![INNATE/NATURAL/NATIVE IMMUNITY
INNATE IMMUNITY MEDIATED BY
• EPITHELIUM – which is a physical barrier, and secretes IgA
antibodies,& other anti microbial peptides eg, defensins
(skin), cryptocidins (intestine), histatins (saliva).
• ACUTE INFLAMMATION INVOLVING CELLS like neutrophils,
macrophages [mononuclear phagocytic system], natural
killer cell & CYTOKINES (chemical mediators)](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-5-320.jpg)
![MONONUCLEAR PHAGOCYTIC SYSTEM [MPS]
RETICULOENDOTHELIAL SYSTEM [RES]
• Cells of the mononuclear
phagocyte lineage, play a very
important role in immunity
• Many organs contain cells
belonging to MPS as shown in
corresponding diagram
• These cells are derived from
blood monocytes, which are
produced in the bone marrow.](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-6-320.jpg)
![ADAPTIVE IMMUNITY
PROCESS
Adaptive immunity has to be activated; unlike innate
immunity it is not present spontaneously in the body
Process includes the following :
• Capture & display of antigen [eg,microbial]
• Cell mediated immunity via T lymphocytes
• Cytokine production
• Humoral immunity via B lymphocytes
• Decline of immune response & immunological memory after
the antigen has been neutralized](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-8-320.jpg)
![CAPTURE & DISPLAY OF MICROBIAL Ag
Processing of extracellular antigens:
• Extracellular Ags like microorganisms & proteins
[eg bacteria] are captured (taken up) by antigen presenting
cells (APC) eg, DENDRITIC CELLS in the subepithelial tissue
and MACROPHAGES, B LYMPHOCYTES, LANGHERHANS CELLS
at other sites
• This antigen then undergoes intracellular processing, the
end product of this process combines with MHC II molecules
present on APCs](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-10-320.jpg)
![CAPTURE & DISPLAY OF MICROBIAL Ag
• APCs also have costimulatory B7 molecules on their cell
surface.
• APCs migrate to lymph nodes
• There the APCs, activate T4 cells by interaction of MHC 2
with T cell receptors (TCR) & B7 with CD28 [present on T L]
Intracellular antigens eg VIRAL Ag & TUMOR Ag
• Intra cellular Ag, combine with MHC I molecules (present on
all nucleated cells ) &
• Activate T8 cells via TCR [T8 cells have receptor for MHC 1]](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-11-320.jpg)
![TH1 subset PRODUCES IFN-y
• TH1 subset is INDUCED by cytokines like, IFN-y [autocrine], IL-12
ACTION
• Activation of macrophages,
• Activates B L to secrete IgG Abs
DEFENCE AGAINST ( NORMAL FUNCTION )
• Intracellular microbes
ROLE IN DISEASE
• Immune mediated chronic inflammatory disease
• Delayed type hypersensitivity reaction [DTH]](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-21-320.jpg)
![TH2 subset PRODUCE IL4, IL-5, IL-13
• TH2 subset is INDUCED by IL-4 [autocrine]
ACTIONS
• IL4 – activates BL to secrete IgE Antibodies
• IL-5 - activates eosinophils
• IL-13 -activates mucosal cells to increase mucous secretion,
activates macrophages to secrete GF for tissue repair (fibrosis)
DEFENCE (NORMAL FUNCTION)
• Against helminthic parasites
ROLE IN DISEASE - in allergies [type 1 hypersensitivity reaction]](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-22-320.jpg)
![ACTIVATION OF B LYMPHOCYTES
occurs by both T cell dependent & independent pathways
T CELL DEPENDENT
• PROTEIN Ag VIA APCs & T4 - CYTOKINES – BL – PLASMA
CELLS - IgG, IgA, IgE Ab
T LYMPHOCYTE ALSO HELP B LYMPHOCYTES IN
• HEAVY CHAIN CLASS SWITCHING (producing functionally
different Ab [eg IgM to IgG] with same specificity)
• AND STIMULATING PRODUCTION OF ANTIBODIES WITH
HIGH AFFINITY [attraction & binding to antigen]](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-30-320.jpg)
