Week 16 Flashcards
Transplants are a solution for organ failure. What are three fundamental problems associated with it?
Transplant must perform its functions
Transplant and recipient health must be retained
Recipient immune system must not reject the transplant
What is an autologous transplant type?
Donor and recipient are the same individual
What is a syngeneic transplant type?
Donor and recipient are genetically identical (identical twins)
What is an allogeneic transplant type?
Donor and recipient are genetically different but of the same species
What is a xenogeneic transplant type?
Donor and recipient are of different species
Organ rejection limits allogeneic transplant survival. List the three types of organ rejection.
Hyperacute
Acute
Chronic
What is a hyperacute organ rejection?
Type 2 hypersensitivity
Occurs minutes to hours
Blood type alloantibodies
What is an acute organ rejection?
Type 4 hypersensitivity
CD4 and CD8 T cells
HLA mismatches (HLA genes code for MHC)
What is a chronic organ rejection?
Type 3 hypersensitivity
Chronic transplant inflammation
____ between the donor and recipient is the biggest predictor of transplant success
Histocompatibility
Depends on blood type, major, and minor HLA genes
___ and ___ improve survival rates of organ transplantation
Donor matching
Immunosuppressants
True or false… erythrocytes do not express MHC 1 or 2 (no HLA matching). This makes it less complicated to match the donor to recipient
True
How often can you donate whole blood, plasma, and platelets?
Whole blood: every 56 days
Plasma: every 28 days
Platelets: every 15 days
What blood type is considered the universal donor?
O negative
What blood type is considered the universal recipient?
AB +
In regards to blood rejection, what type of hypersensitivity reaction occurs?
Type 2
Some transplants can be taken form live healthy patients. Name two of this type
Kidney (because everyone has 2)
Liver (you can remove up to 60% of the liver and it will still regenerate)
The degree of matching varies with tissue type. Describe the type of matching that must occur for the cornea, liver, and kidney
Cornea - no matching or immunosuppression necessary
Liver - only blood type match
Kidney - HLA and blood type match
Pre-existing blood type antibodies cause a ___ rejection
Hyperacute
-this is a type two hypersensitivity that occurs within minutes, resulting in irreversible organ loss. Prevented by compatibility assessment
What is direct allorecognition? How does it cause rejection?
Transplant dendritic cells activate recipient T cells, which then go on to kill the transplant tissue
This occurs days to weeks
This is a type 4 hypersensitivity
Direct allorecognition causes ___ rejection
Acute
True or false… allogeneic MHC activates T-cells directly (antigen is largely irrelevant)
True
Antibodies against transplant MHC1 causes ___ rejection. Explain how.
Alloantibodies that cause chronic rejection of organ transplants are the result of an immune response stimulated by the indirect pathway of allorecognition
Immune complexes form and are deposited in the blood vessel walls of transplanted organ recruit inflammatory cells. Immune cells enter blood vessel wall to cause it to constrict and lead to progressive loss of blood to the organ. It may take years for the organ to die.
Hematopoietic transplants can cause ___vs. ___ disease. Describe this.
Graft vs. host disease
Transplant adaptive immune cells (T cells) target and kill recipient tissue (GI, liver, skin problems most severe)
Alloreactive NK cells can kill recipient ____
Leukemia
Immunosuppressants may help in transplantation acceptance. Corticosteroids suppress __ transcriptional activity. It does this by increasing ___ production, which inhibits ___.
NF-kB
IkBa
NF-kB
Immunosuppressants inhibit T cell activation by interfering what three signals? For example, belatacept binds to CD28 to prevent the activation of ___.
Activation, survival, proliferation
Calcineurin (the second signal)
Name two immunosuppressants that inhibit T cell activation
Cyclosporin
Tacrolimus
____ and ___ prevent T cell survival and proliferation
Baletacept (prevents the second signal)
Anti-CD25
What are autoimmune diseases?
