Microbiology Part II

Antibodies have a structure of two heavy chains and two light chains joined to form a Y-shaped protein. How can the heavy and light chains of an antibody be separated chemically?

reducing agent *A reducing agent will separate the heavy and light chains of an antibody because these are held together by disulfide bonds.

A siderophore is a molecule produced by bacteria that chelates (binds) to and facilitates uptake of iron. The iron-bound siderophore binds to transport receptors on the surface of the bacteria for transport into the cell. Iron is also essential for the host, where it is often bound to a carrier protein (such as hemoglobin or transferrin). Bacterial siderophores compete with the host for soluble iron. How can this host-pathogen tug-of-war for iron be used against the invading bacteria?

antibiotic-siderophore conjugate *An antibiotic-siderophore conjugate would be an effective way to use the siderophore mechanism against the invading bacteria. The conjugate would be imported, and the antibiotic would kill the bacterial cell.

What organism is commonly found in the stomach?

streptococcus app

Antibody Structure cont

-2 light polypeptide chains -2 heavy polypeptide chains -bound by disulfide bonds -Y shaped with 2 antigen binding sites (Fab fragment) (variable region) -stalk is called the Fc fragment (phagocytes have Fc receptors; antibodies "tag" antigens for removal by phagocytes)

IgE

-IgE is a secreted immunoglobulin that only reacts against parasitic antigens. Its non-specific Fc region can also bind to mast cells, contributing to allergic disease. -IgE is the primary antigen associated with an allergic response and is mostly found in the lungs, mucous membranes, and skin. IgE binds to an allergen, triggering the histamine response -IgE is the primary antigen associated with an allergic response, mostly found in the lungs, mucous membranes, and skin. IgE binds to an allergen, triggering the histamine response.

CD8+ Cytotoxic T cells

-kill host cells presenting foreign antigens on MHC class I molecules -prevent viral production and release by eliminating the host cell before viral synthesis or assembly is complete

Antibody Structure

-belong to the immunoglobulin family of proteins -present in the blood, the surface of B cells and other body fluids -there are 5 known structural types, 3 are involved in the defense against infection IgG IgM IgA

Normal flora protect the host by:

-competing for nutrients -producing substances harmful to invading microbes -affecting pH and available oxygen

B cells & Antibody Responses

-develop in bone marrow then migrate to other lymphoid tissue -B cell receptor is an IgM monomer -Antigen binds to B cell receptor and is internalized for initiation of antibody production (T-independent B cell activation) *B cells multiply and differentiate into either memory or plasma cells *Plasma cells secrete lg amts of antibodies *memory cells circulate and "remember" a specific antigen so if that specific antigen returns, the response will be quicker

Pathogenesis- Injury

-disease requires injury to the host -exotoxins- toxic proteins that are secreted by the bacteria -endotoxin- LPS (only in gram - bacteria, lipid A is the toxic portion) -disruption of the host cell function -multiplication in the host cel, causing rupture

The adaptive immune system

-highly specific immune response -discrimination btwn self and non-self -memory function- accelerated response if an invader returns -2 arms of adaptive immunity: *Humoral immunity: B cells & the antibodies that they produce *Cell-mediated immunity: T cells that attack infected cells or secreting cytokines to activate other cells -humoral immunity and cell-mediated immunity are interactive

IgA

-immunoglobulin A -monomer in the blood -dimer connected at the Fc region in the gut, tears, other secretions (secretory IgA;sIgA) -IgA is found in the serum and is the most prominent immunoglobulin class found in mucous membranes. -Antibody isotype IgA is primarily found in mucosal areas, such as the mouth or vagina, and in saliva, tears, and breastmilk. When bound to a target antigen, IgA triggers inflammation -Antibody isotype IgA is primarily found in mucosal areas, such as the respiratory, gastrointestinal, and genitourinary tracts. It is also present in saliva, tears, and breastmilk. When bound to a target antigen, IgA produces inflammation, an important first line of defense against infection.

