Malignant tumors arise due to failures in cell regulation and social behavior that lead to uncontrolled proliferation and dissemination of mutated cells. Carcinogens like radiation and chemicals can cause proto-oncogene and anti-oncogene mutations involved in tumor suppression. The immune system normally eliminates tumor cells, but tumors evade immune responses through antigen variability, lack of costimulation, and inhibitory factors. Immunotherapy aims to stimulate anti-tumor immunity through monoclonal antibodies, cell therapies, vaccines, and cytokines. Transplantation success depends on donor-recipient HLA matching to avoid rejection mediated by antibodies and T cells recognizing non-self antigens. Graft-versus-host disease occurs when donor T cells attack recipient tissues, while the graft-
ROLE OF IMMUNE CELLS IN CANCER AND TARGETING IMMUNE CELLS FOR CANCER THERAPYSIVASWAROOP YARASI
Cancer immunotherapy is a therapy used to treat cancer patients that involves or uses components of the immune system. Some cancer immunotherapies consist of antibodies that bind to, and inhibit the function of, proteins expressed by cancer cells. Other cancer immunotherapies include vaccines and T cell infusions.
Tumor, Tumor immunology, cancer, hallmarks of cancer, carcinoma, lymphoma, metastasis, malignant, benign, angiogenesis, oncogenes and cancer induction, kuby detailed study quick revision, proto-oncogenes, tumor antigens, antibody, experiments for tumor antigens, methods for characterization of TSTA, Immunoediting, Current research n new approaches, monoclonal antibody
Types of immunotherapy
Oncology
cancer vaccines
adoptive T cell transfer
oncolytic viruses
monoclonal antibodies
cytokine
treatment of cancer with immunotherapy
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
ROLE OF IMMUNE CELLS IN CANCER AND TARGETING IMMUNE CELLS FOR CANCER THERAPYSIVASWAROOP YARASI
Cancer immunotherapy is a therapy used to treat cancer patients that involves or uses components of the immune system. Some cancer immunotherapies consist of antibodies that bind to, and inhibit the function of, proteins expressed by cancer cells. Other cancer immunotherapies include vaccines and T cell infusions.
Tumor, Tumor immunology, cancer, hallmarks of cancer, carcinoma, lymphoma, metastasis, malignant, benign, angiogenesis, oncogenes and cancer induction, kuby detailed study quick revision, proto-oncogenes, tumor antigens, antibody, experiments for tumor antigens, methods for characterization of TSTA, Immunoediting, Current research n new approaches, monoclonal antibody
Types of immunotherapy
Oncology
cancer vaccines
adoptive T cell transfer
oncolytic viruses
monoclonal antibodies
cytokine
treatment of cancer with immunotherapy
Dr. ihsan edan abdulkareem alsaimary
PROFESSOR IN MEDICAL MICROBIOLOGY AND MOLECULAR IMMUNOLOGY
ihsanalsaimary@gmail.com
mobile : 009647801410838
university of basrah - college of medicine - basrah -IRAQ
R3 Stem Cells and Kidney Repair A New Horizon in Nephrology.pptxR3 Stem Cell
R3 Stem Cells and Kidney Repair: A New Horizon in Nephrology" explores groundbreaking advancements in the use of R3 stem cells for kidney disease treatment. This insightful piece delves into the potential of these cells to regenerate damaged kidney tissue, offering new hope for patients and reshaping the future of nephrology.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
Empowering ACOs: Leveraging Quality Management Tools for MIPS and BeyondHealth Catalyst
Join us as we delve into the crucial realm of quality reporting for MSSP (Medicare Shared Savings Program) Accountable Care Organizations (ACOs).
In this session, we will explore how a robust quality management solution can empower your organization to meet regulatory requirements and improve processes for MIPS reporting and internal quality programs. Learn how our MeasureAble application enables compliance and fosters continuous improvement.
