Immune Modulators Flashcards
What is the general purpose of B cells?
They produce antibodies
What is the general role of antigen presenting cells?
they prepare the antigen for recognition
What do stimulatory cytokines do? Give an example of one
They activate the immune system
IL1 and IL2, as well as TNF are exmaples
What is the purpose of Cell adhesion molecules?
they are immunoglobulin superfamiies which localize the response
ex) integrins
what is the role of inhibitory cytokines?
they inhibit the response
ex) IL4, IL10, and IL13
Describe the B cell immune defense
- invading microbe recognized as antigen
- antigen recognized by B cell which presents the antigen on its surface
- B cell receptor = antibody
- Bcell connects to helper T cell, which releases IL2
- Plasma cell releases prepared antibodies
- antibodies attack microbe and are thus marked for destruction
- memory cell is coated in now recognizable antibodies
Describe the T cell immune defense
- cell with virus presents part of the viral antigen on its head
- infected cell binds to helper T cell via T cell receptor that fits the particular antigen
- helper T cell releases IL2- which causes the proliferation of cytotoxic T cells specific to this antigen
- cytotoxic T cells bind to infected cells and destroy
What is lupus erythematosus?
–antibody to DNA histone complex ie anti-nuclear factor
What is rheumatoid arthritis?
autoimmune disease –due to formation of rheumatoid factor which is an antibody to IgG leading to complement activation
what is myasthenia gravis?
autoimmune disease –due to antibody formation to nicotinic acetylcholine receptors
what is Thyroiditis?
autoimmune disease
–due to antibodies to thyroid tissue
Graves disease due to increased thyroid hormone production due to antibodies to TSH receptor
What is multiple sclerosis?
- Presence of “scars” on brains
- Autoimmune disease
- Brain-reactive T-cells cause demyelination and destruction of neurons
- Evidence of a role for B-cells as well
- Leads to paralysis and death
What is Chrohn’s disease?
•Form of inflammatory bowel disease affecting all layers of the intestine
Associated with diarrhea, cramps, bloody stools and weight loss
what is psoriasis?
autoimmune skin disease
how to cytotoxic immunosuppressants work?
- They act by targeting dividing cells
- include alkylating agents, folic acid analogs and purine derivatives
- also used as anti-cancer agents
- can be very toxic
Describe how cyclophosphamide is used as an immune suppressant
it is an Alkylator
- include alkylating agents, folic acid analogs and purine derivatives
- also used as anti-cancer agents
- can be very toxic
Describe how methotrexate is used as an immunosuppressant
It is an antifolate
- act by interfering with dihydrofolate reductase necessary for DNA synthesis
- inhibits replication of B and T-cells
- used in rheumatoid arthritis and psoriasis and in combination with cyclosporine to prevent GvHD
- Dose used in RA is much lower than dose used for cancer
- Anti-inflammatory effect is not inhibited by folic acid supplementation
- Method of action is unclear but in RA
–MTX is poly-glutamated (long half-life)
–Inhibits Aminoimidazole carboxamidoribonucleotide (AICAR) transformylase
–Leads to increased adenosine production
Anti-inflammatory via adenosine receptors
describe methotrexate toxicity and how we combat this
- we give Folinic acid supplementation to prevent side effects
- Hepatotoxicity
- Pulmonary damage – pulmonary fibrosis/pneumonitis
- Myelosuppression/blood dyscrasias
- Gastrointestinal problems such as nausea, stomach upset, and loose stools
- Stomatitis or soreness of the mouth
- Infection
- Alopecia
What is Mitoaxantrone? What is it used for?
- Anti-cancer agent approved for MS
- Inhibits topoisomerase II
- Intercalates into DNA
- Serious toxicity esp cardiotoxicity
- Not a first choice treatment
What is Doxorubicin? What is it used for? how does it work?
- anthracycline antibiotics which intercalate with DNA
- doxorubicin inhibits B-cell function more than T-cell and does not inhibit macrophage or NK function
- daunorubicin inhibits macrophage function
- can cause cardiomyopathy
What is Azathioprine? How does it work?
it is a purine analog
- metabolised to mercaptopurine which inhibits DNA synthesis
- inhibits antibody production and cell-mediated immunity
- has no effect on NK cells but inhibits phagocytic cells
- causes monocytopenia
- used with prednisone to
prevent transplant rejection
What is Mycophenolate Mofetil?
- converted to active metabolite mycophenolic acid which inhibits inosine monophosphate dehydrogenase (IMPDH)
- IMPDH is essential for guanine nucleotide synthesis
- immunosuppressive and anti-proliferative
- more potent against IMPDH type II in lymphocytes
- used in renal transplants as prophylaxis with calcineurin inhibitors
What is Leflunomide?
- inhibits B- and T-cells
- mechanism of action is unknown but may involve inhibition of dihydroorotate dehydrogenase (DHODH)
- DHODH is essential for de novo pyrimidine synthesis
- Used for RA
- side effects are mild GI disturbance
- Active metabolite Teriflunomide also approved for MS
What is Cladribine?
- Adenosine analogue
- Inhibits adenosine deaminase
- Orally active
- Approved for treatment of hairy cell leukaemia
- Development for MS halted
–Lack of evidence of benefit
–Indication dropped by Merck
–Currently under consideration by EMA
Discuss Cladribine toxicity
•Myelosuppression
–Neutropenia
–Anemia
–Thrombocytopenia
- Fever
- Infections including sepsis
Describe the effects of glucocorticoids
- These inhibit phospholipase A2
- reduce the production of IL-1 and 2, interferon, prostaglandins and leukotrienes
- decreases basophils, eosinophils and monocytes but increase in neutrophils
- lymphocytes are also reduced (T>B; CD4+>CD8+)
- adverse effects on carbohydrate metabolism
Describe the use of NSAIDs
- inhibit cyclooxygenase production of prostaglandins
- prevent actions of IL-1 which acts through phospholipase A2
- have adverse effects on GIT