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Immunology and Molecular Genetics Slides.pptx
- 1. Immunology and Molecular Genetics Foundationsfor Pharmacogenomics and Genetic Basis of Disease Prepared by: Eliza Shahid Institution: PharmaPro Gulf
- 2. Learning Objectives •Understand thedistinction between innate and adaptive immunity •Explain the structure and principles of antibody actions •Describe the types of hypersensitivity reactions •Explore the roles of molecular genetics, genomics, proteomics, and metabolomics •Connect these biological concepts to pharmacogenomics and personalized medicine
- 3. Importance of Immunology& Genomics in Medicine •Provides understanding of host defense mechanisms •Foundation for vaccine development and immunotherapy •Explains immune system dysfunctions (autoimmunity, hypersensitivity) •Genomic studies reveal the genetic basis of diseases •Enables personalized medicine through pharmacogenomics •Bridges basic biology and clinical practice
- 4. Overview of theImmune System Two main branches: •Innate Immunity → First line, non-specific, immediate •Adaptive Immunity → Specific, long- lasting, memory-based Key functions: •Recognition of self vs non-self •Elimination of pathogens •Development of immune memory Clinical significance: Immunodeficiency, hypersensitivity, autoimmunity
- 6. Innate Immunity: GeneralFeatures •Non-specific defense present at birth •Provides immediate but short-lived protection •Physical barriers: skin, mucous membranes •Chemical barriers: lysozyme, gastric acid, antimicrobial peptides •Cellular components: neutrophils, macrophages, dendritic cells, NK cells •Soluble mediators: complement proteins, cytokines, interferons •First responder against infections before adaptive immunity is activated
- 7. Innate Immunity: CellularComponents Phagocytes: •Neutrophils – rapid response, engulf bacteria •Macrophages – long-lived, antigen presentation •Dendritic cells: bridge between innate and adaptive immunity •Natural Killer (NK) cells: kill virus-infected and tumor cells •Basophils & mast cells: release histamine, mediate inflammation •Eosinophils: defense against parasites, role in allergies
- 8. Innate Immunity: SolubleFactors Complement system •Classical, alternative, lectin pathways •Functions: opsonization, cell lysis, inflammation Cytokines •Interleukins, interferons, TNF •Mediate communication between immune cells Acute-phase proteins •C-reactive protein (CRP), mannose-binding lectin •Enhance pathogen clearance
- 9. Adaptive Immunity: GeneralFeatures Specific response to a particular antigen •Slower onset, but highly effective •Memory cells provide long-lasting protection Divided into: •Humoral immunity – mediated by B cells and antibodies •Cell-mediated immunity – mediated by T cells Requires antigen presentation and activation
- 10. Adaptive Immunity: HumoralResponse •B lymphocytes → differentiate into plasma cells •Antibodies produced: IgM (early), IgG (long-term), IgA, IgE, IgD •Functions: •Neutralization of toxins and microbes •Opsonization for phagocytosis •Activation of complement pathway •Essential for protection against extracellular pathogens
- 11. Adaptive Immunity: CellularResponse T lymphocytes: •Helper T cells (CD4+) – coordinate immune response, activate B cells & macrophages •Cytotoxic T cells (CD8+) – destroy infected or cancerous cells •Regulatory T cells (Tregs) – maintain immune tolerance, prevent autoimmunity •Critical for fighting intracellular infections (e.g., viruses) •Provides long-term immune surveillance against tumors
- 12. Antigen Presentation • Antigen-PresentingCells (APCs): dendritic cells, macrophages, B cells • Major Histocompatibility Complex (MHC): • MHC I: presents endogenous antigens to CD8+ T cells • MHC II: presents exogenous antigens to CD4+ T cells • Antigen presentation is essential for T-cell activation • Links innate and adaptive immunity
- 13. Clonal Selection Theory •Proposedmechanism of adaptive immune response •Antigen selects specific lymphocyte clones with complementary receptors •Activated clones undergo: •Clonal expansion – rapid proliferation •Differentiation – effector cells & memory cells •Explains specificity and memory of immune system
- 14. Innate vs AdaptiveImmunity: Key Differences Innate Immunity •Immediate, non-specific •No memory •Barriers, phagocytes, NK cells, complement Adaptive Immunity •Delayed, highly specific •Memory formation •B cells → antibodies, T cells → cellular response •Work together for complete immune defense