India Clinical Trials Market: Industry Size and Growth Trends [2030] Analyzed...Kumar Satyam
According to TechSci Research report, "India Clinical Trials Market- By Region, Competition, Forecast & Opportunities, 2030F," the India Clinical Trials Market was valued at USD 2.05 billion in 2024 and is projected to grow at a compound annual growth rate (CAGR) of 8.64% through 2030. The market is driven by a variety of factors, making India an attractive destination for pharmaceutical companies and researchers. India's vast and diverse patient population, cost-effective operational environment, and a large pool of skilled medical professionals contribute significantly to the market's growth. Additionally, increasing government support in streamlining regulations and the growing prevalence of lifestyle diseases further propel the clinical trials market.
Growing Prevalence of Lifestyle Diseases
The rising incidence of lifestyle diseases such as diabetes, cardiovascular diseases, and cancer is a major trend driving the clinical trials market in India. These conditions necessitate the development and testing of new treatment methods, creating a robust demand for clinical trials. The increasing burden of these diseases highlights the need for innovative therapies and underscores the importance of India as a key player in global clinical research.
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
CHAPTER 1 SEMESTER V PREVENTIVE-PEDIATRICS.pdfSachin Sharma
This content provides an overview of preventive pediatrics. It defines preventive pediatrics as preventing disease and promoting children's physical, mental, and social well-being to achieve positive health. It discusses antenatal, postnatal, and social preventive pediatrics. It also covers various child health programs like immunization, breastfeeding, ICDS, and the roles of organizations like WHO, UNICEF, and nurses in preventive pediatrics.
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
2. Malignant transformation
Failure of regulation of cell division and regulation
of "social" behavior of the cells
The uncontrollable proliferation, dissemination
to other tissues
Mutations in protoonkogenes and antionkogenes
3. Mutagens (carcinogens)
- physical (eg various forms of radiation)
- chemical (eg aromatic hydrocarbons)
- biological (mainly various oncogenic
viruses)
4. Protoonkogens
promitotic (promoting cell division)
for the malignant transformation is enough
mutation in one copy of the gene protoonkogen
(dominant oncogenes)
5. Antionkogens
tumor-suppressor genes
regulation of cell cycle
for the malignant transformation should be excluded from
function both copies of the gene (recessive oncogenes)
TP53, RB1
6. Anti-tumor immune mechanisms
Hypothesis of immune control
tumor cells normally arise in tissues and are eliminated
by T lymphocytes (probably wrong hypothesis)
Defensive immune response
tumor cells are weakly immunogenic
occurs when tumor antigens are presented to T lymphocytes
by activated dendritic cells
in defense may be involved: non-specific mechanisms
(neutrophilic granulocytes, macrophages, NK cells, interferons)
and antigen-specific mechanisms (complement activating antibodies
or ADCC, TH1 and TC)
7. cancer-associated antigens are processed by APC and
recognized by T lymphocytes in complex with HLA I. and II. class
with providing costimulus signals
predominance of TH1 (IFN TNF)
specific cell-mediated cytotoxic reactivity – TC
activation TH2 → support B lymphocytes→ tumor specific
antibodies (involved in the ADCC)
tumor cells are destroyed by cytotoxic NK cells (low MHC gpI
expression on tumor cells)
interferons - antiproliferative, cytotoxic effect on tumor cells
- INFγ - DC maturation
9. Tumor antigens
Antigens specific for tumors (TSA)
a) complexes of MHCgp I with abnormal fragments of cellular proteins
- chemically induced tumors
- leukemia with chromosomal translocation
