Exam #3 Microbio

HIV vaccine research

- One approach focuses on inducing the person to produce broadly neutralizing antibodies (bnABs) - Production of bnABs appears to be facilitated by a subset of TH cells called T follicular helper cells (Tfh) Broadly Neutralizing HIV-1 Antibodies (bNAbs) are neutralizing antibodies which neutralize multiple HIV-1 viral strains A neutralizing antibody (NAb) is an antibody that defends a cell from an antigen or infectious body by neutralizing any effect it has biologically. An example of a neutralizing antibody is diphtheria antitoxin, which can neutralize the biological effects of diphtheria toxin.

What is the normal WBC count in the peripheral blood? How do certain infections affect the total count?

5,000-10,000 WBC per cubic mL or 5-10 x 10^9 WBC's per liter Abnormal blood cell counts give health care providers important clues for diagnosing infections and other conditions. High WBC's = higher than average leukocytes (normally bacterial infection) could also be from autoimmune disorder Low WCB's = Lower than average leukocytes Viral infection or pneumonia also from autoimmune disease such as lupus, certain cancers, lymphoma also when extremely severe bacterial infection such as septicemia.

Review which parts of the body have microbiota and which should remain sterile, and understand the features that facilitate or inhibit bacterial infection in each.

"Sterile" sites include nervous tissue, kidneys, lower respiratory tract, blood, fluids such as chest, peritoneal, joint; internal body sites) stab wound/contamination/breaking of bone/rupture of organs from something = spread from microbes

Microbiota = Urinary and Reproductive Systems

- Bacteria found in vaginal mucous membranes in women & distal urethra of men and women - Resident microbiota include some opportunistic pathogens - Mucus & periodic shedding prevent bacteria from attaching - pH-controlled communities

Describe the mechanism of action of the antifungal agent miconazole. Is this antibiotic selectively toxic?

Anti fungal: examples: yeast infections/athletes foot Outcome: Disrupts fungal plasma membranes EUKARYOTE Mechanism of action: target the sterols in the plasma membrane. when biosynthesis of ergosterol in a fungal membrane is interrupted, the membrane becomes excessively permeable, killing the cell. In fungal membranes the principle sterol is ergosterol, in animal membranes its cholesterol Because of this: Inhibition of ergosterol biosynthesis is the basis of the selective toxicity of many antifungals.

Why are drugs that target cell walls (specifically peptidoglycan synthesis) generally considered "narrow spectrum" while antibiotics targeting protein synthesis or nucleic acid replication are considered "broad spectrum"?

Because they effect mainly Gram + bacteria because of their thick layer of peptidoglycan and lack of outer membrane to protect them. Antibiotics that target protein synthesis or nucleic acid replication are broad spectrum because both protein synthesis and and nucleic acid replication are both common features in all cells whether prokaryotic or eukaryotic

Explain the strategies to control HAIs.

Control of Healthcare-Associated Infections • Reduce number of pathogens - Handwashing - Disinfecting tubs used to bathe patients - Cleaning instruments scrupulously - Using disposable bandages and intubation • Infection control committees

What is a cytokine?

Cytokines are proteins that regulate the intensity and duration of immune responses. One roll of cytokines is to recruit other macrophages and dendritic cells, as well as other defensive cells, to isolate and destroy the microbes as part of the inflammatory response. Cytokines can also activate the T and B cells involves in adaptive immunity.

What is valence?

Each antibody has at least 2 identical antigen-binding sites that bind to epitopes. The number of antigen binding sites on an antibody is called a Valence of that antibody. Example: human antibodies have 2 binding sites = Bivalent

Edible vaccine

Edible vaccines-eat a plant(e.g.banana) and get immunized! HOW??? • Introduce DNA for pathogen antigen (via a plasmid) into plant cells • Plant cells transcribe/translate the DNA to produce the pathogen protein (antigen) • The antigen protein product is eaten and the human's immune system responds accordingly

What is the fecal-oral route?

Fecal-oral transmission occurs when bacteria or viruses found in the stool of one child (or animal) are swallowed by another child. This is especially common in group-daycare settings, where fecal organisms are commonly found on surfaces and on the hands of providers. Usually, the contamination is invisible.

What are healthcare-associated infections (HAI)? (Old term: nosocomial.) Explain the chain of transmission that establishes the environment for HAI.

HAI: infections patients squire while receiving treatment for other conditions at a healthcare facility (nursing hoe, hospital, same day surgery center) 1) direct contact transmission from hospital staff to patient and from patient to patient 2) indirect contact transmission through fomites and the hospitals ventilation system

Describe the roles of cytokines such histamine and leukotrienes in inflammation.

Histamine: causes vasodilation and increased permeability of blood vessels Leukotrienes: produced by mast cells --> cause increased permeability of blood vessels to help attach phagocytes to pathogens main roles of compliment system: stimulate release of histamine, attract phagocytes, promote phagocytosis

What is a virulence factor? Identify various virulence factors for bacteria as it relates to the process of infection.

How do microbes cause disease? - Virulence factor: any metabolic or structural component that enables an organism to cause disease - E.g. Adhesion factors, biofilm formation, enzymes, toxins, factors that allow evasion of immune system

3 of 3 consequences of complement activation: inflammation

Inflammation: 1) activated C3 splits into C3a and C3b 2) C3a and C5a bind to mast cell and cause them to release histamine and other chemicals that increase blood vessel permeability during inflammation C5a - attracts phagocytes to site of infection with chemotactic factor

Inhibition of nucleic acid synthesis

Rifampin Fluoroquinolones

What types of molecules are good antigens?

Size (large), complex (proteins), easily soluble Most antigens are either proteins or large polysaccharides. Lipids and nucleic acids are only antigenic when combined with proteins and polysaccharides. antigenic compounds often: capsules/cell walls/flagella/fimbriae/and toxins of bacteria

microbiota = skin

Skin - Most accessible, but least hospitable - Dry skin & dead cells are good barriers - Mostly transient microbes - Infections arise from breaks in the skin, some bacteria can enter through glands

Define the term "magic bullet" Explain why selective toxicity is an important parameter to consider when researching or prescribing antimicrobial drugs.

Specific chemicals that destroy pathogens and not harm the host. this concept briefly explains selective toxicity, the goal was to selectively find and destroy pathogens but not harm the host.

TCR

T cell receptor - molecules on T cell surface that recognize antigens; initiates specific immune response

What are the clusters of differentiation (CD)?

T cells are classified by certain glycoproteins on their surface called clusters of differentiation or CD. these are membrane molecules that are especially important for adhesion to receptors. CD's of great interest are CD4 and CD8, the cells that carry these molecules are called CD4+ and CD8+ TH cells are classified as CD4+ (bind to MHC class II molecules on B cells and APC's) CTL cells are classified as CD8+ cells (Bind to MHC I molecules)

Draw and explain the difference between a BCR and a TCR.

TCR: T cell receptor - molecules on T cell surface that recognize antigens; initiates specific immune response BCR: B cell receptor - immunoglobulin receptors on B cell surface that recognize antigens; initiates specific immune response Similar properties: • They are integral membrane proteins. • They are present in thousands of identical copies exposed at the cell surface. • They are made before the cell ever encounters an antigen. • They are encoded by genes assembled by the recombination of segments of DNA. • They have a unique binding site. • This site binds to a portion of the antigen called an antigenic determinant or epitope. BCRs and TCRs differ in: • their structure; • the genes that encode them; • the type of epitope to which they bind.

