The immune system protects organisms through layered defenses. The innate immune system provides an immediate response, while the adaptive immune system has immunological memory. The adaptive immune system is activated if pathogens evade the innate response and has both cell-mediated and humoral components. Cytokines allow communication between immune cells and help regulate both innate and adaptive immune responses. Immunosuppressive drugs target different parts of the immune activation cascade to suppress immune responses, such as by inhibiting cytokine production or lymphocyte proliferation.
Immunopharmacology : Defination, components of immunity, classification of immunity and its explanation.
Drugs used in immune disorder : Immunosuppressants and Immunostimulants.
Immunosupressants and Immunostimulants their pharmacology, uses etc. Basics of immunology, innate immune response, acquired immune response, role of complement in innate immune response. Major histocompatibility complex, antibody structure. classification of immunosupressants, their mechanism of action, uses and adverse effects.
Immunopharmacology : Defination, components of immunity, classification of immunity and its explanation.
Drugs used in immune disorder : Immunosuppressants and Immunostimulants.
Immunosupressants and Immunostimulants their pharmacology, uses etc. Basics of immunology, innate immune response, acquired immune response, role of complement in innate immune response. Major histocompatibility complex, antibody structure. classification of immunosupressants, their mechanism of action, uses and adverse effects.
immunostimulants
Immunomodulators are natural or synthetic materials that regulate the immune system and induce innate and adaptive defense mechanisms. These substances are classified into two types, immunostimulants and immunosuppressants.
Immunostimulants can enhance body's resistance against various infections through increasing the basal levels of immune response.
Immunostimulators are prescribed to enhance the immune response against infectious diseases, tumours, primary or secondary immunodeficiency, and alterations in antibody transfer, among others .
Immunosuppressant are drugs or medicines that lower the body's ability to reject a transplanted organ. Another term for these drugs is anti-rejection drugs. There are 2 types of immunosuppressants: Induction drugs: Powerful antirejection medicine used at the time of transplant.
Nasal decongestants and Respiratory Stimulants.pdfShaikh Abusufyan
At the end of this e-learning session you are able to…
A. Discuss definition and therapeutic uses, limitation, classification and pharmacology of nasal decongestant.
B. Explain definition and uses, limitation, classification and pharmacology of respiratory stimulants.
I am happy to share lecture series on different topics of Pharmacology experiments, Pharmacy practice, Clinical pharmacy and Pharmacology. Wish you all happy learning.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
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For 5+ video lecture series on Drugs used in Special population use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZAed7zkXxyrgomJx2sSwHR
For 5+ video lecture series on Adverse Drug Reaction use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbWpd06N6RcV2q0K3JT29Wv
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Hello friends. In this PPT I am talking about Anti-viral drugs drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
immunostimulants
Immunomodulators are natural or synthetic materials that regulate the immune system and induce innate and adaptive defense mechanisms. These substances are classified into two types, immunostimulants and immunosuppressants.
Immunostimulants can enhance body's resistance against various infections through increasing the basal levels of immune response.
Immunostimulators are prescribed to enhance the immune response against infectious diseases, tumours, primary or secondary immunodeficiency, and alterations in antibody transfer, among others .
Immunosuppressant are drugs or medicines that lower the body's ability to reject a transplanted organ. Another term for these drugs is anti-rejection drugs. There are 2 types of immunosuppressants: Induction drugs: Powerful antirejection medicine used at the time of transplant.
Nasal decongestants and Respiratory Stimulants.pdfShaikh Abusufyan
At the end of this e-learning session you are able to…
A. Discuss definition and therapeutic uses, limitation, classification and pharmacology of nasal decongestant.
B. Explain definition and uses, limitation, classification and pharmacology of respiratory stimulants.
I am happy to share lecture series on different topics of Pharmacology experiments, Pharmacy practice, Clinical pharmacy and Pharmacology. Wish you all happy learning.
