Module 9 Flashcards
What is central tolerance?
The negative selection of self-reactive B and T cells
What is peripheral tolerance?
Tolerance mechanisms that happen outside the bone marrow and thymus gland
What are the three subcategories of peripheral tolerance?
Immune privilege
Suppression
Anergy
What is AIRE?
An autoimmune regulator that eliminates self-reactive T cells that would otherwise cause autoimmune disease
What is the consequence of AIRE deficiency?
APECED, a multiorgan immune syndrome
How are autoreactive B cells in the periphery managed through T cells?
B cell reliance on Th cells provide a safeguard from rouge B cells
What does the peripheral tolerance mechanism of immune privilege consist of?
Certain tissues such as the nervous system, the eyes, testes and uterus are shielded from the immune system
What does the peripheral tolerance mechanism of suppression consist of?
Suppressive cytokines and TReg cells keep immune responses in check
What does the peripheral tolerance mechanism of anergy consist of?
When autoreactive B and T cells go into a frozen state for protection
What are some mechanisms and symptoms of Grave’s disease?
Type 2 hypersensitivity
Agonistic autoantibodies
Overproduction of thyroid hormones
What are some of the mechanisms and symptoms of Hashimoto’s disease?
Type 2 and 3 hypersensitivity
B and T cells destroy thyroid tissue
Reduction of thyroid hormones
What are some of the mechanisms and symptoms of insulin dependent diabetes myelitis (IDDM)?
Type 1 diabetes onset in childhood
Type 2 and 4 hypersensitivity
Organ specific
Loss of ability to produce insulin and metabolize glucose
What are some of the mechanisms and symptoms of systemic lupus erythematosus (SLE)?
Type 3 hypersensitivity Systemic Nuclear antigens and other common target Facial rash More likely in African/Asian women
What are some of the mechanisms and symptoms of rheumatoid arthritis (RA)?
Type 3 and 4 hypersensitivity
Systemic
Anti-IgG antibodies
Chronic inflammation in joints
What are some of the mechanisms and symptoms of myasthenia gravis?
Type 2 hypersensitivity Neuro-muscular system Anti-acetylcholine receptor antibodies Block muscle stimulation Progressive muscular weaknesses
What are some of the mechanisms and symptoms of multiple sclerosis?
Type 4 hypersensitivity
Destruction of insulating myelin sheath of CNS
Progressive paralysis
What are some of the genetic factors associated with autoimmune disease?
Gender
Defects if immunoregulatory proteins
HLA alleles
What are some of the environmental factors associated with autoimmune disease?
Altered self exposure
Molecular mimicry
Exposure to sequestered Ags
Hygiene hypothesis
Why is HLA associated with certain autoimmune disease?
Some alleles may present self antigens to autoreactive T cells better than others
What is molecular mimicry?
When exposure to an infectious microorganism induces memory B and T cells to react with self antigens
How does exposure to sequestered self Ags happen?
When trauma to tissues expose immune system to privileged sites
What are some additional risk factors of autoimmune disease?
Inflammation induced HLA expression
Aging
Hygiene hypothesis
TReg
How are autoimmune diseases treated?
Immunosuppressive and anti-inflammatory agents
Some novel therapies -
Humanized monoclonal antibodies
What is an autograft?
Self to self transplant
What is a syngeneic graft?
A genetically identical transplant, such as with twins
What is an allograft?
A genetically distinct transplant
What is a xenograft?
A transplant between species
What can precautions can prevent organ rejection?
Making sure that ABO blood type and HLA alleles match between donor and recipient
What is the mechanism of organ rejection?
Donor’s APC’s migrate to secondary lymphoid organs from the transplant and activate T cells against the foreign item
What is direct allorecognition?
Acute rejection of transplant within days due to direct interaction of donor APC’s and recipient T cells
What is indirect allorecognition?
Results from processing donor MHC molecules in recipient APC’s and gives way to chronic graft rejection
What are the four major categories of immunosuppressive drugs?
Steroids
Cytotoxic agents
T and B cell activation inhibitors
Antibody based T cell blockers
What is the mechanism of corticosteroids?
A natural steroid derivative that act as a negative regulator on the immune response
What are the side effects of corticosteroids?
Fluid retention
Weight gain
Diabetes
Thinning of bone and skin tissues
What is the mechanism of cytotoxic agents?
They are inhibitors of cellular proliferation which block B and T cells at the core of adaptive immune responses
What are the risks of cytotoxic agents?
Opportunistic infections
What are rapamycin, cyclosporin A and tacrolimus examples of?
T and B cell activation inhibitors
What are anti-CD3 and anti-ILR2 examples of?
Humanized monoclonal antibodies approved for use in transplantation
What types of disease are treatable by BMT?
Any genetic diseases that affect the blood cells or cancer of the blood
What is the goal of BMT?
To repopulate the recipients blood with healthy cells from a donor
What are the order of events during a BMT?
Recipient undergoes chemo or irradiation
Bone marrow collected from donor
Recipient is infused with donor cells
Blood repopulated with donor cells