Rifampin

Type: broad spectrum Outcome: Inhibit synthesis of mRNA. Affects Gene Expression: Stops transcription by inhibiting transcription, ultimately stops protein synthesis Mechanism of Action: Competitive inhibitor of RNA polymerase Notes: Given in combination with other drugs (cocktail) to prevent resistance issues; Broad spectrum of activity

Tetracycline

Type: broad spectrum Outcome: Affects gene expression: stops Protein synthesis Mechanism of Action: Acts at Ribosomal level to interfere with the attachment of tRNA carrying the amino acids to the ribosome at the 30s portion of the 70s ribosome preventing addition of amino acids to the growing polypeptide chain = hereby ruining translation Notes: Broadest spectrum of activity among the protein synthesis-inhibiting antibiotics; toxicity issues (mitochondrial - damage kidney)

Erythromycin

Type: broad spectrum Outcome: Affects gene expression: stops Protein synthesis Mechanism of Action: Acts at Ribosomal level to interfere with translation. target (bacterial ribosomes 70s) Notes: Broad spectrum; Safest of the antibiotics that target protein synthesis; toxicity issues (mitochondrial - damage kidney)

Chloramphenical

Type: broad spectrum Outcome: Affects gene expression: stops Protein synthesis Mechanism of Action: inhibits formation of peptide bonds in growing polypeptide chain by reacting with the 50s portion of the 70s prokaryotic ribosome. Notes: Broad spectrum Not prescribed in US; can cause aplastic anemia; toxicity issues (mitochondrial - damage kidney)

Streptomycin (aminoglycosides)

Type: broad spectrum Outcome: Affects gene expression: stops Protein synthesis Mechanism of Action: interferes with the initial steps if of protein synthesis by changing the shape of the 30s portion of the 70s prokaryotic ribosome. Causes genetic does of the mRNA to be read incorrectly. Notes: Broad spectrum; toxicity issues (mitochondrial - damage kidney)(hearing damage by damage to auditory nerve First antibiotics to have significant activity against gram - bacteria.

Fluoroquinolones

Type: broad spectrum Outcome: Affects gene expression: stops DNA synthesis. Selectively inhibits enzyme DNA gyrate needed for replication of DNA Mechanism of Action: Inhibit two enzymes: Topoisomerase IV (separates new DNAs) 2. DNA gyrase (helps unravel DNA) Notes: Relatively nontoxic - Resistance can develop rapidly, even during course of treatment

Trimethoprim-sulfamethoxazole (TMP-SMX aka TMP-SMZ)

Type: broad spectrum Outcome: Stops synthesis of nucleic acids and amino acids Mechanism of Action: Structurally similar to folic acid precursor PABA, allowing them to competitively bind with the enzyme meant for PABA and blocking folic acid production. Notes: TMP-SMZ is an example of an antibiotic that inhibits the synthesis of essential metabolites. It inhibits the synthesis of FOLIC ACID, a vitamin that acts as a coenzyme for the production of nucleic acid and amino acids.

What is vancomycin? Why is this antibiotic important in combating MRSA?

Vancomycin is one of a small group of glycopeptide antibiotics derived from a species of streptomycin found in the jungles of Borneo. Considered the "antibiotic last resort" Mechanism of action: inhibition of cell wall Synthesis => Has a mode of action against cell wall synthesis that is totally different from that of penicillins. Stops peptidoglycan synthesis Blocks peptides on NAM from crosslinking

Describe the principles of vaccination

Viral diseased cannot be effectively treated once contracted. Therefore vaccination is frequently the only feasible method of controlling the viral disease. Controlling a disease does not necessarily require everyone to be immune to it, if most of the population is immune it leads to herd immunity = Outbreaks are limited to sporadic cases because there are not enough susceptible individuals to support the spread of epidemics.

Adjuvants:

aluminum salts added to vaccine that improve vaccination effectiveness.

whats the difference between an animal reservoir and an animal vector

animal reservoir = can carry organisms that can cause disease/ pathogenic bacteria Animal vector = vectors = Mosquitos/ other bugs

Describe the common sites for microbiota and pathogens. Why are mucous membranes a desirable tissue for microbes?

Mucous membranes are the tissue of choice for microbes - External (exposed to environment) - Warm and moist (more hospitable than dry skin) • Where can microbiota can be found? - distal part of urethra (men & women) - skin - Upper respiratory tract - Oral cavity - intesine (especially large intestine) - Vaginal tract - Very little in eyes and stomach "Sterile" sites include nervous tissue, kidneys, lower respiratory tract, blood, fluids such as chest, peritoneal, joint; internal body sites)

What is the difference between an animal reservoir and an animal vector?

animal reservoir: carries microorganisms that cause disease on humans. Diseases that occur primarily in wild and domestic animals. animal vector: carry pathogens from one host to another (mainly insects and arthropods) -mechanical transmission: passive transport on insects feet or body parts ex: house flies = pathogens from bacillary dysentery from feces of infected people to food -Biological trasmission: bites = ingests infected blood, pathogens reproduce in vector, vector bites human paracites: reproduce in gut of arthropod

Gateway cells in the gastrointestinal tract where antigens are taken up and transferred to APCs are called a) Kuppfer's cells. b) M cells. c) dendritic cells. d) Langerhans cells.

b) M cells.

What recently discovered substances are short chains of amino acids that may be one of the most important components of innate immunity? a) complement proteins b) antimicrobial peptides c) iron-binding proteins d) interferons

b) antimicrobial peptides

Antibody molecules that are produced by a single hybridoma clone are called a) human antibodies. b) monoclonal antibodies. c) hybrid antibodies. d) identical antibodies.

b) monoclonal antibodies.

Which is a bacterial iron-binding protein? a) transferrin b) siderophore c) ferritin d) hemoglobin

b) siderophore

How is the humoral immune response to a T-independent antigen different from the humoral response to a T-dependent response?

NO MEMORY CELLS GENERATED WITH T INDEPENDENT antigens B cell activation by T-independent antigens • Under some conditions, clonal expansion of B-cell can occur without additional help... • T-independent B-cells stimulate the B cell to undergo clonal expansion and differentiation into plasma cells without the help of T cells - Provoke a weak immune response, usually producing IgM - No memory cells generated A better immune response occurs when the activated B-cell is "helped" by an activated TH cell - Called T-dependent B-cell activation

Give an example of a disease from each of the following categories of infectious agents that are transmitted from animal reservoirs: a bacterium; a virus; and a prion.

bacterium: Lyme disease, rabies, bubonic plague Virus: Bird flu prion: Mad Cow Disease

Lymphocytes : Natural Killer cells What do they do? in blood or in tissue? Innate or adaptive?

Natural killer cells NK cells found in blood, spell, lymph nodes and red bone marrow NK kill infected body cells, tumor cells, or any cells displaying abnormal plasma membrane proteins NK cell binds --> releases perforin into plasma membrane, creating holes in membrane --> extracellular fluid flows into cell --> cell bursts = cytolysis NK cell binds --> releases granzymes (protein digesting enzymes) --> induce apoptosis (self destruction) --> killing infected cells not microbes --> microbes released may be intact --> then destroyed by phagocytes

Were humans the original benefactors of antibiotics?

No humans were not the original benefactors of antibiotics. The organism producing them was

What are the principle types of infections found in HAIs

bloodstream: 10% UTI's : 13% other : 16% Gastrointestinal infections: 17% Lower respiratory infections: 22% Surgical site infections: 22%

Contrast obligate and opportunistic pathogens. Describe a few opportunities that an opportunistic bacterium might seize to cause infection.

Obligate pathogens: bacteria that always have a parasitic relationship with a host (e.g. Mycobacterium tuberculosis, Treponema palladium) Opportunistic pathogens: Normally harmless (mutualists or commensals), but can cause disease under the right circumstances (e.g. Pseudomonas aeruginosa, Escherichia coli) 1. Compromised immune system 2. Enters new environment in the body 3. Disturbances in the normal microbiota

What type of molecule is an antibody?

PROTIEN An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein produced mainly by plasma cells that is used by the immune system to neutralize pathogens such as bacteria and viruses. The antibody recognizes a unique molecule of the harmful agent, called an antigen, via the Fab's variable region.

PAMP's

Pathogen-associated molecular patterns

pathogenicity definition

Pathogenicity: ability of a microorganism to cause disease

Why are AMPs (antimicrobial peptides) of interest to researchers?

broad spectrum of activity shown synergy with other antimicrobial agents. so effect of them together is greater than either working separately. very stable over wide range of pH Microbes do not appear to develop resistance even after being exposed for long periods of time can get LPS to shed from Gram - => no endotoxin released Attack dendritic cells => destroying microbes by phagocytosis recruit mast cells = increased blood vessel permeability and vasodilation =. inflammation, destroying microbes, initiating tissue repair

For which of the following diseases does a vaccine NOT currently exist? a) meningococcal meningitis b) human papillomavirus c) hepatitis C d) smallpox

c) hepatitis C

Which of the following is NOT a factor that contributes to healthcare-associated infections? a) compromised host b) chain of transmission in the hospital c) normal microbiota on the patient d) microorganisms in the hospital environment

c) normal microbiota on the patient

The stage of disease that is characterized by early, mild symptoms is called the a) period of illness. b) incubation period. c) prodromal period. d) period of convalescence.

c) prodromal period.

