(a) The macrophage in this figure is presenting a foreign epitope that does not match the TCR of the T cell. Because the T cell does not recognize the epitope, it is not activated. (b) The macrophage in this figure is presenting a superantigen that is not recognized by the TCR of the T cell, yet the superantigen still is able to bridge and bind the MHC II and TCR molecules. This nonspecific, uncontrolled activation of the T cell results in an excessive release of cytokines that activate other T cells and cause excessive inflammation. (credit: modification of work by “Microbiotic”/YouTube)
What are examples of superantigens?
How does a superantigen activate a helper T cell?
What effect does a superantigen have on a T cell?
Superantigens
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 lymphatic system plays several crucial roles in the human body, functioning as a key component of the immune system and contributing to the maintenance of fluid balance. Its main functions include:
1. Immune Response: The lymphatic system produces and transports lymphocytes, which are a type of
asegid
to transport fluids fats proteins and lymphocytes to the blood stream as lymph
Anatomy is the study of the structure of the body, while physiology is the study of the function of the body. Anatomy looks at the body's organs and systems, while physiology looks at how those organs and systems work together to keep the body functioning.
Enzymes are proteins that help speed up chemical reactions in our bodies. Enzymes are essential for digestion, liver function and much more. Too much or too little of a certain enzyme can cause health problems
Kamara
yes
Prince
how does the stomach protect itself from the damaging effects of HCl
the normal temperature is 37°c or 98.6 °Fahrenheit is important for maintaining the homeostasis in the body
the body regular this temperature through the process called thermoregulation which involves brain skin muscle and other organ working together to maintain stable internal temperature