Loss of tolerance leading to hypersensitivity reactions
Adaptive immune targeting to self
Autoimmune diseases are caused by genetics, the environment and both. Are they more common in men or women? Only about ___% of predisposed individuals actually develop the autoimmune disorder
Women’s
20%
___ genes are associated with susceptibility in __% of autoimmune diseases. Class ___ alleles are most frequently implicated. ___ T cells are also closely tied to AD development
HLA
2
CD4
True or false… in a type 2 hypersensitivity autoimmune disease, the antibodies may act as agonists or antagonists
True
rheumatic fever is caused by ___. Two bacterial species, __ and ___ have antigens that are similar to human antigen causing the AD
Molecular mimicry
Streptococcus pyogenes
Staphylococcus aureus
Describe how grave’s disease works
Antibody binding causes metabolic dysfunction
Antibodies act as TSH agonists causing excessive thyroid hormone release
The antibodies themselves do not cause overt tissue damage.
This is a CD4 Th2 response
What are the signs of hyperthyroidism?
Weight loss
Heat intolerance
Anxiety and irritability
Exophthalamos
Describe how newborns can be born with Graves’ disease. How can this be cured?
Mother with Graves’ disease makes anti-TSHR antibodies. Since its IgG, it crosses placenta into fetus. Newborn suffers from Graves’ disease
Plasmapheresis (filtering of plasma) to removal mother anti-TSHR can cure this
What is hashimoto’s disease?
Destruction of normal thyroid tissue
CD4 Th1 response
Causes hypothyroidism
Ectopic lymphoid tissue formed in the thymus
Enlarged thyroid present, swallowing difficulty
Hashimoto’s disease is hypothyroidism whereas Grave’s disease is hyperthyroidism. Describe the different oral manifestations seen in them
Hypothyroidism: salivary gland enlargement, comprised periodontal health, macroglossia and thick lips, mouthbreathing, anterior open bite.
Hyperthyroidism: increased susceptibility to caries, burning mouth syndrome, maxillary and mandibular osteoporosis
What is Sjögren’s syndrome?
Progressive destruction of the exocrine glands
One of the most common ADs
Type 2 hypersensitivity
Form periodontal aggregates that are germinal center like aggregates
Dry eyes, dry mouth, and arthritis
What is systemic lupus erythematos?
Widespread self-antigen targeting and complex deposition
Complexes deposit in blood vessels, kidneys and joints
Epitope spreading leads to intracellular antigen targeting
Mouth ulcers and plaques (not necessarily painful at the onset)
SLE causes intermolecular epitope spreading. Describe what this is.
This is different antigens being targeted because they are associated with the same macromolecular complex as another antigen
Slowly expanding adaptive response
Loss of tolerance
What in intramolecular epitope spreading?
This is when a small conserved region of a self-antigen shares an epitope with a pathogenic antigen. When you develop antibodies against the pathogenic antigen, it will also target the self antigen. .. it is called intramolecular epitope spreading because soon the other epitopes located on the self antigen will also be targeted.
True or false… thymic involuntion is tied to increased AD incidence
True (celiac disease)
Describe autoimmunity in type 1 diabetes
CD4 and CD8 T cell response kills beta cells
HLA-DR3/4 linkage
Viral cross-reactivity model
Molecular mimicry
Stress
Epitope spreading
What are four oral manifestations of diabetes?
Reduced salivary flow
Altered saliva composition
Impaired wound healing
Sweet breath
Periodontitis is tied to ___ and ___
Rheumatoid arthritis
Epitope spreading
What are the expected survival rates at 5 years for the following organs? Kidney Liver Heart Lungs Bone marrow
Kidney - 90%
Liver - 75%
Heart - 70%
Bone marrow - 60%
Lungs - 50%
Name five major classes of immunosuppressants used for organ transplants
Calcineurin inhibitors
MTOR inhibitors
Antiproliferative agents
Antibodies
Corticosteroids
What are the two stages of rejection in host vs. graft reaction?
