/lactic acid being an end product sugar fermentation, performative oxidative phosphorylation when oxygen present, salt tolerant -superficial boils and styles, tissue infections, deep seated, most localized by immune system -cause pathologies---> elevated temp, swelling, accumulation of pus, walling off fibrin clot and abscess formation -pathogenesis---> deadly cocktail of surface molecules and toxins -surface proteins promote colonization of host tissues, invasion promote bacterial spread in tissues, surface factors inhibit phagocytic engulfment, substances enhance survival in phagocytes, immunological disguises, membrane damaging toxins that lyse eukaryotic cell membranes -food poisoning---> bacterium grows in food -produces staphylococcal emetic toxin---> heat stable, induces vomiting, rapid onset, self-limiting, w/recovery in 24-48 hours -toxic shock syndrome -high fever, diffuse rash, peeling of skin, low blood pressure -TSS toxin -hydrophobic---> cross mucosal surface -produced during stationary phase, over stimulates immune system, massive release of cytokines and TSS toxins and enterotoxin are super antigens
HIV
-spreads through sexual contact and contaminated blood, long period of asymptomatic infection, easily activated -pathogenesis---> CD4 expressing T cells and macrophages, macrophages initially infect and persistently infected and serve as reservoirs -kills t cells and removes immune system overtime -complications---> opportunistic infections, malignancies, dementia, and wasting -treatments---> reverse transcriptase, protease fusion, and integrase inhibitors, CCRs antagonists
retroviruses
-ss+ strand enveloped virus that demonstrates reverse transcriptase
epidemiology
-study of occurrence, distribution, and determinants of health and disease -field work---> determines extent of an outbreak, network of hospitals, clinics, and health departments, reports notifiable diseases, and policy decisions are made -common source---> everyone was in contact -host to host---> not everyone exposed but more person to person contact
chronic wasting disease
-symptoms---> weight loss, isolation, loss of coordination, hypersalivation, frequent urination, excessive thirst -transmission---> oral ingestion of prions, excrement of dead carcasses, and PrP binds to soil -no treatment
adaptive immunity
-system learns to recognize pathogen -bilateral response -antibody immunity---> antibodies -cell mediated immunity---> group of cells that attack pathogen
even after adaptive response starts, innate response is still active
adaptive response enhances innate response
prevention/control
air filtration, pasteurization, chemical disinfectants, antibiotics, immunization, quarantine, wash hands, USDA, and local gov.
public health
art and science of preventing die4ase and disability prolonging life, promoting health of populations, healthful environment
symbiosis
association between 2 different types of organisms
phagocytes differentiation
originate in bone marrow -neutrophils---> leave bone marrow and circulate in bloodstream -1st phagocytic cells that encounter infection -monocytes---> unsegmented nucleus, circulate in blood for period of time, and settle in a tissue and mature into macrophages -macrophages---> mature monocytes that're attached to lymph tissues -roles---> remove dead cells when they reach end of their usual life, remove pathogens, creation of important immune proteins and peptides (transferrin, complement proteins, and certain cytokines)
dendritic cells
part of innate response but also initiates adaptive response as antigen presenting cell -produce cytokines that recruit leukocytes
Innate immunity
phagocytosis and inflammatory response
heard immunity
protected individuals protect the rest of the population -strong case for vaccines
antigenic shift
several different viruses mix inside and incubator/animal -certain segments of different viruses mix in one virus and replicate in the same cell
reservoirs
sites where pathogen remains viable and from which individuals may be infected -environment---> soil, water, plants -zoonosis---> wild animals and domesticated animals -humans---> high carrier rate
signs of inflammation
swelling, redness, heat, and pain
20% of cancers are caused by viral infections
unregulated cell growth and results from synergistic mutations
antigenic drift
virus replicates in humans as a mutation and there's a small change causing an epidemic strain
disease decreases due to
better environment, improved nutrition, better living conditions, sanitation for food/water, antibiotics, and vaccines
mutualism
both benefit (+,+)
pathogen
causes damage/disease in host
opportunistic pathogen
causes disease only in compromised hosts
primary pathogen
causes disease only in compromised hosts
rumen
complex community of bacteria, archaea, and eukarya -fermentation produces short chain fatty acids and used as food -significant community of methanogens
immune system
complex network of organs and tissues -extensive interdependence -tissues are primary or secondary
primary tissues
create and educate -bone marrow---> b cells- source of all immune cells -thymus gland---> t cells are educated -MALT---> t and b cells
Pattern recognition receptors (PRR)
family of receptors present on immune cells -expressed on phagocytes, dendritic cells, epithelial cells, endothelial cells, and some lymphocytes -recognize macromolecules made -in macrophage---> activation of PRR causes induction of inflammatory response
prebiotics
food you feed your probiotic microbes
hologenome (metaorganism)
host genome plus microbiome (microbiota genome)
holobiont (metaorganism)
host plus its microbiota
how humans acquire microbiota
in utero, birth process, break milk because glycans promote microbial colonization, and ecological succession of different communities
secondary tissues
look after mature cells that're an active part of defense -spleen (role in primary too), lymphatic system, lymph nodes, MALT (role in primary too)
lymphocytes
major type of white blood cells for adaptive immunity
B lymphocytes
make antibodies react w/antigens -clumping activates a signaling cascade that activates various B cell genes -differentiation -rapid division -plasma cells---> make antibodies -memory cells---> cells that remember the antigen -maturation -animals---> B cells mature in bone marrow and MALT -travel in bloodstream -antibody structure -proteins -variable regions---> react w/antigen -constant regions---> interacts w/ immune system - 2 light and 2 heavy chains and forms a Y structure -immunoglobin diversity---> many combos of units -antibody rxns---> complement activation, toxin neutralization -course of antibody response---> primary response is slow and weak, secondary response is rapid and strong, and affinity of antibody increases w/repeated exposure
commensal pathogen
member of normal microbiota that may cause disease under some conditions
cytokines-immune hormones
method of communication between immune cells
white blood cell types
neutrophils, monocytes, T-lymphocytes, B-lymphocytes
role of microbiota
nutrition, barrier/protective, immune function, community function (alter ecosystem and interact with other microbes)
communities of microbes are found
on mucosal surface, in body cavity, and in specific organs
amensalism
one benefits while the other is harmed (+,-)
commensalism
one benefits, the other isn't harmed or benefited (+,0)
Normally microbes work together in metabolic partnerships
one will produce something that the other one uses