Melissa, an otherwise healthy 22-year-old woman, is brought to the emergency room by her concerned boyfriend. She complains of a sudden onset of high fever, vomiting, diarrhea, and muscle aches. In her initial interview, she tells the attending physician that she is on hormonal birth control and also is two days into the menstruation portion of her cycle. She is on no other medications and is not abusing any drugs or alcohol. She is not a smoker. She is not diabetic and does not currently have an infection of any kind to her knowledge.
While waiting in the emergency room, Melissa’s blood pressure begins to drop dramatically and her mental state deteriorates to general confusion. The physician believes she is likely suffering from
toxic shock syndrome (TSS) . TSS is caused by the toxin TSST-1, a superantigen associated with
Staphylococcus aureus , and improper tampon use is a common cause of infections leading to TSS. The superantigen inappropriately stimulates widespread T cell activation and excessive cytokine release, resulting in a massive and systemic inflammatory response that can be fatal.
Vaginal or cervical swabs may be taken to confirm the presence of the microbe, but these tests are not critical to perform based on Melissa’s symptoms and medical history. The physician prescribes rehydration, supportive therapy, and antibiotics to stem the bacterial infection. She also prescribes drugs to increase Melissa’s blood pressure. Melissa spends three days in the hospital undergoing treatment; in addition, her kidney function is monitored because of the high risk of kidney failure associated with TSS. After 72 hours, Melissa is well enough to be discharged to continue her recovery at home.
In what way would antibiotic therapy help to combat a superantigen?
Part 2
Olivia’s swollen lymph nodes, abdomen, and spleen suggest a strong immune response to a systemic infection in progress. In addition, little Olivia is reluctant to turn her head and appears to be experiencing severe neck pain. The physician orders a complete blood count, blood culture, and lumbar puncture. The cerebrospinal fluid (CSF) obtained appears cloudy and is further evaluated by Gram stain assessment and culturing for potential bacterial pathogens. The complete blood count indicates elevated numbers of white blood cells in Olivia’s bloodstream. The white blood cell increases are recorded at 28.5 K/µL (normal range: 6.0–17.5 K/µL). The neutrophil percentage was recorded as 60% (normal range: 23–45%). Glucose levels in the CSF were registered at 30 mg/100 mL (normal range: 50–80 mg/100 mL). The WBC count in the CSF was 1,163/mm
3 (normal range: 5–20/mm
3 ).
Based on these results, do you have a preliminary diagnosis?
What is a recommended treatment based on this preliminary diagnosis?
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Key concepts and summary
Immature T lymphocytes are produced in the red bone marrow and travel to the thymus for maturation.
Thymic selection is a three-step process of negative and positive selection that determines which T cells will mature and exit the thymus into the peripheral bloodstream.
Central tolerance involves negative selection of self-reactive T cells in the thymus, and
peripheral tolerance involves
anergy and
regulatory T cells that prevent self-reactive immune responses and autoimmunity.
The
TCR is similar in structure to immunoglobulins, but less complex. Millions of unique epitope-binding TCRs are encoded through a process of genetic rearrangement of V, D, and J gene segments.
T cells can be divided into three classes—
helper T cells, cytotoxic T cells, and
regulatory T cells— based on their expression of CD4 or CD8, the MHC molecules with which they interact for activation, and their respective functions.
Activated helper T cells differentiate into
T
H 1, T
H 2, T
H 17 , or
memory T cell subtypes . Differentiation is directed by the specific cytokines to which they are exposed. T
H 1, T
H 2, and T
H 17 perform different functions related to stimulation of adaptive and innate immune defenses. Memory T cells are long-lived cells that can respond quickly to secondary exposures.
Once activated, cytotoxic T cells target and kill cells infected with intracellular pathogens. Killing requires recognition of specific pathogen epitopes presented on the cell surface using MHC I molecules. Killing is mediated by
perforin and
granzymes that induce apoptosis.
Superantigens are bacterial or viral proteins that cause a nonspecific activation of helper T cells, leading to an excessive release of cytokines (
cytokine storm ) and a systemic, potentially fatal inflammatory response.
Fill in the blank
A ________ T cell will become activated by presentation of foreign antigen associated with an MHC I molecule.
A TCR is a protein dimer embedded in the plasma membrane of a T cell. The ________ region of each of the two protein chains is what gives it the capability to bind to a presented antigen.
the transfer of energy by a force that causes an object to be displaced; the product of the component of the force in the direction of the displacement and the magnitude of the displacement
A wave is described by the function D(x,t)=(1.6cm) sin[(1.2cm^-1(x+6.8cm/st] what are:a.Amplitude b. wavelength c. wave number d. frequency e. period f. velocity of speed.
A body is projected upward at an angle 45° 18minutes with the horizontal with an initial speed of 40km per second. In hoe many seconds will the body reach the ground then how far from the point of projection will it strike. At what angle will the horizontal will strike
Suppose hydrogen and oxygen are diffusing through air. A small amount of each is released simultaneously. How much time passes before the hydrogen is 1.00 s ahead of the oxygen? Such differences in arrival times are used as an analytical tool in gas chromatography.
the science concerned with describing the interactions of energy, matter, space, and time; it is especially interested in what fundamental mechanisms underlie every phenomenon