b) complexes of MHC gp with fragments of proteins of oncogenic viruses
- tumors caused by viruses (EBV, SV40, polyomavirus)
c) abnormal forms of glycoproteins
- Sialylation of surface proteins of tumor cells
d) idiotypes of myeloma and lymphoma
- clonotyping TCR and BCR
10. Antigens associated with tumors (TAA)
- also on normal cells
- differences in quantity, time and local expression
- auxiliary diagnostic markers
a) onkofetal antigens
- on normal embryonic cells and some tumor cells
- -fetoprotein (AFP) - hepatom
- canceroembryonal antigen (CEA) - colon cancer
b) melanoma antigens
- MAGE-1, Melan-A
11. c) antigen HER2/neu
- receptor for epithelial growth factor
- mammary carcinoma
d) EPCAM
- epithelial adhesion molecule
- metastases
e) differentiation antigens of leukemic cells
- present on normal cells of leukocytes linage
- CALLA -acute lymphoblastic leukemia (CD10 pre-B cells)
12. Mechanisms of tumors resistance to immune
system
high variability of tumor cells
low expression of tumor antigens
sialylation
tumor cells do not provide costimulus signals → T lymphocyte
anergy
some anticancer substances have a stimulating effect
production of factors inactivating T lymphocytes
expression of FasL → T lymphocyte apoptosis
inhibition of the function or durability dendritic cells (NO, IL-10, TGF-
13. Tumor immunotherapy
Therapy - surgical removal of tumor
- chemotherapy or radiotherapy
- immunotherapy
Immunotherapy - induction of anti-tumor immunity, or the use
of immune mechanisms to targeting drugs
to the tumor site
15. 1) Monoclonal antibodies
- against TAA
- mouse and humanised antibodies
- imunotoxins, radioimunotoxins
- the possibility of damage surrounding tissues
- HERCEPIN - Ab against HER2/neu, breast cancer
- RITUXIMAB - Ab against CD20, lymphoma
2) Bispecific antibodies
- bind a tumor antigen and the T lymphocyte or NK cell
- Fc fragment of antibody binds to Fc receptors on phagocytes
and NK cells
3) Elimination of tumor cells from the suspension of bone
marrow cells
using monoclonal antibodies for autologous transplantation
16. Immunotherapy using cell-mediated
mechanisms
1) stimulation of inflammation at the tumor site
2) stimulation of LAK and TIL
- isolation of T and NK cells, stimulation by cytokines, and return
to the patient
- LAK (lymphokine activated killers)
- TIL (tumor infiltrating lymphocytes)
3) improving of tumor cells antigenpresenting function
- genetic modification of tumor cells - expression of CD80, CD86
- production of IL-2, GM-CSF
- modified cells are irradiated and returned to the patient
17. 4) tumor vaccines
- in vitro stimulation of TH1 cells and TC with tumor antigens
5) the dendritic cell immunotherapy
- in vitro cultivation of monocytes in an appropriate cytokine
environment (GM-CSF, IL-4) → transformation into dendritic cells
- cultivation of dendritic cells with tumor antigens
6) immunotherapy by donor T lymphocytes
- after allogeneic transplantation
- causing graft-versus-host disease
7) immunotherapy by immune system products
- IL-2 - renal cell carcinoma
- IFN - hematoonkology
19. Transplantation
= transfer of tissue or organ
● autologous - donor = recipient
● syngeneic - genetically identical donor recipient (identical
twins)
● allogeneic - genetically nonidentical donor of the same
species
● xenogenic - the donor of another species
● implant - artificial tissue compensation
20. Allogeneic
- differences in donor-recipient MHC gp and secondary histocompatibility Ag
- alloreactivity of T lymphocytes - the risk of rejection and graft-versus-host
- direct detection of alloantigens – recipient T lymphocytes recognize the
different MHC gp and non-MHC molecules on donor cells
- indirect recognition of alloantigens - APC absorb different MHC gp from
donor cells and present the fragments to T lymphocytes
- CD8+ T cells recognize MHC gp I.
- CD4+ T cells recognize MHC gp II.
