IMMUNE RESPONSE TO TUMORS-Humoral immunity
-Cellular Immunity- Failure of Host Defenses
- Evasion of Immune Responses by Tumors
- Cancer Immunosurveillance vs Immunoediting- Immunotherapy
Secondary Immunodeficiency
By Dr. Usama Ragab Youssif
Reference: Included in Slides
Include causes of secondary immunodeficiency including AIDS and other viral infections
IMMUNE RESPONSE TO TUMORS-Humoral immunity
-Cellular Immunity- Failure of Host Defenses
- Evasion of Immune Responses by Tumors
- Cancer Immunosurveillance vs Immunoediting- Immunotherapy
Secondary Immunodeficiency
By Dr. Usama Ragab Youssif
Reference: Included in Slides
Include causes of secondary immunodeficiency including AIDS and other viral infections
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
Immunological Basis of Graft Rejection
Transplantation in immunology, refers to the act of transferring cells, tissues, or organs from one site to another.
A healthy organ, tissue, cells which is provided by a donor is termed as a GRAFT.
The immune system has evolved elaborate and effective mechanisms to protect the organism from attack by foreign agents, and these same mechanisms cause rejection of grafts from anyone who is not genetically identical to the recipient.
The complement system is a part of the immune system that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the innate immune system, which is not adaptable and does not change over the course of an individual's lifetime.
consists of three pathways: 1. alternative
2. classical
3. lectin pathway
Immunological Basis of Graft Rejection
Transplantation in immunology, refers to the act of transferring cells, tissues, or organs from one site to another.
A healthy organ, tissue, cells which is provided by a donor is termed as a GRAFT.
The immune system has evolved elaborate and effective mechanisms to protect the organism from attack by foreign agents, and these same mechanisms cause rejection of grafts from anyone who is not genetically identical to the recipient.
Primary Immunodeficiencies
SEVERE COMBINED IMMUNODEFICIENCY (SCID)
Different causes for SCID
WISKOTT-ALDRICH SYNDROME (WAS)
INTERFERON-GAMMA–RECEPTOR DEFECT
X-LINKED AGAMMAGLOBULINEMIA
X-LINKED HYPER-IgM SYNDROME
COMMON VARIABLE IMMUNODEFICIENCY (CVI)
HYPER-IgE SYNDROME (JOB SYNDROME)
ATAXIA TELANGIECTASIA
Immune Disorders Involving The Thymus
Immunodeficiencies Of The Myeloid Lineage Affect Innate Immunity
Complement Defects Result in Immunodeficiency or Immune-Complex Disease
AIDS and Other Acquired or Secondary Immunodeficiencies
This presentation is an overview of primary and secondary immunodeficiency disorders with highlights on the genetic basis of primary disorders and associated factors underlying secondary disorders, as well a management of these disorders
Immunodeficiency is a state in which the body is incapable of of protecting it from foreign pathogens. It is classified into two categories primary - which can be inherited and secondary - which is caused due to life style factors, drugs, nutrition. Treatments include - antibiotics- to suppress the symptoms , stem transplantation- done to introduce the deficient immune cells. There are many diseases associated with immunodeficiency.
BREEDING METHODS FOR DISEASE RESISTANCE.pptxRASHMI M G
Plant breeding for disease resistance is a strategy to reduce crop losses caused by disease. Plants have an innate immune system that allows them to recognize pathogens and provide resistance. However, breeding for long-lasting resistance often involves combining multiple resistance genes
hematic appreciation test is a psychological assessment tool used to measure an individual's appreciation and understanding of specific themes or topics. This test helps to evaluate an individual's ability to connect different ideas and concepts within a given theme, as well as their overall comprehension and interpretation skills. The results of the test can provide valuable insights into an individual's cognitive abilities, creativity, and critical thinking skills
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
ANAMOLOUS SECONDARY GROWTH IN DICOT ROOTS.pptxRASHMI M G
Abnormal or anomalous secondary growth in plants. It defines secondary growth as an increase in plant girth due to vascular cambium or cork cambium. Anomalous secondary growth does not follow the normal pattern of a single vascular cambium producing xylem internally and phloem externally.
2. Immunodeficiency
1. What is immunodeficiency ?
2. What are the types immunodeficiency ?
3. What is importance of studying immunodeficiency ?
3. Immunodeficiency
• Immunodeficiency is a condition caused by one or more
immune system defects and is characterized clinically by
increased susceptibility to infections with consequent severe,
acute, recurrent or chronic disease.
• Immunodeficiencies may be either primary or secondary
• Understanding the immunodeficiency, various diseases caused
it can be cured or managed
4. Primary Immunodeficiency
• Genetic or developmental defects of the immune system
impair host defence and lead to an increased susceptibility
to recurrent, severe or unusual infections
• Primary immune deficiency diseases (PIDD), an umbrella
term referring to more than 130 genetic defects involving
the immune system, affect as many as 10 million people
worldwide.