For 30+ video lecture series on Pharmacology Experiment as per PCI B Pharm Syllabus refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Ba6WSJjeBaK0HMF79hdad3g
For 2+ video lecture series on Pharmacoeconomics refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BY8U1TnlcHttsRB8hwpoJRL
For 5+ video lecture series on Pharmacoepidemiology refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbqIaLoMmuF0Bf66SMFZtnb
For 5+ video lecture series on Drug discovery refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1Bbn9IE6c4MagVHZMNNinJov
For 5+ video lecture series on Drugs used in Special population use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZAed7zkXxyrgomJx2sSwHR
For 5+ video lecture series on Adverse Drug Reaction use link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BbWpd06N6RcV2q0K3JT29Wv
For 2+ video lecture series on Therapeutic drug monitoring refer link given below: https://www.youtube.com/playlist?list=PLBVbJ9HCa1BZQtOerZuDjx4yo0eOeTHIy
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Hello friends. In this PPT I am talking about Anti-viral drugs drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
CYTOKINES
NOMENCLATURE OF CYTOKINES
PROPERTIES OF CYTOKINES
CYTOKINES BELONG TO FOUR FAMILIES
CYTOKINES RECEPTORS
CLASS I AND CLASS II CYTOKINE RECEPTORS
ACTIVATION OF SIGNAL TRANSDUCTION PATHWAY BY CYTOKINE
1.Immunoglobulin superfamily receptors
2. Class I cytokine receptor family (also known as hematopoietin receptors family)
Three subfamilies of the class I cytokine receptor family (hematopoietin)
3. Class II cytokine receptor family (also known as Interferon receptors family)
4. TNF receptor superfamily
5. Chemokine receptors
Functional Categories of Cytokines
A. Mediators of natural immunity
B.Cytokines acting as mediators and regulators of adaptive immunity
C. Cytokines acting as stimulators of haematopoiesis
Cytokine Antagonists
IMMUNE REGULATION
A. Regulation by cytokines
B. Regulation by regulatory T cells (Tregs)
Cytokine cross-regulation
Therapeutic Uses of Cytokines and their Receptors
CYTOKINES (Introduction and Description) by Mohammedfaizan ShaikhFaizanShaikh690659
Secreted, low-molecular-weight proteins that
Regulate the nature, intensity and duration of the immune
Response by exerting a variety of effects on lymphocytes and/or
Other cells.
- Cytokines bind to specific receptors on target cells.
- Originally were called lymphokines because they were initially
- Thought to be produced only by lymphocytes. Then monokines
Because they were secreted by monocytes and macrophages.
- Then interleukin because they are produced by some
Leukocytes and affect other leukocytes. The term “cytokine” is
Now used more widely and covers all of the above.
- Don’t forget chemokines, they are also considered cytokines.
Cytokines are a broad and loose category of small proteins important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrine, paracrine and endocrine signaling as immunomodulating agents.
When a pathogen enters the body, it’s confronted by elements of the innate immune system, which constitute the first line of defense.
Once breached, the adaptive response takes over, but it typically takes few days to be effective.
Immunity is the processes that occur to defend the body against foreign organisms or molecules.
Immunity includes:
Inflammation.
Complement activation.
Phagocytosis.
Antibody synthesis.
Effector T lymphocytes.
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Factory Supply Best Quality Pmk Oil CAS 28578–16–7 PMK Powder in Stockrebeccabio
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micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
2. • An immune system is a system of biological
structures and processes within an organism
that protects against disease by identifying
and killing pathogens and tumor cells.
• Detects a wide variety of agents, from
viruses to parasitic worms.
• Needs to distinguish them from the
organism's own healthy cells and tissues.
• Detection is complicated as pathogens can
evolve rapidly, producing adaptations that
avoid the immune system.
3. Layered defense
The immune system protects organisms from infection
with layered defenses of increasing specificity.
physical barriers prevent pathogens such from entering
the organism.
If a pathogen breaches these barriers, the innate immune
system provides an immediate, non-specific response.
If pathogens successfully evade the innate response,
vertebrates possess a third layer of protection, the
adaptive immune system, activated by the innate
response. Specific and has an immunological memory
so immune system mount faster and stronger
subsequent attacks.
