MB Exam 4 Lec 20 Vaccinations & Antimicrobials

inflammation lymphocyte

Adjuvants -To make the vaccine antigens more attractive to the adaptive immune system, we inject them with a mixture called adjuvant. -Adjuvants help the APC by inducing _________ and/or making sure the antigen protein doesn't get cleared from the injection site too quickly. -The original adjuvant, called Freund's complete adjuvant, is a mixture of oil and water together with inactivated mycobacteria. Mix an antigen with this, and the injection site will be extremely painful and inflamed, increasing the likelihood of ____________ activation. -Of course, people wouldn't like that. So, Freund's is not used in humans, only in animals. -Only Alum and MF59 are FDA approved

dilution uric acid

Adjuvants -alum is an aluminum salt that is widely used as an adjuvant in human vaccines. (like DTaP, Hepatitis B, and Human Papillomavirus). -Originally alum was thought to provide an antigen depot effect through absorption of antigen onto particulate alum that is phagocytosed, but recent evidence argues against this. -More likely, it works by simply slowing antigen ________ from injection site and by inducing localized necrosis. -Necrotic cells release ________ acid, which activates resident DCs that acquire the alum/antigen, and then traffic to the LN and present to CD4 T cells.

antivirals antivirals

Although antibiotics are not effective at treating viral infection, we do have therapeutics that are effective, these are called ________. -Recall that there is a 5 step process for viral replication. In order for _________ to work against viral infection, they must target and inhibit steps in that replication pathway.

disk diffusion (Kirby Bauer)

Assessing Effectiveness The most widely used, method of testing susceptibility of a microbe to a chemotherapeutic agent is using the ___________ method.

E-test

Assessing Effectiveness: A more advanced method of assessing effectiveness called the __________ enables a lab technician to estimate the minimal inhibitory concentration, MIC (the lowest antibiotic concentration that prevents visible bacterial growth) -limitation: can't tell from diffusion tests if it is bacteriostatic or bacteriocidal.

peptidoglycan peptidoglycan

-Antimicrobial drugs are either bactericidal (they kill microbes directly) or bacteriostatic (they prevent microbes from growing). -In bacteriostasis, the host's own defenses, such as phagocytosis and antibodies, will usually come in and destroy the microbes. -The mechanisms of action for these drugs are varied, many drugs target certain essential functions of the microbe. -We have just discussed penicillin, it works by inhibiting cell wall synthesis. Other antibiotics in this family are the cephalosporins, bacitracin, and vancomycin. - The cell wall is a good target since ___________ is found only in bacterial cells, because human cells do not have ________________ cell walls, penicillin is not toxic to the host (the idea of selective toxicity again).

antigens

-Both the innate and adaptive immune responses protect the host from infections by pathogens and are essential for survival. - Immunity may be naturally occurring or artificially induced by exposure to _________ (vaccination). -We acquire immunity either actively, for example when we generate an immune response through exposure to an antigen, or passively, when we receive antibodies or immune cells from an immune individual.

selective toxicity

-Some work by inhibiting protein synthesis. Since it is a common feature of all cells (prokaryote and eukaryote), it would seem to be an unlikely target, but there is a notable difference between the structure of their ribosomes. -Eukaryotes have 80S and prokaryotes have 70S ribosomes. -The difference in ribosomal structure accounts for the _____________ of antibiotics that affect protein synthesis. -Examples include chloramphenicol, erythromycin, tetracyclines, azithromycin, and streptomycin.

polypeptide biochemical

-There are a number of antibiotics that interfere with the processes of DNA replication and transcription in microbes. However, some of these have a very limited usefulness because they interfere with mammalian DNA and RNA as well. Certain antibiotics, especially _____________ antibiotics, bring about changes in the permeability of the plasma membrane; these changes result in the loss of important metabolites from the microbial cell. -Examples of these are polymyxin B, miconazole (yeast). -Some work by inhibition of synthesis of essential metabolites. Stopping the microbial production of essential enzymes involved in __________ pathways. For example, sulfanilamide inhibits folic acid synthesis.

ear infections pneumonia

-There is a growing conviction in some communities in the US that measles is a harmless childhood illness and kids shouldn't need to be protected from it. -In fact, by preventing measles, the anti-vaxxers argue, we are denying our children a proper immunological education in keeping with the hygiene hypothesis. Parents are starting to invite kids over for "Measles Parties" to intentionally inoculate kids with the Measles virus. -Though generally mild on its own, measles is frequently associated with a number of complications including ____________, encephalitis, and ___________, and even death. -1 in 5 measles cases will result in hospitalization, and 1 in about 3000 cases will result in an absolutely preventable death. -And as the numbers of people that choose not to vaccinate grow, the effectiveness of our vaccination programs wanes.

Adaptive actively passively

-____________ Immunity refers to the protection animal develops against certain specific microbes or foreign substances. -Immunity can be acquired either actively or passively: Immunity can be acquired _________ when a person is exposed to microbes or foreign substances and the immune system responds. Immunity is acquired ___________ when antibodies are transferred from one person to another. -Passive immunity in the recipient lasts only as long as the antibodies are present-in most cases only a few weeks. -Both actively acquired immunity and passively acquired immunity can be obtained by natural or artificial means.