- 15. Integration of Innate& Adaptive Immunity Innate immunity initiates adaptive responses •Dendritic cells present antigens to T cells •Cytokines guide lymphocyte differentiation •Antibodies enhance innate mechanisms (opsonization, complement activation) •Continuous feedback loop between both systems
- 16. Clinical Relevance ofImmune Responses •Vaccines: rely on adaptive memory response •Infections: innate immunity controls spread until adaptive response develops •Cancer immunotherapy: harnesses T cells and antibodies •Immune disorders: •Immunodeficiency (e.g., HIV, SCID) •Hypersensitivity & autoimmunity •Understanding immunity guides diagnosis, prevention, and treatment
- 17. Introduction to Antibodies •Alsocalled immunoglobulins (Ig) •Produced by plasma cells (activated B cells) •Structure: •Fab region: antigen binding •Fc region: effector functions •Classes: IgG, IgA, IgM, IgE, IgD
- 19. Functions of Antibodies(Overview) • Neutralization of toxins and pathogens • Opsonization to promote phagocytosis • Activation of complement cascade • Antibody-dependent cellular cytotoxicity (ADCC) • Regulation of immune responses
- 20. Neutralization •Antibodies block bindingsites on viruses or bacterial toxins •Prevent pathogen entry into host cells •Example: Neutralizing antibodies in polio and COVID-19 vaccines •Key role of IgG and IgA
- 21. Opsonization •Antibodies coat pathogens→ enhance recognition by phagocytes •Fc region binds to Fc receptors on macrophages and neutrophils •Leads to efficient phagocytosis •Example: clearance of encapsulated bacteria
- 23. Complement Activation •Antigen–antibody complexestrigger classical complement pathway •Outcomes: •Opsonization (C3b) •Inflammation (C3a, C5a) •Membrane attack complex (MAC) → pathogen lysis •Mostly mediated by IgM and IgG
- 24. Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) •Antibodies bind antigens on target cell surface • NK cells recognize Fc region via FcγR • NK cells release perforin and granzymes → target cell death • Important in defense against virus-infected and tumor cells
- 25. Diagnostic & TherapeuticApplications of Antibodies •Diagnostic uses: ELISA, Western blot, immunofluorescence •Therapeutic uses: •Monoclonal antibodies (mAbs) in cancer and autoimmune disease •Anti-TNF agents for rheumatoid arthritis •Antibodies for passive immunization (rabies, hepatitis B)
- 26. Clinical Example ofAntibody Therapy • Rituximab: monoclonal antibody against CD20 on B cells • Used in non-Hodgkin’s lymphoma & autoimmune disorders • Trastuzumab (Herceptin): targets HER2 in breast cancer • Demonstrates antibody action via ADCC and complement activation • Highlights role of antibodies in precision medicine
- 27. Hypersensitivity: Definition &Overview •Exaggerated or inappropriate immune response causing tissue damage •Occurs on second or repeated exposure to antigen •Mediated by antibodies, immune complexes, or T cells •Classified into four main types (I–IV) •Clinical relevance: allergy, autoimmunity, transplant rejection
- 28. Type I Hypersensitivity (Immediate/Allergic) Mediatedby IgE antibodies •First exposure → IgE binds to mast cells & basophils •Re-exposure → cross-linking of IgE → release of histamine, leukotrienes •Clinical examples: •Allergic rhinitis (hay fever) •Asthma •Anaphylaxis (life-threatening)
- 29. Type II Hypersensitivity(Cytotoxic) IgG or IgM antibodies bind to antigens on host cell surface •Complement activation or ADCC leads to cell destruction •Examples: •Hemolytic anemia •Goodpasture’s syndrome •Blood transfusion reaction
- 30. Type III Hypersensitivity(Immune Complex-Mediated) • Antigen–antibody complexes deposit in tissues → inflammation • Complement activation and neutrophil recruitment cause damage • Examples: • Systemic lupus erythematosus (SLE) • Rheumatoid arthritis • Serum sickness • Post-streptococcal glomerulonephritis
- 31. Type IV Hypersensitivity(Delayed-Type, T-cell Mediated) •Mediated by T lymphocytes (not antibodies) •Sensitized T cells release cytokines → macrophage activation → inflammation •Takes 24–72 hours to appear •Examples: •Contact dermatitis (nickel, poison ivy) •Tuberculin skin test (Mantoux test) •Chronic transplant rejection
- 32. Summary Table ofHypersensitivity Types Type Mediator Onset Mechanism Examples I IgE, mast cells Immediate (minutes) Histamine release Allergy, asthma, anaphylaxis II IgG/IgM, complement Hours Cytotoxicity Hemolytic anemia, transfusion reaction III Immune complexes Hours–days Immune complex deposition SLE, RA, serum sickness IV T cells (CD4+, CD8+) 24–72 hrs Cytokine release, cytotoxicity TB test, contact dermatitis