A patient's blood did NOT have any antibody titer before an illness but has a significant titer while the disease is progressing. This phenomenon, which occurs in HIV infections, is called a) variolation. b) attenuation. c) seroconversion. d) agglutination.

c) seroconversion. Seroconversion is the period of time during which HIV antibodies develop and become detectable. Seroconversion generally takes place within a few weeks of initial infection. It is often, but not always, accompanied by flu-like symptoms including fever, rash, muscle aches and swollen lymph nodes

The spread of pathogens via contaminated water is an example of ________ transmission. a) indirect contact b) direct contact c) vehicle d) vector

c) vehicle

How do NK cells participate in antibody-dependent cell-mediated cytotoxicity (ADCMC)?

if an organism, such as a parasitic worm is too large for ingestion and destruction by phagocytosis, it can be attacked by immune system cells that remain external to it. NK cells = release vesicles containing toxic substances -Perforin: channels => extracellular fluid leaks => cell bursts -Granzymes : protein digesting enzymes => apoptosis NK cells bind to Fc regions of attached antibodies => target cell is lysed

Explain the strategy behind combination therapy for treating: b. HIV/AIDS

in consideration of the large number of drugs required to treat HIV, especially to minimize development of resistant strains, combinations of drugs have been developed. An example is atripla which combines tenofovir, emtricitabine, and efavirenz. - If resistance occurs to one drug, there is another to continue to eradicate the pathogen - Attack multiple parts of a pathogen's metabolism cocktail : HAART = highly active anti retroviral therapy

Toxoids

inactivated toxins, directed at toxins produced by a pathogen. Examples: tetanus and diphtheria Requires a series of boosters to gain full immunity followed by boosters every 10 years. streptococcus pneumoniae = virulent primarily because their polysaccharide capsule makes them resistant to phagocytosis = vaccine targets capsule

Describe the process of phagocytosis using the macrophage as an example.

infection -> shift occurs in the type of WBC's in bloodstream --> granulates (especially neutrophils) dominate during initial phase of bacterial infection, at which time they are actively phagocytic As infection processes --> macrophages dominate phagocytizing remaining living bacteria and dead or dying bacteria.

Microbial antagonism/competitive exclusion Explain the general abundance of microorganisms associated with the human body, and distinguish the different types of relationships they have with the human host

normal microbiota can benefit the host by preventing overgrowth of harmful microorganisms, this is called microbial antagonism. involves competition among microbes normal microbiota protect the host against colonization by potentially pathogenic microbes by competing for nutrients, producing substance harmful to the invading microbes, and after affecting conditions such as pH and available oxygen

Natural Killer (NK) Cells

not immunologically specific but can kill cells that do not display MHC I surface glycoproteins

Describe how bacteria can cause infectious disease. What are some portals of entry/exit and how do they usually relate to the site of infection?

Portal of Entry: place where a pathogen enters the body • For a microbe to establish disease, it must come in contact with its preferred site. Often (not always) port of entry is site of infection (or nearby) and, for most, attach to host tissues. - E.g. Mycobacterium tuberculosis infects lower respiratory tract, portal of entry = nasal passages - E.g. Streptococcus pneumoniae causes bacterial meningitis (meninges are part of nervous system), portal of entry = Eustachian tube - Often the portal of exit is the same as entry (e.g. respiratory dz; STD/STI)

Differentiate between resident and transient microbiota. Why can transient microbiota not persist permanently on the human body?

Resident microbiota: permanently colonize the host, do not produce disease (under normal conditions) Transient microbiota: present for days, weeks or months, but cannot persist permanently on the human body Transient microbiota that have been picked up can be easily washed from the skin. In contrast, the normal microbiota cannot be cleansed from the skin during normal hand washing.

Describe the evolution of methicillin-resistant Staphylococcus aureus (MRSA). What is the mechanism of resistance to methicillin?

Resistance of staphylococcal infections to penicillin became a problem because of a plasmid-borne gene for B-Lactamase. Antibiotics that were relatively resistant to this enzyme, such as methicillin, were introduced, but resistance to them soon appeared. These organisms became called methicillin-resistant staphylococcus aureus (MRSA) Mechanism of resistance: Plasmid born gene for B-Lactamase/Penicillinase

Pathology:

the study of disease

1 of 3 consequences of complement activation: Cytolysis

together C5b through C8 and multiple C9 fragments form MAC (Membrane attack complex) MAC creates hole in pathogen's cell membrane--> transmembrane channels -> extracellular fluid into pathogen -> Fluid bursts cell Gram - bacteria = More susceptible to cytolysis ; less layers of peptidoglycan protecting membrane Gram + = many layers of peptidoglycan, limit complements access to plasma membrane ; interfere with cytolysis Bacteria not killed by MAC = MAC resistant

vehicle transmission

transmission of disease agents by nonliving medium such as food, water, air other media include blood, and other body fluids, drugs, and intravenous fluids

What is margination?

within hour of inflammation -> phagocytes appear -> flow of blood decreases -> phagocytes stick to inner surface of blood vessels -> cytokines alter cellular adhesion molecules ->this sticking process in response to local cytokines is called Margination

What is the term used for diseases that occur primarily in wild and domesticated animals and can be transmitted to humans?

zoonosis

What are considerations for managing the current "epidemic" of antibiotic resistance as discussed in class?

»Patients should always finish the full regimen of their antibiotic prescriptions to discourage the survival and proliferation of antibiotic microbes »Patients should never use leftover antibiotics to treat new illnesses or use antibiotics that were prescribed to someone else » Health care workers should avoid unnecessary prescriptions to ensure that the choice and dosages of antimicrobials also decreases the changes that the antibiotic will inadvertently cause resistance among patients normal microbiota

What are the possible outcomes of Ag/Ab binding?

• Agglutination • Opsonization • Activation of complement • Antibody-dependent cell-mediated cytotoxicity • Neutralization

• What is an antibiotic? • Where do they come from?

• Antibiotics originated in the environment to play a much more selective role for the microbes • Human use of antibiotics resulted in overgrowth of resistant strains

Zika vaccine

• DNA vaccine - Recombinant plasmid contains two Zika genes that encode for epitopes - Inject into human - Human cells transcribe/translate to produce the two epitopes - Human immune system responds accordingly

Injury to the plasma membrane

• Daptomycin

Describe the five stages of disease (course of infection). At what stage are the symptoms nonspecific and at which point are they severe? During which stage(s) is a person contagious?

• Development of disease: • Incubation period - time between infection & first symptoms (hours to years) • Prodromal period - short period with mild, early symptoms. • Period of illness- the disease is most severe. Overt signs and symptoms displayed. • Period of decline • Period of Convalescent - healing and tissue repair as body returns to pre-disease state, still contagious

Eosinophil What does it do? in blood or in tissue innate or adaptive?

• Eosinophils (Kill parasites with oxidative burst) production of toxic proteins against certain parasites some phagocytosis Attach to outer surface of parasite and discharge peroxide ions that destroy them. in blood Innate

What is the role of the T regulatory (Treg ) cell?

• Formerly called T suppressor cells • make up 5-10% of T cell population. • Subset of CD4+ T helper cells. Primary function is to combat autoimmunity by suppressing T cells that were not fully "educated" to avoid reacting with body's self, and escaped thymus before doing so Useful in protecting intestinal bacteria required for digestion/protecting fetus from rejection as non self - from overreactive immune system

Ebola vaccine

• Highly protective in trials conducted in 2015 - 2016 • Ring vaccination approach • VSV-EBOV is a live, attenuated vaccine - Altered a mild virus to contain the gene for the Ebola envelope glycoprotein (immunogen)

Inactivated killed vaccines

• Inactivated killed vaccines - e.g. rabies, influenza, polio - Used for pathogens where live vaccine is too hazardous - Only induce humoral immunity; no cell-mediated immunity) - Often require booster doses - considered safer than live vaccine

Live attenuated vaccine

• Live attenuated vaccines - e.g. MMR - Use weakened (attenuated) pathogens - Closer mimic to actual infection (humoral and cell-mediated immunity) - Confers lifelong immunity

Describe the humoral immune response to a T-dependent antigen. Include the terms clonal selection and expansion and address the roles of: • Macrophages/Dendrites • Cytokines • TH cells • B cells • What is the difference between a plasma cell and a memory cell?