70S Aminoglycosides

2) Inhibitors of Protein Synthesis -Target bacterial _______ ribosomes, with its two subunits (the 50S and the 30S) -__________________ class of antibiotics that inhibit protein synthesis. -other classes: chloramphenicol, tetracyclines, macrolides

30S streptomycin

2) Inhibitors of Protein Synthesis Aminoglycosides Class: -Amnio sugars linked by glycoside bonds -change the shape of the ______ subunit of the 70S ribosome (causes mRNA to be read incorrectly) -Among first of the antibiotics to work against Gram negatives. -can cause auditory damage -ex: _______________ (most famous - discovered in 1944), neomycin, gentamicin

transcription Rifamycin

3) Inhibiting nucleic acid synthesis -interferes with DNA replication and __________ -Ex: __________: inhibits mRNA synthesis by binding to the RNA polymerase enzyme; penetrates tissues and has antitubercular activity (used to treat TB) -Other examples include quinolone & fluoroquinolones which inhibits DNA gyrase.

polypeptide

4) Injuring the plasma membrane -When the membrane is damaged, changes in membrane permeability can occur and lead to cell lysis. -______________ antibiotics change membrane permeability -antifungal drugs combine with membrane sterols

Daptomycin Polymyxin B

4) Injuring the plasma membrane -affects synthesis of bacterial plasma membranes -an example of antimicrobial drug class that injures the plasma membrane is Lipopeptides -Two examples of lipopeptides: 1. _______________: produced by stretomycetes; used for skin infections; attacks bacterial cell membrane 2. ______________: topical/bacteriocidal; effect against gram-negatives; combined with bacitracin & neomycin in nonprescription ointments

Sulfonamides synergism

5) Inhibiting the synthesis of essential metabolites -antimetabolites compete with normal substrates for an enzyme Ex: _______________ -Inhibit the folic acid synthesis needed for nucleic acid and protein synthesis -competitively bind to the enzyme for PABA production, a folic acid precursor -combination of trimethoprim and sulfamethoxazole (TMP-SMZ) is an example of drug ____________.

resistant

And the antibiotic development pipeline has slowed in recent decades A perfect storm: as bacterial infections grow more __________ to antibiotics, companies are pulling out of antibiotics research and fewer new antibiotics are being approved

mutation horizontal plasmids

Antibiotic Resistance -Antibacterial antibiotics changed the practice of medicine in the 1940s and 1950s -antibiotic resistance is acquired by random __________ or ___________ gene transfer -resistance genes are often in __________ or transposons that can be transferred between bacteria -a variety of mutations can lead to antibiotic resistance

resistance conjugation resistance (R) factors

Antibiotic Resistance -Bacterial populations are large and have some genetic differences -When you apply the use of antibiotics to such a population, the antibiotic has selected for their survival, and they are the ones to thrive and pass on their ___________ genes. -Such genetic differences arise from random mutations, and they can be spread horizontally among bacteria by ___________ or transduction. -Drug resistance is often carried by plasmids or by transposons. Some plasmids can even be transferred between different species. -Some plasmids, including those called __________ factors, may contain genes for resistance to several antibiotics. -Due to the rapid reproductive rate of bacteria, it is only a short time before practically the entire selected population is resistant to the new antibiotic.

penetration (entry) Enzymatic target ejection

Antibiotic Resistance Mechanisms of antibiotic resistance: 1. Prevention of __________ of drug 2. ___________ destruction of drug 3. Alteration of drug's ________ site 4. Rapid ________ of the drug

outdated regimen animal

Antibiotic Resistance Misuse of antibiotics selects for the maintenance of resistance mutations. What are some misuses of antibiotics? -Using ___________ or weakened antibiotics - using antibiotics for the common cold and other inappropriate conditions -failing to complete the prescribed _________ -using someone else's leftover prescription -using antibiotics in ________ feed to promote growth

therapeutic index (therapeutic window)

Antibiotics are selectively toxic toward microbes. Each antibiotic has its own ______________ (concentration range where it is active against microbes without being toxic to the host)

receptors

Antiviral Drugs Entry & Fusion Inhibitors: -block the __________ on the host cell that bind to the virus -block fusion of the virus and cell

neuraminidase

Antiviral Drugs Exit Inhibitors: -inhibit ____________, an enzyme required for some viruses to bud from the host cell

protease

Antiviral Drugs Interference with assembly and release of viral particles: -__________ Inhibitors: block the cleavage of protein precursors

nucleoside analogs

Antiviral Drugs Uncoating, genome integration, and nucleic acid synthesis inhibitors: -prevent viral uncoating -inhibit viral DNA integration into the host genome -_____________ inhibit RNA or DNA synthesis

Entry nucleic acid Exit

Antiviral Drugs actions: -________ & Fusion Inhibitors -Uncoating, genome integration, and __________ synthesis inhibitors -Interference with assembly and release of viral particles -________ Inhibitors

