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Explain how autotolerance can breakdown resulting in autoimmune diseases.
Autoimmune disorders causes the body to loss autotolerance, which is the ability of the immune system to differentiate self and non-self (foreign) antigen loss.
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What are the characteristics of systemic lupus erythematosus (SLE)?
- A chronic condition
- An autoimmune disease
- Potential fatal
- Unpredictable period of remission and exacerbations
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What are the most common clinical presenting signs and symptoms at the time that SLE is diagnosed?
- Skin involvement with a photosensitive rash and arthralgia (joint pain) and/or arthritis (joint inflammation).
- Fever with single organ involvement, such as glomerulonephritis, or autoimmune hemolytic anemia, or neuropsychiatric disturbance
- Least common: severe, generalized lupus crisis with multiorgan involvement
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Explain the pathophysiological mechanisms underlying the following conditions, which can occur in SLE: vasculitis, renal disorders, arthritis, hemolytic anemia, thrombocytopenia, and CNS dysfunction.
Inflammation is involved in SLE. This can lead to vasculitis (inflammation injury of vascular lining in the blood vessels), and arthritis (inflammation injury in the joint tissues)\
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- CNS disorder is caused by vasculitis in the cerebral blood vessels in the brain, or due to the present of antiphospholipids antibody that damage phospholipids in nerve cell membrane.\
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- Hemolytic anemia thrombocytopenia is due to immune attack against these different types of blood cells leading to their destruction and a decrease in the level of these cells circulating in the blood.\
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Why is the erythrocyte sedimentation rate (ESR) increased and the level of antinuclear antibodies (ANA) increased in SLE?
The speed of ESR sedimentation is related to the size of clumps of RBCs, and that is depended upon the fibrinogen in the blood. Fibrinogen is an acute phase protein whose production is increase in inflammatory conditions. Therefore, an increase in ESR is a nonspecific indicator inflammation. An inflammation is a component of SLE.\
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Does an elevated ANA level always mean the person has lupus?
An elevation of ANA does not always mean that person has lupus. ANAs are the most common type of autoantibodies present in people with SLE. Some healthy adult women w/o having lupus have somewhat elevated ANA levels, and ANA levels are also increase in some viral infections.\
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Explain the potential adverse effects resulting from the production of antiphospholipid antibodies?
Antiphospholipid antibodies binds to phospholipids in cell membrane, such as platelet cell membrane or vascular endothelial cell membrane, that can damage those cells and lead to thrombosis.\
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Define alloimmunity.
Alloimmunity is a form of immunity in which an individual's immune system reacts against antigens from individuals of the same species.\
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Explain the ABO red blood cell antigen system in regard to the type of antigen present on red blood cells and type of antibody in the plasma in individuals with blood types A, B, AB, and O.
- Type A blood have the A blood group antigen on their RBC, plus in the plasma they have IgM type antibody directed against B blood group antigen, which they don't have. They have anti-B antibody in their plasma.\
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- Type B blood have the B type antigen on their RBC surface, and in their plasma they have IgM antibody against the A type antigen (anti-A antibody).\
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- Type AB blood have both the A & B antigens on the surface of their RBCs, but they have neither anti-A nor anti-B antibodies in their plasma.\
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- Type O blood have neither A nor B blood type antigens on their RBCs surface, but in their plasma they have IgM type antibodies against both A and B antigens, so they have anti-A and anti-B antibodies in their plasma.\
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Why is blood type O a universal donor and blood type AB a universal recipient?
Type O blood lacks both A and B antigens, so washed type O (without the plasma) can be administered to basically anyone.\
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Type AB blood has antigen A and B on the surface of their RBC, but they lack anti-A and anti-B antibodies in their plasma, so they can be transfuse with wash RBC (without plasma) of any ABO blood type.\
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Why does an alloimmune reaction occur when a person with type A blood is transfused with blood from a person with type B or type AB blood?
- If a person is accidentally transfuse with blood from a donor whose RBCs have an antigen that the individual that is the recipient do not have on their RBC surface, IgM antibodies against the antigen on the donor's RBCs will mount an immune attack and destroy the donor RBC.\
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What role do the MHC (HLA) antigens have in organ transplantation?
Everyone is unique in the self antigens on their cells. Differences in the self antigens, such as the MHC antigens, can caused rejection in transplant organs. It is important to match the pattern of MHC in the donor and the recipient of the organ transplant in regard to their self antigens as much as possible.\
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between a host versus graft rejection and a graft versus host rejection.
- Host versus graft disease: the donor's antigen that are present in the transplanted organ are recognized as being foreign, and the recipient's immune system produces antibodies and/or activated T cells that attack the transplanted organ. \
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- Graft versus host disease: in this situation, the immune attack is coming from the grafted or transplanted bone marrow, attacking the host's organ which can lead to organ failure.\
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What causes severe combined immunodeficiency (SCID) syndrome?
