Inate immunity
- 1. IMMUNOLGY Study of all biological, chemical, and physical event surrounding the function of the immune system.
- 2. Function of the Immune System (Self/Non-self Discrimination) • Operates as a surveillance system • To protect from pathogens • Intracellular (e.g. viruses and some bacteria and parasites) • Extracellular (e.g. most bacteria, fungi and parasites) • To eliminate modified or altered self
- 3. IMMUNITY
- 4. Immune System Immune System Innate (Nonspecific) Adaptive (Specific) Cellular Components Humoral Components Cellular immunity Humoral immunity
- 5. Innate Immunity Specific Immunity Comparison of Innate and Adaptive Immunity • No memory • No time lag • Not antigen specific • A lag period • Antigen specific • Development of memory
- 6. Innate Host Defenses Against Infection FIRST LINE OF DEFENCE • Anatomical barriers– Mechanical factors – Chemical factors – Biological factors SECOND LINE OF DEFENCE • Humoral components– – Complement – Coagulation system – Cytokines • Cellular components – Neutrophils – Monocytes and macrophages – NK cells – Eosinophils
- 7. Non-Specific Defense Mechanism in Humans
- 8. Anatomical Barriers - Biological Factors System or Organ Component Mechanism Skin and mucous membranes Normal flora Antimicrobial substances Competition for nutrients Colonization
- 9. Anatomical Barriers - Mechanical Factors System or Organ Cell type Mechanism Skin Squamous epithelium Physical barrier Desquamation Mucous Membranes Non-ciliated epithelium (e.g. GI tract) Peristalsis Ciliated epithelium (e.g. respiratory tract) Mucociliary elevator Epithelium (e.g. nasopharynx) Flushing action of tears, saliva, mucus, urine
- 10. Anatomical Barriers - Chemical Factors System or Organ Component Mechanism Skin Sweat Anti-microbial fatty acids Mucous Membranes HCl (parietal cells) Tears and saliva Low pH Lysozyme and phospholipase A Defensins (respiratory & GI tract) Antimicrobial Sufactants (lung) Opsonin
- 11. Humoral Components Component Mechanism Complement Lysis of bacteria and some viruses Opsonin Increase in vascular permeability Recruitment and activation of phagocytic cells Coagulation system Increase vascular permeability Recruitment of phagocytic cells Β-lysin from platelets – a cationic detergent Lactoferrin and transferrin Compete with bacteria for iron Lysozyme Breaks down bacterial cell walls Cytokines Various effects
- 12. Cellular Components Cell Functions Neutrophils Phagocytosis and intracellular killing Inflammation and tissue damage Macrophages Phagocytosis and intracellular killing Extracellular killing of infected or altered self targets Tissue repair Antigen presentation for specific immune response NK and LAK cells Killing of virus-infected and altered self targets Eosinophils Killing of certain parasites
- 14. CELLULAR MECHANISM 1) PHAGOCYTIC CELLS • Neutrophilic polymorphonuclear leucocytes • Monocytic macrophages( phagocytosis) 2 ) NATURAL KILLER CELLS • Non phagocytic lymphoid cells • Lack surface markers • Damage virus laden tissue cells • Immunological surveillance against neoplasia
- 15. • Characteristic nucleus, cytoplasm • Granules • CD 66 membrane marker Phagocytes - Neutrophils (PNMs)
- 16. Primary granules contain cationic proteins, lysozyme, defensins, elastase and myeloperoxidase Secondary granules contain lysozyme, NADPH oxidase components, lactoferrin and B12-binding protein azurophilic; characteristic of young neutrophils; specific for mature neutrophils Characteristics of Neutrophil Granules
- 17. • Characteristic nucleus • Lysosomes • CD14 membrane marker Phagocytes - Macrophages
- 18. PHAGOCYTOSIS • CHEMOTACTIC FACTORS • CONTACT AND INGESTION (PHAGOSOME FORMATION) • FORMATION OF PHAGOLYSOSOME • KILLING, DIGESTION OF MICROBES • RELEASE OF DEBRIS
- 21. Attachment via Receptors: IgG Fc R Scavenger R Complement R Toll-like R Initiation of Phagocytosis
- 22. Phagocytosis • Attachment •Pseudopod extension •Phagosome formation •Granule fusion •Phagolysosome formation
- 24. Intracellular Killing Pathways Intracellular Killing Oxygen Dependent Oxygen Independent Myleoperoxidase Dependent Myleoperoxidase Independent
- 25. Effector Molecule Function Oxygen-Independent Killing in the Phagolysosome Cationic proteins (cathepsin) Damage to microbial membranes Lysozyme Hydrolyses mucopeptides in the cell wall Lactoferrin Deprives pathogens of iron Hydrolytic enzymes (proteases) Digests killed organisms
- 26. NON-SPECIFIC KILLER CELLS NK and LAK cells ADCC (K) cell Activated macrophages Eosinophils They all kill foreign and altered self targets
- 27. Natural Killer (NK) cells also known as large granular lymphocytes (LGL) kill virus-infected or malignant cells identified by the presence of CD56 & CD16 and absence of CD3 activated by IL2 and IFN-γ to become LAK cells
- 28. Lymphokine Activated Killer (LAK) cell IL2 IFN IFN IL2 kills malignant cells kills transformed and malignant cells
- 29. KILLER -K Cells--- ADCC morphologically undefined mediate ADCC have Fc receptor recognize antibody coated targets could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)
- 30. Opsonization by IgG Ab by phagocyte
- 32. INTERFERON • Small proteins produced by certain WBC and tissues. • Three major types: alpha– lymphocytes, macrophages • beta--- fibroblasts • gamma—T cells • USED against viral infections and cancer. MECHANISM IN VIRUS INFECTED CELL: • Transcription and translation of IFN gene in infected cell • IFN diffuses out of infected cells • Attachment --- specific receptors of un infected cells– enters the nucleus • IFN activates genes– synthesis of anti-viral proteins --- BLOCK viral replication --- ANTI-VIRAL STATE • IFN does not prevent virus from entering cells but block viral replication
- 33. ACTION OF INTERFERONACTION OF INTERFERON
- 34. Mechanism of alpha and beta Interferon
- 35. Ant-viral activity of Interferon
- 36. Effects of IFN gamma
- 38. ACQURIED SPECIFIC IMMUNITY • HUMORAL: immune response– B cells stimulated– plasma cells– Ab (Ig)– destruction extracellular pathogens • CELLULAR: immune response– T cells sensitized + macrophages– destruction intracellular pathogens, tumor cells HUMORAL & CELLULAR CAN BE: • ACTIVE: Foreign antigens– activate cells of immune system– Recognition, specificity, destruction, memory NATURAL- INFECTION ARTIFICIAL- VACCINATION, IMMUNIZATION • PASSIVE: preformed antibodies introduced– non immune person--- protection NATURAL– TRANSPLACENTAL, BREAST MILK ARTIFICIAL– GEMMAGLOBULIN, ANTI TOXINS •