Zone of Inhibition solubility

Assessing Effectiveness: Disk Diffusion Method -Tests the effectiveness of chemotherapeutic agents -Paper disks with a chemotherapeutic age are placed on agar containing the test organism -_____________ around the disk determines the sensitivity of the organism to the antibiotic -the larger the diameter = the greater will be the sensitivity of the bacterium to the antibiotic. -this test doesn't consider __________ of the chemical agent, incubation periods have to be strictly controlled, etc. but it is inexpensive and relatively easy to do; however it may be inadequate for some clinical purposes.

normal microbiota superinfection

Broad Spectrum - Because the identity of the pathogen is not always immediately known, a broad spectrum drug would seem to have an advantage in treating a disease by saving valuable time. -The disadvantage is that these drugs destroy many ______________ that ordinarily will compete with and check the growth of pathogens. -If the antibiotic does not destroy certain organisms in the normal microbiota but does destroys their competitors, the survivors might flourish and become opportunistic pathogens. -An example is the overgrowth of the fungus Candida albicans, which is not sensitive to bacterial antibiotics. This overgrowth is called a ________________. This is also a term applied to growth of an antibiotic resistant strain that replaces the original sensitive strain and the infection continues.

dilutions

Broth Dilution Tests To determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of an antimicrobial drug: -the test organism is placed into the wells of a tray containing _________ of a drug and growth is determined

spontaneously

But don't think that antibiotics create antibiotic resistance. -Genes responsible for antibiotic resistance occur ______________ -By looking at the gut microbiomes in these mummies, scientists found that antibiotic resistance genes were present long before the dawn of antibiotics therapy and modern medicine.

Chemotherapy syphilis

Chemical Methods of Microbial Control-Antimicrobial Drugs -Generally speaking, antimicrobial drugs: Interfere with the growth of microbes within a host. The use of a specific chemical to treat a disease causing pathogen without causing harm to the host was called "____________" and was proposed in the early 20th century by the German scientist Paul Ehrlich. -It was a radical idea at that time, to propose that there were these "magic bullets" that could kill pathogens, but not hurt humans. -He discovered Salvarsan, the first effective chemotherapeutic agent against __________. -Salvarsan is a derivative of an synthesized arsenical compound. -Now the term chemotherapy is considered archaic in this field, and more broadly applies to the treatment of cancer.

revolution selective toxicity

Chemical Methods of Microbial Control-Antimicrobial Drugs -In the early 1930s, another antimicrobial compound found to be effective against streptococcal infections was discovered. This was a class of chemicals called sulfanilamides, which were wholly synthetic compounds. -Around the same time, Alexander Fleming discovered a mold (Penicillium notatum) that inhibited the growth of Staphylococcus aureus. The active compound was called penicillin. -It took another 12 years before Florey and Chain succeeded in the first clinical trials of penicillin. This started the antibiotic _________. -Technically, an antibiotic is a substance produced by a microbe that, in small amounts, inhibits another microbe, it has ____________ (A drug that kills harmful microbes without damaging the host)

Alexander Fleming penicillin

Chemical Methods of Microbial Control-Antimicrobial Drugs 1928: _________ discovered penicillin, produced by Penicillium 1930s: Sulfonamides (sulfa drugs) 1940: Howard Florey and Ernest Chain performed the first clinical trials of __________

immunization neutralize

Cowpox and Smallpox -Cowpox and smallpox viruses share some surface antigens -______________ with cowpox induces antibodies against cowpox surface antigens -cowpox antibodies bind to and __________ the smallpox virus

triple cocktail

HIV -Combination drug therapy has proven successful in controlling HIV replication and thus suppressing the symptoms of AIDS. -Combinations are typically comprised of two nucleoside-analogue reverse transcriptase inhibitors (RTIs) and one non-nucleoside-analogue RTI or a protease inhibitor. This three drug combination is commonly called a __________.

mutation

HIV -Triple Cocktail -Combinations of antiretroviral drugs create multiple obstacles for HIV replication and reduce the viral load - keeping the number of viral progeny low. But they do not eradicate the HIV virus. Why? -The imprecise HIV Reverse Transcriptase generates a diverse population of progeny HIV virus RNA sequences - always with a few viruses whose replication isn't susceptible to the antiviral drugs. -Because of the frequent _________ rate of HIV, a combination drug therapy is required. -Combinations of antiretrovirals create multiple obstacles to HIV replication to keep the number of offspring low and reduce the possibility of a superior mutation. -If a mutation that conveys resistance to one of the drugs being taken arises, the other drugs continue to suppress reproduction of that mutation.

Variolation Variolation

History of Vaccination: Smallpox -11th century China & India: "___________" -Chinese ___________ involved blowing dried, ground smallpox scabs into the nose to induce a mild form of the disease (if they don't die, they are immune for life) -For hundreds of years in China, the thick coagulated fluid from the blisters of a smallpox patient was used to immunize people that had yet to become infected. - involved blowing dried, ground smallpox scabs into the nose to induce a mild form of the disease.

