Immunopharmacology Flashcards
Agents that suppress the immune system play 2 important roles in medicine, what are they?
- preventing rejection of organ or tissue grafts
- treatment of diseases that arise from dysregulation of immune response
What is the goal of immunologics?
to manipulate the immune response for a therapeutic effect
What is the immune system?
part of body that attacks and removes the body of antigens
T/F it is important the immune system recognizes self from non-self.
T
Name 4 types of WBC that are involved in immune responses.
- neutrophils
- lymphocytes
- macrophages
- NK cells
Name 2 types of adaptive immunity cells.
T & B cells
How does the normal immune response fxn?
to neutralize and remove toxins, viri, and pathogens from body
how does abnormal immune responses damage the body?
- extensive tissue damage (hypersensitivty)
- reaction against self Ag (autoimmunity)
what are the three types of abnormal immune responses?
- autoimmunity
- hypersensitivity
- immunodeficiency
what causes autoimmunity?
failure to distinguish self from non-self; mechanisms in place to attack FB attacks self
what are some examples of autoimmunity?
- RA
- SLE
- MS
- IDDM
what are some ways to treat autoimmunity?
- diet changes
- immunosupressives
what is hypersensitivity?
over rxn to an foreign Ag
what are common examples of Ag that elicit hypersensitivity rxns?
- environmental (pollen)
- drugs
what is a term frequently used for hypersensitivity rxns?
allergic rxns
what are some examples of hypersensitivty rxn outcomes?
- asthma
- allergic rhinitis
- contact dermatitis
what is immunodeficiency?
decreased response of immune system
what are the risks of immunodeficiency?
infection and cancer
Where is immunodeficiency most common?
AIDS: depletes CD4 T helper cells gives rise to increased frequency of opportunistic infections
What are drugs that cause immunodeficiency called?
immunosuppressant
What are 6 types of immunosuppressives?
- glucocorticoids
- cyclosporine
- tacrolimis
- sirolimus
- mycophenolate
- thalidomide
what are 4 types of cytotoxic agents?
- azathioprine
- cyclophosphamide
- leflunomide
- hydroxychloroquine
what are 3 types of immunosuppressive antibodies?
- IVIG
- Rho immunoglobulin
- Hyperimmune globulin
what are 3 types of monoclonal antibodies?
- ximab
- mumab
- zumab
What is the goal of immunosuppressive drugs?
decrease immunity
With is the MOA of glucocorticosteroids?
modify fxn of lymphocytes
When are immunosupressive drugs used?
- kidney transplants
- chronic myeloid leukemia
- transplants
what is tacrolimus used for?
immunosupressant
topically - psoriasis
orally - immunosuppression
what are the anti-inflammatory effects of glucocorticoids?
- decrease concentration, distribution, and fun of leukocytes in tissue at site of inflammation
- increase concentration of leukocytes in blood
- suppress inflammatory cytokines, macrophages, and Ag presenting cell fxn
- decrease release of inflammatory mediators
what are cytokines?
proteins produced by cells involved in inflammation
what are some examples of inflammatory mediators?
- histamine
- prostaglandins
- leukotrienes
- eosinophils
As doses of anti-inflammatories increase they cross over to being ______.
immunosupressive; very large doses can decrease production of Ab needed for an immune response
T/F Inflammation and the immune system are the same.
false: they are related
Cyclosporine and tacrolimus MOA?
inhibit production and release of IL-2 and other cytokines that are necessary for cytotoxic t cell activations when there is a allogenic challenge
what are cyclosporine and tacrolimus often paired with?
steroids
what are the uses for cyclosporine and tacrolimus?
- transplant rejection prophylaxis
- psoriasis
- RA
what type of agent is mycophenolate considered to be?
antiproliferative agent
what is the MOA of mycophenolate?
inhibits key enzyme needed for new synthesis of guanosine (DNA precursor)
this blocks proliferation of B& T cells
What is mycophenolate used for?
