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124 Cards in this Set
- Front
- Back
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what initiates type I hypersensitivity?
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IgE binding soluble proteins
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what initiates type II hypersensitivity?
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IgG / IgM binding proteins on cell membranes
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what initiates type III hypersensitivity?
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Ag-Ab complexes aggregates
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what initiates type IV hypersensitivity?
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T cells
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what is the physiologic role of type I hypersensitivity?
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multicellular parasites
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what is the physiologic role of type II hypersensitivity?
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cellular pathogens
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what is the physiologic role of type III hypersensitivity?
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removal of Ag-Ab
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what is the physiologic role of type IV hypersensitivity?
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intracellular pathogens
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which hypersensitivity type occurs within seconds to minutes?
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I
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which hypersensitivity type occurs within minutes to hours?
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II
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which hypersensitivity type occurs within hours to days?
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III
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which hypersensitivity type occurs within days?
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IV
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what type of cell causes the physiologic effects of type I hypersensitivty?
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mast cell
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redness and edema due to vasodilation produced by releasing of mediators by mast cells?
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Wheal
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redness later dilation surrounding the area of injection of the allergen?
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Flare
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Describe the 6 hallmark features of a person in anaphylactic shock?
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1. Increased capillary permeability and entry of fluid into tissues
2. Swelling of tissues including upper airway 3. Drop in blood pressure 4. Decrease of oxygen in tissues 5. Rapid pulse 6. Loss of consciousness |
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what type of hypersensitivity is the abo blood type an example of?
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type II
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which type of hypersensitivity mediates the formation of C5a and C3a anaphylatoxins?
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Type two by activation of compliment
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activation of compliment induces what cells to release lysosomal enzymes and reative oxygen intermediates?
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neutrophils
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what causes the inflammation that leads to necrosis and fibrosis in type III hypersentivities?
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immune-complexes activate compliment and recruite neutrophils which release enzymes and reactive products leading chronic inflammation
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why dont immune complexes build up in everybodies blood vessel walls?
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macrophages clear them in normal individuals
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serum sickness is an example of what type of hypersensitivity?
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type III
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a child presents with chills, fever, rash, arthritis, vasculitis, and glomerulonephritis after a recent injection. What might the injection have been and what type of hypersensitivity is responsible for symptoms?
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injection of hyperimmune serum from an animal (ex horse), type III hypersensitivity
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most cases of type IV hypersensitivity are mediated by what cells?
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CD4 TH1
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chronic asthma is an example of what type of hypersensitivity? Also what cells/other players cause this reaction?
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Type IV, CD4 TH2 cells
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a positive ppd test for TB occurs due to what type of hypersensitivity?
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Type IV
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Contact hypersensitivity (Type IV) is mediated by what two cell types?
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TH1 and CD8 cells
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what is APS1: Autoimmune Polyendocrine Syndrome type 1, also called (APECED)?
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Lack of expression of endocrinous glands’ antigens in thymus
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Fas (CD95) and CD95L
Autoimmunity leads to? |
defective apoptosis
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what causes IPEX:
Immune dysregulation, Polyendocrinopathy, Enteropathy? |
Lack of TR cells due to defect in Foxp3 gene
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what STD causes autoimmune anemia and why?
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Glycolipids on Chlamydia trachomatis resembling glycolipids on red blood cells in Autoimmune Hemolytic Anemia
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what is the name of the autoimmune disease in which antibodies become agonists for the TSH receptor in thyroid?
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Graves disease
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autoimmune disease in which antibodies become antagonists for the TSH receptor in thyroid?
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Myasthenia gravis
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what do I have?
I present with a difuse enlargment of my thyroid gland and bulging eyes? |
Graves disease
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explain how type II autoimmunity is initiated?
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IgG and IgM antibodies form against endogenous antigens present on cell surfaces
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explain how type III autoimmunity is initiated?
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immune-complexes composed of endogenous antigens activating compliment and recruiting phagocytes through Fc receptors
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explain how type IV autoimmunity is initiated?
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CD4 TH1 cells are activated against an endogenous peptide leading to macrophage mediated inflammationand CD8 activity
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Graves and Myasthenia gravis are examples of what type of autoimmunity?
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Type II
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Systemic Lupus Erythematosus is an example of what type of autoimmune disease?