Variola

History of Vaccination: Smallpox -Smallpox killed or maimed 10% of humankind -killed > 300,000,000 people in the 20th century -Ancient Chinese history: a once in a lifetime disease -The smallpox virus, _________, initially causes small red blisters or pox to form from capillary infections in the face, throat and skin, before eventually causing blindness and death in as many as 30% of patients.

dangerous

It is said that we are approaching the post-antibiotic era. What does this mean? What are some of the potential impacts? -This is a projection of the deaths due to antibiotic resistant infection in the year 2015. Look at North America alone - more than 300,000 deaths per year. -While there are obvious concerns about having antibiotics to treat emerging and re-emerging infections, think about those things that are less obvious. -Things like cesarean sections or dental surgeries. -What about the use of antibiotics to treat cancer patients with suppressed immune systems? These are all instances where are antibiotics are routinely used. -In a post-antibiotic era, routine medical procedures might become a very ___________ proposition.

effective infectious diseases

Large scale vaccination programs -Before vaccines are approved by FDA, they are tested extensively by scientists to ensure they are _______ and safe. -Vaccines are the best defense we have against _____________; but no vaccine is actually 100% safe or effective for everyone b/c each person's body reacts to vaccines differently. -As infectious diseases become less common, we hear less about the serious consequences of preventable illnesses like diphtheria and tetanus and more about the risks associated with vaccines. -Public reaction to such risks has changed; most parents have never seen a case of polio or measles, and therefore tend to view the risk of these diseases as a remote abstraction.

small pox polio

Large scale vaccination programs -Dramatic improvements in public health -Nobody in this room has had smallpox, polio, measles, mumps, rubella, diphtheria, pertussis, chicken pox (maybe) ... because of vaccination -___________ is the only human disease to ever be eradicated; though we have nearly eliminated wild _______ virus.

MMR birth risks

Large scale vaccination programs -Reports or rumors of harmful effects often lead people to avoid certain vaccines for themselves or children. -In particular, a possible connection between the _______ vaccine and autism has received widespread publicity. -Autism is still a poorly understood developmental condition, because autism is usually diagnosed between 18-30months old, which is about the time vaccine immunization schedules are nearing completion, some people have attempted to make a cause and effect connection. -Medically, most experts agree that autism is a condition with a major genetic component and begins before _______. -Extensive scientific surveys have provided no evidence to support a connection between the usual childhood vaccines and autism or any other disease condition. -It's good to be informed about health choices, but the reality is that Americans have never been healthier than we are today and vaccines have never been safer than they are today. -The benefits of vaccines far outweigh the ______. -Vaccines remain the safest and most effective means of preventing infectious disease in children.

Gram-negative porins porin

Mechanisms of antibiotic resistance: 1) Blocking Entry/preventing penetration Blocking entry of the drug into the cell, particularly by __________ bacteria: -These bacteria are relatively more resistant to antibiotics because of the nature of their cell wall, which restricts absorption of many molecules to movements through special openings called _______. -If a drug cannot penetrate through the cell wall, it may not reach its target. -For ex., some bacterial mutants modify the ______ opening so antibiotics are unable to enter the cell.

Edward Jenner

The father of modern vaccinology is ____________, whose smallpox vaccine in 1780 cemented our concepts of adaptive immunity and immunological memory, while bringing the ravages of smallpox to an end in Europe.

B-lactamases leukocidin

Mechanisms of antibiotic resistance: 2) Inactivation by enzymes -Inactivation or enzymatic destruction of the drug. -Ex: the production of _____________ that can cleave the antibiotic and make it inactive. -There are nearly 200 variations of this enzyme, each effective against minor variations in the Beta-lactam ring structure. The best known of these resistant bacteria is MRSA. -At first, it used to be primarily a hospital acquired infection (nosocomial infection), but now it is recognized as a frequent outbreak in the general community (community associated MRSA), is more virulent, and affects otherwise healthy individuals. -These strains produce a toxin, __________, that destroys neutrophils, a primary innate defense against infection.

protein synthesis penicillin binding protein (PBP)

Mechanisms of antibiotic resistance: 3) Alteration of target molecule -Antibiotics like tetracycline, and macrolides utilize a mode of action that inhibits ______________, specifically by interrupting interactions between the ribosome and mRNA. -However, minor modifications at this site can neutralize the effects of these antibiotics. -the main mechanism by which MRSA gained ascendency over methicillin was not by inactivation of Beta-lactamases but by modifying the target, a _______________, on the cell's membrane. -Beta-lactam antibiotics work by binding the PBP, but if PBP is a different shape, then methicillin no longer works on it.

concentration

Mechanisms of antibiotic resistance: 4) Efflux of antibiotic (Rapid ejection of the drug) -certain bacterial proteins pump and expel antibiotics from the cell, preventing them from reaching an effective ___________.