![NULL CELLS [non B & T cells active in immunity]
(LARGE GRANULAR LYMPHOCYTES)
THEY ARE FURTHER CATEGORIZED AS :
ANTIBODY DEPENDENT CYTOTOXIC CELL (ADCC)
• Neutralize cells/Ag coated by antibodies
NATURAL KILLER CELL (NKC)*
• Kill tumor cells, virus infected cells & transplanted foreign cells
• Activity is non immune ie, not dependent on MHC or antibody, IL-2 is a growth
factor for these cells
• They act by secreting perforin, which induces apoptosis of cell
LYMPHOKINE ACTIVATED KILLER CELL (LAK)
• Very effective against tumor cells](https://image.slidesharecdn.com/pa9-200811094859/85/OVERVIEW-OF-NORMAL-IMMUNE-SYSTEM-34-320.jpg)
OVERVIEW OF NORMAL IMMUNE SYSTEM
- 1. PA9.1 DESCRIBE THE PRINCIPLES & MECHANISMS INVOLVED IN IMMUNITY Dr IRA BHARADWAJ MCI TEACHER ID: PAT 2300569 KUHS FACULTY ID: M21512
- 2. TEXT BOOK REFRENCES • ROBBINS BASIC PATHOLOGY • HARSH MOHAN TEXTBOOK OF PATHOLOGY • GHAI ESSENTIAL PEDIATRICS OP GHAI, VINOD K PAUL, ARVIND BAGGA • TEXTBOOK OF MICROBIOLOGY DR C P BAVEJA • OTHER STANDARD REFRENCES
- 3. SPECIFIC LEARNING OBJECTIVES • Role of immune system • Innate immunity • MPS / RES • Adaptive immunity: process • MHC • Cytokines • T lymphocytes • B lymphocytes • Null cells • Decline of immunity • Immunological memory
- 4. ROLE OF IMMUNE SYSTEM • PROTECTION OF BODY FROM MICROBES • PROTECTION OF BODY FROM ABNORMAL SELF CELLS Eg, tumor cells, cells with intracellular microorganisms BY • INNATE IMMUNITY • ADAPTIVE IMMUNITY
- 5. INNATE/NATURAL/NATIVE IMMUNITY INNATE IMMUNITY MEDIATED BY • EPITHELIUM – which is a physical barrier, and secretes IgA antibodies,& other anti microbial peptides eg, defensins (skin), cryptocidins (intestine), histatins (saliva). • ACUTE INFLAMMATION INVOLVING CELLS like neutrophils, macrophages [mononuclear phagocytic system], natural killer cell & CYTOKINES (chemical mediators)
- 6. MONONUCLEAR PHAGOCYTIC SYSTEM [MPS] RETICULOENDOTHELIAL SYSTEM [RES] • Cells of the mononuclear phagocyte lineage, play a very important role in immunity • Many organs contain cells belonging to MPS as shown in corresponding diagram • These cells are derived from blood monocytes, which are produced in the bone marrow.
- 7. ROLE OF INNATE IMMUNITY & ADAPTIVE IMMUNITY Innate immunity is immediate & via phagocytic cells Adaptive immunity takes time to develop & is mediated via lymphocytes
- 8. ADAPTIVE IMMUNITY PROCESS Adaptive immunity has to be activated; unlike innate immunity it is not present spontaneously in the body Process includes the following : • Capture & display of antigen [eg,microbial] • Cell mediated immunity via T lymphocytes • Cytokine production • Humoral immunity via B lymphocytes • Decline of immune response & immunological memory after the antigen has been neutralized
- 10. CAPTURE & DISPLAY OF MICROBIAL Ag Processing of extracellular antigens: • Extracellular Ags like microorganisms & proteins [eg bacteria] are captured (taken up) by antigen presenting cells (APC) eg, DENDRITIC CELLS in the subepithelial tissue and MACROPHAGES, B LYMPHOCYTES, LANGHERHANS CELLS at other sites • This antigen then undergoes intracellular processing, the end product of this process combines with MHC II molecules present on APCs
- 11. CAPTURE & DISPLAY OF MICROBIAL Ag • APCs also have costimulatory B7 molecules on their cell surface. • APCs migrate to lymph nodes • There the APCs, activate T4 cells by interaction of MHC 2 with T cell receptors (TCR) & B7 with CD28 [present on T L] Intracellular antigens eg VIRAL Ag & TUMOR Ag • Intra cellular Ag, combine with MHC I molecules (present on all nucleated cells ) & • Activate T8 cells via TCR [T8 cells have receptor for MHC 1]