IgG

-immunoglobulin G -monomer Function: -most abundant immunoglobulin and provides the most extensive and long-lived antibody response -memory cells are programmed for rapid IgG response upon a repeat infection (lifelong immunity) -most important antibody for neutralizing bacterial exotoxins and viruses usually by blocking their attachment to cell receptors -the only immunoglobulin able to cross the placenta barrier; so passive immune protection is provided to the newborn in the form of maternal antibody -IgG is the most abundant antibody in the blood. -Immunization triggers the production of the antibody isotype IgG, which comprises approximately 75% of antibodies in humans. It activates an immune cascade that can eliminate some infections and neutralize toxins. -IgG is the antibody isotype produced in response to immunization, comprising about 75% of antibodies in humans.

IgM

-immunoglobulin M -pentamer Function: -special role in local immunity in protecting epithelial surfaces from colonization and infection -sIg is present on mucosal layers on epithelial surfaces and in glandular secretions -prevent attachment of potential pathogens to receptors on mucous membrane epithelia -IgM can be found on the surface membrane of B cells serving as an antigen-binding receptor. When found on the surface, IgM is a monomer, but it can also be secreted into the serum as a pentamer. -IgM is one of the initial types of antibodies produced in response to a pathogen entering the body. It is critical in the early stages of infection. -IgM is one of the initial types of antibodies produced in response to a pathogen entering the body, important in the early stages of infection.

Cell-mediated immunity

-important in the response to intracellular pathogens (viruses and some bacteria/fungi) -macrophages are mobilized and enhanced

Siderophores

-iron is required by bacteria in order to grow -there is very little free iron in human blood orebody fluids bc it is sequestered by iron-binding proteins (transferrin, lactoferrin) -bacteria secrete siderophores to compete with host iron-binding protein (siderophores bind iron more tightly than the host iron-binding proteins) -these siderophores are then transported into the bacterium

Normal flora:

-microorganisms that live in or on the human body -can be transient (present for days, weeks or mo) or residents (permanent) -carrier state-when organisms that are known to be pathogenic are present, but not causing disease -bladder, upper urinary tract, and lower resp. tract are all sterile -Microbial antagonism (exclusionary effect)- is a competition btwn microbes

MHC class II

-only present on certain leukocytes (macrophages, dendritic cells, etc) -binds to protects that originated outside the cell, but have been phagocytize and are now in a vacuole inside the cell -the product is digested, and peptide fragments are combined with MHC II molecules and transported to the surface for presentation -recognized by CD4+T cells

Capsules

-only some bacteria have them -made of hydrophilic polysaccharide gel -if the gel forms a discrete layer, it is called a capsule -if it is amorphous it is called a slime layer -function to protect the bacteria from the immune system -prevents phagocytosis by binding to a host complement regulating protein that is found in the serum called factor H -factor H degrades complement proteins as they attach to the bacterial cell surface preventing opsonization: (the coating of a pathogen with complement proteins, which allows WBCs to phagocytize pathogen)

The T cell Response

-originate in the bone marrow and migrate to the thymus for differentiation -have specific T cell receptors (TCRs) on their surface

MHC Class I

-present on almost all human cells -mark cells as "self" -binds to protects generated inside the cell such as in the case of a viral infection -viral proteins are digested to peptides in proteasome in the cytoplasm and attached to MHC I molecules in the ER where they are then transported to the surface for presentation -recognized by CD8+T cells

Exceptions to Koch's postulates:

-some pathogens can cause several different disease conditions -some pathogens cause disease only in humans -some microbes have never been cultured

Pathogenesis- damage caused by inflammation or immune responses

-some pathogens produce disease without using any known virulence factors -injury can still occur by acute or chronic inflammation or misdirected immune response triggered by antigens on the pathogen -inflammation is a 2-enged sword; enzymes produced by PMNs and macrophages kill invaders, but also damage host tissue -misdirected immune response (bacterial antigens can trigger autoimmune cross-reactions_

CD4+ Helper T cells

-stimulated and activated by antigens presented on MHC class II molecules on the surface of host cells -upon activation, the T cell differentiates and divides -3 major subsets of effector cells that the T cell can differentiate to: *TH 1: produce IFN-y, target macrophages, and effective against intracellular pathogens (viruses; M.turberculosis) *TH 2: produce multiple interleukins and promote the destruction of parasites via eosinophils and mast cells *TH 17: produce multiple interleukins, stimulate neutrophils and are effective against extracellular bacterial and fungal pathogens