Betalactamase

Natural Penicillins The Effect of Penicillinase (B-lactamase) on Penicillins: -Bacteria that produce the __________ enzyme can break the B-lactam ring, and is the most common form of resistance to penicillins. -R is an abbreviation for the chemical side groups that differentiate similar or otherwise identical compounds. -Numerous B-lactamase varieties (or forms) and can be transferred between individuals since the gene for this enzyme is often borne on a plasmid.

common nucleus side chains penicillinases G V

Natural Penicillins The portion that all penicillins have in common (which contains the B-lactam ring) is called the ____________. -The portion called the __________ distinguish one penicillin from another. -These compounds have a narrow but useful spectrum of activity, they work against most staphylococci, streptococci, and some spirochetes. -Natural penicillins are sensitive to _____________ (enzymes that are made by many bacteria that will cleave the B-lactam ring, making the compound useless) Due to this characteristic, penicillinases are also called B-lactamases. 2 Natural Penicillins: -Penicillin ____ (requires injection) -Penicillin ____ (can be taken orally)

reverse transcription variability

Poor virus replicase fidelity is a pathogenesis factor for some viruses This replicase quality enhances the survival of HIV: -HIV lacks proofreading enzymes to correct errors made when it converts its RNA into DNA via ______________ -Its short life-cycle and high error rate cause the virus to mutate very rapidly, resulting in a high genetic __________ of HIV. -Most of the mutations either are deleterious or convey no advantage, but some of them provide an advantage such as withstanding the human immune system and antiretroviral drugs.

proofreading antiviral HIV

Poor virus replicase fidelity is a pathogenesis factor for some viruses. -RNA virus polymerases make frequent mistakes during replication. -Virus replicase enzymes lack the strict, __________ fidelity of cellular DNA enzymes. -The result is altered virus genomes, proteins and glycoproteins. This can result in many defective virions as well as virions resistant to ________ drugs and host immune responses. -This replicase quality enhances the survival of ________.

non immune

Principles and Effects of Vaccination -This slide shows a graphic of this: In panel "a" : In an unprotected population, an infected individual (red) can successfully infect (arrows) all of the healthy individuals. Newly infected individuals will in turn transfer the pathogen directly to other healthy individuals. In panel "b" if you are able to vaccinate a number of individuals in this population (yellow), then this greatly reduces or even breaks the cycle of transmission.

primary secondary Herd

Principles and Effects of Vaccination -Provokes a ___________ immune response (leads to the formation of antibodies and memory cells -produces a rapid, intense ___________ response -__________ Immunity: immunity in most of the population (outbreaks are sporadic due to the lack of susceptible individuals) -When immune people are present in a community, we call this Herd immunity, and this type of immunity in some individuals will protect non-immune individuals from infection.

infectious disease

Safety of Vaccines -On rare occasions, vaccines can cause the disease -no medical or scientific proof of MMR vaccines being linked to autism -safest and most effective means of preventing ___________ in children

methicillin-resistant Staphylococcus aureus (MRSA) ampicillin

Semisynthetic penicillins -semisynthetic penicillins have the common nucleus with the Beta-lactam ring derived from the natural penicillin, but has synthetic side chains attached off of it (part of the penicillin is made by the mold, the other part is added synthetically) -These were made to combat the disadvantages of natural penicillins, mainly the Betalactam resistant bacteria. -Methicillin was one of the first semisynthetic penicillins, but resistance soon appeared, thus the organisms were termed ______________. The term has now come to apply to strains that developed resistance to a wide range of penicillins and cephalosporins. -Broader (extended) spectrum antibiotics were developed, such as __________ and amoxicillin. When resistance became more common to these, a different approach was needed. -_______________ = Amoxicillin + potassium clavulanate (This compound is a an inhibitor of Beta-lactamase, and is one of the most prescribed antibiotics)

antigenically memory

Smallpox vaccine -The smallpox vaccine worked because ___________ similar cowpox was "cross-protective" against Variola with only limited pathogenicity. -Although successful, this approach hasn't been replicated for many other disease vaccines because few such cross-protective pathogen dopplegangers exist for us to use as vaccine strains. -Absent cross-protective organisms, modern vaccines take advantage of the science behind variolation, relying on part or all of the actual pathogen in the vaccine mixture to induce immunological __________ against the pathogen antigen without having to actually introduce the virulent pathogen.

common nucleus crosslinking positive

The Action of Antimicrobial Drugs 1) Inhibition of Cell Wall Synthesis -Penicillin: group of >50 chemically related antibiotics -all penicillin have a common core structure containing a B-lactam ring called the ____________, which is the active component of the molecule -Penicillins work by preventing the ___________ of peptidoglycans, interfering with the final stages of cell wall construction, primarily of Gram-___________ bacteria

inhibition of cell wall synthesis inhibition of protein synthesis inhibition of nucleic acid replication & transcription injury to plasma membrane inhibition of essential metabolite synthesis

The Action of Antimicrobial Drugs Antimicrobial drugs target certain essential functions of the microbe. Name the 5 actions of antimicrobial drugs

Superbugs methicillin

The Development of Antibiotic resistant mutant during antibiotic therapy: -Bacteria that are resistant to a large number of antibiotics are popularly called __________. -The most publicized is ____________ resistant Staphylococcus aures (MRSA)

progeny reproductive

The Development of Antibiotic resistant mutant during antibiotic therapy: How does this resistance arise? -When first exposed to a new antibiotic, the susceptibility of the microbe is high, and the mortality rate is high, but a few microbes survive. -The surviving microbes usually have some genetic characteristic that accounts for their survival, and their _________ are similarly resistant. -These surviving microbes have always been in the population, its just that application of the antibiotic selected for their survival, and they are the ones to thrive and pass on their resistance genes. -Such genetic differences arise from random mutations, and they can be spread horizontally among bacteria by conjugation, or transduction. -Drug resistance is often carried by plasmids or by transposons. Some plasmids can even be transferred between different species. -Due to the rapid ___________ rate of bacteria, it is only a short time before practically the entire selected population is resistant to the new antibiotic.