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Type III
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Rheumatoid arthritis is an example of what type of hypersensitivity?
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Type III
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A woman with non-dodgkins lymphoma present with diminished secretions causing dry eyes and dry mouth. What does she have and what autoimmune type does this disorder fall into?
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Sjogrens Syndrome, Type III
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Sjogrens syndrome is thought to be a response to what?
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viral infections such as EBV and Hep C
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what is abnormal accumulation of collagen produced by fibroblasts due to activation of CD4T cells in the dermis called?
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Scleroderma (hardskin)
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If your Scleroderma patient presents with wide spread skin and viscera involvement how would you describe their prognosis?
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poor
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A patient comes into your office with fibrosis on the skin of his face, fingers, and forearms. What does he have and what can you tell him about his prognosis?
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He has Scleroderma and a good prognosis
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what is the term for tiny calcium deposits under the skin?
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Calcinosis
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what is the term for numbness, pain and color changes in fingers?
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Raynaud's phenomenon
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what is the term for heartburn, inflammation and scarring of esophageal tissues?
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Esophageal dysfunction
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what is the term for hallmark of scleroderma which shows up in the fingers?
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Sclerodactyly
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what is the term for closely packed dilated blood vessels in dermis?
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Telangiectasia
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what problems with compliment could account for a general increase in infections and SLE-like symptoms?
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C1, C2, and C4 deficiency
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if a person has a increased susceptibility to pyogenic infections what compliment component is likely defective?
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C3
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what happens when people have a deficiency in C5-C9 compliment components?
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they are susceptible to pyogenic infections
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what is released from the adrenal glands that limits the extent of inflammation?
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cortisol
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explain the process whereby inflammatory cytokines can result in increased cortisol?
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1. inflammatory cytokines reach hypothalmus and cause release of CRH
2. CHR goes to pituitary and causes release of ACTH 3. ACTH goes to adrenal gland and causes release of cortisol |
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why does severe hepatic disease reduce the effectiveness of glucocorticoid drugs?
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while all of the glucocorticoids are fully absorbed in the intesting, they must be activated in liver, thus if liver is damaged then drugs cant work
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what is the class of molecules which inhibits gene expresion to modulate inflammatory responses?
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glucocorticoids (the ones that end in -one) they are steroids
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glucocorticoids, while having a great effect on cellular immunity, have little effect on what type of immunity?
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humoral
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what is important to remember when perscribing steroid anti-inflammatories?
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you have to tapper the dosage or else you can cause acute adrenal insufficiency
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why does cortisol decrease inflammation?
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it feeds back to macrophages preventing the formation of inflammatory cytokines such as IL1, IL6, and TNF-alpha
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what are the 4 antimetabolites that we have to know?
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1. Azathioprine
2. Mycophenolate 3. Leflunomide 4. Methotrexate |
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which of the anitmetabolites blocks de novo synthesis of purines by creating a fraudulent nucleotide thereby blocking IM -> AMP and GMP?
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Azathioprine
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6-mercaptopurine is the product of what pro-drugs interaction with glutathione?
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Azathioprine
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Mr. X needs a heart transplant, but is on allopurinal for gout. What immunosuppressant drug should not be administered because its digestion is mediated by an enzyme that is inhibited by allopurinal?
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Azathioprine
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what immunosuppressant drug selectively and reversibly inhibits inosine monophosphate deydrogenase (IMPDH) thereby disrupting de novo purine synthesis?
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Mycophenolate mofetil
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what cell lack an salvage pathways by to suppliment de novo purine synthesis blocked by Mycophenolate mofetil?
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T and B cells
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what effect does Mycophenolate mofetil have that make it ideal for decreasing chronic allograft rejections?
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inhibits the formation of smooth muscle thereyby preserving blood flow into the organ
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A man develops devastating polyoma nephritis when he is on immunosuppressants tacrolimus and ___ ?
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Mycophenolate mofetil
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which immunosuppressant drug interupts de novo pyrimidine synthesis by inhibiting dihydroorotate dehydrogenase?
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Leflunomide
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A patient on ___ presents with little synthesis of UMP and a very diminished B cell population?
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Leflunomide
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which antimetabolite drug would best for treatment of Wegeners granulomatosis?
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Leflunomide
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how do you quickly washout Leflunomide from enterohepatic recirculation?