4. Components of the immune system
Innate immune system Adaptive immune system
Exposure leads to Lag time between
immediate maximal exposure and maximal
response response
Cell-mediated andhumoral Cell-mediatedand
components humoral components
No immunological Exposure leads to
memory immunological memory
Response isnon-specific Pathogen andantigen
specific response
Found in nearlyall forms Found only invertebrates
of life
10. CYTOKINES
• Definition:
Cytokines are soluble hormone-like
proteins that allow for communication
between cells and the external
environment. The term cytokine, or
immunocytokine, was used initially to
separate a group of immunomodulatory
proteins, called also immunotransmitters,
from other growth factors that modulate the
proliferation and bioactivities of non-
immune cells .
11. The cytokines are important components of
the immune system. They act in concert
with specific cytokine inhibitors and
soluble cytokine receptors to regulate the
human immune response. Their physiologic
role in inflammation and pathologic role
in systemic inflammatory states are now
well recognized.
12. • Cytokines are secreted by white blood cells as
well as variety of other cells (fibroblasts,
endothelial cells, epithelial cells, etc.) in
response to inducing stimuli, and are not
constitutively expressed. Cytokines comprise:
(1) Interleukins initially thought to be produced
exclusively by leukocytes,
• (2) Lymphokines, initially thought to be
produced exclusively by lymphocytes,
• (3) Monokines initially thought to be produced
exclusively by monocytes,
13. • (4) Interferon, initially thought to be involved in
antiviral responses.
• (5) colony stimulating factors, initially thought to
support the growth of cells in semi-solid media.
• (6) Chemokines thought to be involved in Chemotaxis,
and a variety of other proteins and tumor necrosis factor
(TNF).
• The term Type-1 cytokines refers to cytokines produced by
Th1 cells while Type-2 cytokines are those produced by
Th2 cells. Type-1 cytokines include IL2, IFN-γ, IL12 and
TNF-beta, while Type-2 cytokines include IL4, IL5, IL6,
IL-9, IL10, and IL13 .
14. • It has been shown that a number of viral
infectious agents exploit the cytokine
repertoire of organisms to evade immune
responses of the host. Virus-encoded factors
appear to affect the activities of cytokines in at
least four different ways:
• (1) by inhibiting the synthesis and release of
cytokines from infected cells;
• (2) by interfering with the interaction between
cytokines and their receptors.
15. • (3) by inhibiting signal transmission
pathways of cytokines.
• (4) and by synthesizing virus-encoded
cytokines that antagonize the effects of host
cytokines mediating antiviral processes.
• An imbalance in cytokine production or
cytokine receptor expression and/or
dysregulation of a cytokine process
contributes to various pathological
disorders.
16. :properties of cytokines **
• Cytokines are short-lived and may act
locally either on the same cell secreted it
(autocrine), on other cells (paracrine)
or like hormones they may act
systemically (endocrine)
17. Cytokines interact in a network by:
• a- including each other (cascade-like
activity)
• b- transmodulating cytokine cell surface
receptors
• c- interacting synergistically, additively or
antagonistically on cell function
- cytokines are nonspecific and
antigen-independent in mode of
activity
18. All cytokine receptor have the
typical receptor structure: an extra
cellular domain, single membrane-
spanning domain & a cytoplasmic
domain.
• Cytokines may exhibit considerable
overlap in their biologic effects on
lymphoid, myeloid & connective
tissue
19. classifications of **
: cytokines
• 1- proinflammatory cytokines:
- make the disease worse because they produce
fever, inflammation, tissue destruction &
sometimes shock & death including IL-1, IL-6,
IL-12 & GM-CSF G-CSF, IFN-γ & TNF- α
20. Anti-inflammatory -2
:cytokines
• Potent activators of B- Lymphocytes.
Include IL-1 receptor antagonist, IL-4,
IL-6, IL-11 & IL-13.
• They are anti-inflammatory cytokines by
their ability to suppress genes for
proinflammatory cytokines such as
IL-1, TNF & chemokines.
21. 3- Growth factors:
• Such as platelet-derived growth factor
(PDGF), transforming growth factor-β
(TGF-β) & Epidermal growth factor (EGF)
influence the proliferation of many
structural cells such as fibroblasts &
airway smooth muscle cells.
22. Functional Categories of **
Cytokines
Cytokines classified according to their biologic
actions into three groups:
1) Mediators and regulators of innate
immunity
- Produced by activated microphages and NK cells
in response to microbial infection.