- 33. Clinical Relevance &Treatment Approaches •Type I: antihistamines, corticosteroids, epinephrine (for anaphylaxis) •Type II: immunosuppressive therapy, plasma exchange •Type III: anti-inflammatory drugs, immunosuppressants •Type IV: corticosteroids, avoidance of trigger antigen •Hypersensitivity knowledge is essential for allergy testing, autoimmunity diagnosis, and transplant medicine
- 34. Introduction to MolecularGenetics •Study of structure and function of genes at a molecular level •Involves DNA, RNA, and protein synthesis •Explains how genetic variation contributes to disease •Foundation for genomics and pharmacogenomics
- 35. DNA Structure &Organization •Double helix structure, composed of nucleotides •Nucleotides: adenine, thymine, cytosine, guanine •DNA packed into chromosomes within nucleus •Human genome: ~3 billion base pairs, ~20,000 protein- coding genes
- 36. Gene Expression &Regulation •Transcription: DNA → mRNA •Translation: mRNA → protein •Regulation through: •Promoters, enhancers, repressors •Epigenetic mechanisms (DNA methylation, histone modification) •Gene expression changes → disease or altered drug response
- 37. Mutations & GeneticBasis of Disease •Types of mutations: point, insertion, deletion, duplication •Can be silent, missense, nonsense, or frameshift •Lead to loss of function or gain of function •Examples: •Cystic fibrosis (CFTR gene mutation) •Sickle cell anemia (β-globin mutation)
- 38. Genomics: Definition &Applications •Study of the entire genome of an organism •Tools: whole-genome sequencing, GWAS (genome-wide association studies) •Applications: •Identifying disease-causing genes •Tracing evolutionary relationships •Discovering genetic markers for drug response
- 39. Pharmacogenomics: Concept •Study ofhow genetic variation influences drug response •Integrates pharmacology + genomics •Explains why individuals respond differently to the same drug •Goal: personalized medicine for safer, more effective therapy
- 40. Genetic Variability inDrug Response •Variations in drug-metabolizing enzymes •CYP450 family (CYP2D6, CYP2C19, CYP3A4) •Variations in drug transporters (P-glycoprotein) •Variations in drug targets (receptors, enzymes) •Affects efficacy, toxicity, and dosage requirements
- 41. Clinical Example: Warfarin& VKORC1 • Warfarin metabolism influenced by genetic variants • CYP2C9 polymorphism: alters drug metabolism • VKORC1 gene: affects warfarin target sensitivity • Genetic testing helps guide safe and effective dosing
- 42. Proteomics: Definition &Techniques •Study of entire protein set (proteome) of an organism •Techniques: •Mass spectrometry •2D gel electrophoresis •Protein microarrays •Proteins = functional molecules → direct link to disease processes
- 43. Proteomics in DrugDiscovery •Identifies protein biomarkers for diseases •Reveals drug targets for therapy •Tracks protein–drug interactions •Example: discovery of HER2 protein in breast cancer
- 44. Metabolomics: Role inPharmacology •Study of small-molecule metabolites in biological systems •Reflects real-time physiological state •Applications: •Understanding drug metabolism •Identifying metabolic biomarkers •Predicting drug toxicity and side effects
- 45. Integration of OmicsApproaches •Genomics: blueprint (DNA sequence) •Transcriptomics: gene expression (RNA) •Proteomics: proteins produced •Metabolomics: biochemical activity •Together → provide comprehensive view of health, disease, and drug response
- 46. Case Study: BreastCancer & HER2 Therapy •HER2 gene overexpression → aggressive breast cancer •Trastuzumab (Herceptin): monoclonal antibody targeting HER2 receptor •Example of integrating genomics + proteomics •Demonstrates role of pharmacogenomics in precision oncology
- 47. Future of PersonalizedMedicine •Routine genetic testing to guide therapy •Development of targeted drugs based on genetic profile •Integration of AI and bioinformatics for data analysis •Potential for disease prevention through predictive genomics •Shift from “one-size-fits-all” → individualized care
- 48. Conclusion & KeyTakeaways •Innate and adaptive immunity provide body’s defense •Antibodies function via neutralization, opsonization, complement activation, ADCC •Hypersensitivity reactions classified into four types with clinical implications •Genomics, proteomics, and metabolomics form foundation of pharmacogenomics •Pharmacogenomics enables personalized medicine by linking genes to drug response •Future healthcare will increasingly rely on integrated omics and precision medicine
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