Micro 2
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
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 until IgG antibodies peak at 1 month.
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
How does the capsule in Streptococcus pneumoniae help the organism attain increased virulence?
It prevents adhesion of the immune cell to the pathogen.
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
IgM function
-IgM monomers are present on the surface of B cells in the form of B cell receptors -pentameric IgM in the blood is very good at agglutinating particles because of its many binding sites -works closely with the complement system
T cell response
-Originates in the bone marrow and migrates to the thymus for differentiation -has specific T cells receptors (TCRs) on their surface -Two major types of T cells --Helper T cells (CD4+) --Cytotoxic T cells (CF8+)
Exceptions to Koch's Postulates
-Some pathogens can cause several disease conditions -Some pathogens cause disease only in humans -Some microbes have never been cultured
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 -three major subsets of effector cells that the cell can differentiate to --Th 1: produce IFN-y, target macrophages, and effective against intracellular pathogens --Th 2: produces multiple interleukins and promotes 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
T-dependent vs T-independent activation
-There are 2 types of antigen trigged B cell activation -T-dependent requires helper T cells to help activate the B cell --usually evoked by proteins --macrophages 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 -T-independent do not require helper T cells --usually evoked by large molecule with repeating units like polysaccharides --slower response with no memory cells produced
Antibody structure
-belong to the immunoglobulin family of proteins -present in the blood, the surface of B cells, and other body fluids -there are five known structural types, three are involved in the defense against infection -2 light polypeptide chains -2 heavy polypeptide chains -bound by disulfide bonds -Y shaped with 2 antigens binding sites -stalk is called the Fc fragment -IgG --monomer -IgA --monomer in the blood --dimer connected at the Fc region in the gut, tears, other secretions IgM --pentamer
Recognition of foreignness
-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 1: present on almost all human cells; mark cells as "self" --MHC class II: only present on certain leukocytes --Both MHC class i and II are involved in the antigen processing
B cells and antibody respones
-develop int he bone marrow then migrate to other lymphoid tissue -b cells receptor is an IgM monomer -antigen binds to B cell receptor and is internalized for initiation of antibody production --b cells multiple and differentiate into either memory or plasma cells ---plasma cells secrete large amounts of antibodies ---memory cells circulate and remember a specific antigen so that specific antigen returns, the response will be quicker
The adaptive immune system
-highly specific immune system -discrimination between self and non-self -memory function-accelerated response if an invader returns -2arms of adaptive immunity --humoral immunity: B cells and 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
Cell-mediated immunity
-important in the response to intracellular pathogens -macrophages are mobilized and enhanced
Antibody production timeline
-initial contact with a new antigen evokes the primary response --lag phase of 1 week between the challenge and the detection of antibodys -levels of antibody rise exponentially to maximal steady state in 3 weeks -antibody levels then decline gradually if no further antigenic stimulation is given -first antibodies synthesized are IgM, then, IgG arises and eventually predominates -after a subsequent exposure or booster injection of the same antigen, the secondary response occurs --involves memory --lag time is shortens, rate of exponential increase to the maximum 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
Siderophores
-iron is required by bacteria in order to grow -there is very little free iron in human blood or body fluid because it is sequestered by iron-binding proteins (transferrin, lactoferrin) -bacteria secrete siderophores to compete with host iron-binding proteins --siderophores bind iron more tightly than the host iron-binding proteins -these siderophores are then transported into the bacterium
CD*+ cytotoxic T cells
-kills host cells presenting foreign antigens on MHC class 1 molecules -prevents viral production and release by eliminating the host cell before viral synthesis or assembly is complete
Antigens
-large complex antigens such as proteins and viruses must be processed before their epitopes can be effectively recognized by the immune system --macrophages and specialize epithelial cell sin 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
Normal flora
-microorganism that live in or on the human body -can be transient or residents carrier state-when organism that are known to be pathogenic are present but not causing diesase -bladder, upper urinary tract, and low respiratory tract are all sterile. -microbial antagonism (exclusionary effect) is a competition between microbes
IgG function
-most abundant immunoglobulin and provides most extensive and long-lived antibody response -memory cells are programmed for rapid IgG response upon a repeat infection (lifetime 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 placental barrier; so passive immune protection is provided to the newborn in the form of maternal antibody
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 UTI **candida albicans can overgrow and cause thrust/yeast infections if antibiotics suppress the normal bacterial flora -mouth flora can cause dental caries
Capsules
-only in some bac. -made of hydrophilic polysaccharide gel -if the gel forms a discrete layer, its called a capsule -if its amorphous, its called a slime layer -function is to protect the bac. from the immune system -prevents phagocytosis by binding a host complement regulating proteing that is found in the serum called factor H -factor H degrades complement proteins as they attach to the bacterial cell surface --opsonizaton: coating of a pathogen with complement proteins, which allows WBC's to phagocytize the pathogen
IgA
-special role in local immunity in protecting epithelial surfaces from colonization and infection -sIgA is present on mucosal layers on epithelial surfaces and in glandular secretions -prevents attachment of potential pathogens to receptors on mucous membrane epithelia
Kochs postulates
-used to prove cause of an ID -1-same pathogen must be present in every case of the disease -2-pathogen must be isolated from the diseased hot and grown in pure culture -3-pathogen from the pure culture must cause the disease when it is inoculate into a healthy, susceptible lab animal -4-pathogen must be isolated from the inoculated animal and must be shown to be the original organism
Risk factors for disease severity
AGE -immune system of newborns are not fully developed -immune systems of elderly have weakended OCCUPATION -healthcare workers are at a higher risk 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 WBC's PREEXISTING CONDITIONS -copd -cardiovascular disease HIV depletes CD4+ T cells
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
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
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.