Pathogenicity

-the ability to causes disease -virulence: the degree of pathogenicity -pathogens must be able to: enter the host, find a unique niche, avoid host defenses, multiply and injure the host

Koch's Postulates:

-used to prove the cause of an infectious disease 1- the same pathogen must be present in every case of the disease 2- the pathogen must be isolated from the diseased host and grown in pure culture 3- the pathogen from the pure culture must cause the disease when it is inoculated into a healthy, susceptible lab animal 4- the pathogen must be isolated from the inoculated animal and must be shown to the original organism

Antibody production timeline

1. initial contact with a new antigen evokes the primary response -lag phase of ~1 week btwn the challenge and the detection of antibodies -levels of antibody rise exponentially to a maximal steady state in ~3 weeks -antibody levels then decline gradually if no further antigenic stimulation is given -the 1st antibodies synthesized are IgM; then IgG arises and eventually predominates (IgM/IgG switch) 2.After a subsequent exposure or booster injection of the same antigen, the secondary response occurs -involves memory -lag time is shortened, rate of exponential increase to the max steady-state level is more rapid and the steady-state level is higher -mostly IgG is formed -IgG antibodies formed have a higher affinity to their antigen

Risk Factors for disease severity:

Age - immune systems of newborns are not fully developed -immune systems of elderly have waned Occupation -healthcare workers are at a higher risk factor for infectious disease Nutrition Lifestyle -unprotected sex with many partners -alcoholism Climate/weather -certain arthropod vectors will be present in some climates but not others Gender Inherited traits -sickle cell gene Chemotherapy -can deplete WBCs Preexisting conditions -COPD= inc. risk of pneumonia -cardiovascular disease -HIV depletes CD4+T cells

Antigen

Any substance (usually foreign) with the ability to stimulate an immune response when presented in an effective fashion -usually proteins, polysaccharides or glycolipids -large complex antigens such as proteins and viruses must be processed before their epitopes can be effectively recognized by the immune system -macrophages and specialized epithelial cells in the skin and lymphoid organs do this by ingesting the antigen, degrading it into smaller pieces, and presenting those pieces on major histocompatibility molecules on their cell surface to be recognized by T cells

Pathogenesis: Entry

Beating innate host defenses -there are many portals of potential entry into the body, and these potential portals are protected by many different factors -skin is a major protective barrier -mucus membranes are coated with mucin and secretory IgA (sIgA) -some bacteria excrete the enzyme sIgA protease, which degrades sIgA -infection is dose-related; infectious dose is the number of bacteria required to produce infection

Factors that play a role in immune evasion:

Capsule: glycocalyx around the cell wall -impairs phagocytosis and complement activation Antigenic variation: pathogens can alter their surface antigens -antibodies previously formed against these surface antigens are now ineffective Intracellular growth -some pathogens grow within a host cell where antibodies and WBCs cannot reach them

Recognition of Foreignness (self vs non-self)

Controlled by a collection of genes called the major histocompatibility complex (MHC) -codes for molecules present on the surface of almost all human cells -MHC class I -MHC class II -Both MHC I and II are involved in antigen processing

T-independent

Do not require helper T cells -usually evoked by lg molecules with repeating units like polysaccharides -slower response with no memory cells produced

What virulence factor in Streptococcus pneumoniae makes the disease more severe in the host?

Encapsulation

Pathogenesis: Invasion

Getting into cells -some bacteria are obligate intracellular pathogens; some are facultative intracellular pathogens(they can live and reproduce inside or outside of host cells) -viruses must enter a host cell to replicate

2 major types of T cells:

Helper T cells (CD4+) Cytotoxic T cells (CD8+)

What antibody class can be found on the membrane of a B cell?

IgM

An 8-year-old boy presents with runny nose, fever, and muscle aches. His mother reports that he has had these symptoms for the past week and they have become more severe. Rapid influenza testing is positive. After instructing the mother to provide the child with supportive care, the mother asks if the child is in danger of catching the exact same flu virus again if she sends him back to school. What is the most appropriate response?