• Affect either adaptive or innate immune function
7. Lymphoid Immunodeficiency
• Involve either B orT cell or both
List of diseases due to Lymphoid Immunodeficiency
1. Severe combined immunodeficiency (SCID)
2. Wiskott-Aldrich syndrome (WAS)
3. Interferon gamma receptor defect
4. X- linked agammaglobulinemia
5. X-linked hyper-IgM syndrome
6. Common variable Immunodeficiency (CVI)
7. Hyper-IgE syndrome (Job syndrome)
8. Selective deficiency of immunoglobulin classes
9. Ataxia telagiectasia
10. Immune disorders involving the thymus
8. 1. Severe combined immunodeficiency (SCID)
• It involve defectT cells alone or in combination with B or NK cells
• Defect inTCR rearrangement
• Patients with SCID are susceptible to a variety of bacterial, viral,
mycotic and protozoan infections
• The x-linked SCID is due to a defect in gamma-chain of IL-2 also
shared by IL-4, -7, -11 and 15, all involved in lymphocyte proliferation
and/or differentiation
• Deficiency in kinase JAK 3
• Defect in Adenosine deaminase (ADA) or purine nucleoside
phosphorylase (PNP)
• Defect in Recombinase activating gene (RAG-1 and RAG-2)
• Defect in Artemis gene (DNA repair and recombination enzyme)
11. •Associated with normalT cell numbers with reduced
functions, which get progressively worse.
•IgM concentrations are reduced but IgG levels are normal
•Both IgA and IgE levels are elevated.
•Boys with this syndrome develop severe eczema.
•They respond poorly to polysaccharide antigens and are
prone to pyogenic infection
•Involve thrombocytopenia
•Defect in Sailophorin, cytoskeleton glycoprotein that
help assembly of actin filameent during microvesicles
formation
2. Wiskott-Aldrich syndrome:
12. 3. Interferon gamma receptor defect
• Defect in receptor for interferon gamma
• Infection with Mycobacteria
• Defect in NF kappa b
• Defect in IKK protein subunit designated NEMO,
help releasing NF kappa b from inhibitor
13. 4. X-linked a gammaglobulinaemia/
Bruton’s hypogammaglobulinemia
• In X-LA early maturation of B cells fails
• Affect males
• Few or no B cells in blood
•Very small lymph nodes and tonsils
• No Ig
• Small amount of Ig G in early age
• Recurrent pyogenic infection
• B cell not capable of signal transduction
• Defect in transduction molecule Bruton’s tyrosine kinase
14. Immunodeficencienies of the Myeloid lineage
• Affect innate immunity
• Impaired phagocytic process
List of diseases due to Myeloid Immunodeficiency
1. Reduction in neutrophil count
2. Chronic granulomatous disease
3. Chedaik Higashi syndrome
4. Leukocyte adhesion deficiency
15. 1. Reduction in neutrophil count
• Deficiency in the neutrophil count
• Congenital or acquired neutropenia
• Decrease in G-CSF affect differentiation of myeloid stem
cell to granulocyte
• Neutropenia due to bacterial or viral infection
16. 2. Chronic granulomatous disease (CGD)
• Either in X- linked form (70%) or autosomal recessive form
• Defect in the oxidative pathway by which phagocyte generate H2O2 and
resulting reactive product hypochlorus acid
• Extensive inflammatory reaction, gingivitis, swellon lymph node and non
malignant granulomas
• Myloperoxidase
• Missing or defective cytochrome (cyt b558) or phagosome oxidase which
stabilize cytochrome
• Decreased ability of the monocyte as APC
• Interferon gamma restore the function
19. 3. Chedaik Higashi syndrome
• Autosomal recesive disease
• Partial oculo-cutaneous albinism
• Phagocyte contain gaint granules unable to kill bacteria
• Protein (LYST) mutation involved in intracellular trafficking that impair
targeting of the protein to lysosome
20. 4. Leukocyte adhesion deficiency
• Beta common chain of the adhesion molecule is altered (LFA-1, Mac-1
and gp150/95
• Susceptibility to gram negative as well as gram positive bacteria
21. Compliment defect results immunodeficiency or
Immune complex disease
• Increase rate of bacterial infection
• Deficiency in properdin (stabilize c3 convertase of alternative pathway) due to
gene defect located on X chromosome
• Defect in mannose binding lectin
22. Immunodeficiency disorder treatment by replacing
the defective element
• Replacement of a missing protein
• Replacement of missing cell type or lineage
• Replacement of missing or defective gene
Although there are no cures for immunodeficiency disorders, there are various
treatment possibilities. In addition to complete isolation from exposure to any
microbial agent, treatment options for the immunodeficiencies include:
23. Experimental Model of Immunodeficiency Include
Genetically Altered Animal
• To study primary immunodeficiency
• Two animal models
• Nude mouse
• SCID mouse
• Gene knocked out technology to study precise role of specific gene
24. Nude (Athymic) Mice
• nu/nu homozygous mouse
• Genetic trait nu controlled by recessive gene on chromosome 11
• nu/nu homozygous are hairless and have defective thymus
• Require complete sterile condition for survival
• Lack of cell mediated immune response
• Except allo as well as xenograft
• T cell show γδ receptor instead
of αβ receptor
25. SCID mouse
• Autosomal recessive mutation lead to deficiency in
mature lymphocytes
• T & B precursor cells fail to differentiate into mature cells
• No antibody, delay type hypersensitivity reaction and
graft rejection
• Leaky mutation (some SCID mice produce Ig) developed
by mutation in DNA protein kinase
• RAG-1 & 2 mutation produce SCID mice
• SCID mice to study cellular immunology
• Also used to study cell & organs from various sources
26. Secondary Immunodeficiency
Secondary (acquired) immunodeficiency is the loss of
immune function that results from exposure to various
agents. The most common example is AIDS or acquired
immunodeficiency syndrome, which results from infection
with the HIV-1. or human immunodeficiency virus 1.
