Immunopharmacology & Immunostimulants Flashcards
What is immunopharmacology?
part of pharmacology that deals with drug action on the immune system and the pharmacological actions of substances derived from the immune system
What is the immune system? What are 2 common ways can it dysfunction?
normally occurring protective mechanism that helps the body defend itself against potentially harmful agents (immunis = safe)
- may perceive normally harmless substances, like allergens and host body tissues, as harmful invaders and try to eliminate them (allergy, autoimmune disease)
- may be weak or become weak as a consequence of suppressive influences, like tumor microenvironments (cancer)
What are the main primary lymphoid organs? Secondary?
PRIMARY
- bone marrow: pluripotent hematopoietic stem cells (B-cells)
- thymus: T-cell maturation
SECONDARY
- spleen: blood filter, iron
- lymph nodes: filter, storages, and activation for B and T cells
What 2 things make up the innate immune system?
NONSPECIFIC, FAST
1. physical barriers, first line of defense - skin, mucous membranes, saliva, urine, tears, stomach acids
2. inflammatory phagocytes/WBCs - neutrophils, macrophages, basophils, eosinophils, NK cells
What 2 responses are part of the adaptive immune system?
SPECIFIC, SLOW, MEMORY
1. cell-mediated: T-lymphocytes (suppressor, helper, and cytotoxic T-cells)
2. humoral: B-lymphocytes, antibodies
Innate vs adaptive immunity:
Innate vs adaptive immunity:
What are the 2 major characteristics of the adaptive immune response? How does cell-mediated and humoral immunity compare?
specificity and memory
CELL-MEDIATED = relies on contact between immune sells and the pathogen and is controlled by activated -cells
HUMORAL = antibody-mediated response relying on antibodies to relay signals between immune cells; controlled by activated B-cells
How do helper T-cells and cytotoxic T-cells compare?
HELPER = CD4+/TCR binds MHC II
- Th1 = IL-2, IFN–γ, TNF-α
- Th2 = IL-4, 5, 10, 13
CYTOTOXIC = CD8+/TCR binds MHCI
What are immunomodulators? What are the 2 types?
natural or synthetic substances that modulate or modify the immune system
- IMMUNOSTIMULANTS: enhance the body’s resistance against infections (vaccines, interferons)
- IMMUNOSUPPRESSANTS: suppress the immune system to reduce the risk of rejection of foreign bodies or super active immune system (organ transplants, autoimmune disease)
In what 5 situations is it appropriate to use immunomodulators?
- nonresponse or intolerance to antibiotics or corticosteroids
- steroid-dependent disease or frequent use of steroids
- perianal disease that does not respond to antibiotics
- bolster or optimize the effect of a biologic drug and prevent the development of resistance
- prevent recurrence after surgery
What are the 2 types of immunostimulants?
- SPECIFIC: stimulate immune response to specific antigenic types (vaccines)
- NON-SPECIFIC: no antigenic specificity and are widely used in chronic infections, immunodeficiency, autoimmunity and neoplastic disease
What is the difference between endogenous and exogenous immunostimulants?
ENDOGENOUS = naturally produced by cells affected by antigens, like granulocyte colony-stimulating factor, interferons, and interleukins
EXOGENOUS = synthetic drugs derived from bacteria, plants, anthelmintics, and viruses
What does granulocyte colony-stimulating factor (G-CSF) do? What are the 5 major uses?
induces bone marrow production of neutrophils
- bacterial and viral infections (canine ehrlichiosis, FeLV, FIV)
- chemotherapy-induced myelosuppression (lymphoma)
- neoplasia of the bone marrow
- bone marrow immune-mediated aplasia
- immune-mediated neutropenia in dogs
What are interferons? What are the 3 classes?
cytokines produced by host cells that are infected with viruses, bacteria, parasites, fungi, and other pathogens that activate other cells in the immune system and destroy pathogens
IFNα - WBC (viruses)
IFNβ - fibroblasts (multiple sclerosis)
IFNγ - lymphocytes (chronic disease)
What 2 interferons are used as endogenous immunostimulants? What do they do? What 5 infections are they used to treat?