IgM antibodies will protect him IgG antibodies peak at 1 month

Antibodies present in the mucosa of the respiratory, genitourinary, and gastrointestinal tracts are a crucial first line of defense against infection by triggering inflammation. What isotype are these antibodies?

IgA

What type of antibody is secreted and binds to the antigen to prevent it from attaching to mucosal epithelial cells?

IgA

Vaccines act as an artificial means of activating the immune system to protect against infection. Immunization induces B lymphocytes to produce which class of antibodies?

IgG

What type of antibody penetrates easily into tissue spaces and is the only antibody that can cross the placental barrier, offering passive immunity to the developing fetus?

IgG

An 8-year-old boy presents for evaluation of a sore throat and fever that he has had for 3 days. His parents report that they "do not believe in vaccines." Inspection of the pharynx reveals a thick gray membrane coating the tonsil. Gram stain reveals Gram-positive club-shaped bacilli. Toxin production by the responsible bacteria depends on the presence of what nutrient?

Iron

What approach to expressing disease prognosis identifies deaths in intervals in order to show how many patients died over a given period?

Kaplan meier

During an infection, pathogens acquire iron by the secretion of siderophores, molecules that bind with ferric iron. What siderophore-binding protein is secreted by host immune cells in response to block the reuptake of iron-loaded siderophores by the pathogen?

Lipocalin 2

Opportunistic infection

Normal flora can cause disease if they reach sterile sites or if the population of the flora is disrupted -E.coli that is normal in the gut can cause UTIs if they reach the urinary tract -Candida albicans can overgrow and cause thrush/yeast infections if ab suppress the normal bacterial flora with which it normally competes Mouth flora can cause dental caries

T-dependent

Requires helper T cells to "help" activate the B cell -usually evoked by proteins -macrophages (APC) ingest and process antigen then present antigen to helper T cells, then helper T cells activate B cells -strong response including the production of memory cells

Epitope

Subregion of an antigen that is the actual antigenic determinant (the site where an antibody binds) -epitopes fit the combining site of T cell receptors and antibodies

What portal of entry is part of the parenteral route of getting a disease?

broken skin

2 types of antigen triggered B cell activation

T-dependent T-independent

What activated T helper cell stimulates neutrophils and is central to the destruction of extracellular bacteria and fungal pathogens?

Th17

Pathogenesis: Adherence

The search for a unique niche -requires adhesion (on the microbe) and a receptor (on the host cell) -adhesins are usually proteins but carbohydrates and teichoic acids may be involved -Pili are "sticky" as well and tend to bind to mannose and fibronectin -biofilms can also help with adherence

What part of the antibody binds specifically to the antigen when it participates in the antigen-antibody interaction?

Variable region *The variable region of the antibody is the part that specifically binds to the antigen

Emerging infectious diseases like influenza are infections that have recently appeared within a population or have incidences that are rapidly increasing or threaten to increase in the near future. What factor contributes to the risk for an emerging outbreak related to the influenza virus?

ability to change genetic information *The primary natural factor associated with the influenza virus is its ability to mutate, changing its genetic profile. This represents a risk for recurrent influenza outbreaks because the human immune system does not recognize and defend against the altered antigen.

What is the purpose of antigen presentation in professional antigen-presenting cells?

activate T cells

Adaptive immunity consists of humoral immunity and cell-mediated immunity. Which attribute is specifically characteristic of humoral immunity?

acts against extracellular microbes and related toxins *Humoral immunity, generated by circulating antibodies, protects the extracellular spaces against microbes and their related toxins. In humoral immunity, B cells secrete antibodies, which circulate in the blood as soluble proteins.

What antigen-antibody interaction involves binding pathogens together, making the pathogens easier to phagocytize?

agglutination

The word antigen comes from a combination of the words "antibody" and "generator." An antigen is anything that activates the adaptive immune response. The part of the antigen that the immune system recognizes is called the epitope, a small fragment of the total antigen. How else do epitopes relate to antigens?

antigens can have epitopes for B cells and T cells -Antigens can have multiple epitopes for both B and T cells. The larger the antigen, the more epitopes available.

