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Immuno-Pharmacology: Dr. Harshika Patel Pharmacology and Therapeutics II Date:23/05/2018 Time: 11am - 1pm
Immuno-Pharmacology: Dr. Harshika Patel Pharmacology and Therapeutics II Date:23/05/2018 Time: 11am - 1pm
PHARMACOLOGY
Dr. Harshika Patel
Pharmacology and therapeutics II
Date:23/05/2018
Time : 11am – 1pm
Introduction
• Immune system plays an essential role to protect our body from
pathogens
• In certain instances its powerful destructive mechanisms do more harm
than good, example
1. Hypersensitivity reactions, Treated by
2. Autoimmune disorders, Immunosuppressive
3. Rejection reactions to transplanted tissues Drugs
• Drugs that suppress immune action play a vital role to treat these
conditions.
• Now-a-days monoclonal Ab widely used as targeting proteins that count in
immunosupreesive agents
Innate IS Adaptive IS
Autoimmunity
Hypersensitivit
y
Immunodeficiency
diseases
Normal Immune response
• Protect host from invading pathogens and
eliminate the diseases
• Functions: delicately responsive to invading
pathogens
• While capacity to recognize "self" antigens
to which it is tolerant
• Protection by innate or adaptive immune
system
Innate immune system
• first line of defense against an antigenic insult
• Includes :
physical (eg, skin)
biochemical (eg, complement, lysozyme,
interferons)
cellular components (neutrophils, monocytes,
macrophages)
Adaptive Immune System
• Arise when innate immune response is inadequate to cope
with infection
• the adaptive immune system is mobilized by signals from the
innate response
• has a many characteristics that contribute to eliminating
pathogens successfully :
1. To respond to a variety of antigens, each in a specific manner
2. To discriminate between foreign antigens and self antigens of
the host
3. To respond to a previously encountered antigen in a learned
way by initiating a vigorous memory response
• Response culminates in the
1. Production of antibodies, by activated B lymphocytes
which are the effectors of humoral immunity; and
2. Activation of T lymphocytes, which are the effectors of
cell-mediated immunity
• The subsets of lymphocytes that mediate different parts
of the immune response can be identified by specific cell
surface components or clusters of differentiation (CDs)
• Example :
• helper T (Th) cells bear the CD4 protein complex,
• whereas cytotoxic T lymphocytes express the CD8 protein
complex
• Induction of specific immunity requires the
participation of APCs (include macrophages, dendritic
cells, Langerhans cells, and B lymphocytes)
FATE:
• They have the potentiality to cause: disease and
risk of infection ,malignancies
Tests of Immunocompetence
• Applied to test immunologic competence and drug-
induced immune dysfunction
• Simplest tests that can be used to detect:
Immunosuppressive, or
Immunostimulating agents effects
• PK: oral/ IV * ()
• More potent than cyclosporine, highly serum protein
bound even concentrated well in RBCs
• Same metabolism and elimination as cyclo. (one of
metabolite have immunosuppressive action)
• Infection
– Tuberculosis
– Serious resulting in death
• Neurologic
– Multiple Sclerosis, seizures, inflammation of the ocular
nerve
• Worsening of Congestive Heart Failure
• Remember
STOP if develop a fever, have an infection,
• Tendency to cause lymphomas
Etanercept
• Dimeric fusion protein composed of human IgG1
constant regions fused to TNF receptor.
• Binds to both TNF- alpha and TNF- B have same
effect as infliximab inhibition of TNF-alpha
-mediated inflammation,
• Dissimilarity from:
half-life is shorter due to its physical form (fusion
protein)
the route of injection(SC twice weekly)
Antimetabolites
• In immunotherapy, they are used in smaller
doses than in the treatment of malignant
diseases.
Hyperimmune Immunoglobulins:
Various hyperimmune IGIVs are available for treatment:
• infections with respiratory syncytial virus, cytomegalovirus,
varicella-zoster virus, human herpes virus 3, hepatitis B
virus and
• for patients with rabies, tetanus, and digoxin overdose.
Monoclonal Antibodies
1. Trastuzumab
2. Rituximab :patients with relapsed or refractory low-
grade or follicular B cell non-Hodgkin's lymphoma
3. Ibritumomab tiuxetan is an anti-CD20 murine
monoclonal antibody labeled with either Yttrium-90 or
Indium-111 approved for use in relapsed or refractory
low-grade or follicular B cell non-Hodgkin's lymphoma pt.
4. Daclizumab
5. Basiliximab
6. Abciximabthat binds to the integrin GPIIb/IIIa receptor
on activated platelets, inhibiting fibrinogen, Von
Willebrand factor (coagulation diseases)
•7. Palivizumab: binds to the fusion protein of
respiratory syncytial virus, preventing infection in
susceptible cells in the airways(neonates: dec’d
hospitalization, infection frequency)
8. Infliximab, etanercept, and adalimumab :
inhibition of TNF
9. Alemtuzumab: binds to CD52 found on normal &
malignant B and T lymphocytes, NK cells,
monocytes, macrophages, and a small population
of granulocytes* (whats may go down?)
Anti-CD3 Ab
• To suppress the activity of subpopulation of T-cells.
• To block co-stimulatory signals.
• Anti-inflammatory effects
Clinical use
• Glucocorticoids are first-line immunosuppressive therapy for
both solid organ and hematopoietic stem cell transplant
recipients and graft-versus-host disease (GVHD). (combination
therapy)