Immunomodulatory Agents Flashcards
Classes of immunomodulatory agents?
- Immunosuppressant
- Immunostimulant
- Tolerogen
What occurs when the body cannot differentiate self from non-self?
Autoimmune disease
Examples of immunological diseases
- Rheumatoid arthritis
- type 1 diabetes mellitus
- Asthma
- Solid tumors
- Hematological malignancies
Classification of immunity?
- Innate/ Natural
Broadly reactive, no priming, low affinity - Adaptive/learned
Antigen-specific, requires priming or exposure, high affinity
Examples of innate immunity effectors
Complement, Granulocytes, monocytes/macrophages, NK cells, mast cells, basophils
Two cells responsible for cellular response are?
B- lymphocytes : make antiBodies
T-lymohocytes: helper, cyToToxic, suppressor cells
Any foreign agent which may provoke an immune reaction when introduced into the body is?
Antigen
Characteristics of Antigens
- They are usually proteins
- Or Glycoproteins
- Or High molecular weight carbohydrates
- M.W of 5000 Da
- Processed by macrophages before presented to T-cells
Types of immune responses?
- Humoral immune responses
(B lymphocytes, antibody production, plasma cells) - Cellular immune responses
T-lymohocytes
Humoral immunity response occurs in two stages namely?
- Primary reactions
Occur at 1st exposure, consists largely of IgM, short-lived - Secondary reaction
Occur with subsequent exposure, consists mainly of igG, long-lived
Immunity that is developed in response to infection or following inoculation with a strain is?
Active immunity
Immunity that is transferred by administration of preformed antibodies either from host or recombinant techniques inVitro is?
Passive immunity
When immune response to an antigen results in tissue damage,it is called?
Hypersensitivity
Types of hypersensitivity
ICIC
Type I (immediate)- Anaphylactic Rx
Type II (cytotoxic) -Antibody dependent
Type III (immune complex run
Type IV (cell-mediated) -delayed hypersensitivity
Gell and coombs classification of hypersensitivity chart
IgE Mediated
Type I- within 1hr (Anaphylaxis)
IgG or IgM mediated
Type II- hours to days (hemolytic anemia)
Non-IgE mediated(others)
Type III: 7-21 days (serum sickness)
Type IV: days to weeks (contact dermatitis, maculopapular rash)
Major classes of immunosuppressive drugs
CAMS
- Calcinuerin inhibitors: Tacrolimus and cyclosporine
- Anti proliferative agents: Mofetil, azathioprine, Mycophenolate
- mTOR inhibitors: Sirolimus
- Steroids/glucocorticoid: Prednisone
Among the major classes of immunosuppressant, which does not fall under “immunophilin ligands”?
Steroids/glucocorticoids
Broad classification of immunosuppressant
Non-selective (CIA)
1. Corticosteroids
2. Anti metabolite/ Antiproliferatives
3. Immunoglobulins
Selective (CMS)
1. Calcinuerin inhibitors
2. Selective IL-2 receptor antagonists; basilicimab, daclizumab, infliximab
3. mTOR inhibitors
Main uses of glucocorticoids?
Treatment of transplant rejection and auto-immune disorders
Most effective immunosuppressive drugs are?
Calcinuerin inhibitors
Cyclosporine is produced by the fungus?
Beauveria nivea
Adverse effects; CNS disorders, immunosuppression, HPA axis suppression, metabolic disorders, fall under which class of drugs?
Glucocorticoids
Agents of solubilisation of cyclosporine are always?
Lipophylic
Mechanism of action of Cyclosporine?
Binds to cytosolic protein cyclophilin and interacts with Ca2-calmodulin dependent calcinuerin complex and inhibits it’s phosphorylase
Principle metabolism of cyclosporine is in?
The liver (with half life of 5-18 hours)
How to mitigate the nephrotoxic effect of cyclosporine?
Concomitant use of Calcium channel blockers
Tacrolimus is _____ times more potent than cyclosporine
10-100 times
Adverse effects of cyclosporine include?
Relate organs that use Ca2 calmodulin
Hypertension ,tremor, hyperkalemia,hirsutism, nephrotoxicity, hepatotoxicity,etc
What organism is responsible for production of Tacrolimus?
Streptomyces tsukabaensis
What’s the first line immunosuppressive agent?
Calcinuerin inhibitors
List of drugs that interact with calcinuerin inhibitors?
Azoles, macrolides, diltiazem
Sirolimus (Rapamycin) is derived from?
Streptomyces hygroscopicus
MOA of azathioprine (anti metabolite) is?
Interfere with purine metabolism at steps required for lymphoid cell proliferation
The chief toxic effect of azathioprine and mercaptopurine is?
Bone marrow suppression
Other cytotoxic agents include;
- Cyclophosphamide
- Hydroxychloroquine
- Methotrexate
A substance that increased the ability of the immune system to fight infections is?
Immunostimulant
Humanized antibodies end in?
-umab and -zumab
Chimeric antibodies end in?
-imab or -ximab
Classes of immunostimulants include;
- Vaccines; bacterial, viral,therapeutic, combinations
- Interferons
- Interleukins
- Colony stimulating factors
Others
what are antibody forming cells fused to plasmacytoma cells?
Hybridomas
Under biologics, Monoclonal antibodies are used for?
- Anti tumors
- Delivery of isotopes to tumors
- As immunosuppressants and anti-inflammatory
- Antiplateles
Hepatitis B, MMR and yellow fever are under what class of vaccines?
Viral vaccines
Bacille Calmette Guérin and DPT is an example of what type of vaccine?
Bacterial vaccine
Vaccines that protect against cancer are known as?
Therapeutic vaccines
A foreign antigen that suppresses immune response is known as?
Tolerogen