- they act mainly on endothelial cells and
leukocytes to stimulate the early
inflammatory response to microbes.
23. 2) Mediators and regulators of acquired immunity:
- Produced mainly by T lymphocytes in response to specific
recognition of foreign antigens.
- They include IL-2, IL-4, IL-5,, IL-13, IFN, Transforming growth
factor-β (TGF-β) and lymphotoxin (TNF- β).
3) Stimulators of haematopoiesis:
- Produced by bon marrow, stormal cells, leukocytes.
- Stimulate growth and differentiation of leukocytes.
- Stem cell factor, IL-3, IL-7, GM-CSF.
24. (Interferons (IFNs
* Interferons (IFNs): are proteins secreted in response
to viral infections or other stimuli
* They include:
- INF-α produced by leucocytes
induced by virus infected cells
- INF-β produced by fibroblasts
- INF-γ produced by NK cells,TH1 cells, CD8 T-cells
25. : Action of INF-α and IFN-β
- Prevent viral replication
- Increase MHC-I expression on viral infected
cells helping their recognition by CD8 T
cells
- Increase cytotoxic action of Nk cells
- Inhibit cell proliferation and tumor growth
26. : Action of IFN-γ
• Activate Macrophages.
• Increase expression of MHC-I and II on
APCs.
• Enhance cytotoxic actions of Nk cells.
• Promote production of TH1 and inhibits
proliferation of TH2.
27.
28. summary of selected cytokines **
Cytokine Actions
IL-1 NK cells -Attract Enhance activity of-
neutrophil¯ophage
IL-2 antigen-primed Induce proliferation of-
T-cells
NK cells Enhance activity of-
IFN-γ macrophages & NK enhance activity of -
cells - increased expression ofMHC
molecules - enhance production of
IgG2a
IFN-α cytotoxic effect ontumor cells - induces -
cytokine secretion in the inflammatory
response
30. :Immune activation cascade **
1- Signal-1
APC activates specific receptors on outer surface of T-
cell (CD3)
2- Signal-2 :
Costimulation of CD80:86 on APC to T-lymphocytes
3- Signal-3:
Activation of different cellular pathway in T-cells the
most important is calcium calcineurin pathway where
intracellular Ca++ activates calcineurin.
31. Activated calcium calcineurin activates
inactive (phosphprylated) NFATc into
activated (dephosphorylated) NFATc
4- Signal-4
NFATc associates with other nuclear factors
leading to activation of genes encoding
cytokines
5- gene expression leads to IL-2 & IL-2 receptors
release
6- IL-2 activates lymphocytes proliferation
32.
33. Immunosuppressive drugs
** Immunosuppressive drugs can be categorized
according to their mechanism of action to:
• Some agents interfere with cytokines
production or action.
• Others disrupt cell metabolism , preventing
lymphocyte proliferation .
• Mono- or polyclonal antibodies block T-cell
surface molecules.
34. - Earlier immuno-suppressant suppress both
humoral & cell mediated immunity
but recent drugs suppress lymphocyte
function by drugs or antibodies aginst
immunoproteins.
- No single agent is used but 2-4
combination drugs or agent with
different mechanisms of actions which
disturb various level of T—cell activation.
35. I- selective inhibitor of cytokine
:production & function
A) Cyclosporine:
** Source & nature:
- lipophilic cyclic polypeptide extracted from soil
fungus
** Uses:
1 - Prevent rejection of kidney, liver & cardiac allogeneic
transplants:
Prevent acute phase rejection specially when taken with
corticosteroids & mycophenolate mofetil.
2- Alternative to methotrexate for severe active rheumatoid
arthritis.
3- In patient with psoriasis not respond to other drugs.
36. :mechanism of action **
Cyclosporine enters T- lymphocyte to bind
with cyclophillin forming complex which binds
to & inhibits calcineurin that responsible for
dephosphorylation & activation of NFATc (cytosolic
Nuclear Factor of Activated T-cell) so this NFATc
cannot enter the nucleus so decrease production
of IL-2 & IL-2 receptors essential for proliferation
of T- cells.
37.