- 12. MHC Major Histocompatibility Complex • MHC is a genetic “LOCUS” on Chromosome 6p, which codes for cell surface compatibility i.e., they regulate expression of cell surface antigen • Also called HLA (Human Leukocyte Antigens) in humans and H-2 in mice • It’s major job is to make sure all self cell antigens are recognized and “tolerated”, because the general rule of the immune system is that all UN-recognized cells will NOT be tolerated
- 13. MHC MOLECULES (Gene Products) MHC 1 • Expressed on all nucleated cells and platelets on the surface of the cell, • It is a glycoprotein & antigenic. • T8 lymphocytes recognize & interact with it to become activated & cause cytolysis • They are involved in graft rejection
- 14. MHC MOLECULES (Gene Products) MHC II • Expressed on all APC’s, i.e., macrophages, dendritic cells & B lymphocytes on cell surface • It is a glycoprotein & antigenic • T4 lymphocytes interact with it and are activated immunologically • It is primarily responsible for graft vs host disease MHC III is related to Complement System Proteins
- 15. CYTOKINES – chemical messengers PRODUCED BY • APC (DC, macrophages ), endothelial cells, lymphocytes, mast cells & other cells IN RESPONSE TO • External stimuli – microbial products, dead cells & other cytokines FUNCTIONS • Innate immunity & inflammation • Adaptive immunity & Hemopoiesis
- 16. CYTOKINES – chemical messengers ACTIONS • AUTOCRINE, PARACRINE, ENDOCRINE – acting on self, cells in vicinity, cells at a distance • PLEOTROPISM, REDUNDANCY – one cytokine has several functions, one feature eg vasodilatation is controlled by several cytokines • EFFECTIVE IN LOW CONCENTRATION, therefore difficult to measure in clinical labs, tests used only in research labs • SYNERGY & ANTAGONISM – some cytokines act together, while other cytokines act against each other
- 17. CYTOKINES IN INNATE IMMUNITY & INFLAMMATION • TNF • IL-1 • CHEMOATTRACTANT CYTOKINES (CHEMOKINES) – IL-12, IFN-y, IL-6, IL-23 & OTHERS
- 18. CYTOKINES IN ADAPTIVE IMMUNITY PRODUCED BY ACTIVATED T LYMPHOCYTE • TH1 cells produce IFN-y • TH2 cells secrete IL4 , IL-5, IL-13 • TH17 cells produce IL17 & 22 & CHEMOKINES
- 19. CELL MEDIATED IMMUNITY T LYMPHOCYTES • THYMUS DERIVED T L, present in blood, spleen, lymph nodes, recognize peptides bound to MHC, various subtypes are - • T4 ( T HELPER ) ( 60%) • T8 ( CYTOTOXIC T L ) (40%) • MUCOSAL T CELLS • NATURAL KILLER T (NKT) CELLS • REGULATORY T CELLS
- 20. T4 (T HELPER) CELLS • RECOGNIZE PEPTIDES BOUND TO MHC ll (on antigen presenting cells) • APC activate naïve T4 cells by binding to TCR & CD28 leading to proliferation & differentiation into various subsets: TH1,TH2,TH17 These activated subtypes of T4 cells secrete cytokines, which: • Help B cells in antibody production • Help macrophages in phagocytosis • Promote inflammation
- 21. TH1 subset PRODUCES IFN-y • TH1 subset is INDUCED by cytokines like, IFN-y [autocrine], IL-12 ACTION • Activation of macrophages, • Activates B L to secrete IgG Abs DEFENCE AGAINST ( NORMAL FUNCTION ) • Intracellular microbes ROLE IN DISEASE • Immune mediated chronic inflammatory disease • Delayed type hypersensitivity reaction [DTH]
- 22. TH2 subset PRODUCE IL4, IL-5, IL-13 • TH2 subset is INDUCED by IL-4 [autocrine] ACTIONS • IL4 – activates BL to secrete IgE Antibodies • IL-5 - activates eosinophils • IL-13 -activates mucosal cells to increase mucous secretion, activates macrophages to secrete GF for tissue repair (fibrosis) DEFENCE (NORMAL FUNCTION) • Against helminthic parasites ROLE IN DISEASE - in allergies [type 1 hypersensitivity reaction]