Defensins and bacteriocins are types of what?

antimicrobial peptides

A patient presents with loss of appetite, nausea, and persistent mucoidal liquid stools. The patient states they have recently been treated for a bacterial infection using multiple antibiotics. It can be assumed the patient is suffering from an infection from the over-colonization of what bacterial species?

clostridium difficile

What is the transfer of genetic material from one cell to another through cell-to-cell connections?

conjugation

What portal of entry is an external mucosal membrane?

conjunctiva

The human immune system consists of 2 major subsets: the innate immune system and the adaptive immune system. Which of the following applies to adaptive immunity but not innate immunity?

consists of both humoral and cell-mediated immunity

Which cell in the adaptive immune system is most associated with killing large numbers of infected cells or cancerous cells?

cytotoxic T cells

There are two categories of antigen-presenting cells (APC): professional and nonprofessional cells. What type of professional cells has the broadest range of antigen presentation, presenting to both helper and cytotoxic T cells?

dendritic cells *Dendritic cells (professional APC) have the broadest range of antigen presentation and are needed for the activation of naïve T cells, presenting antigen to both helper and cytotoxic T cells. *B cells (professional APC) can recognize soluble antigen that binds to their receptor, then act as an APC, capturing and presenting peptide epitopes from exogenous antigens to effector T4-lymphocytes. *Leukocytes (nonprofessional APC) can be induced to present antigen to CD4+ cells, but they are not able to activate CD4+ cells. *Macrophages (professional APC) surround the site of infection or tissue damage, clearing the infection through phagocytosis.

A 51-year-old man with a history of chronic hypertension and type 2 diabetes mellitus poorly controlled with medications presents for a routine checkup. He has had no problems since his last medical checkup. His BMI is 40, and he smoked previously from age 16 to 26. You recommend he receive the pneumococcal polysaccharide vaccine. What risk factor for severe pneumococcal infection warrants receiving the vaccine?

diabetes mellitus

A 30-year-old male patient on the fourth day of a course of oral antibiotics for pneumonia comes to your clinic due to diarrhea. The diarrhea is non-bloody and watery, happening 3-4 times a day. On examination, his mucous membranes are dry. Clostridioides difficile PCR laboratory examination returns positive. What is the most likely underlying pathophysiology of this patient's diarrhea?

disruption of normal colonic microbiome

A 26-year-old female counselor presents with 2 days of profuse diarrhea and fever. She reports she recently completed a week-long course of antibiotics for an upper respiratory tract infection but takes no other medications. Stool antigen testing for Clostridium difficile toxin A/B is positive. What contributed most to her diarrheal infection?

eradication of native gastrointestinal bacteria

What type of T cell releases lymphokines and stimulates the production of antibodies against a pathogen?

helper T cells *Helper T cells facilitate the organization of the immune response, releasing messenger substances (lymphokines), stimulating the production of antibodies against a specific pathogen, and dispersing the antibodies throughout the bloodstream.

What extracellular serum substances work with complement to break down red blood cells?

hemolysis

What observation appropriately applies Koch's postulates for identifying Legionella pneumophila as the causative agent of Legionnaires' disease?

immunosuppressed pts that are exposed to pure cultures of pneumophila contract an atypical pneumonia

Typhi, a Salmonella enterica serovar, invades epithelial cells and subsequently secretes the A2B5 toxin. What mechanism of pathogenicity involves this release of toxin?

injury

Which of the following terms refers to the capacity of the pathogenic microbe to enter and spread into the tissues of the host?

invasion *Invasion is a condition in which the infectious microorganisms perform endocytosis or pinocytosis in order to disrupt the cell membranes of the host and eventually gain entry into the cell.

How does the capsule in Streptococcus pneumoniae help the organism attain increased virulence?

it prevents adhesion of the immune cell to the pathogen

What kind of vaccine exposes an individual to a weakened strain of a pathogen to establish a subclinical infection to activate the adaptive immune system?

live attenuated vaccines *Live attenuated vaccines expose a person to a weakened strain of a microorganism, which allows for a subclinical infection and activates the adaptive immune defenses. The pathogens are attenuated for the purpose of decreasing virulence through genetic manipulation or long-term culturing.

