What transports peptides across the ER membrane to associate with newly formed MHC I molecules?
A specialized protein called the transporter associated with antigen processing (TAP)
What is bare lymphocyte syndrome?
A rare genetic disease in which the TAP protein is nonfunctional. Patients have less than 1% of normal MHC class I molecules on cell surfaces, so develop weak CD8+ T cell responses to intracellular pathogens.
What interacts with MHC class II molecules on the surface of APCs, and what type of antigen is affected?
The T-cell co-receptor CD4; antigens of extracellular origin
Which antigen presenting cells (APCs) are associated with MHC class II?
Dendritic cells, macrophages, and B cells (presented to CD4+ T cells)
What is another term for the human leukocyte antigen complex (HLA) class I and class II molecules?
Human major histocompatibility complex (MHC) molecules, class I and class II, respectively
What are the isotypes of the MHC class I molecule?
There are 6: HLA-A, -B, & -C, and HLA-E, -F, & -G
What are the isotypes of the MHC class II molecule?
There are 5: HLA-DM, -DO, -DP, -DQ, & -DR
What is a haplotype?
The particular combination of HLA alleles that an individual inherits
In a cross-match test, what is assessed?
Blood serum from the prospective donor
In a cross-match test, what is a positive result?
Occurrence of complement-mediated lysis, indicating reactive antibodies present against donor T or B cells
In a mixed lymphocyte reaction, what is assessed?
A tissue sample of recipient lymphocytes is mixed in vitro with irradiated (dead) cells from the potential donor
In a mixed lymphocyte reaction, what is a positive result?
Measurement of high levels of recipient T cell proliferation (MHC II) and recipient cytotoxicity (MHC I)
What is the mechanism of action of a superantigen?
Bacteria bind simultaneously to MHC class II molecules and T cell receptors, causing a massive, ineffective polyclonal (T cell) response.
What are two examples of superantigens?
Staphylococcal enterotoxins and toxic shock syndrome toxin
What changes occur in the T cell receptor after it has been stimulated by an antigen?
None. (Different from immunoglobulins which can undergo somatic hypermutation = class switching)
What signals are required for T lymphocyte activation?
1) peptide binds to MHC and 2) co-stimulation of the T cell's CD28 molecules by the APC's B7 cell-surface molecule
What is anergy?
A nonresponsive state that a T cell can enter
Under what conditions does anergy occur?
When an APC has the required peptide:MHC complex but does not have B7 on its surface for co-stimulation
What is positive selection?
Marking a T cell with a TCR that binds self-MHC class I for survival; occurs in cortex of thymus
What is the purpose of positive selection?
It's necessary so that an individual has T cells that can interact with self-MHC molecules.
What is negative selection?
Deletion of strongly self-reactive T cells; occurs in the thymus
What is the purpose of negative selection?
It's necessary so that an individual's T cells do not bind self-MHC molecules too strongly.
What is CTLA-4 and what is its role?
Cytotoxic T lymphocyte-associated antigen-4 protein; it can bind to B7, shutting off T cell responses
What do most regulatory T cells have in common?
They are CD4+ and express high levels of CD25.
What is the development and function of regulatory cells dependent on?
A transcription factor called Foxp3 and the cytokine IL-2
With respect to transplantation, what is a donor?
The individual who provides the graft
With respect to transplantation, what is a recipient or host?
The individual in whom the graft is placed
With respect to transplantation, what does syngeneic mean?
Animals (or grafts) that are genetically identical to one another
With respect to transplantation, what does allogeneic mean?
Animals (or grafts) of one species that differ genetically from other animals of the same species
With respect to transplantation, what does xenogeneic mean?
Animals (or grafts) of different species
With respect to transplantation, what are allografts?
Grafts between members of the same species
With respect to transplantation, what are xenografts?
Grafts between members of two different species
What is the most likely cause of acute rejection of transplanted tissues or organs?
The direct pathways of allorecognition; involves activation of recipient T cells by donor dendritic cells
What is the most likely cause of hyperacute rejection of transplanted tissues or organs?
It's mediated by circulating antibodies; it occurs within minutes.
What is yellow fever and how is it transmitted to humans?
It is a viral hemorrhagic fever; it's transmitted via the bite of an infected mosquito.
What ensures the transmission of yellow fever from one year to the next?
An infected mosquito can pass the virus in its eggs, which lie dormant when dry and hatch in the rainy season.
How many people enter the toxic phase of yellow fever and under what time frame? How many die?
15% enter the toxic phase within 24 hours; half of these patients die within 10-14 days
What is affected in the toxic phase of yellow fever?
Several body systems: jaundice & abdominal pain ? bleeding from mouth, nose, eyes, stomach ? blood in vomit & feces ? kidney function deteriorates (albuminuria or anuria)
What are some key facts about the vaccine for yellow fever?
It's safe & highly effective; it's a live attenuated virus (17D); one dose gives 10+ years protection (probably life); not given to infants < 6mo, pregnant women, immunocompromised patients, and patients allergic to eggs
What does recovery from dengue imply?
Lifelong immunity against that serotype; partial & transient protection against the other three serotypes
What are the risks of sequential infection of dengue?
Increased risk of more serious disease resulting in dengue hemorrhagic fever (DHF)
What is the predominant vector for dengue?
The urban mosquito Aedes aegypti.
How can an Aedes aegypti mosquito transmit dengue to her offspring?
Via transovarial transmission (through the eggs)
What are the Arenaviruses and how are they transmitted to humans?
Lassa virus & others (Junin, Machupo, Guanarito, Sabia); shed into environment in the urine or droppings of infected Old World rats & mice (the rodents don�t show signs of illness)
What is the animal host for Lassa Virus?
The "multimammate rat" of the genus Mastomys
How is Crimean-Congo Hemorrhagic Fever (CCHF) transmitted to humans?
The reservoir & vector are Ixodid (hard-bodied) ticks, eps. genus Hyalomma; amplifying hosts include many animals (cattle, goats, sheep, hares); transmission occurs through contact with animal or human blood or ticks
How is Hemorrhagic Fever with Renal Syndrome (HFRS) transmitted to humans?
Carried & transmitted by rodents; infection occurs after exposure to aerosolized urine, droppings, or saliva
What are the most common epidemologic associations with Rift Valley Fever (RVF)?
Mosquito-borne epidemics during years of unusually heavy rainfall
How is Rift Valley Fever (RVF) transmitted to humans?
Usually through bites from infected mosquitoes (& possibly other biting insects)
Which drug used to treat HIV is a fusion inhibitor and what is its mechanism of action?
Enfuvirtide; binds to gp41, blocking fusion of virus envelope with host cell membrane
Which drugs used to treat HIV are nucleoside(/-tide) reverse transcriptase inhibitors?