• Macrophages and dendrites: APC's that induce immune response by T cells. (engulf microbes, degrade the, transfer them to lymph nodes for display to T cells there) Macrophages phagocytic capabilities are GREATLY increased when they are stimulated to become ACTIVATED MACROPHAGES. (stimulated by ingestion of antigenic material) • Cytokines (produced by Activated T helper cells) further enhance the capabilities of macrophages • TH cells = Produce cytokines which help in proliferation and activation of macrophages • B cells = Proliferation Plasma cells : are clones that produce endless antibodies Memory B cells: memory cells that remember the same pathogen for faster antibody production in future infections.

Mast cell What does it do? in blood or in tissue innate or adaptive?

• Mast cell Kills infected cells - often virus infected via cytolysis or apoptosis (when in tissue) Innate

Monocyte What does it do? in blood or in tissue innate or adaptive?

• Monocyte precursor of macrophages, some macrophages are fixed in certain organs while others wander tissues, causing inflammation. not actively phagocytic until they leave circulating blood and enter body tissues and mature into macrophages in blood (monocyte) in tissue (macropage) Both innate and adaptive

Neutrophil What does it do? in blood or in tissue innate or adaptive?

• Neutrophil Phagocytosis of bacteria and fungi in blood (have ability to leave blood and enter infected tissue and destroy microbes and foreign particles. both innate and adaptive

Inhibitors of cell wall synthesis

• Penicillin G -natural • Penicillin V - natural • Ampicillin; Amoxicillin - semi-synth • Methicillin • Cephalosporons • Carbapenems • Vancomycin

How does resident microbiota influence the host? What is the Gut-Brain Axis?

• Peripheral serotonin - Enterochromaffin cells in the gut produce large quantities of the neurotransmitter serotonin, which may have an effect on signaling in the brain • Production is influenced by gut microbes • Immune system - The intestinal microbiome can prompt immune cells to produce cytokines that can influence neurophysiology Bacterial molecules - Microbes produce metabolites, such as butyrate, which can alter the activity of cells in the blood-brain barrier

Subunit Vaccine

• Subunit vaccines - use antigenic fragments that elicit strongest immune response, e.g. hep B (viral protein coat) Produced by genetic modification techniques = microbes programed to produce the desired antigenic fraction - CAN BE MADE IN RECOMBINANT SYSTEMS Example: Hep B vaccine consists of viral protein coat that is produced by genetically modified yeast.

Explain how an antibiotic might target bacterial DNA synthesis and protein synthesis without hindering our own. Explain toxicity issues related to mitochondrial DNA and protein synthesis.

one difference between prokaryotes and eukaryotes is the structure of their ribosomes. Eukaryotic cell have 80s ribosomes while prokaryotic cells have 70s ribosomes = this difference accounts for selective toxicity of antibiotics that affect protein synthesis and DNA synthesis Toxicity issues arise because eukaryotic mitochondria also contain 70s ribosomes similar to those of bacteria. Therefore, antibiotics targeting 70s ribosomes can have adverse effects on the cells of the host.

2 of 3 consequences of complement activation: Opsonization

opsonization : immune adherence = promotes attachment of phagocyte to microbe. Enhances phagocytosis 1) activated C3 splits into activated C3a and C3b 2) C3b binds to the surface of a microbe, and receptors on phagocytes attach to C3b

Virus like particle (VLP) vaccine

resemble intact viruses but do not contain any viral genetic material. Example: Hep B - protein coat/ HPV vaccine

Describe the role of antimicrobial peptides (AMPs) in innate immunity.

short peptides that consist of a chain of about 12 to 50 amino acids synthesized on ribosomes. Have broad spectrum antimicrobial activities AMP Synthesis => triggered by protein & sugar molecules on surface of microbes AMP produced when chemicals in microbes attach to TLR's MOA: inhibiting cell wall synthesis forming pores in plasma membrane = Lysis destroying DNA and RNA

etiology

the cause of a disease

pathogenesis

the development of disease

TLR's

Toll-like receptors - receptor on host cell surface that recognizes PAMPs

Disease definition

Disease: any disturbance such that the body cannot carry out its normal functions - Can be genetic, congenital, mental, infectious, autoimmune - We are only concerned with infectious disease, those caused by pathogens

Explain the strategy behind combination therapy for treating: a. Tuberculosis

- If resistance occurs to one drug, there is another to continue to eradicate the pathogen - Attack multiple parts of a pathogen's metabolism Multiple-drug therapy to treat TB means taking several different antibiotics at the same time. Treatment with several medicines makes it more likely that all TB-causing bacteria will be killed.

Microbiota = Oral Cavity & GI Tract

- Many resident microbiota in the oral cavity - Acidity of stomach (pH 2) prevents most microbes from growing - Large intestine contains highest number of resident microbiota in the body (108/mL)

Explain the role of Risk factors in amplifying the problem of HAIs.

- Microorganisms in the healthcare environments - Weakened status of the host - Chain of transmission in a hospital - Role of R factors: amplify resistance • Compromised host: an individual whose resistance to infection is impaired by disease, therapy, or burns

Microbiota = respiratory system

- Nasopharynx & upper respiratory tract heavily colonized • Opportunistic pathogens are kept in check by antagonistic interactions, nasal secretions, ciliary action - Lower respiratory tract is relatively sterile • Ciliary escalator

Describe the consequences or diseases that result when the immune system doesn't respond, responds incorrectly, or overreacts.

1) Doesn't respond : Example = HIV 2) Responds incorrectly : Example = autoimmune diseases 3) Overreacts - allergies, anaphylactic shock

1) Can each B cell make antibodies to many different antigens or only one antigen?

1) Just like T-cells, each B-cell has a receptor that will connect to only one antigen shape. An important difference between T-cells and B-cells is that B-cells can connect to antigens right on the surface of the invading virus or bacteria. This is different from T-cells, which can only connect to virus antigens on the outside of infected cells.

1) What does "MHC" stand for? 2) What is the function of the MHC glycoproteins? 3) Where do you see MHC I? 4) Where do you see MHC II?

1) Major histocompatibility Complex 2) The function of MHC molecules is to bind peptide fragments derived from pathogens and display them on the cell surface for recognition by the appropriate T cells. 3) MHC I are found on plasma membranes of mammal nucleated cells. They identify "self" preventing the immune system from making antibodies that would be harmful against host 4) MHC II exist only on surface of antigen presenting cells (APC's) including B cells.

β-lactams. 1) Mechanism of action (MOA) 2) penicillins and cephalosporins 3) What is the structure of these drugs? 4) Are these drugs more effective against gram negative or gram-positive organisms? Why? 5) What is the enzyme that confers resistance to cell wall-inhibiting drugs and how does it work?

1) Prevents the synthesis of Peptidoglycan (Cell wall weakened - undergoes lysis) 2) Penicillin - Prevent the cross linking of the peptidoglycan which interferes with the final stages of construction of the cell walls, Primarily Gram+ Cephalosporins - Similar structure to penicillin. Inhibit cell wall synthesis the same. More widely used than other B-lactams. 3) B-lactam Ring called a nucleus - differentiated by the chemical side chain attached to their nuclei 4) Gram + affected the most because of thick peptidoglycan walls 5) Penicillinases are enzymes produced by many bacteria that cleave the B lactic Ring of the Penicillin molecule. Because of this they are also called B-lactamases

1) Know the molecular make-up of prions. 2) What is the role of normal prions? 3) What happens when an abnormal prion is introduced into a human? 4) What part of the body is affected in a prion disease?

1) Prions - not organisms; more like "entities": proteinacious infectious particles 2) Normal prions appear to play a protective role for the central nervous system = involved I'm regulating cell death 3) PrPsc molecules accumulate in brain, forming plaques (don't appear to be the cause of cell damage) leads to large vacuoles developed in brain 4) the brain

1) Define Toll-like receptors 2) Describe pathogen-associated molecular patterns (PAMPs) 3) What happens when PAMPs and TLRs bind?