Humoral immunity is mediated by B cells. Cellular immunity is mediated by T cells. The two branches of adaptive immunity have much in common. What quality is unique to T cells?

major histocompatibility complexes required for antigen presentation

What is the most common portal of entry for microbes into humans?

mucosal membranes

Where is IgA primarily located in the human body?

mucous membranes

An 8-month-old child presents after a visit to the emergency department due to pneumonia caused by Staphylococcus aureus. This is the second episode of Staphylococcal pneumonia in this child in 2 months. You suspect a biochemical disturbance and administer antibiotics as appropriate. What cell group is responsible for the increased Staphylococcal infections in this child?

neutrophils

According to Koch's first postulate, what defines a healthy host organism?

no presence of infectious organism *According to Koch's first postulate, the infectious organism must not be present in a healthy host

Which of the following refers to a type of infection that is caused by pathogenic microorganisms that took advantage of the present vulnerable condition of the person?

opportunistic infection *Opportunistic infection refers to a type of infection caused by pathogenic microorganisms that took advantage of the present vulnerable condition of the person such as a weaker immune system or a break in skin integrity.

Which of the following is the type of host wherein the virus or parasite has already attained sexual or reproductive maturity?

primary host *A primary host, which is also known as the definitive host, is a type of host that harbors a virus or parasite that is already matured and ready for reproduction.

B cells constitute humoral immunity and mature in the bone marrow. What is their role?

produce antibodies to defend against pathogens in an extracellular environment *B cells mature in the bone marrow and produce glycoproteins, called antibodies or immunoglobulins, which act as the body's defense mechanism against pathogens and toxins in an extracellular environment. B cells do not produce antigens

Which of the following is a T-dependent antigen?

protein

What pathogenic organism expresses siderophores that assist in its ability to survive in wounds?

pseudomonas aeruginosa

What type of T cell exerts an immunosuppressive effect, slowing down the body's defenses?

regulatory T cells *Suppressor (regulatory) T cells inhibit the cell-mediated immune response and destroy autoimmune T cells, exerting an immunosuppressive effect.

What type of cellular transport do siderophores employ?

secondary active transport *Siderophores interact with a ligand to chelate ferric iron and deliver the soluble iron across the cell membrane via an ion transport mechanism—an example of secondary active transport—from regions of low concentration to regions of higher concentration. This type of transport requires energy.

Both branches of adaptive immunity (humoral and cellular response) involve specialized cells with a diverse array of specified receptors. What is exclusive to B-cell mediated humoral immunity?

secreted receptors that recognize pathogenic epitopes

Antigen-presenting cells present foreign protein fragments (peptides) to the T cells of the adaptive immune system. This antigen presentation activates T cells to take action against the foreign molecule. The macrophage is one type of antigen-presenting cell that phagocytoses pathogens and presents the peptides bound to MHC I molecules. What is a part of the mechanism for macrophage antigen presentation?

the macrophage engulfs a pathogen, then degrades it into fragments that are presented

A 52-year-old man is diagnosed with bacterial meningitis. Cerebrospinal fluid grows out Gram-positive cocci in short chains and diplococci. You suspect Streptococcus pneumoniae meningitis. Which of the following virulence factors contributes to this organism's ability to evade host defenses?

thick polysaccharide capsule that protects against phagocytosis

What pathogen has a portal of entry through the placenta, making it a TORCH disease?

toxoplasma gondii

Which of the following refers to an animal that has been introduced with new genetic information acquired from foreign DNA?

transgenic *Transgenic animals have undergone genetic engineering resulting in the introduction of a transgene. The transgene is segment of DNA isolated from one organism and introduced into the host. The vehicle used to carry the foreign DNA of the transgene is called a vector.

Mosquito bites as a portal of entry are capable of transmitting some viruses, such as dengue. A mosquito that bites a dengue-infected person becomes a viral reservoir and can then transmit the virus by biting another person. What mode of transmission is at work?

vector transmission