broad spectrum

The Spectrum of Antimicrobial Activity -_________ spectrum: some drugs have a larger range that they affect. -Antibiotics that affect Gram-positive and Gram-negative bacteria -Examples include tetracycline (which work against both Gram-positive and Gram-negative cell wall types), phenols, fluoroquinolones, "third-generation" and fourth-generation" cephalosporins

Narrow Spectrum

The Spectrum of Antimicrobial Activity -______________ spectrum antibacterials have limited activity and are primarily only useful against particular species of microorganisms. -i.e. only effects gram-negatives or only gram-positives, or only against aerobes or only against anaerobes

Natural Penicillins Semisynthetic penicillins Extended-spectrum penicillins Penicillins + B-lactamases inhibitors

The Structure of Penicillins 4 types of penicillins based on structure

Penicillins + B-lactamases inhibitors

The Structure of Penicillins ______________ Penicillins: Augmentin (amoxicillin and potassium clavulanate)

Extended-spectrum penicillins

The Structure of Penicillins ______________ Penicillins: broader spectrum, gram-negatives too (Eg. ampicillin, amoxicillin)

Natural penicillins

The Structure of Penicillins ______________ Penicillins: extracted from mold Penicillium (Eg. Penicillin G, Penicillin V). -Narrow spectrum, gram-positives -are susceptible to penicillinase (B-lactamases), an enzyme that cleaves the B-lactam ring

Semisynthetic penicillins

The Structure of Penicillins ______________ Penicillins: part of the penicillin made by the mold, the other part added synthetically (Eg. Methicillin) -due to MRSA, discontinued methicillin -Oxacilin: Narrow spectrum, only gram-positives, but resistance to penicillinase -Ampicillin: Extended spectrum, many gram-negatives

toxicity

Therapeutic Index -This is a comparison of the amount of the antibiotic that causes the therapeutic effect (efficacy) to the amount of antibiotic that causes __________. -Sometimes this window can be wide, which is ideal. This means there is a large difference between the dose that is efficacious and the dose that causes adverse effects

narrow wide

Therapeutic Index -if therapeutic margin is ___________, the antibiotic has a low therapeutic index (ex: streptomycin) (this means that inconsequential factors like food-drug interactions, drug-drug interactions, or small errors in dosing can have harmful clinical effects) -if an antibiotics therapeutic margin is _______, it has a high therapeutic index (ex: many beta lactic antibiotics)

infection

Types of Adaptive Immunity 1.Naturally acquired active immunity: -Antigens enter the body naturally; body induces antibodies and specialized lymphocytes -resulting from ___________ -develops when a person is exposed to antigens, becomes ill, recovers. Once acquired, immunity is lifelong for some diseases, such as measles. For other diseases, especially intestinal ones, the immunity may only last a few years.

placenta mothers milk

Types of Adaptive Immunity 2. Naturally acquired passive immunity: -Antibodies pass from mother to fetus via ______________ or to infant via the _____________ -involves the natural transfer of antibodies from mother to infant. -Antibodies in a pregnant woman can cross the placenta and provide immunity to the fetus, however, this passive immunity generally lasts only as long as the transmitted antibodies persist, usually a few weeks or months. -Certain antibodies are also passed from mother to her nursing infant. These maternal antibodies are essential for providing immunity to the infant until its own immune system matures.

immunization

Types of Adaptive Immunity 3. Artificially acquired active immunity: -Antigens are introduced in vaccines; body produces antibodies and specialized lymphocytes -injection of vaccination (_____________) -This is the deliberate introduction of vaccines into the body. -These vaccines are made of antigens such as killed or living microorganisms, or inactivated bacterial toxins.

antigens antiserum acute

Types of Adaptive Immunity 4. Artificially acquired passive immunity: -Preformed antibodies in immune serum are introduced by injection -Injection of antibodies (rather than ___________) -These antibodies come from an animal or person who is already immune to the disease. -The individual receiving the antibodies played no active part in antibody production; he or she receives pre-formed antibodies through injection of an _______________ (serum containing antibodies from the blood of an immune individual) or from purified antibodies (immunoglobulin) derived from an immune individual. -These antibodies gradually disappear from the body, and a later exposure to the antigen cannot elicit a secondary response. This type of immunity is used to prevent or treat ___________ infectious diseases such as tetanus and in the treatment of bites by venomous animals.

Naturally acquired active immunity Naturally acquired passive immunity Artificially acquired active immunity Artificially acquired passive immunity

Types of Adaptive Immunity There are 4 different types of adaptive immunity:

Live attenuated vaccines

Types of Vaccines -Weakened pathogen -closely mimic an actual infection -confers lifelong cellular and humoral immunity

Live attenuated vaccines Inactivated killed vaccines Subunit vaccines Conjugated vaccines Nucleic acid (DNA) vaccines

Types of Vaccines The Five types of vaccine used today are: (5)

Inactivated killed vaccines

Types of Vaccines: -safer than live vaccines -require repeated booster doses -induce mostly humoral immunity

Subunit vaccines

Types of Vaccines: __________ vaccines use antigenic fragments of a microbe to stimulate an immune response -This avoids the dangers associated with the use of a live or killed pathogen.