1) Responses of the innate system are activated by protein receptors in the plasma membrane of defensive cells. 2) Among the activators are (TLRs) (Toll-like Receptors) these TLRs attach to various components commonly found on pathogens that are called PAMP's (Pathogen-associated molecular pattern) Examples: • LPS (Lipopolysaccharide) of the outer membrane of gram - bacteria • Flagellin in Flagella • Peptidoglycan in the cell wall of gram+ bacteria, • DNA of bacteria • And the DNA and RNA of viruses Also components of fungi and parasites 3) When the TLR's on these cells encounter the PAMP's of microbes, such as the LPS of gram- bacteria, the TRLs induce the defensive cell to release cytokines.

1) Are there B cells in our bodies that can respond to any antigen? 2) Explain the difference between a "naïve" B cell and an activated B cell.

1) Yes, Naive B cell Each type of B cell carries ONE type on antibody on its surface - B cell receptor or BCR - Created in the course of its development before ever exposed to any antigen - Allows us to respond to ANY antigen • Called naïve B cell before exposure - Only 1 or 2 copies of each type of B cell B cells MUST BE ACTIVATED before they can produce antibodies

1)What three white blood cells types can present antigens in MHC II? 2) Which can present several antigens? 3) Which presents only one type of antigen?

1) a) macrophages b) dendritic cells c) B cells 2) Dendritic cells and macrophages can present several antigens 3) Unlike the other two APCs, B cells only produce antibodies (immunoglobulin) that are specific to certain antigens B-cells are able to efficiently present the antigen to which their antibody is directed, but they are considered inefficient APCs for most other antigens.

1) What is the process of antigen binding called? 2) What is the process of proliferation and differentiation called? 3) What are the many small protein molecules that signal the process called?

1) antigen-antibody complex formed when antibody encounters antigen (antigenic specificity ) 2) Clonal expansion 3) cytokines

Describe three pathways of activating complement.

1) classical pathway 2) Alternative pathway 3) Lectin pathway

classical pathway of compliment

1) classical pathway = initiated when antibodies bind to antigens a) antibodies attach forming Ag-At complex -> bind to and activate C1 b) C1 activates C2 and C4 by splitting them. C2 = C2a and C2b ; C4 = C4a and C4b c) C2a and C2b combine and activate C3 = splitting into C3a and C3b, C3a participates in inflammation and C3b functions in cytolysis and opsonization

1) Explain how TC cells and Natural Killer (NK) cells combat cancerous cells (mechanism of action). 2) Why is it accurate to say that TC cells function in an adaptive capacity and NK cells function "independently" to destroy cancerous cells?

1) the surface of the tumor cells aware tumor-associated antigens that mark them as non self to the immune system, MHC class I molecules are found on nucleated cells, therefore the CTL can attack almost any cell of the host that has been altered = Apoptosis 2) NK cells = not immunologically specific, do not to be stimulated by an antigen - can distinguish normal cells from transformed cells, or cells infected with intracellular pathogens => with tumor, NK cell causes pores to form in the target cell which leads to lysis or apoptosis Some cancer cells can cause a down-regulaCon in MHC I so it is no longer present on the cell membrane

Describe the importance of attachment and colonization in causing disease

1. Attachment to host cells - fimbria, glycocalyx, adhesins (sticky proteins) 1. Colonize extracellularly or penetrate the cell (intracellular) - Bacteria must be able to survive & reproduce, despite host defense mechanisms 2. Infection ensues, assisted by other virulence factors, such as: - Exoenzymes, e.g. Staphylococcus aureus produces coagulase - Bacterial endotoxins & exotoxins, e.g. Lipid A (endotoxin) of the LPS; botulism toxin (neurotoxin)

Cell-mediated immunity involves TC cells. Describe the mechanism by which TC cells are activated to become cytotoxic T lymphocytes (CTLs) and kill viral-infected cells. Include the roles of Helper T cells (TH ), MHC I, perforin, granzyme, and apoptosis.

1. Cytotoxic T (TC) cells recognize antigens in MHC I (Clonal Selection) 2. TC cells are activated by cytokines produced by TH cells • Activated TC cells undergo Clonal Expansion to form effector cells & memory cells • Effector cell called a cytotoxic T lymphocyte (CTL) CTL's bind to MHC I • CTLs secrete - perforin (protein) which creates holes in cell membrane, and - granzymes (enzyme; protein) that follow through pores and cause apoptosis (programmed cell death) 3. Note that free virus is also in body and subject to humoral immunity Therefore viruses require BOTH humoral & cell-mediated immunity

Name the five major targets of antibiotics

1. Inhibiting Cell wall synthesis 2. Inhibiting protein synthesis 3. Injuring plasma membrane 4. Inhibiting nucleic acid synthesis 5. Inhibiting the synthesis of essential metabolites

Discuss mechanisms of resistance to antibiotics

1. blocking the drugs entry into cell 2. inactivation of drug by enzymes 3. alteration of drugs target site 4. efflux of antibiotic from cell 5. Alteration of metabolic pathways of the host

Alternative pathway of complement

2) unlike classical pathway, does not involve antibodies. Activated by contact between certain compliment proteins and a pathogen a) C3 present in blood combines with compliment proteins called factor B, factor D and factor P on microbes surface. They are attracted to microbial cell surface (lipid=carbohydrate complex of certain bacteria and fungi) b) once compliment proteins bind and interact, C3 splits into fragments C3a and C3b, C3a -> inflammation ; C3b -> cytolysis and opsonization

Lectin pathway

3) lectin pathway: most recently discovered when macrophages ingest bacteria, viruses, and other foreign maters by phagocytosis, they release cytokines that stimulated the liver to produce lectins (proteins that bind to carbohydrates) a) mannose binding lectin (MLB) binds to carbohydrate mannose. MBL binds to many pathogens because MBL molecules recognize a distinctive pattern of carbohydrates that includes mannose found in bacterial cell walls and in some viruses b) As a result of binding, MBL functions as opsonin to enhance phagocytosis and activates C2 and C4 c) C2a and C4b activate C3, as with other mechanisms, C3 splits into C3a and C3b ; C3a -> inflammation ; C3b -> cytolysis and opsonization

What is an epitope?

An epitope refers to the specific target against which an individual antibody binds. When an antibody binds to a protein, it isn't binding to the entire full-length protein. Instead, it is binding to a to a segment of that protein known as an epitope. In general, an epitope is approximately five or six amino acids in length. So, a typical full-length protein sequence actually contains many different epitopes against which antibodies can bind.

exoenzymes and disease

An exoenzyme, or extracellular enzyme, is an enzyme that is secreted by a cell and functions outside of that cell. Exoenzymes are produced by both prokaryotic and eukaryotic cells and have been shown to be a crucial component of many biological processes. Most often these enzymes are involved in the breakdown of larger macromolecules. Many exoenzymes are also used as virulence factors. Pathogens, both bacterial and fungal, can use exoenzymes as a primary mechanism with which to cause disease. The metabolic activity of the exoenzymes allows the bacterium to invade host organisms by breaking down the host cells' defensive outer layers or by necrotizing body tissues of larger organisms. Many gram-negative bacteria have injectisomes, or flagella-like projections, to directly deliver the virulent exoenzyme into the host cell using a type three secretion system

localized infection

An infection that affects only one body part or organ is called a localized infection

systemic infection

An infection that is in the bloodstream or lymph is called a systemic infection

Define the term "antibiotic" and explain where they came from.

Antibiotic: A substance produced by microorganisms that in small amounts inhibits another microorganism. Alexander flemming: first antibiotic Growth of Staphylococcus Aureus was inhibited in the area surrounding the colony of a mold that contaminated a Petri plate. The mold was identified as Penicillium notatum, and its active compound, which was isolated a short time later, was named Penicillin.

As a transition to the cell-mediated side of adaptive immunity, explain why humoral immunity alone is not enough to clear a viral infection. When is humoral immunity effective against a viral infection?

