MIỄN DỊCH BÀI 1

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Information about MIỄN DỊCH BÀI 1

Published on November 15, 2007

Author: lebahiep

Source: slideshare.net

Eugene P. Mayer Office: Bldg. #2, Rm. B18 Phone: 733-3281 Email: MAYER@MED.SC.EDU

Overview of the Immune System Interactions between the two systems Immune System Innate (Nonspecific) 1 o line of defense Adaptive (Specific) 2 o line of defense Protects/re-exposure Cellular Components Humoral Components Cellular Components Humoral Components

Comparison of Innate and Adaptive Immunity No memory No time lag Not antigen specific A lag period Antigen specific Development of memory Innate Immunity Adaptive Immunity

No memory

No time lag

Not antigen specific

A lag period

Antigen specific

Development

of memory

Cells of the Immune System Immune System Myeloid Cells Lymphoid Cells Granulocytic Monocytic T cells B cells Neutrophils Basophils Eosinophils Macrophages Kupffer cells Dendritic cells Helper cells Suppressor cells Cytotoxic cells Plasma cells NK cells

Development of the Immune System ery pl mye neu m φ lym nk thy CD8 + CD4 + CTL TH2 TH1

Function of the Immune System (Self/Non-self Discrimination) 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

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

Infection and Immunity Balance infection immunity Bolus of infection x virulence immunity Disease =

Effects of the Immune System Beneficial: Protection from Invaders Elimination of Altered Self Detrimental: Discomfort and collateral damage (inflammation) Damage to self (hypersensitivity or autoimmunity)

Beneficial:

Protection from Invaders

Elimination of Altered Self

Detrimental:

Discomfort and collateral damage (inflammation)

Damage to self (hypersensitivity or autoimmunity)

Innate (Nonspecific) Immunity

Overview of the Immune System Immune System Innate (Nonspecific) Adaptive (Specific) Cellular Components Humoral Components Cellular Components Humoral Components

Innate Host Defenses Against Infection Anatomical barriers Mechanical factors Chemical factors Biological factors Humoral components Complement Coagulation system Cytokines Cellular components Neutrophils Monocytes and macrophages NK cells Eosinophils

Anatomical barriers

Mechanical factors

Chemical factors

Biological factors

Humoral components

Complement

Coagulation system

Cytokines

Cellular components

Neutrophils

Monocytes and macrophages

NK cells

Eosinophils

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

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

Anatomical Barriers - Biological Factors System or Organ Component Mechanism Skin and mucous membranes Normal flora Antimicrobial substances Competition for nutrients and colonization

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

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

Phagocytosis and Intracellular Killing

Phagocytes - Neutrophils (PNMs) Characteristic nucleus, cytoplasm Granules CD 66 membrane marker

Characteristic nucleus, cytoplasm

Granules

CD 66 membrane marker

Characteristics of Neutrophil Granules 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

Characteristic nucleus Lysosomes CD14 membrane marker Phagocytes - Macrophages

Characteristic nucleus

Lysosomes

CD14 membrane marker

Phagocyte Response to Infection The SOS Signals N-formyl methionine-containing peptides Clotting system peptides Complement products Cytokines released by tissue macrophages Phagocyte response Vascular adherence Diapedesis Chemotaxis Activation Phagocytosis and killing

The SOS Signals

N-formyl methionine-containing peptides

Clotting system peptides

Complement products

Cytokines released by tissue macrophages

Phagocyte response

Vascular adherence

Diapedesis

Chemotaxis

Activation

Phagocytosis and killing

Attachment via Receptors: IgG FcR ScavengerR Complement R Toll-like R Initiation of Phagocytosis

Phagocytosis Attachment Pseudopod extension Phagosome formation Granule fusion Phagolysosome formation

Attachment

Pseudopod extension

Phagosome formation

Granule fusion

Phagolysosome formation

Respiratory Burst Oxygen-Dependent Myeloperoxidase-Independent Reactions Toxic compounds – Superoxide anion (O 2 - ), Hydrogen peroxide (H 2 O 2 ), Singlet oxygen ( 1 O 2 ) and Hydroxyl radical (OH*) Pentose-P + NADPH G-6-P-dehydrogenase Glucose +NADP + NADPH oxidase Cytochrome b558 NADP + + O 2 - NADPH + O 2 Superoxide dismutase H 2 O 2 + 1 O 2 2O 2 - + 2H + 2O 2 - + H 2 O 2 OH* + OH - + 1 O 2

Respiratory Burst Oxygen-Dependent Myeloperoxidase-Dependent Reactions myeloperoxidase OCl - + H 2 O H 2 O 2 + Cl - 2OCl - + H 2 O 1 O 2 + Cl - + H 2 O Toxic compounds – Hypochlorous acid (OCl - ), and Singlet oxygen ( 1 O 2 )

Respiratory Burst Detoxification Reactions H 2 O 2 + O 2 Superoxide dismutase H 2 O + O 2 Catalase 2O 2 - + 2H + 2 H 2 O 2

Oxygen-Independent Killing in the Phagolysosome Effector Molecule Function 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

Summary of Intracellular Killing Pathways Intracellular Killing Oxygen Dependent Oxygen Independent Myleoperoxidase Dependent Myleoperoxidase Independent

Nitric Oxide Dependent Killing IFN γ  TNF TNF Nitric Oxide Nitric Oxide

Non-specific Killer Cells NK and LAK cells ADCC (K) cell Activated macrophages Eosinophils They all kill foreign and altered self targets

NK and LAK cells

ADCC (K) cell

Activated macrophages

Eosinophils

They all kill foreign and altered self targets

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

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

Lymphokine Activated Killer (LAK) cell IL2 IFN IFN IL2 kills malignant cells kills transformed and malignant cells

Regulation of NK Cell Function MHC I KIR KAR KAL No Killing Killing

MHC I

KIR

KAR

KAL

No Killing

Killing

K Cells morphologically undefined mediate ADCC have Fc receptor recognize antibody coated targets could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)

morphologically undefined

mediate ADCC

have Fc receptor

recognize antibody coated targets

could be NK cells (IgG), macrophages (IgG), eosinophils (IgE) or other cells (IgG)

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