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administer cholestyramine which binds to bile acids
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which antimetabolite is a folate analogue which causes cytotoxicity in active CD4 and CD8 T cells?
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methotrexate
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methotrexate is also an anti-inflammatory agent. Why might this be?
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it increases the levels of adenosine, a potent anti-inflammatory agent
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which of the antimetabolite drugs is most used to treat Rheumatoid Arthritis?
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Methotrexate
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chronic administration of ___, a antimetabolite, can result in hepatic fibrosis and cirrhosis?
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Methotrexate
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In general, an agent which interferes with DNA replication and gene expression by adding alkyl groups to DNA is called?
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Alkylating Agent
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what is the example of an alkylating agent that we have to know?
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Cyclophosphamide
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what drug is derived from nitrogen mustard and requires activation by cytochrome P450 oxidase?
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Cyclophosphamide
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what is the major mechanism of alkylating agents toxicity?
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bis-alkylation of DNA
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What are the two classes of molecules that inhibit lymphocyte signaling and activation?
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1. Calcineurin inhibitors
2. mTOR inhibitors |
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what are the two Calcineurin inhibitors inhibitors we have to know?
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1. Cyclosporine A
2. Tacrolimus |
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what are the 2 types of mTOR inhibitors?
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1. Sirolimus
2. Everolimus |
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what immunosuppressant drug blocks T cell specific antigen stimulation resulting in very little T cell response?
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Cyclosporin A
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what important perscription fact is commonly confused among physicians and pharmacists with cycosporin A?
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the different generic and brand name formulations are NOT bioequivalent
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Mr X comes to you two weeks after a liver transplant and because he notices a tremor in his hands. What immunosuppressant drug might be causing this symptom?
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Cyclosporin A
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What immunosuppressant drug caused this?
elevated LDL, interstitial fibrosis do to increased TGF-beta production, worsened gout, and formation of diabetes? |
Cyclosporin A
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what organ is most effected by cyclosporin toxicity, and why is this important to keep in mind when deciding treatment?
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the kidney, don't give with other nephrotoxic agents like NSAIDS
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macrolide antibiotic inhibits calcineurin thereby stopping transcription of genes to activate T cells.
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Tacrolimus
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Drugs or other molecules that inhibit CYP3A should never be given to patients on what two immunosuppressant drugs?
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1. Cyclosporin A
2. Tacrolimus |
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what two drugs a macrolides which block IL2 receptors and bind to FKBP-12 to inhibit mTOR enzyme activity?
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1. Sirolimus
2. Everolimus |
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what is the function of the mTOR enzyme?
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key for cell progression from G1 -> S phase
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what is the main difference between the two mTOR enzyme inhibitors?
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everolimus has a shorter half-life than sirolimus this can reach steady-state concentrations faster
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for transplant therapy, the mTOR enzyme inhibitors should be used with what other two drugs?
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1. calcineurin inhibitors
2. glucocorticoids |
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what is an alternative to calcineurin inhibitors for use with mTOR inhibitors?
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mycophenolate mofetil
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what is the relatioship between calcineurin inhibitors and mTOR inhibitors when they are given together?
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mTOR inhibitor increases renal toxicity of calcineuron inhibitors and calcinuerin inhibitors increase hyperlipidemia and myelosuppression of mTOR inhibitors
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what cytokines are specifically targeted by immunosuppressant drugs?
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1. IL1
2. IL6 3. TNF-alpha |
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what drugs target TNF-alpha for inhibition? (5)
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1. Etanercept
2. Infliximab 3. Adalimumab 4. Certolizumab pegol 5. Thalidomide |
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what drug targets IL1 for inhibition?
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Anakinra
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what drug targets IL6 for inhibition?
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Tocilizumab
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what is the effect of TNF-alpha?
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stimulates macrophages to produce cytotoxic metabolites
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TNF-alpha has been implicated as a central cause of what two important autoimmune disorder?
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rhuematoid arthritis and Crohns disease
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what is an important risk factor that must be screened for before initiating TNF-alpha inhibition?
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TB because it can reactivate
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what is the function of IL1?
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increase production of IL6
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what is the function of IL6?
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increase production of cell adhesion molecules and to increase cell proliferation
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when a person presents with elevated serum levels of IL6 what might you expect they have?
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rhuematoid arthritis, but you would also want to check snovial joint fluid
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what can be given in conjunction with tocilizumab to increase inhibition of IL6?