A defective gene that would normally produce an enzyme, adenosine deaminase, so the child might be born missing the gene that codes for this enzyme. As a result of this, adenosine accumulates in the stem cells to a level where it will be toxic and it usually destroys the stem cells, that is the precursor for all other immune and inflammatory cells.\
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What types of immune deficiencies will be present in a child with this condition (SCID)?
A deficiency of the precursor cells in the bone marrow, which develop into mature inflammatory or immune cells.\
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How is SCID treated?
- Experimental treatment include gene replacement to have long term survival and normal life.\
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- Bone marrow transplant.\
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- Children need to be in a completely germ free environment to survive, so they will not be able to come in contact with human skin.\
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- Foods and toys need to be sterilized, cannot inhale air unless it has been filter.\
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If a child is born with a genetic deficiency of only humoral immunity, why might the child not develop \
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recurring infections immediately after birth?
Newborn has some degree of immune protection by ways of IgM molecules that were transferred from the mother's circulation across the placenta into the fetal circulation before birth. These maternal IgM molecules will be present for a few months after birth. It will gradually decline until there's no more, so the child may not have recurring infection until a few months after birth.\
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How do glucocorticoid hormones affect immunity?
- Glucocorticoid hormones can have immunosuppressant effects by a variety of mechanisms\
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- interfere with T and B lymphocyte function\
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- Decrease production with variety of interleukins (cytokines involve in chemical signaling amongst the immune cells)\
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- Can leads to the lysis of T and B cells\
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- Have anti-inflammatory properties.\
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What body fluids contain a high concentration of HIV in an HIV-infected individual?
Blood, semen, and cerebrospinal fluids (can become contact with it during spinal tap, or when an individual has a head injury and has a skull fracture and CSF leaks out of ear and nose).\
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Why do you take precautions against all body fluids if only some fluids contain high concentrations of HIV?
Lower concentration of HIV (lower viral load) have been found in infected individuals in tears, saliva, breast milk, and urine.\
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Explain 4 mechanisms whereby HIV exerts its cytotoxic (killing) effects on the cells it infects.
- When the HIV cells infects the human cells, the new viral particles will leave the cell that they have infected. Sometimes they gently bud off the cell membrane, sometimes the large number of viral cells may leave the infected cell at once, and tear the cell membrane. The cell ruptures and the intercellular content leaks out. \
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- It can cause a number of different cells to fuse together creating a syncytium (a giant cell with multinuclei), which causes the cell to not function properly in immune defense, and it has premature apoptosis.\
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- The NK cell recognized the infected helper T cells and starts to destroy them\
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- The immune cells are tricked into killing an uninfected helper T cell. Free GP120 attaches to CD4 receptors on the uninfected T cells. Now the body's cytotoxic T lymphocytes will be able to recognizes the GP120 on these cells and mistaken interpreted that as that cell being infected, and release cytotoxic chemicals that kills the uninfected T cells.\
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Compare the progression of HIV infection in adults and infants.
Infants do not have a fully developed immune system, so they will be less likely to keep the HIV under control in the early stages in the infection compared to adults. When infants are infected with HIV, the disease progress much faster than the adults.\
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Describe conditions that are considered to be AIDS indicator states, that is, conditions that indicate that a person has progressed from a state of being HIV seropositive to actually having AIDS.
The classification is based on both the circulating CD4 count, plus other clinical manifestations of immunosuppression, such as the present of certain infections and cancers.\
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Explain how HIV infection results in immunosuppression, opportunistic infections, and cancers such \
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as Kaposi's sarcoma, cervical cancer, and B cell lymphomas.
If the person progresses to category C, which is considered to be AIDS, the individual has such severe immune suppression that they develop infections not only with pathogenetic organisms, but they are also developing reoccurring opportunistic infections.\
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What is the rationale for combination anti-retroviral therapy for HIV infection using a combination \
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of drugs from the following categories: nucleoside reverse transcriptase inhibitors, integrase inhibitors, protease inhibitors, and fusion inhibitors?
- By using medication that blocks the virus at different points of their life cycle, there's a greater chance of inhibiting viral replication. All these drugs can do is slow the virus from replicating.\
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- The HIV has a high tendency to mutate. Anytime any cell divides, there's a chance that a mistake can be made in replicating the genetic material that could lead to mutation. In the case of HIV, it can make the virus unresponsive to medications.\
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What do the ELISA and the Western blot tests, commonly used screening tests for HIV infection, actually measure? Why do these tests sometimes give a false negative or false positive result?\
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What does the polymerase chain reaction (PCR) measure in regard to HIV infection?
- Both the Western blot and ELISA (Enzyme-linked immunosorbent assay) test measures antibodies that the person who's infected with HIV is producing against HIV\
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- A false positive result can be obtained, it means it looks like the individual has antibodies against HIV, however, the antibodies that are reacting with the HIV antigen are not truly anti HIV antibodies. \
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- A false negative means the individual is truly infected with the HIV, but the test show a negative result. This can happen if the test is done before the individual's immune system body had enough time to produced a measurable amount of antibodies \
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- The PCR test measures the viral genetic material, either the HIV RNA or DNA. Test will be positive within several days after being infected with HIV.}
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