38. ** Pharmacokinetics:
- Oral or I.V infusion
- Hepatic metabolism by CYP3A4 to inactive metabolites
excreted billiary
** Adverse effects:
- Nephrotoxicity: irreversible in 15% of patients
- Hepatotoxicity
- Viral infection due to herpes group or cytomegalovirus
(CMV)
- Anaphylactic reactions on parentral administration
- Hypertension, hyperlipidema , hyperkalemia, hirsutism
& gum hyperplasia
39. :(B( Tacrolimus : (FK506
Differs from cyclosporine in the following:
1- Preferred than cyclosporine due to :
a- more potent.
b- lower dose of corticosteroids is needed so less toxicity.
c- ointment preparation has been approved for moderate to
severe atopic dermatitis.
2- Mechanism of action as cyclosporine but bind to
different immunophyllin (FK-binding protein
(FKBP1-2) ) .
3- Pharmacokinetics: as cyclosporine but better bioavailability.
4- Adverse effects:
Mainly neurotoxic & insulin dependent diabetes mellitus but
less C.V.S toxicity & no hirsutism or gum hyperplasia.
40.
41. ( C( Sirolimus: (earlier name rapamycin
** Source & nature:
Macrolide obtained from fermentations of soil mold.
** Uses:
1-In combination with cyclosporine & corticosteroids in
renal transplantation values:
a- lower doses of drugs so less toxicity.
b- combination of CsA & SRL has synergistic effect as SRL
acts later in immune activation cascade .
N.B) to limit toxicity of CsA, SRL usually is used during
calcineurin inhibitor withdrawal protocols.
2- Due to its anti-proliferative effect: SRL-coated stents
inserted into cardiac Vasculature inhibit restenosis of blood
vessels by ↓ proliferation of endothelial cells.
42. ** Mechanism of action:
• Binds to the same cytolpasmic binding protein of
TAC ( KFBP) but not form complex with calcineurin
but form complex with mTOR ( mammalian
target of rapamycin)
• mTOR is kinase enzyme responsible for:
a- T-cell proliferation by promote transmission of
cells from G1 to S phase of cell cycle
b- DNA repair
c- Regulator in protein translation
binding of SRL to mTOR inhibits T-cell proliferation
43. N.B) CsA & TAC inhibits IL-2 production
while SRL inhibits IL-2 function
** Adverse effects:
• Hyperlipidemia
• Headache
• Leucopenia
• Thrombocytopenia
• Impaired wound healing
44. II- Immunosuppressive
antimetabolites :
Usually used in combination with corticosteroids &
calcineurin inhibitors CsA & TAC :
A- Azathioprine:
** mechanism of action:
Prodrug converted to 6-mercaptopurine (6-MP) then to
corresponding nucleotide, thioinosinic acid which interferes
with purines synthesis which are essential for proliferation
of lymphocytes.
** was widely used in organ transplantation.
** adverse effects:
- Bone marrow suppression - nausea & vomiting
** Captopril & cotrimoxazole exaggerate
leukopenic response while allopurinol inhibit
the metabolism of azathioprine .
45.
46. B- Mycophenolate mofetil ( MMF(:
- Replace azathioprine in organ transplantation because it is
more safe & more efficacious.
** Mechanism of action:
Potent reversible uncompetitive inhibitor of inosine
monophosphate dehydrogenase so blocking the de novo
formation of guanosine phosphate so deprive proliferating T-
& B-cells of a key precursor required for nucleic acid
synthesis.
** Adverse effects:
• diarrhea , nausea & vomiting
• abdominal pain, leucopenia & anemia
• higher risk of CMV infection
47.
48. C- Enteric coated
:mycophenolate sodium
In order to minimize gastrointestinal effects
associated with MMF so used delayed
release formulation of active drug
mycophenolic acid
49. ** Mono- and Poly-clonal Antibodies
Prepared by either immunization of rabbits
or horses with human lymphoid cells
(producing a mixture of polyclonal
antibodies directed against a number of
lymphocyte antigens) or by hybidroma
technology ( producing antigen-specific,
monoclonal antibodies)
50. N.B) Recombinant DNA technology can also
be used to replace part of the mouse gene
sequence with human genetic material thus
humanizing antibodies produced. Replace of
FC portion of animal antibodies by
human FC region not affect on antigen
specificity.
N.B) The name of monoclonal antibodies contain
muro if they are from murine (mouse) source
and xi or iz if they are humanized.
