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