MCH II
Binds to products that originated outside of the cell, but have been phagocytized and are now in a vacuole inside the cell -the product is digested and peptide fragments are combined with MHC II molecules ad transported to the surface for presentation -recognized by CD4+ T cells
What virulence factor in Streptococcus pneumoniae makes the disease more severe in the host?
Encapsulation
Damange
-some pathogens produce side wout using any know virulence factors
Normal flora protect the host by:
-competing for nutrients -producing substances harmful to invading microbes -affecting pH and available oxygen
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
Antigens and Epitopes
Antigen-any substance (usually foreign) with the ability to stimulate an immune response when presented in an effective fashion --usually proteins, polysaccharides, or glycolipids Epitope-subregion of an antigen that is the actual antigenic determinant (the side where an antibody binds) --epitopes fit the combining site of T cell receptors and antibodies
Defensins and bacteriocins are types of what?
Antimicrobial peptides
MHC I
Binds to products 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 endoplasmic reticulum where they are then transported to the surface for presentation -recognized by CD8+ T cells
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
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
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
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 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
Invasion
Getting into cells -some bac are obligate intracellular pathhogens, some are facultative intracellular pathogens -viruses must enter a host cell to replicate
What type of T cell releases lymphokines and stimulates the production of antibodies against a pathogen?
Helper T cells
What extracellular serum substances work with complement to break down red blood cells?
Hemolysins
What antibody class can be found on the membrane of a B cell?
IgM
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
What observation appropriately applies Koch's postulates for identifying Legionella pneumophila as the causative agent of Legionnaires' disease?
Immunosuppressed patients that are exposed to pure cultures of L. 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
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
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
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
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
What portal of entry is part of the parenteral route of getting a disease?
broken skin
Which of the following is the type of host wherein the virus or parasite has already attained sexual or reproductive maturity?
Primary host
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
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
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
Reducing agent
What type of T cell exerts an immunosuppressive effect, slowing down the body's defenses?
Regulatory T cells
What type of cellular transport do siderophores employ?
Secondary active transport
What organism is commonly found in the stomach?
Streptococcus spp
What activated T helper cell stimulates neutrophils and is central to the destruction of extracellular bacteria and fungal pathogens?
Th17
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.
What part of the antibody binds specifically to the antigen when it participates in the antigen-antibody interaction?
Variable region
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
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
Pathogenicity
ability to cause disease
entry
beating innate host defenses -skin is a protective layer mucus membranes are coated with mucin and secretory IgA -some bac excrete the enzyme sIgA protease which degrades sIgA
What portal of entry is an external mucosal membrane?
conjunctiva
virulence
degree of pathogenicity
capsule
glycocalyx around the cell wall -impairs phagocytosis and complement activation
Which of the following terms refers to the capacity of the pathogenic microbe to enter and spread into the tissues of the host?
invasion
antigenic variation
pathogens can alter their surface antigens -antibodies previously formed against these surface antigens are now ineffective
Adherence
search for a unique niche -requires adhesin and receptor -adhesins are proteins -pili are sticky and bind to mannose and fibronectin -biofilms can help
intracellular growth
some pathogens grow within a host cell where antibodies and WBC cannot reach them
Which of the following refers to an animal that has been introduced with new genetic information acquired from foreign DNA?
transgenic