- 23. TH17 subset PRODUCES IL17 & 22 & CHEMOKINES • TH17 subset is INDUCED by IL-6,1, 23, TGF B ACTIONS • Recruit neutrophils & monocytes – promote inflammation DEFENSE AGAINST ( NORMAL FUNCTION ) • Extracellular bacteria & fungi ROLE IN DISEASE • Immune mediated chronic inflammatory disease , often autoimmune
- 24. T8 (CYTOTOXIC T L) CELLS • T8 cells have receptors for MHC l (present on all nucleated cells, platelets) • Peptides displayed by MHC l are recognized by T8 L • Cells bearing MHC l peptides activate T8 L via TCR & coreceptors • Activated CTL cause direct killing of infected cells • Cells expressing ag (peptide) are killed by apoptosis (granzyme), • They also secrete cytokines
- 25. OTHER T CELLS • MUCOSAL T CELLS – recognize bacterial lipoglycans & act directly • NK T CELLS - recognize microbial glycolipids & act directly • REGULATORY T CELLS – suppress immune response • MEMORY T CELLS – on re-exposure to antigen initiate immediate specific immune response
- 26. T LYMPHOCYTES
- 27. T LYMPHOCYTES
- 28. HUMORAL IMMUNITY B LYMPHOCYTES • Derived from bone marrow • Present in blood, bone marrow, LNs, spleen, tonsils & other mucosal tissues • Recognize antigens via B L receptors (IgM/IgD) • CD 21, receptor for complement also activates B L • T4 L also activate B L • Activated B L differentiates to plasma cell, which secretes antibodies – IgG, IgM, IgA, IgE, IgD
- 29. ACTIVATION OF B LYMPHOCYTES occurs by both T cell dependent & independent pathways T CELL INDEPENDENT • POLYSACCHRIDE & LIPID Ag + Antigen Receptor on B cells (IgM/IgD) – ACTIVATE B L- PLASMA CELLS – IgM • B LYMPHOCYTES ALSO ACT AS APC TO ACTIVATE T CELL AFTER PROCESSING Ag & COMBINING WITH MHC ll
- 30. ACTIVATION OF B LYMPHOCYTES occurs by both T cell dependent & independent pathways T CELL DEPENDENT • PROTEIN Ag VIA APCs & T4 - CYTOKINES – BL – PLASMA CELLS - IgG, IgA, IgE Ab T LYMPHOCYTE ALSO HELP B LYMPHOCYTES IN • HEAVY CHAIN CLASS SWITCHING (producing functionally different Ab [eg IgM to IgG] with same specificity) • AND STIMULATING PRODUCTION OF ANTIBODIES WITH HIGH AFFINITY [attraction & binding to antigen]
- 31. B LYMPHOCYTES
- 32. ROLE OF ANTIBODIES • BIND MICROBES & NEUTRALIZE THEM • IgG coat Ag (opsonization) & help phagocytosis, • IgG & IgM activate complement, • IgE coat helminths • IgG cross placenta – passive immunity, • IgA mucosal defense, • Anti Body Dependent Cytotoxicity – Natural Killer cells – help NKCs to destroy antibody coated cell
- 33. SUMMARY OF B&T LYMPHOCYTES FUNCTIONS
- 34. NULL CELLS [non B & T cells active in immunity] (LARGE GRANULAR LYMPHOCYTES) THEY ARE FURTHER CATEGORIZED AS : ANTIBODY DEPENDENT CYTOTOXIC CELL (ADCC) • Neutralize cells/Ag coated by antibodies NATURAL KILLER CELL (NKC)* • Kill tumor cells, virus infected cells & transplanted foreign cells • Activity is non immune ie, not dependent on MHC or antibody, IL-2 is a growth factor for these cells • They act by secreting perforin, which induces apoptosis of cell LYMPHOKINE ACTIVATED KILLER CELL (LAK) • Very effective against tumor cells
- 35. DECLINE OF IMMUNE RESPONSE & IMMUNOLOGICAL MEMORY DECLINE OF IMMUNE RESPONSE After antigen/ microbe is neutralized, activated immune system returns to normal status by action of suppressor T cells IMMUNOLOGICAL MEMORY Preservation of memory of immune response so next encounter with antigen directly activates the effector cells
- 36. DISEASES OF IMMUNE SYSTEM • IMMUNODEFICIENCY – deficiency, which may be congenital or acquired • HYPERSENSTIVITY – inappropriate immune response • AUTOIMMUNITY- immune reaction against self antigens • ORGAN TRANSPLANT REJECTION • AMYLOIDOSIS – deposition of abnormal protein in tissues, which may be associated with an Immunological cause