Nucleic acid (DNA) vaccines

Types of Vaccines: -injected naked DNA produce the protein antigen encoded in the DNA -protein antigens carried to the red bone marrow stimulate humoral and cellular immunity

Conjugated vaccines

Types of Vaccines: ____________ vaccines: used for disease in children with poor immune response to capsular polysaccharides

ethyl discontinuation

Vaccines Controversy -some are convinced thimerosol in certain vaccines may induce autism (though autism rates have continued to clime despite its widespread removal from most vaccines) -Anti-vaxxers cite the devastating effects of methyl mercury on brain function during mercury poisoning -thimerosol is a derivative of _______ mercury, which is far less toxic than methyl mercury, and was used in minute concentrations -Despite public opinion, a comprehensive study of autism in Yokohama, Japan found that autism rates continued to rise at rates similar to the US even after _______________ of the MMR vaccine

capsular proteins antibody

Types of Vaccines: Conjugated vaccines -Conjugated vaccines have been developed to deal with the poor immune response of children to vaccines based on _________ polysaccharides. -These polysaccharides are T-independent antigens; children's immune systems do not respond well to these antigens until they are between 15- 24months. -Polysaccharide antigens are large molecules consisting of repeating epitopes which are not processed by antigen-presenting cells (APC) but interact directly with B cells, inducing antibody synthesis in the absence of T cells (thus designated T-independent antigens). -T-independent responses are limited, but most importantly, they fail to induce significant and sustained amounts of _________ in young children. -The solution is to combine these polysaccharides with __________ such as diphtheria or tetanus toxoids, which will enhance the immunogenicity and prime the memory response

rabies and influenza booster humoral

Types of Vaccines: Inactivated killed vaccines -these vaccines use microbes that have been killed, usually by chemical agents such as phenol, formaldehyde, and even physical agents such as heat. -Eg. Formaldehyde is used to inactivate viruses for vaccines, such as in the inactivated (Salk) polio vaccine. -Other inactivated virus vaccines used in humans also include the ________ and _________ vaccines. -Killed virus vaccines tend to provide short lived immune responses with less long term memory, but they are relatively easy to store and maintain their potency for long periods of time. -Compared to live attenuated vaccines, these inactivated vaccines often require repeated __________ doses. -They also induce mostly _________ antibody immunity, which makes them less effective than live attenuated vaccines in inducing cellular immunity.

rabies chicken cholera

Types of Vaccines: Live attenuated vaccines -Ex:Pasteur's experiments with _______ and _________. -His experiments used weakened strains of the pathogens to induce immunity. This is a vaccine made from live cells or virus pathogens that has lots its virulence (has been attenuated or weakened) but still retains the immunizing antigens; -because these attenuated strains are still viable, some individuals (i.e. the immunocompromised) may acquire active disease.

effective T cell measles

Types of Vaccines: Live attenuated vaccines -Immunization with live cells or virus is usually more __________ than with dead or inactivated material (b/c live vaccines more closely mimic an actual infection) -As the pathogen reproduces within the host cells, cellular, as well as humoral immunity is usually induced. -Many effective viral vaccines are live attenuated vaccines. These vaccines provide the long lasting ___-cell mediated immunity, as well as vigorous antibody immunity and a strong secondary response upon re-immunization of infection with the targeted pathogen. -However, attenuated strains are hard to select, standardize, and maintain. -Live, attenuated vaccines, like _________ vaccines (part of the MMR vaccine), have a limited shelf life and require refrigeration for storage.

expression plasmids plasmid West Nile

Types of Vaccines: Nucleic acid (DNA) vaccines -Nucleic acid (DNA) vaccines: often called DNA vaccines, are very new and promising. -It is based on __________ of cloned genes in host cells. -They tend to be bacterial _________ that contain cloned DNA with the antigen of interest. -This vaccine is injected intramuscularly into a host animal. -Once the ________ is taken up by host cells, the DNA is transcribed and translated to produce the immunogenic proteins, triggering a conventional immune response including Tc cells, Th1 cells, and antibodies directed to the protein encoded by the cloned DNA. -Some DNA vaccines have been approved, one that protects horses from _________ virus has been introduced.

Toxoids toxoids toxoids

Types of Vaccines: Subunit vaccines -__________, which are inactivated toxins, are vaccines directed at the toxins made by a pathogen, which can be considered subunits of the pathogen. -The active form of a toxin cannot be used as a vaccine because of the toxic effects, but many (exo)toxins can be modified chemically so they retain their antigenicity but are no longer toxic. -These modified toxins are called ___________. -this vaccine induces long term protective immunity against the exotoxin. Examples include the Clostridium tetani exotoxin that has been made into a _________

recombinant hepatitis B whooping cough

Types of Vaccines: Subunit vaccines -subunit vaccines that are produced by genetic modification (i.e. other microbes are programmed to make the desired antigenic fraction) are called ___________ vaccines -The vaccine against the __________ virus consists of a portion of the viral protein coat that is made by a genetically modified yeast. -The acellular pertussis (____________) vaccine is made of inactivated pertussis toxin and filamentous hemagglutinin antigens.