21. Testing before transplantation
Compatibility in the system ABO -risk of hyperacute or accelerated
rejection = formation of Ab against A or B Ag on graft vascular
endothelium)
HLA typing (determining of MHC gp alelic forms) phenotyping and
genotyping by PCR
Cross-match - lymfocytotoxic test - testing preformed Ab
(after blood transfusions, transplantation, repeated childbirth)
Mixed lymphocyte test - testing of alloreactivity T lymphocytes
monitor for reactivity of lymphocytes to allogeneic HLA
22. HLA typing
a) phenotyping: Evaluation of HLA molecules using typing
serums
Typing antiserums = alloantiserums of multipar (created cytotoxic
Ab against paternal HLA Ag of their children), serum of patients
after repeated blood transfusions, monoclonal Ab
- molecules HLA class I: separated T lymphocytes
- molecules HLA class II: separated B lymphocytes
b) genotyping: evaluation of specific alleles
DNA typing of HLA class II: DR, DP, DQ by PCR.
23. Cross-match test
● determination of preformed antibodies
● recipient serum + donor lymphocytes + rabbit complement
→ if cytotoxic Ab against donor HLA Ag are present
in recipient serum (called alloantibodies = Ab activating
complement) → lysis of donor lymphocytes. Visualization of
dye penetration into lysis cells.
● positive test = the presence of preformed Ab → risk of
hyperacute rejection! → contraindication to transplantation
24. Mixed lymphocyte reaction (MRL)
● determination of alloreactivity T lymphocytes
● mixed donor and recipient lymphocytes → T lymphocytes
after recognition allogeneic MHC gp activate and proliferate
One-way MRL
● determination of recipient T lymphocytes reactivity against
donor cells
● donor cells treated with chemotherapy or irradiated lose
the ability of proliferation
25. Rejection
Factors:
The genetic difference between donor and recipient, especially in
the genes coding for MHC gp (HLA)
Type of tissue / organ - the strongest reactions against vascularized
tissues containing much APC (skin)
The activity of the immune system of the recipient - the
immunodeficiency recipient has a smaller rejection reaction;
immunosuppressive therapy after transplantation – suppression of
rejection
Status transplanted organ - the length of ischemia, the method of
preservation, traumatization of organ at collection
26. Hyperacute rejection
● minutes to hours after transplantation
● antibodies type of immune response
mechanism:
● in recipients blood are present before transplantation
preformed or natural Ab (IgM anti-carbohydrate Ag)
→ Ab + Ag of graft (MHC gp or endothelial Ag) → graft
damage by activated complement (lysis of cells)
● the graft endothelium: activation of coagulation factors
and platelets, formation thrombi, accumulation of neutrophil
granulocytes
prevention:
● negat. cross match before transplantation, ABO
compatibility
27. Accelerated rejection
● 3 to 5 days after transplantation
● caused by antibodies that don´t activate complement
● cytotoxic and inflammatory responses activated
by antibodies binding to Fc-receptors on phagocytes and
NK cells
prevention:
● negative cross match before transplantation, ABO
compatibility
28. Acute rejection
● days to weeks after the transplantation or after a lack
of immunosuppressive treatment
● cell-mediated immune response
mechanism:
● recipient TH1 and TC cells response against Ag of graft tissue
● infiltration of lymphocytes, mononuclears, granulocytes
around small vessels → destruction of transplant tissue
29. Chronic rejection
● from 2 months after transplantation
● the most common cause of graft failure
mechanism is not fully understood:
● non-immunological factors (tissue ischemia) and TH2
responses with production alloantibodies, pathogenetic role
of cytokines and growth factors (TGF β)
● replacement of functional tissue by connective tissue,
endothelial damage →impaired perfusion of graft → gradual
loss of its function
dominating findings: vascular damage
30. Graft-versus-host disease (GVHD)
● after bone marrow transplantation
● GVHD also after blood transfusion to immunodeficiency
recipients
● T-lymphocytes in the graft bone marrow recognize recipient
tissue Ag as foreign (alloreactivity)
Acute GVHD
● days to weeks after the transplantation of stem cells
● damage of liver, skin and intestinal mucosa
● Prevention: appropriate donor selection, T lymphocytes removal