Sensitization stage (recognition of alloantigens)
Effector stage (inflammatory response to the injury, antibody production, cell recruiting)
What are the two different pathways in the sensitization stage? Describe them
Direct pathway - host T cells recognize allo-MHC molecules as non-self
Indirect pathway - T cells recognize processed alloantigen presented by self-APCs
What are the three phases for post HSCI?
Phase 1 (pre engraftment) (day0-30) - prolonged neutropenia, damage to mucocutaneous barriers
Phase 2 (post-engraftment) (day31-100) - impaired cell-mediated immunity. - GVHD
Phase 3 (late) (day>100) - depends on immunosuppression
Name 7 pre-transplant dental care procedures
Dental prophylaxis/cleaning
Treat all active dental disease
Remove all potential sources of acute or chronic disease
Remove all non-restorable teeth
Reinforce oral hygiene and home care
Perform necessary denture adjustments
Daily use of antibacterial mouthwash
Name 5 things that should be included as part of pre-transplant care
Consultation with MD
Educate patient about oral hygiene
Perform dental prophylaxis
Careful with certain drugs
Evaluate dental status and treat as indicated
True or false… if the patient has severe leukopenia and thrombocytopenia, the patient should avoid flossing
True
They should also disinfect and rinse toothbrush and change tooth brush regularly
What is mucositis and what is it commonly caused by?
Mucosal damage (including lower GI) affecting the nonkeratinized mucosal surfaces in mouth. Intense pain and discomfort
Most frequent complication post-BMT
Radiation/chemotherapy
What drug may cause gingival hyperplasia?
Cyclosporine
How long does the peak immunosuppression last post-transplantation?
3-6 months
What are the two types of HIV? Which may be less virulent and have a longer latency period?
HIV-1 and HIV-2
HIV-2 may be less virulent and have a longer latency period
Which is more predominant worldwide, HIV-1 or HIV-2?
HIV-1
HIV-2 is mostly in west Africa
How are both types of HIV (1 and 2) transmitted?
Sexual contact
Through blood and body fluids
From mother to child during the perinatal period
What three cells are infected by HIV?
CD4 T cells ***
Monocytes
Macrophages/dendritic cells
What are the two most effective HIV treatments?
HAART (highly active antiretroviral therapy)
CART (combined antiretroviral therapy)
Describe the HIV life cycle. What drugs can be used to interfere with each step?
Binding (CCR5 antagonist)
Fusion (fusion inhibitors)
Reverse transcription (NNRTIs, NRTI)
Integration (integrate inhibitors)
Assembly
Budding (protease inhibitors)
What is the current HAART (cART) therapy?
Usually 3 or more drugs combined
Two nucleoside analogue RT inhibitors
And one of the following…
NNRTI (non-nucleoside reverse transcriptase inhibitor), or protease inhibitor, or integrate strand transfer inhibitor
What are the four goals of HAART (cART) therapy?
Decrease viral load
Increase CD4s
Improvement of quality of life
Reduction of morbidity and mortality
HIV can now be considered a ___ infection. However, HAART therapy cannot be considered an ___ success
Chronic
Unqualified
True or false… HAART is associated with lots of adverse effects
True
What is lipodystrophy?
Peripheral fat wasting more associated with NRTIs
Central fat accumulation more associated with PIs
Direct effects of HIV
What is hyperlipidemia?
Elevations in total cholesterol, LDL, and triglycerides
Which leads to hypertension, coronary artery disease, increase myocardial infarction
What is included in the “three way street”? Where does HAART come into play?
Obesity (HAART affects this)
Diabetes
Periodontal disease
HAART is associated with osteonecrosis, even though the mechanism is unknown, what things increase osteonecrosis?