Antibodies are specific to extracellular antigens Virus infection needs more than Humoral Immunity! = Needs cell mediated response Majority of viral life cycle is intracellular Free virus can be picked up by BCRs of B cell and processed but what about intracellular virus?? = Cytotoxic T cells have ability to recognize and kill target cells that are considered Non-self Primarily these target cells have been altered by infection with pathogen(viruses) The adaptive immune response itself has two components, the humoral response (the synthesis of virus-specific antibodies by B lymphocytes) and the cell-mediated response (the synthesis of specific cytotoxic T lymphocytes that kill infected cells).

Distinguish between antibodies and antigens

Antibodies: GOOD! protective molecules = combat foreign molecules Antigens: BAD! Foreign invading molecules

Explain how memory cells help to speed up immune responses to pathogens that the body has already "seen". Use terms primary, secondary, and anamnestic.

Antibody-mediated immune responses of the host intensify after second exposure to antigen Primary: after initial contact with an antigen, the exposed person's serum contains no detectible antibodies for 4-7 days. => slow rise in antibody titer Secondary response: also called memory (anamnestic) response = More rapid (sometimes hours). reaching peak in only 2-7 days = lasts for longer, greater in magnitude. Antibody titer = Relative amount of antibodies in serum.

How do dendrites and macrophages initiate the adaptive immune response?

Antigen presentation is a process in the body's immune system by which macrophages, dendritic cells and other cell types capture antigens, then present them to naive T-cells. Antigen presentation broadly consists of pathogen recognition, phagocytosis of the pathogen or its molecular components, processing of the antigen, and then presentation of the antigen to naive (mature but not yet activated) T cells. The ability of the adaptive immune system to fight off pathogens and end an infection depends on antigen presentation.

APC

Antigen presenting cell - a macrophage, dendritic cell, or B cell that engulfs an antigen and presents fragments to T cells. Fragments are "sandwiched" between MHC molecules.

What is another drug that can treat MRSA/VRSA?

Are there alternatives to vancomycin? Yes - daptomycin, a lipopeptide Outcome: Disruption of cytoplasmic membrane Mechanism of action: Forms transmembrane channels

Upon antigen binding, identify which 3 types of lymphocytes proliferate and differentiate to make many copies (clones) of effector cells and memory cells.

B cell = proliferates into large clone of cells. Plasma cells: produce antibodies (short lived) Memory B cells: Long living (enhanced second response to antigen) T helper cell = proliferates to secrete cytokines differentiated into 2 types of T-H cells TH1 and TH2, TH17 (each specific to the type of cytokine admitted from them) Memory T-Helper cells : Long lived precursor CTL: when activated by antigen processed by dendritic cell and after interaction with T-H cell CTL-P can proliferate and differentiate into effector CTL (though Ag-activated CTL-P can produce some IL-2).

BCR

B cell receptor - immunoglobulin receptors on B cell surface that recognize antigens; initiates specific immune response

Which type of lymphocyte makes antibodies?

B lymphocytes produce antibodies - proteins (gamma globulins) that recognize foreign substances (antigen) and attach themselves to them. The recognition of different antigens depends on B cell receptors for antigens that coat surface of B cell.

Draw and explain the difference between a BCR and a TCR.

BCR = remade antibody on surface= ready and able to react to specific antigen. Only proliferate upon clonal selection TCR = The T-cell receptor, or TCR, is a molecule found on the surface of T cells, or T lymphocytes, that is responsible for recognizing fragments of antigen as peptides bound to major histocompatibility complex (MHC) molecules.

Describe the role of iron-binding proteins in innate immunity.

Bacteria and human cells compete for available iron => both need it to function concentration of free iron in human body is low because most of it is bound to iron binding proteins (transferrin, lactoferrin, ferritin, and hemoglobin) whose function is to store and transport iron transferin = blood and tissue fluids lactoferrin = milk, saliva and mucus ferritin = liver, spleen and red bone marrow Hemoglobin = red blood cells

Basophil What does it do? in blood or in tissue innate or adaptive?

Basophil (release histamines that cause inflammation) In blood Innate

Differentiate the lymphatic and blood circulatory systems.

Blood = plasma, formed elements (cells and cell fragments suspended in plasma, and platelets. Lymphatic = made up of lymph fluid, lymphatic vessels, and various organs containing lymph tissue, and red bone marrow, where stem cells develop into blood cells, including lymphocytes lymphoid tissue: Large number of lymphocytes (T cells, B cells and phagocytic cells) Lymph nodes: site of activation of T and B cells Trap microbes and macrophages and dendritic cells which destroy them by phagocytosis

Briefly explain the differentiation of B and T cells as illustrated in F. 17.1, p. 470.

Both start as stem cells in bone marrow or fetal liver B Cells differentiate in Adult bone marrow. T cells differentiate in thymus BOTH migrate to lymphoid tissue such as spleen. but especially lymph nodes

When would it be preferable to prescribe a broad-spectrum antibiotic? What is the "downside" of prescribing a broad-spectrum antibiotic?

Broad spectrum antibiotics are used when the identity of the pathogen is not immediately known, because it saves valuable time. The downside of these drugs is that they destroy many normal microbiota of the host. These normal bacteria normally compete with and check the growth of pathogens or other known microbes. If the antibiotic does not destroy certain organisms in the normal microbiota but does destroy their competitors, the survivors may flourish and become opportunist pathogens.

Broad spectrum vs Narrow spectrum antibiotic

Broad spectrum: Antibiotics that affect a broad range of gram positive or gram negative bacteria Narrow spectrum: only a small range of different microbial types they affect. Example: penicillin G, affects Gram + but very few gram -

Explain how the macrophage is related to the monocyte and the mast cell is related to the basophil.

Called a Monocyte when in circulating blood --> enter body tissues and mature into macrophages (phagocytic) as blood and lymph containing microorganisms pass through organs, macrophages remove them via phagocytosis, also dispose of worn out blood cells Called a basophil when in circulating blood --> Matures into Mast cell and Enters body tissues to kill infected cells (often virus infected via cytolysis or apoptosis

What is fever and how is it caused?

Cause: infection from bacteria (and their toxins) or viruses • Abnormally high body temperature • Hypothalamus normally set at 37°C • Gram-negative endotoxin cause phagocytes to release interleukin-1 (IL-1; a cytokine) • Hypothalamus releases prostaglandins that reset the hypothalamus to a high temperature • Body increases rate of metabolism and shivering which raise temperature • Vasodilation and sweating: Body temperature falls (crisis)

Know about the Centers for Disease Control and Prevention (CDC) Collects epidemiological information in the U.S. Publishes Morbidity and Mortality Weekly Report (MMWR).

Collects and analyzes epidemiological information in the United States • Publishes Morbidity and Mortality Weekly Report (MMWR) - Morbidity: incidence of a specific notifiable disease - Mortality: deaths from notifiable diseases

commensalism: mutualism: parasitism:

Communalism: an association between two organisms in which one benefits and the other derives neither benefit nor harm. Example: Staphylococcus on skin Mutualism: symbiosis that is beneficial to both organisms involved Example: gut bacteria Parasitism: A parasitic relationship is one in which one organism, the parasite, lives off of another organism, the host, harming it and possibly causing death. Example: Tuberculosis bacteria in human lung; H1N1 virus

Dendritic cell What does it do? in blood or in tissue innate or adaptive?

Dendritic cell believed to be derived from the same precursor cells as monocytes. have long extensions that resemble nerve dendrites abundant in epidermis of skin, mucous membranes, the thymus, and lymph nodes. Destroy microbes by phagocytosis and innate adaptive immunity response both innate and adaptive

Define the following terms, and be able to give an example of each: epidemic, endemic, pandemic.

Epidemic: sudden and significant increase in incidence in a particular geographic area - E.g. cholera, diphtheria, SARS, West Nile virus Endemic: infectious agent is continually present in the population in a particular geographic area - E.g. malaria Pandemic: epidemics of global proportion - E.g. AIDS, flu (1918), bubonic plague

Differentiate between prevalence and incidence.

Epidemiology • Study of disease spread and all poten>al factors involved - Incidence: # of new cases of disease in a specific population in a particular time period - Prevalence: total # of cases of disease in a population - Cause of disease - Modes of transmission

Describe the roles of toxins (including endotoxins and exotoxins) and exoenzymes in causing disease.