from the graft and effective immunosuppression
31. Chronic GVHD
● months to years after transplantation
● TH2 lymphocytes infiltration of tissues and organs, production
of alloantibodies and production of cytokines → fibrotization
● process like autoimmune disease: vasculitis, scleroderma,
sicca-syndrome
● chronic inflammation of blood vessels, skin, internal organs
and glands, which leads to fibrotization, blood circulation
disorders and loss of function
32. Graft versus leukemia effect (GVL)
● donor T lymphocytes react against residual
leukemick cells of recipient
● mechanism is consistent with acute GVHD
● associated with a certain degree of GVHD (adverse
reactions)
33. Immunologic relationship of mother and
allogenic fetus
● fetal cells have on the surface alloantigens inherited from his father
Tolerance of fetus by mother allow the following mechanisms:
● the relative isolation of the fetus from maternal immune system
(no mixing of blood circulation)
● trophoblast - immune barrier witch protect against mother
alloreaktive T lymphocytes
- don‘t express classical MHC gp, expresses
non-classical HLA-E and HLA-G
● depression of TH1 immune mechanisms in pregnancy
Complications in pregnancy: production of anti-RhD antibodies by
RhD- mother carrying RhD+ fetus (hemolytic disease of newborns)
35. Classification by Coombs and Gell
Immunopathological reactions: immune response, which caused
damage to the body (secondary consequence of defense
responses against pathogens, inappropriate responses to harmless
antigens, autoimmunity)
IV types of immunopathological reactions:
Type I reaction - response based on IgE antibodies
Type II reaction - response based on IgG and IgM antibodies
Type III reaction - response based on the formation of immune
complexes
Type IV reaction - cell-mediated response
36. Immunopathological reaction based
on IgG and IgM antibodies (reaction type II)
Cytotoxic antibodies IgG and IgM:
● complement activation
● ADCC
● binding to phagocytes and NK cells Fc receptors
Haemolytic reactions after transfusion of ABO incompatible blood:
Binding of antibodies to antigens of erythrocytes → activation
of the classical way of complement → cell lysis
Hemolytic disease of newborns:
Caused by antibodies against RhD antigen
37. Autoimmune diseases:
● organ-specific cytotoxic antibodies (antibodies against
erythrocytes, neutrophils, thrombocytes, glomerular basement
membrane ...)
● blocking or stimulating antibodies
Graves - Basedow disease - stimulating antibodies against the
TSH receptor
Myasthenia gravis - blocking of acetylcholin receptor→ blocking
of neuromuscular transmission
Pernicious anemia - blocking of vitamin B12 absorption
Antiphospholipid syndrome - antibodies against fosfolipids
Fertility disorders - antibodies against sperms or oocytes
38. Immunopathological reactions based on immune
complex formation (reaction type III)
● caused by IgG antibodies → bind to antigen → creation
of immunecomplexes
● immunocomplexes - bind to Fc receptors on phagocytes
- activate complement
● immune complexes (depending on the quantity and structure)
are eliminated by phagocytes or stored in tissues
● pathological immunocomplexes response arises when is a large
dose of antigen, or antigen in the body remains
● immune complexes are deposited in the kidneys (glomerulonephritis),
on the endothelial cells surface (vasculitis) and in synovial joints
(arthritis)
39. Serum sickness
● after therapeutic application of xenogeneic serum
(antiserum to snake venom)
● creation of immune complexes and their storage
in the vessel walls of different organs
● clinical manifestations: urticaria, arthralgia, myalgia
Systemic lupus erythematosus
● antibodies against nuclear antigens, ANA, anti-dsDNA
Farmer's lung
● IgG antibodies against inhaled antigens (molds, pollens)
Poststreptococcal glomerulonephritis
40. Immunopathological delayed-type reaction
(reaction type IV)
● delayed-type hypersensitivity (DTH)
● local reaction caused by TH1 cells and monocytes / macrophages
Experimental model (testing of cellular immunity):
● intradermal immunization by antigen → creation of antigen-
specificTH1 cells
● after a few weeks intradermal administration of antigen → creates
local reaction (granuloma) - TH1 cells and macrophages
Tuberculin reaction
Tissue damage in tuberculosis and leprosy
Sarcoidosis