Flashcards in Type IV Immunopathology Deck (44):
What are the two stages of delayed hypersensitivity?
Describe initiation phase of delayed hypersensitivity.
1. Antigen enters skin
2. Dendritic cells take antigen to lymph node
3. Show antigen to T cells
4. T cells expand but by the time they get to the skin the antigen is gone
Describe elicitation phase of delayed hypersensitivity.
1. Antigen penetrates skin
2. T cells are already expanded so they release INF-gamma
3. Recruitment of macrophages
4. 6-12 hours later there is visible redness on a firm red area
How do memory T cells activate so quickly?
They are already expanded and they have a lower activation threshold
Describe the TB Skin Test (Mantoux skin test).
1. Antigen given intradermally
2. If patient has TB- then memory T cells bind antigen (Standardized preparation of M. tuberculosis antigens) and secrete INF-gamma
3. Recruits marcrophages (remember: 1 T Helper Cell can recruit 1000 macrophages)
How is a TB skin test read?
Read by the induration (macrophages in the site of inflammation)
What diameter of induration from a skin test would indicate a positive TB test?
15mm in diameter
5-10mm in diameter would indicate some type of immunodeficiency
Why isn't the TB test itself immunizing?
Because the dose of PPD needed to elicit a positive reaction in an immune person is far lower than would be required to immunize a person
How can you tell if a patient has normal T cell function?
A skin test using a panel of common antigens. If the person doesn't respond to any of them then they are anergenic
What is anergy?
Lack of reaction of body's defense mechanisms to foreign substance
What are three ways in which you can get a positive TB skin test?
1. If you were exposed to TB (may not even know it because you were immunized but did not get elicitation)
2. Exposure to other mycobacterium
3. Bacille Calmette-Guerin (BCG)
What is Bacille Calmette-Guerin (BCG) vaccine?
Attenuated bovine tuberculosis bacteria given to newborns outside of the US
Paula wants to volunteer for the local hospital and has to get a TB skin test. When she does it comes back positive. Paula was born in Columbia and immigrated to the US when she was 12. How can we distinguish if she truly was exposed to TB or just got the BCG vaccine?
QuantiFERON-TB Gold test
How does the QantiFERON-TB Gold test work?
1. Obtain whole blood sample
2. Add purified M. tuberculosis protein to the whole blood sample and incubate
3. Use ELISA to measure the INF-gamma levels
4. Increased INF-gamma = TB exposure
No INF-gamma= BCG vaccine
Why does the BCG vaccine cause a positive TB test?
Because BCG vaccine is cross-reactive for TB
How can you test the function of cytotoxic T lymphocytes?
1. Soak cells in antigenic peptide (in some cases the peptide will be loaded onto MCH Class I without being processed)
2. Incubate with patients' T cells
3. Measure amount of cell death
Contact dermatitis occurs due to what cell type?
A 27-year old man living with AIDS came to the clinic complaining of continual low fever, a rash on body and limbs, malaise, and variable GI, respiratory, and musculoskeletal symptoms. A careful work-up revealed no current infections with opportunists that could explain these symptoms. He daated their onset to 5 months previously, when his medications were changed. The doctors decided to increase the does of one of his antiretrovirals, ABACAVIR, thinking his HIV may not have been adequately controlled. Within 2 weeks he returned to the emergency room with exacerbations fo almost all of the previous symptoms, at which time a third-year medical student identifies the problem. What is the problem?
Up to 8% of people who are given ABACAVIR, a nucloside reverse transcriptase inhibitor, for HIV, develop ABACAVIR HYPERSENSITIVITY SYNDROME which is quite awful and difficult to diagnose correctly.
HLA-B*5701 (this is Class I NOT Class II) recognized by Th1
ABACAVIR changes the structure of HLA-B*5701 >>>Binding certain self-peptides
HLA-B*1502 is associated with drug-induced hypersenitivity to carbamazepine (used to treat seizures, nerve pain, and bipolar disorder).
What disorder does it cause and in what population?
In Han Chinese population. Also in Thai, Malay, and Indian populations.
Why do recipient T cells attack a graft?
They attack cells which have MHC Class I and II (all cells) because foreign MHC looks like MHC+antigen.
Hyperacute or "white graft" reactions can occur in what two scenarios?
1. If you keep putting the same graft into one recipient
2. Occurs commonly in xenografts due to ubiquitous carbohydrate epitopes which are present in the foreign species but not in the human.
Multiple sclerosis is a demyelinating disease due to what?
T cells that are reactive to myelin basic protein
If a T cell were to get into the brain would it cause a immune response?
No because it needs professional antigen presenting cells to become activated
The brain is __________, but not ____________
Why did the meat-packing plant workers in Minnesota get progressive inflammatory neuropathy, with weakness, partial paralysis, and peripheral nerve root demyelination?
They inhaled aerosolized brain which immunized them to brain. This caused T cells to become activated that could go into the brain and cause destruction
Could prior infection of a virus cause MS symptoms?
Yes. Prior infection with such a virus produce activated T cells that could then enter the brain and attack the myelin.
A patient comes in complaining of dry eyes and mouth. You suspect which autoimmune reaction?
Sjogren Syndrome. Autoimmune reaction against exocrine glands. Involves CTL and has genetic and environmental predispositions
What cells dominate in the pathogenesis of Type I diabetes?
Cytotoxic killer cells
HLA-DR3 and HLA-DR4 have a strong association with what disease?
Type I Diabetes
Describe the course of Type I diabetes.
HLA-DQ2 and HLA-DQ8 have unusual amino acids placements in the antigen-binding groove
This allows antibodies to bind to the islet cells
Cytotoxic Killer Cells destroy the antibody covered islet cells
What patient population has a higher incidence of rheumatoid arthritis?
What joints does rheumatoid arthritis usually effect first?
Small joints especially those in the fingers
What is Rheumatoid factor?
It is a marker of rheumatoid arthritis
IgM anti-IgG antibody
What can be used to treat rheumatoid arthritis?
Rixtuximab- monoclonal antibody against CD20 on B cells
What is the cell responsible for pathogenesis in rheumatoid arthritis?
T cells- HLA-DRB1 is the group most often seen with rheumatoid arthritis
What increases your risk of RA?
Air pollution especially smoking
What three conditions must be met in order for graft-versus-host disease (GvHD) to occur?
1. Graft must contain immunocompetent T cells
2. Must be at least one antigen in the host which the graft's T cells can recognize
3. Host must be relatively immunoincompetent or unable for genetic reasons to recognize the graft's MHC antigens
What is the timeline for acute GvHD?
What are the symptoms of a patient with acute graft vs host disease?
Maculopapular skin rash
Hepatic inflammation with jaundice
How do you treat acute graft vs. host disease?
Corticosteroids and immunosuppressives
What is the timeline for chronic GvHD?
months to years
Can chronic GvHD happen in someone who is a perfect HLA match?
Yes. They probably don't match at some of the minor histocompatibility antigens
How can you decrease the risk of GvHD in a bone marrow recipient?
Removing the T cells from the bone marrow may decrease the risk of acute GvHD, but it can lead to poorer engraftment of the bone marrow stem cells