- recombinant human IFN-α (not for long term use)
- recombinant feline IFN-ω
enhance antiviral activity
- FeLV
- FIV
- FIP
- herpesvirus (ω)
- calicivirus (ω)
What interleukin is used as an endogenous immunostimulant? How does it work? When is it used?
recombinant IL-2
enhances antitumor immune response by activating peripheral immune/inflammatory cells
canine neoplasia
What 3 adverse effects are common with the use of interleukins are immunostimulants? What major problem should be monitored?
vomiting, diarrhea, lethargy
it is a human recombinant protein, so the immune system may perceive it as a pathogen and produce antibodies against it, which lowers its efficacy
What 2 drugs use Propionibacterium acnes bacterin?
- ImmunoRegulin
- EqStim
What is the mechanism of action P. acnes bacterin?
non-specific bacterin that stimulates NK cell activity and activates macrophages to produce IL-1, IL-6, and TNFα to stimulate T-lymphocyte function
What are 3 uses for P. acnes bacterins?
- acute and chronic canine staphylococcal pyoderma
- feline rhinotracheitis infection and FeLV
- bacterial and viral respiratory tract infections in horses
What 2 drugs use Staphylococcal aureus bacterins? What is the mechanism of action?
- Staphage lysate (SPL)
- S. aureus bacterin toxoid (Staphoid AB)
activation of phagocytic cells and stimulation of T-lymphocytes
When are Staphage lysate (SPL) and Staphoid AB used?
SPL = adjunct therapy in dogs with recurrent superficial pyoderma and related staphylococcal hypersensitivity
SAB = prevention of staphylococcal mastitis in cows
What 4 drugs use Mycobacteria cell wall extracts as immunostimulants? What are their 3 mechanisms of action?
- Equimune
- Muramyl tripeptide (MTP) - Mifamurtide
- Regressin-V
- Immunocidin
causes the release of IL-1 from macrophages, TLR-mediated effects on macrophages and DC, and activated NK-cell cytotoxicity
What are the uses of Equimune, Muramyl tripeptide (MTP), Regressin, and Immunocidin?
(mycobacterial cell wall extracts)
E = equine viral and bacterial respiratory infections
M = adjunct treatment for canine osteosarcoma, hemangiosarcoma, and malignant melanoma
R = mammary adenocarcinomas in dogs
I = cancer and infectious diarrhea in calves
What plant derivative works as an immunostimulant? What are 4 mechanisms of action?
Acemannan extracted from aloe vera leaves
- stimulates macrophages to produce IL-1, IL-6, TNFα, and NO
- enhances NK cell and T-lymphocyte activity
- antiviral
- antineoplastic
What are the main 2 uses of Acemannan? What are some adverse effects?
- treat fibrosarcoma in cats and dogs
- boost immune system in FeLV and FIV
anorexia, diarrhea, depression, tachycardia, collapse, pain at injection site
What anthelmintic can be used as an immunostimulant? What is thought to be its mechanism of action?
Levamisole - synthetic antinematodal
enhances phagocytosis by monocytes and restores cell-mediated immunity
What are the 5 uses of Levamisole?
- vaccine adjuvant to stimulate non-specific responses
- canine microbial, fungal, and neoplastic diseases
- canine chronic pyoderma
- feline plasma-cell gingivitis/pharyngitis
- boosts pregnant mares IgG production
How does Levamisole compare to other immunostimulants?
lower margin of safety
- neurotoxicity
- GI disturbance
- pulmonary edema
- mydriasis and hypersalivation in cats
What virus derivative can be used as an immunostimulant? What drug uses this?
Parapoxvirus ovis
Zylexis
What are the 4 mechanisms of action of Zylexis?
- stimulates NK cell activity and phagocytosis
- causes the release of IL-2, TNFα, and G-CSF
- Th1-type response - IL-12, IL-18
- Th2-types response - IL-4, IL-10
In what 2 instances is Zylexis used?
- prevention of stress-associated infection in horses
- herpesvirus EHV-1 and EHV-4 infections