- prevention of organ rejections in patients receiving allogenic renal, cardiac, or hepatic transplants
MOA of cytotoxic drugs?
inhibit proliferation of cells in the body (thus decreasing immune system)
what is azathioprine used for?
cytotoxic drug
- prevention of organ transplant rejection
- inflammatory bowel disease
- RA
- Lupus
what is cyclophosphamide used for?
cytotoxic drug
- tx of leukemia
- non-hodgkin lymphomas
what is leflunomide used for?
cytotoxic drug
- RA
MOA of immunomodulators?
modify but do not suppress the immune system (so that you don’t get more infections)
what is the goal of immunomodulators?
decrease risk of opportunistic infections
what is hydroxychloroquine used for?
immunomodulator
- lupus
- malaria
- RA
what is the risk of hydroxychloroquine?
glaucoma/eye plaques
what are the three types of immunosuppressive antibodies?
- intravenous immunoglobulin (IVIG)
- Rho immune globulin
- Hyperimmune globulin
what is intravenous immunoglobulin?
a polyclonal (many different donors) human immunoglobulin
what is the target for IVIG?
non-specific Ag target
Ab in IVIG?
IgG
MOA of IVIG in immune deficient individuals?
humoral Ab replacement
IgG Ab increases phagocytosis and elimination of pathogens from circulation
indications for IVIG?
- guillian barre
- kawasaki’s disease
- idiopathic thrombocytopenia purport (ITP)
Adverse rxn of IVIG?
10% get chills, nausea, abdominal pain
what drugs can be given to reduce S/E of IVIG?
steroids (diphenhydramine and meperidine)
when are individuals more sensitive/allergic to IVIG?
IgA deficient
what is rho (D) immune globulin?
solution of human IgG with a higher titer of Ab against Rh+
what is Rh factor?
Ag found on RBC
How is Rh- child a problem?
1st child born: mom and baby swap RBC and mom makes Ab against Rh+
2nd child: during 3rd trimester mom will make Ab against Rh+ child’s RBC causing severe anemia and death
Rho D immune globulin given to mom at birth of Rh+ child. How does this benefit second Rh+ child?
Ab cover 1st child’s RBC so mom’s immune system never see them and don’t make Ab against them.
what are hyperimmune immnoglobulns?
made from humans or animals with high titers of Ab to a particular disease
a bunch of different Ab for one disease
what is the difference between IVIG and hyperimmune Ig?
hyperimmune is specific
IVIG is generalized
What source is preferred for disease specific Ab?
humans:
- fewer rxns
- Ab lasts longer
Define ximab, zumab, and mumab.
ximab: 70% human
zumab: 90% human
mumab: 100% human
what are do we currently have immunoglobulins on the market for?
Human:
- Hep B
- Hep A
- Measles
- Rabies
- Rubella
- Varicella
- Tetanus
- Digoxin
- Respiratory syncytial virus
Horse:
- Botulism
- Snakebite
- black widow
What are monoclonal antibodies?
antibodies made in lab for 1 Ag
what source is used to make MABs?
mouse and human (chimeric mixture)
or humanized
How are MABs used in targeting tumors or anti-tumor ab?
develop Ab to Ag only found on tumor
What is Rituximab used for?
chemotherapy treatment
How are MABs with isotopes attached used?
ab to Ag found on tumor and add radioactive isotope for imaging (some therapeutic use)
How are MABs used as immunosuppressant and anti-inflammatory agents?
to stop or slow down the autoimmune process
Examples of MABs used as immunosuppressants and anti-inflammatory agents?
- humira
- enbrel
- remicade
What conditions are immunosuppressive/anti-inflammatory MABs used for?
- RA
- organ rejection
- crohn’s
What are the S/E of drugs that alter the immune system?
- infections
- decreased ability to fight infections
- cancer
should only be used when absolutely needed by someone who is experienced
what risk do Humera/MABs also carry?
risk of TB
what are the clinical uses of drugs that affect the immune system?
- transplant medicine
- autoimmune disorders
- immunomodulation
What antigens must match during solid organ or bone marrow transplant?
Human leukocyte Antigens (HLAs) or body will attack it
suppress immune system incase they do not match
During chemotherapy and radiation cancer cells are killed; the bone marrow and immune system is also killed. Bone marrow transplants replace this loss. What is the risk of transplant? How is it managed?