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methotrexate
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What drug(s) match this mechanism?
Recognize multiple epitopes on human T cells and opsonize for macrophage clearance Target T cells and induce broad immunosuppression |
Antithymocyte and antilymphocyte globulin (ATG and ALG)
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What drug(s) match this mechanism?
Passive administration at the time of antigen exposure blocks the host’s primary antibody response |
Rho (D) Immune Globulin Micro Dose
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What drug(s) match this mechanism?
CD3 expressed on CD4+ and CD8+ T cells Binding to CD3 depletes T cells by complement activation and immune clearance |
OKT3
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Which antibody immunosuppressant matches this description?
Polyclonal human Ig prepared from plasma pooled from thousands of healthy donors |
Immune Globulin Intravenous (IGIV)
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What drug(s) matches this mechanism?
CD25 only expressed on activated T cells Targets and depletes T cells activated by an MHC-antigenic stimulus Functions as an IL-2 antagonist |
Daclizumab and Basiliximab
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What drug(s) matches this mechanism?
CD20 expressed on only mature B cells Complement-mediated lysis, antibody-dependent cellular cytotoxicity, and induction of apoptosis Decreased population of circulating B cells |
Rituximab
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What drug(s) matches this mechanism?
Targets CD52 expressed on B cells, T cells, NK cells, monocytes, macrophages Antibody-dependent cellular cytotoxicity |
Alemtuzumab
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how do the costimulation inhibitor drugs work to produce immunosuppression?
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block lymphocyte costimulation to inhibit activation or induce anergy
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what are the 5 costimulation inhibitors?
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1. Alefacept
2. Abatacept 3. Belatacept 4. Bilimumab 5. Anti-CD40L antibody |
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what drug(s) matches the mechanism described below?
Competitively inhibits CD28 by binding to CD80 (B7-1) and CD86 (B7-2) on antigen presenting cells prevent delivery of a B7-CD28 costimulatory signal and T cells become anergic or undergo apoptosis |
Abatacept and Belatacept
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what drug(s) matches the mechanism described below?
Binds BLyS (soluble protein) and blocks its interaction with BLyS receptors expressed on the B cell surface Inhibit BLyS-induced stimulation of B-cell development Reduce the levels of circulating B cells (precursor to plasma B cells) Restore the potential for apoptosis in autoantibody-producing B cells |
Belimumab
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what drug(s) matches the mechanism described below?
Binds CD40L (CD154) on T cells and prevents CD40L binding to CD40 expressed on antigen-presenting cells Inhibits B cell activation, isotype switching, and affinity maturation Inhibits B7 expression on macrophages |
Anti-CD40L antibody
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what drug(s) matches the mechanism described below?
Inhibits activation of T cells by binding to CD2 on T cell surface and interfering with CD2 binding to LFA-3 on... # antigen presenting cells: inhibit T cell activation and proliferation # target cells: inhibit cell killing by cytotoxic T cells, natural killer (NK) cells and lymphokine-activated killer (LAK) cells |
Alefacept
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what are the two cell adhesion inhibitors which prevent lymphocytes from homing?
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1. Efalizumab
2. Natalizumab |
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what drug(s) match this mechanism?
Inhibits LFA-1 and ICAM interaction LFA-1 expressed on thymocytes, T and B lymphocytes, granulocytes, monocytes, and macrophages ICAM expressed on endothelial cells, lymphocytes, and monocytes Inhibit cell migration as well as antigen presentation and cellular cytotoxicity |
Efalizumab
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what drug(s) match this mechanism?
Inhibits interactions of VLA-4:VCAM-1 and LPAM-1:MAdCAM-1 VLA-4 and lymphocyte Peyer’s patch HEV adhesion molecule-1 (LPAM-1) are expressed on leukocytes (same as LFA-1) VCAM-1 expressed on endothelial cells Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on endothelial cells of small blood vessels lining the walls of the gut and other mucosal surfaces |
Natalizumab
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what drug(s) match this mechanism?
S1P-R expressed on T cells and B cells Sphingosine kinase-2 phosphorylates FTY720 and the FTY720-phosphate binds S1P-R Specifically and reversibly sequesters host lymphocytes into the lymph nodes and Peyer’s patches away from circulation and does not impair lymphocyte function |
FTY720
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