27. • Loss of immune function that results from exposure to various
agents.
• Acquired Hypogammaglobulinemia
Recurrent infection that manifests itself in young adults. There are
usually very low levels of total immunoglobulin, thoughT-cell
numbers and function may be normal. It is treated with
gammaglobulin therapy.
• Agent-Induced Immunodeficiency
Results from exposure to any of a number of chemical and
biological agents that induce an immunodeficient state.
• AIDS: Acquired Immunodeficiency Syndrome
28. HIV/AIDS
• AIDS was first reported in the United States in 1981 in Los
Angeles, NewYork, and San Francisco.
•The first patients displayed unusual infections by opportunistic
agents, such as Pneumocystis carinii, which causes PCP or P. carinii
pneumonia, as well as other rare opportunistic infections.
• Opportunistic agents are microorganisms that healthy
individuals can harbor with no ill consequences but that cause
disease in those with impaired immune function.
• They also displayed Kaposi’s sarcoma—an extremely rare skin
tumor.
32. HIV 1 (Retrovirus)
• Causative agent of AIDS was found to be HIV 1 virus
• Discovered by Luc Montagnier in Paris and Robert Gallo in
Bethesda
• HIV-1 not similar to HTLV-I
37. • Requirement of co receptors (CXCR4 & CCR5)
• cDNA from viral RNA using reverse transcriptase
• Provirus production lead to many viruses
• T-trophic and M-trophic strains
• Giant cells or syncytia formation
• Syncytia Inducing (SI) strain are corelated toT-trophic
strain
• Non Syncytia Inducing (NSI) strain are corelated to M-
trophic strain
• Choice of receptor related toV3 loop of gp120 protein
38. Opportunistic Infection in HIV-1
• Detection of HIV-1 infection
• Antibody detection against virus protein
• CD4+ cell decreased
• Impaired or absence of delayed type of hypersensitivity
•Opportunistic infection
Tuberculosis, pneumonia, severe wasting diarrhea or
various malignancies
• Primary infection
• Chronic phase
40. Therapeutic agent inhibit retrovirus infection
• Vaccine development is target
• Drug development is critical
• Drug development by targeting susceptible point of virus life
cycle
• First drug against reverse transcriptase
• Second against protease inhibitor
• Third was fusion inhibitor prevent virus entry
42. Reverse transcriptase inhibitor
• Zidovudine or AZT (azidothymidine)
• AZT is nucleaoside analogue causes chain termination
• Can’t be used for long term ad develop resistance
• Interfere with human DNA polymarese
• RBCs are sensitive to AZT lead to anemia
43. • Protease inhibitor used in conjugation with AZT
• HAART (highly active anti-retroviral therapy)
• Overcome susceptibility by mutation
• HAART also not effective as latent infection
• Fusion inhibitor eg. Enfuvirtide
• Other class of drug include integrase inhibitor
• Take long time for drug development
44. HIV/AIDS vaccine
• Need of vaccine as no effective treatment and to prevent
spread of the infection
• Most effective vaccine mimic the natural state of infection
• Most vaccine prevent disease not infection
• Most vaccine prevent infection by virus that show little variability
• The majority of successful vaccine are live attenuated or heat
killed organism
• For most viruses, frequency of exposure to infection is rare or
seasonal
• Most vaccine protect against respiratory or gastrointestinal
infection
• Development of most vaccines through to clinical trails relies
on animal experiment