Corticosteroid treatment
Alcohol abuse
Hemoglobinopathies
Hyperlipidemia
Hypercoagulable states
True or false… the HAART era occurrence of oral manifestations markedly decreased
True, however not all patients get HAART
HAART has caused an overall ___ of oral lesions, with significant ___ in HL and NUP. __ significant change has occurred in the incidence of oral candidiasis, oral ulcers, and kaposi’s sarcoma. There has been an __ in salivary gland disease and incidence of oral warts
Reduction
Reduction
No
Increase
Name four predisposing factors for oral lesions
Low CD4 count
High viral load
Xerostomia
Poor oral hygiene
Smoking
What is a zoonotic pathogen?
An infection that naturally occurs in an insect or animal host that can also subsequently infect humans
True or false… most newly identified pathogens are zoonotic
True
What is an emerging pathogen?
A new infection, never seen before. Or maybe an infection that is known, but newly emerging in new hosts or geographical locations. Or maybe an infection that has always been there but not tested for
Describe how the following pathogens are transmitted.
Microsporidia and cryptosporidium
Naegleria fowleri
Ebola virus
SARS (severe acute respiratory syndrome)
Dengue virus
Microsporidia/cryptosporidium - contaminated water
Naegleria fowleri- lake water exposure in nostrils
Ebola virus - infected human body fluids and animals
SARS - human to human respiratory via animal exposure
Dengue - mosquito
What kind of a virus is the chikungunya virus?
Positive sense, ssRNA virus
In the togaviridae virus family
O’nyong’nyong is a closely related, serologically cross-reactive virus
What family of virus is the chikungunya virus? What family are most other viruses associated with mosquitoes in?
Togaviridae
Flavivirus
In the chikungunya virus, over half of cases result in long-lasting relapsing ___
Arthralgia
What mosquito is the vector for dengue, Zika, and yellow fever viruses, and chikungunya?
Aedes aegypti
What kind of a virus is the Zika virus? What family is it in? What mosquito is it spread in?
Positive sense ssRNA
Flavivirus
Aedes spp. Of mosquito
Discovered in the Zika forest of Uganda
What are the common symptoms of Zika?
Fever, rash, joint pain,
**conjunctivitis
What are the mechanisms of transmission for Zika?
Infected mosquito bite
**blood transfusions
Sexual transmission
Congenital infection (maternal blood to placenta to fetus)
Congenital transmission of Zika can cause what? How does the virus get to the fetus?
Microcephalic
Brain malformation
Ocular/auditory defects
Growth retardation
-virus from maternal bloodstream is found in fetal brain samples, cord blood, and placental tissue
True or false… Zika can be spread person to person without sexual contact
True
What is the diagnostic test for Zika?
MAC-ELISA
IgM Antibody Capture ELISA
What is cyclospora cayetanensis? Describe its route of transmission?
It is an emerging gastrointestinal pathogen
It is a coccidian protozoa, diagnosed in stool by stain or autofluorescence
Humans are the only vector (fecal oral route)
What is the hallmark symptom of cyclospora? True or false… oocytsts are infective when shed
Watery diarrhea
False.. oocysts not infective when shed (no direct human-to-human contact)
What is the best treatment for cyclospora cayetanensis?
Trimethoprim sulfamethoxazole
What kind of a virus is the Middle Eastern Respiratory Sydnrome Virus?
Positive sense, ssRNA virus
coronavirus family.
How is MERS likely spread? What are its symptoms?
Spread through respiratory secretions
Symptoms: fever, cough, shortness of breath
True or false… MERS has a high risk for the dental clinic
True
True or false… the following less pressing emerging zoonotic pathogens have no direct human-to-human transmission. … avian flu, borrelia miyamotoi, anaplasma, and ehrlichia
True
What family of virus is the Ebola virus? How is it spread?
Filovirus
Associated with African bush meat
Patient body fluids are also highly infectious (including blood and saliva, so this is a danger in dentistry)
Some emerging pathogens are too virulent and kill themselves off. Give three examples of these
SARS, MERS, Ebola
What is the respiration of parasitic protozoa?
Facultative anaerobic
How to parasitic protozoa reproduce?
Via binary fission