T cells of transplanted marrow attacking host as a foreign object.
(graft-vs-host disease)
Managed with immunosupression
What autoimmune disorders are immunosuppressives commonly used in?
- chronic severe asthma
- RA
- SLE
how are immunomodulator’s used to manipulate the immune system?
- MABs used to manipulate cytokine release
- Crohn’s
- possibly useful in immunosuppressed (AIDs or cancer)
- RA
Hypersensitivity rxn against drugs should be noted in Hx as an allergy so that they do not receive drug again. How do we treat these drug rxns?
zantec= H2 clariten = 2nd generation (x2wks) benadryl = H1 (x2d) steroids epi if anaphylactic drug avoidance
what causes idiosyncratic drug rxns?
we don’t know
What are type I sensitivity rxns called?
immediate drug allergy
examples of type I sensitivity rxns?
- allergic rhinitis
- allergic asthma
- food allergy
- anaphylaxis
when does the early phase of type I hypersensitivity rxns start? phase 2?
stage I: minutes
stage 2: 2-24 hours after exposure
what happens during stage I of type I hypersensitivity rxn? what does it result in?
release of histamine from mast cells
- vasodilation
- edema
- congestion
what happens during stage II of type I hypersensitivity rxn?
eosinophils, neutrophils, and t cells infiltrate the area
MOA of type I hypersensitivity rxn?
- IgG mediated rxn
- drugs binds to host protein
- immune system detects it
- make IgE Ab against drug
- next time body sees drug IgE causes mast cells to release histamine & leukotrienes
what are the symptoms of type I hypersensitivity rxns?
- urticaria
- edema
- bronchoconstriction
- anaphylaxis (if enough histamine release)
how can you confirm allergy to drug?
scratch test
scratch skin with a tiny bit of drug and see if it reacts in 10-15 minutes (can get false positives)
If you need to use a drug someone is allergic to what do you do?
try desensitizing them to the drug
10:1 dilution and increase over hours to full therapeutic dose
what is a type II hypersensitivity rxn?
Autoimmune/Ab mediated to drug
drug binds to and modified host cells (RBC or other tissue)
IgG or IgM binds to drug modified tissue, activates complement, and destroys tissue
what is the antigen in type II hypersensitivity rxns?
drug-host cell complex
treatment for type II hypersensitivity?
remove drug (autoimmunity resolve)
can give immunosuppressives while this happens if severe
Examples of type II hypersensitivity rxns?
- methyldopa
- transfusion rxn
- graves disease
- myasthenia gracis
what happens during type II hypersensitivity rxn with methyldopa?
this anti-HTN binds to RBC, activates immune system, causing destruction of RBC
= hemolytic anemia
What is type III hypersensitivity rxn?
serum sickness and vasculitic reactions
drug-antibody complex occur in blood
complexes deposit on membranes causing symptoms
what are the symptoms of type III rxns?
- vasculitis (from deposit on blood vessel walls)
- nephritis (from kidney glomerulitis)
- arthritis (from deposits on synovial membranes)
- rash
Sx occur 3-4 d after exposure
treatment for type III rxns?
- corticosteroids
- plasmapheresis
what is plasmapheresis?
separation of plasm in blood from cells in blood to remove Ag-Ab complexes and replace with healthy plasma
examples of type II hypersensitivity rxn?
non-human immunoglobulins
what is type 4 hypersensitivity?
t-cell mediated allergy
t- cells release cytokines leading to tissue inflammatory and injury
examples of type 4 hypersensitivity?
- allergic contact dermatitis (poison ivy)
- chemicals in cosmetics
- medications
- jewelry
- cleaning products
- industrial reagents
- topical drugs
what t- cells are involved in type 4 hypersensitivity rxns?
- CD4 T helper cell
- CD8 T killer cell
symptoms of type 4 hypersensitivity rxn?
1st exposure: nothing
2nd exposure: takes 2-3 days to see Ag
Skin rashes
Treatment for type 4 hypersensitivity rxn?
drug avoidance
steroids