51.
52. A( Antithymocyte globulins
:((ATG
• Thymocytes are developed from thymus and
acts as precursors of T-cells.
• ATG prepared by immunization of large rabbits
or horses with human lymphoid cells so
considered polyclonal.
• Rabbit is usually preferred than horses as more
potent.
53. - The produced antibodies bind to surface of
circulating T-lymphocytes which then undergo
complement mediated destruction or
antibody-dependent cytotoxicity or
apoptosis.
- ATG used with immunosuppressive drugs at
time of transplantation to prevent early phase of
graft rejection.
Also used to treat severe rejection episodes in
corticosteroids-resistant cases.
N.B) Because humoral mechanism still active antibodies can be
formed against these foreign protein.
54. Monoclonal antibodies:
Monoclonal antibodies (mAb or moAb) are
monospecific antibodies that are the same
because they are made by identical immune
cells that are all clones of a unique parent
cell. This has become an important tool in
biochemistry, molecular biology and
medicine. When used as medications, the non-
proprietary drug name ends in –mab.
55. : Production
Hybridoma cell production:
Monoclonal antibodies are typically made by
fusing myeloma cells with the spleen cells
from a mouse that has been immunized with
the desired antigen. However, recent
advances have allowed the use of rabbit B-
cells. Polyethylene glycol is used to fuse
adjacent plasma membranes, but the success
rate is low so a selective medium in which
only fused cells can grow is used.
56. • This mixture of cells is then diluted and clones
are grown from single parent cells on microtitre
wells. The antibodies secreted by the different
clones are then assayed for their ability to bind
to the antigen (with a test such as ELISA or
Antigen Microarray Assay). The most
productive and stable clone is then selected for
future use.
• The hybridomas can be grown indefinitely in a
suitable cell culture media, or they can be
injected in mice (in the peritoneal cavity, the
gut), they produce tumors containing an
antibody-rich fluid called ascites fluid.
57.
58.
59.
60. Recombinant:
• Recombinant antibody engineering involves
the use of viruses or yeast to create
antibodies, rather than mice. These techniques
rely on rapid cloning of immunoglobulin
gene segments to create libraries of
antibodies with slightly different amino acid
sequences from which antibodies with desired
specificities can be selected
63. • Humanized monoclonal antibodies that
acts on the HER2neu (erbB2)
receptors.
• As inhibition of cell growth by
trastuzumab is limited to HER2-
positive cancers, testing tumors for
HER2 expression became integral to
selecting patients
• HER2 testing of breast cancer patients
becomes a routine
65. Uses:
Herceptin is used mainly to treat women with
breast cancer.
It may be used in the early stages to increase
the chances of a cure.
It also used in metastatic breast cancer.
In most cases it is used in combination with
chemotherapeutic agents paclitaxel or
docetaxel.
68. • Cetuximab attaches to the EGFRs and
prevents the receptors from being activated.
• This stops the cells from dividing. therefore
stop the cancer cells from growing.
• Cetuximab also make the cancer cells more
sensitive to chemotherapy and radiotherapy
• Tests may be done to find the level of EGFR
in the tumour cells before cetuximab is given.
69. IMMUNOSTIMULATIO
N
• In contrast to immunosuppressive agents that
inhibit the immune response, a few
immunostimulatory drugs have been
developed with applicability to infection,
immunodeficiency, and cancer.
• Problems with such drugs include systemic
(generalized) effects at one extreme or limited
efficacy at the other.
70. • Levamisole
It was synthesized originally as an anthelmintic
but appears to "restore" depressed immune
function of B-lymphocytes, T-lymphocytes,
monocytes, and macrophages.
Its only clinical indication is as adjuvant
therapy with 5-fluorouracil after surgical
resection in patients with stage C colon
cancer, where it occasionally has been
associated with fatal agranulocytosis.
71. •Thalidomide
Known for the severe, life-threatening birth
defects it caused when administered to
pregnant women. For this reason, it is
available only under a restricted distribution
program and can be prescribed only by
specially licensed physicians who understand
the risk of teratogenicity if thalidomide is
used during pregnancy. Thalidomide should
never be taken by women who are pregnant
or who could become pregnant while taking
the drug.