Exotoxins: produced inside bacteria -> part of their growth and metabolism, secreted by bacteria into surrounding medium or released following lysis -outside cells -proteins / enzymes that catalyst certain biochemical reactions -gram + or gram - -can easily diffuse into blood/soluble in most body fluids -work by destroying cells/inhibiting metabolic functions -highly specific effects -extremely lethal Endotoxins: Located within bacterial cell. part of outer portion of cell of gram - bacteria -part of outer membrane (lipoproteins/LPS/phospholipids) -lipopolysaccharides -released during bacterial multiplication when gram - dies = after lysis -endotoxins stimulate macrophages to release cytokines in very high concentrations = toxic -All endotoxins = same symptoms: chills, fever, weakness, aches, sometimes shock and death -could lead to miscarriage -can cause activation of blood clotting proteins = blood clots

Define interferons.

Family of cytokines called interferons produced by lymphocytes or macrophages interferons are small proteins that interfere with viral replication they react with plasma of nuclear membrane receptors inducing the uninfected neighboring cells to manufacture mRNA for AVP's (antiviral proteins) Proteins are enzymes that disrupt various stages of viral multiplication

Identify the major reservoirs for pathogens, and describe the mechanisms by which pathogens can be transmitted.

Human reservoirs: - Humans with active infections (at any stage) can transmit pathogens - Carrier: individual that harbors an infectious pathogen and transmits it without having any clinical symptoms Animal Reservoirs: - Many pathogens can infect other animals as well (especially physiologically similar ones) - E.g. anthrax (domestic livestock), flu (birds), mad cow disease (cows, sheep) - Zoonoses: a disease that occurs primarily in wild and domestic animals but can be transmitied to humans • Examples : lyme disease/rabies Nonliving Reservoirs: - Major source of pathogens (especially opportunists) - E.g. soil (Clostridium tetani), water (Vibrio cholera) Vector: living organisms that transmit infec>ous disease to humans - Infectious agent doesn't cause disease (or not same type of disease) in the vector; human is the primary & desired host - Most are arthropods (fleas, ticks, mosquitos, flies) - Transmission can be mechanical (passive transport on insect's feet or body) or biological (active process, more complex)

Explain why viral infections require both humoral and cell-mediated immunity.

Humoral antibodies are effective against pathogens such as viruses and bacteria that are circulating freely, where the antibodies can contact them intercellular antigens such as virus within an infected cell are not exposed to circulating antibodies. T cells evolved in response to need to combat intracellular pathogens (viruses)

Explain four mechanisms by which antibodies coating bacteria (or binding to exotoxin or virus) can help eliminate a pathogen. (Use F. 17.8 for guidance.)

Immunity can be acquired actively or passively 1) Actively: exposure to microorganisms or foreign substances that the immune system responds to • Naturally acquired active immunity: exposure to organism in life • Artificially acquired active immunity: vaccination with killed or living organisms or inactivated bacterial toxins 2) Passively: when antibodies are transferred from one person to another (only lasts as long as antibodies are present - a few weeks) • Naturally acquired passive immunity: Antibodies from mother to infant • Artificially acquired passive immunity: injection of antibodies into bodies. (come from animal or human who is already immune to disease)

What role does the Fc region play in the antibody response?

Important in immunological reactions. If left exposed after both antigen binding sites attach to an antigen, the Fc regions of adjacent antibodies can blind to complement. Leading to the destruction of the bacterium. conversely, the Fc region may bind to a cell, leaving the antigen binding sites of adjacent antibodies free to read with antigens.

Explain how C3 is central to all complement activation pathways

In All 3 pathways activate C3 which cascades and C3 splits into fragments C3a which participates in inflammation and C3b which functions in cytolysis and opsonization

DNA vaccines

Inject the DNA encoding pathogen antigens into human muscle; DNA is transcribed/translated to produce the protein (antigen) the protein antigens are carried to the res bone marrow and stimulate both humoral and cellular immunity. • Recent experiments have shown that the efficacy of DNA vaccines are increased using cytokine adjuvants

Explain the general differences between the innate (nonspecific) and the adaptive (specific) immune response.

Innate Immunity • Nonspecific Defenses of the Host - Present at birth - Quick to respond - Not specific to a given microbe - No memory Adaptive • Specific response to microbe • Slower to respond than innate • Memory

What is the role of interleukin-1(IL-1) in triggering the fever response?

Interleukin 1 is A cytokine, derived primarily from mononuclear phagocytes, that enhances the proliferation of T-helper cells and the growth and differentiation of B cells. Il-1 induces the release of Il-2. When secreted in larger quantities, IL-1 is a mediator of inflammation, entering the bloodstream and causing fever, inducing synthesis of acute phase proteins, and initiating metabolic wasting.

Diapedesis

Leukocyte extravasation, less commonly called diapedesis, is the movement of leukocytes out of the circulatory system and towards the site of tissue damage or infection. This process forms part of the innate immune response, involving the recruitment of non-specific leukocytes. Monocytes also use this process in the absence of infection or tissue damage during their development into macrophages.

T cell

Lymphocyte; T cytotoxic cells; can become active cytotoxic T Lymphocytes (CTLs)

TH cell

Lymphocyte; T helper cells

What is the oxidative burst? How does exocytosis "set the stage" for the adaptive immune response?

Lysosomes contain enzymes that produce toxic oxygen products such as superoxide radical, hydrogen peroxide, nitric oxide, singlet oxygen, and hydroxyl radical. Toxic oxygen products are produced by and oxidative burst. after enzymes have digested contents of phagolysosome, the ingestible material (residual body) moves towards the cell boundary and discharges its waste, and presents it on the surface of cell

MHC

Major histocompatibility complex - a set of transmembrane molecules (glycoproteins) on cell surfaces encoded by a large gene family in all vertebrates. MHC I - On all nucleated cells MHC II - found only on APCs

What are haptens?

Most antigen have a molecular weight of 10,000 or higher, a foreign substance that has a low molecular weight is often not antigenic unless attached to a carrier molecule These low molecular weight compounds are called Haptens. Once and antibody against a happen has been formed, the antibody will react with the patin independent of the carrier molecule. Example: penicillin = not antigenic by itself, but some people develop and allergic reaction to it.

Compare/contrast Cell-mediated Immunity and Humoral Immunity

The humoral response (or antibody‐mediated response) involves B cells that recognize antigens or pathogens that are circulating in the lymph or blood ("humor" is a medieval term for body fluid). The cell‐mediated response involves mostly T cells and responds to any cell that displays aberrant MHC markers, including cells invaded by pathogens, tumor cells, or transplanted cells. The responses of cellular immunity center on attacking antigens that make their way inside cells, whereas humoral immunity responses are directed at antigens that are EXTRACELLULAR (such as in blood and other body fluid) Cellular immunity = Best at fighting viruses/ fungal and parasitic infections Humoral = Invaders outside of cells (bacteria, and other toxins as well as viruses before they penetrate target cells)

What is the therapeutic index of an antibiotic?

The therapeutic index (TI) (also referred to as therapeutic ratio) is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes toxicity. therapeutic index: a drug should have a large therapeutic index TI = Toxic dose/therapeutic dose

MHC I

Their function is to display peptide fragments of non-self proteins from within the cell to cytotoxic T cells; this will trigger an immediate response from the immune system against a particular non-self antigen displayed with the help of an MHC class I protein

Drug companies have developed new "generations" of these drugs by altering their side chains. How do they do this? Why alter the side chains? (Consider penicillin as an example.)

These new generations are created by either by interrupting synthesis of the molecule by Penicillium and obtain only the common penicillin nucleus for use Second, they can remove the side chains from the completed natural molecules and then chemically add other side chains Altering the side chains can • Improve administration of drug • Increase spectrum of activity • Resist β-lactamases Semisynthetic: Part of penicillin is produced by mold, other part is added synthetically

Activated B cell

When a B cell's immunoglobins(antibodies) bind to the epitope for which they become specific. the B cell becomes activated. An activated B cell undergoes --> Clonal expansion: proliferation Some = plasma cells(produce antibodies) Others (long lived memory B cells = enhance second immune response) which normally requires the help of Th cells. Antigens that require Th cells for antibody production are known as T-dependent antigens. (Usually proteins on viruses, bacteria, or foreign blood cells) When an inactive B cell meets an antigen that can bind to its specific surface receipts, it will engulf and process it = displaying antigen fragments bound to MHC II molecules --> attracting T helper cells to B cells T helper ell begins producing cytokines that activate B cell.

explain the activation of a TH cell upon binding to a specific MHC II:Ag complex on an APC. Include the terms clonal expansion and address the role of cytokines.

