IMMUNE SYSTEM MARLON M. MARAMION, MD, DPSP
IMMUNE SYSTEM
MARLON M. MARAMION, MD, DPSP
THE IMMUNE SYSTEM
• OBJECTIVES1.Know the components of the immune system2.Understand how each component functions in
the elimination of microorganisms
IMMUNE SYSTEM
PHYSIOLOGIC FUNCTION protect the body against infectious pathogens
MECHANISM:INNATE IMMUNITYADAPTIVE IMMUNITY
INNATE IMMUNITY
Natural ImmunityDefense mechanisms that are present even
before infection and have evolved to specifically recognize microbes and protect multicellular organism against infection
nonspecificFIRST LINE OF DEFENSE
Mechanisms of Innate Immunity
• PhysiologicBarriers at the Portal of EntrY- skin- mucous membranes
• Alternative Pathway of Complement Activation
• Phagocytosis• Interferons• Natural Killer (NK) Cells
SKIN• acid pH and certain chemical
substances (especially fatty acids)
• Lysozyme
MUCUS MEMBRANES
• Mucus & cilia• Secretions (saliva, tears)• Lysozyme• IgA antibody• Phagocytes• pH• Normal flora
Reticuloendothelial System
• mononuclear phagocytic cellsbloodlymphoid tissuesliverspleenbone marrowlungs and other tissues
- FILTER BLOOD AND TISSUE
COMPLEMENT SYSTEM
COMPLEMENT SYSTEM
• OPSONIZATION• MEMBRANE ATTACK COMPLEX FORMATION
PHAGOCYTOSIS
• polymorphonuclear leukocytes (granulocytes)• phagocytic monocytes (macrophages)• fixed macrophages of the reticuloendothelial
system
OPSONIZATIONa. C3 component of the complement systemb. Fc portion of antibody
NEUTROPHILS
•60-70% of WBC•12-15 µm•Nucleus – 2-5 lobes•Lifespan – 6-7 hrs
•Function- PHAGOCYTOSIS
NEUTROPHILS• MICROBIAL KILLING1. Non oxidative process
- lytic enzymes- Lysozyme (destroys Peptidoglycan of
bacterial cell wall)- Lactoferrin (binds iron)
2. Oxidativea. generation of H2O2- acted upon MPO + cofactors (halides) + acid = HOClb. production of superoxide anion (O2
–)- directly lethal for many microorganisms
PUS
Monocytic (Mononuclear) Phagocytic System
• Principal cells– Monocytes and Macrophages
• Monocytes circulate in the blood (1-3%) for a few days, then migrate in the tissues as macrophages
Macrophages Types
• Tissue and fixed macrophages– Kupffer cells, histiocytes, splenic macrophage,
alveolar macrophages, mesangial cells, microglial cells, osteoclasts
• Giant and epitheloid cells– Granuloma formation
MacrophagesReceptors
• Chemokines and cytokines• Complement components• Fc receptors• Class I and II antigens for Ag presentation
MacrophagesActivation
• By gamma interferon which are released by activated T helper 1 subset
• More efficient in intracellular killing activities
MacrophagesFunctions
• Phagocytosis• Antigen processing• Antigen presentation• Secretory cells
– IL-1, IL-6, TNF-a
Phagocytosis
Phagocytosis Mechanisms Of Microbial Killing
• Oxygen-dependent reactions– Myeloperoxidase-mediated
• MPO + H2O2 form aldehydes and hypochlorites which have powerful antimicrobial activity
– MPO-independent• H2O2, superoxide anions, hydroxyl radicals and singlet
O2
Phagocytosis Mechanism Of Microbial Killing
• Oxygen-independent reactions– Intracellular accumulations of lactic acid– Lysozymes– Cationic proteins– Lactoferrin and transferrin– Ceruloplasmin– LYTIC ENZYME
INTERFERONS
• Antiviral proteins• Interferon α (IFN- A) and interferon β (IFN-B)
& interferon γ (IFN-G)• produced by virally infected cells & activated
lymphocytes• control viral replication by inhibiting protein
synthesis & viral multiplication.
Natural Killer Cells- 10-20% of the circulating lymphocytes- Larger than small lymphocytes- Abundant azurophilic granulesRECEPTORSa. "activating receptor" - recognizes
carbohydrate ligandsb. "inhibitory receptor" - recognizes MHC
class I molecules- Kill:
Tumor cellsVirally infected cells
First line of defense
INNATE IMMUNE MECHANISM
• Phagocytosis• Inflammation
- IL-1 & TNF α release by macrophages- generation of prostaglandins- fever