72. • It is indicated for the treatment of patients
with erythema nodosum leprosum and also
is used in conditions such as multiple
myeloma. Its mechanism of action is
unclear. Reported immunologic effects vary
substantially under different conditions. For
example, thalidomide has been reported to
decrease circulating TNF-α in patients with
erythema nodosum leprosum, severe
refractory rheumatoid arthritis.
73. • Bacillus Calmette-Guerin
(BCG(:
Live bacillus Calmette-Guerin is an attenuated,
live culture of the bacillus of Calmette and
Guerin strain of Mycobacterium bovis, that
induces a granulomatous reaction at the site
of administration. By unclear mechanisms,
this preparation is active against tumors and
is indicated for treatment and prophylaxis of
carcinoma in situ of the urinary bladder
Adverse effects include hypersensitivity,
shock, chills, fever, malaise, and immune
complex disease.
74. Recombinant Cytokines
Interferons: Although interferons (alpha,
beta, and gamma) initially were identified by
their antiviral activity, these agents also have
important immunomodulatory activities:
• Induction of certain enzymes.
• Inhibition of cell proliferation.
• Enhancement of immune activities, including
increased phagocytosis by macrophages and
augmentation of specific cytotoxicity by T
lymphocytes.
75. • Recombinant interferon
alfa-2b (IFN-alpha 2, INTRON A)
Produced and secreted by cells in response to
viral infections and other inducers. Interferon
alfa-2b is indicated in the treatment of a
variety of tumors, including hairy cell
leukemia, malignant melanoma, follicular
lymphoma, and AIDS-related Kaposi's
sarcoma.
It also is indicated for infectious diseases,
chronic hepatitis B & in combination with
ribavirin for treatment of chronic hepatitis
C.
76. • Side effects:
Flu-like symptoms, including fever, chills,
and headache, are the most common
adverse effects after administration.
Other adverse reactions involving the
cardiovascular system (hypotension,
arrhythmias, and rarely cardiomyopathy
and myocardial infarction) and CNS
(depression, confusion) are less-frequent
side effects.
77. • Interferon beta-1a (AVONEX, REBIF),
and interferon beta-1b (BETASERON),
have antiviral and immunomodulatory properties.
They are FDA approved for the treatment of
relapsing and relapsing-remitting multiple
sclerosis to reduce the frequency of clinical
exacerbations . The mechanism of their action in
multiple sclerosis is unclear.
• Flu-like symptoms (fever, chills, myalgia) and
injection-site reactions have been common adverse
effects.
78. **Tumor necrosis factor
(TNF α ( inhibitors :
• Infliximab:
A monoclonal antibody against tumor
necrosis factor alpha (TNFα).
Infliximab was approved by the U.S. Food
and Drug Administration (FDA) for the
treatment of psoriasis, Crohn's disease,
ankylosing spondylitis, psoriatic arthritis,
rheumatoid arthritis and ulcerative colitis.
80. Etanercept
Etanercept is a dimeric molecule, and this
dimeric structure is necessary for its
proper therapeutic activity.
To reduces the effect of naturally present
TNF, and hence is a TNF inhibitor,
functioning as a decoy receptor that
binds to TNF.
81.
82. Drug allergy **
(immunological reactions to
:(drugs
• Drug reactions mediated by immune
responses may have different mechanisms
thus any of the four major types of
hypersensitivity can be associated with
allergic drug reactions:
Type I:
• IgE-mediated acute allergic reactions to
stings, pollens, & drugs including
anaphylaxis, urticaria, angioedma. IgE is
fixed to tissue mast cell.
83. • Type II:
Drugs modify host proteins eliciting antibody
responses to modified protein. These allergic
response involve IgG& IgM in which the
antibody become fixed to a host cell which is
then subject to complement-dependent lysis
or to antibody-dependent cellular
cytotoxicity.
• Type-III:
Drugs may cause serum sickness which involves
immune complexes containing IgG & is
multisystem complement-dependent vascuilitis
that may result in urticaria.
84. • Type-IV:
Cell-mediated allergy is the
mechanism involved in allergic
contact dermatitis from topically
applied drugs or induration of the skin
at site of an antigen injected
intradermally.