When a B cells antigens bind to their specific epitope, they become activated. They undergo Clonal expansion (proliferation) -> Plasma cells and Memory B cells with the help of TH cells => T helper cell in contact with antigenic fragment produced on surface of B cell begins producing cytokines to activate B cell.

The antibody that is produced in the secondary response is mostly a) IgG. b) IgE. c) IgM. d) IgA.

a) IgG.

The FIRST antibody B cells make during primary response to an antigen is a) IgM. b) IgG. c) IgE. d) IgA.

a) IgM.

a) Understand what types of vaccines are used for influenza, and why flu shots only last one year. b) What is antigenic drift?

a) Inactivated/killed virus vaccine Occasionally errors (or mutations) are made during nucleic acid replication in virus reproduction - More common for RNA viruses (like influenza) since they lack proofreading mechanisms b) • These errors lead to new forms of surface proteins, which our immune system will not recognize => antigenic drift

a. What is the role of T regulatory (Treg) cells? b. Which type of disease would these cells protect us against?

a) To combat autoimmunity by suppressing T cells that escape deletion in the thrums without the necessary education to avoid reacting to the body's self b) autoimmune disease

Septic shock can result from using antibiotics to treat a) gram-negative bacterial infections. b) fungal infections. c) viral infections. d) protozoan infections.

a) gram-negative bacterial infections.

The Salk polio vaccine is an example of a(n) ________ vaccine. a) inactivated killed b) toxoid c) live attenuated d) conjugated

a) inactivated killed

IgG antibodies inactivate microbes by blocking their attachment to host cells in the process of a) neutralization. b) agglutination. c) apoptosis. d) opsonization.

a) neutralization.

Traditionally, healthcare-associated infections were called ________ infections. a) nosocomial b) opportunistic c) chronic d) emerging

a) nosocomial

Explain the role of the complement system in innate immunity.

consists of over 30 proteins produces by liver that circulate in blood serum and within tissues "completes" or assists cells of the immune system in destroying microbes. Never changing = part of innate immune system can be recruited by adaptive immune system together, proteins of the complement system destroy microbes by cytolysis, opsonization and inflammation, also prevent excessive damage to host tissues. act in cascade where one reaction triggers another which in turn triggers another. The more product formed with each succeeding reaction in the cascade amplifying the effects.

conjugated vaccine

covalently attach a poor antigen to a strong antigen to elicit a stronger immunological reaction to the poor antigen polysaccharides are T-independent antigens and children immune systems don't respond well in months 15-24. polysaccharides combined with proteins such as diptera or tetanus toxoid. this approach led to successful vaccine for haemophilus influenza type b which gives significant protection even at 2 months

Today, what is the leading cause of healthcare- associated infections? a) Staphylococcusaureus b) E.coli c) Pseudomonas aeruginosa d) Clostridium difficile

d) Clostridium difficile

The substance in perspiration that breaks down cell walls of gram-positive bacteria is a) cerumen. b) keratin. c) salt. d) lysozyme.

d) lysozyme.

Diseases NOT transmitted from one host to another are a) communicable. b) contagious. c) nosocomial. d) noncommunicable.

d) noncommunicable.

Explain how antibiotic resistance arises in terms of a. Genetics b. Population dynamics c. Human use

first exposure to new antibiotic = susceptibility high/mortality rate high handful of survivors replicate, and their genetic characteristic that helped them survive is passed on and they replicate. These are called Persister cells. The evolution of antimicrobial resistance is the result of microbial genetics, microbial population dynamics (growth), and human use • Antibiotics originated in the environment to play a much more selective role for the microbes • Human use of antibiotics has resulted in an overgrowth of resistant strains » Horizontal gene transfer and spontaneous mutations » Microbes replicate fairly rapidly

Which WBC arrives first to the site of injury? Which WBC follows?

first phagocyte to arrive at the site of injury = neutrophil (short life - a few days) second cell to arrive: monocyte - macrophage (great phagocyte)

CD8+

glycoproteins on TC cell surface called clusters of differentiation; important for adhesion to receptors

CD4+

glycoproteins on TH cell surface called clusters of differentiation; important for adhesion to receptors

Define differential white blood cell count.

leukocyte increase or decrease can be detected by a differential WBC count = A calculation of the percentage of each kind of white cell in a sample of 100 white blood cells.

Describe a mechanism by which MRSA could become vancomycin resistant (VRSA).

main mechanism MRSA became resistant to methicillin - not new inactivating enzyme but from modifying the penicillin-binding protein on the cell's membrane B-lactam antibiotics act by binding with the PBP, which is required to initiate the cross linking of peptidoglycan and form the cell wall. MRSA strains become resistant because the have additional, modified PBP. But the additional PBP present on the mutants, although it binds weakly with the antibiotic, still allows synthesis of cell walls that adequate for survival of MRSA strains In vancomycin-susceptible strains: • Vancomycin binds to its target, D-alanyl-D-alanine dipeptide on the peptide side chain of newly synthesized peptidoglycan subunits, preventing them from being incorporated into the cell wall by penicillin- binding proteins (PBPs). In many vancomycin-resistant strains: • The D-alanyl-D-alanine dipeptide is replaced with D- alanyl-D-lactate. Vancomycin can not bind to this dipeptide so the peptidoglycan subunit is appropriately incorporated into the cell wall.

List two bacterial pathogens that reside in non-living reservoirs

major nonliving reservoirs: soil and water Soil: -Clostridium botulinum: ringworm and systemic infections -C. tetani: bacterium that causes tetanus water: -Vibro cholera: causes cholera -Cryptosporidum: causes diarrhea -Salmonella typhi: causes typhoid fever 3

How can bacteria avoid destruction by phagocytosis?

some bacteria have structures that inhibit adherence such as M protein and capsules. M protein: inhibits attachment of phagocytes and makes adherence more difficult Large capsules: heavy encapsulated organisms can only be phagocytize if the phagocyte traps the microorganism against a rough surface, such as a blood vessel, blood clot or connective tissue fiber from which the microprobe cannot slide away. may kill phagocytes by causing the release of the phagocytes own lysosomal enzymes into its cytoplasm some secrete pore forming toxins that phagocyte cell membranes once inside phagocyte. can prevent proper acidification of digestive enzymes. Microbes then multiply within phagocyte

Types of Vaccines

• Subunit vaccines - use antigens that elicit strongest immune response, e.g. hep B (viral protein coat) - CAN BE MADE IN RECOMBINANT SYSTEMS • Conjugate vaccines - covalently attach a poor antigen to a strong antigen to elicit a stronger immunological reaction to the poor antigen • Adjuvants - an agent that is added to a vaccine to increase its effectiveness • Inactivated killed vaccines - e.g. rabies, influenza - Used for pathogens where live vaccine is too hazardous - Only induce humoral immunity; no cell-mediated immunity) - Ohen require booster doses • Toxoids - inactivated toxins, e.g. tetanus & diphtheria • Live attenuated vaccines - e.g. MMR - Use weakened (attenuated) pathogens - Closer mimic to actual infection (humoral and cell-mediated immunity) - Confers lifelong immunity

Competitive inhibitors of synthesis of essential metabolites

• Sulfonamides

Inhibitors of protein synthesis

• Tetracycline • Erythromycin • Streptomycin (aminoglycosides) • Chloramphenical

List the stages of inflammation.

• Vasodilation (histamine, kinins, prostaglandins, and leukotrienes) • Redness • Swelling (edema) • Pain • Heat

How does the innate immune system fulfill the fundamental requirement for immunity: recognition of "nonself"?

• While innate is nonspecific it is triggered by molecules that are recognized as non self : • Host cells have Toll-like receptors (TLRs) that recognize and attach to Pathogen- associated molecular patterns (PAMPs) associated with microbes. • This attachment induces the host cell to produce and secrete cytokines that have far-reaching effects on the innate and adaptive immune response.