Virus-like particle (VLP) vaccines

Types of Vaccines: Subunit vaccines -subunit vaccines that resemble intact viruses but do not contain viral genetic material are called ______________ vaccines

recombinant vaccines virus-like particle (VLP) vaccines toxoids

Types of Vaccines: Subunit vaccines types of subunit vaccines

Vaccinia virus

Vaccination -During the mid 1700s, multiple people made the observation that cows suffered a disease relatively similar to smallpox, and that dairy milkmaids could contract this cowpox from the cows they milked. -However, the cowpox was rapidly eliminated by the maids' immune systems & milkmaids were far less likely to acquire smallpox -Though multiple people sought to test if cowpox (which is caused by the _________) could protect against smallpox, the definitive study was conducted by Jenner in 1796 in a study that NOBODY would sanction today.

variolous inflammation immunization

Vaccination -in 1796 Jenner famously vaccinated 8 year old James Phipps, who was protected from exposure to "_________ matter" 6 weeks later -made 2 cuts on arm and inserted dried matter from a cowpox sore on a dairymaid's hand -A week later James Phipps, was sick for a day, but woke the next day feeling fine. -A month and a half later, Jenner took dried matter from pox blisters on a smallpox patient and inserted it into multiple incisions he made on both of the boy's arms. -Despite local _____________ over the next few days, James never got sick. Jenner tried again several months later, and again James was resistant to the disease. -and so this introduction of Vaccinia matter (or vaccination) to replace variolation is a form of ____________

memory memory

Vaccines stimulate immune memory Secondary (__________) response occurs after the second exposure to an antigen -more rapid, lasts many days, greater in magnitude -____________ cells produced in response to the initial exposure are activated by the secondary exposure

infection vaccination

Vaccines stimulate immune memory -Recall that Adaptive immunity can be acquired through _________ or ____________. -We can further characterize an adaptive response as a Primary response or secondary response. -The primary response occurs the first time the immune system combats a particular foreign substance.

lymphocyte IgM IgM IgG

Vaccines stimulate immune memory -The goal of vaccination is to produce a memory _____________ response to specific pathogen antigens. -Vaccination or immunization is the purposeful artificial induction of active immunity. -In active immunity, introduction of antigen induces changes in the host, the immune system produces antibodies in a primary immune response, and more importantly, produces a large number of immune memory cells. -A second ("booster") dose of the same antigen results in a faster response yielding much higher levels of antibodies and immune T cells due to this memory, or secondary immune response. -When we mount an antibody response ______ is the first antibody produced first. Eventually, the _______ response is overtaken by the more powerful by _______ response.

antibody titer IgG

Vaccines stimulate immune memory One way we can assess a memory response is by determining a person's ___________: the relative amount of antibody in the serum. -It reflects intensity of the humoral response. -When we mount an antibody response IgM is the antibody produced first. Eventually, the IgM response is overtaken by the more powerful _______ response.

B reservoire

Vaccines stimulate immune memory Since we'd like to prevent pathogen from reproducing in the body, the specific goal of vaccination is to produce memory ____ cells that can serve as a ______________ for neutralizing and opsonizing antibodies that would bind bacteria or virus or protist or fungus, or toxins secreted by a pathogen, and either neutralize the pathogen or toxin, or opsonize it to allow efficient removal by other immune cells.

virus

Variolation -The idea behind this approach was disease taken from a person fighting it would be less harmful than disease acquired "naturally." -Obviously, the doctors at this time had no idea the disease was caused by a _________ or that natural transmission was typically person to person. -However, what these doctors did quickly come to appreciate was that administering the disease in this way led to far fewer deaths than not (doctors killed only 1-2% of their inoculation patients, whereas smallpox mortality was 30%).

random mutations Horizontal Gene Transfer:

What Biological mechanisms gives rise to antibiotic resistance? 2 mechanisms:

transformation transduction conjugation

What Biological mechanisms gives rise to antibiotic resistance? Horizontal Gene Transfer: 1. Bacterial ____________ 2. Bacterial ___________ 3. Bacterial ___________

spectrum antimicrobial activity

____________ = the range of different microbial types that drugs affect.

Adjuvants

______________ are chemical additives added to vaccines to improve effectiveness -Alum (aluminum hydroxide) and MF59 (a mixture of water and squalene, which is an oil found in all organisms, but especially in the livers of sharks) are the only approved one in the U.S. -these improve the immune response

antibiotic antimicrobial drugs

______________: a substance produced by a microbe that, in small amounts, inhibits another microbe _____________: synthetic substances that interfere with the growth of microbes (compounds that kill or control the growth of microbes in the host/in vivo)

bactericidal bacteriostatic

_______________: kills microbe directly _______________: prevent microbes from growing

selective toxicity chemotherapy

_________________: selectively finding and destroying pathogens without damaging the host _____________: the use of chemicals to treat disease (Termed by Paul Ehrlich)