Inate immunity

IMMUNOLGY Study of all biological, chemical,

and physical event surrounding the function of the immune system.

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

IMMUNITY

Immune System

Immune System

Innate(Nonspecific)

Adaptive(Specific)

Cellular Components Humoral Components Cellular immunity Humoral immunity

Innate Immunity Specific Immunity

Comparison of Innate and Adaptive Immunity

• No memory

• No time lag

• Not antigen specific

• A lag period

• Antigen specific

• Developmentof memory

Innate Host Defenses Against InfectionFIRST 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

Non-Specific Defense Mechanism in Humans

Anatomical Barriers - Biological Factors

System or Organ Component Mechanism

Skin and mucous membranes

Normal flora Antimicrobial substances

Competition for nutrients

Colonization

Anatomical Barriers - Mechanical Factors

System or Organ Cell type Mechanism

Skin Squamous epithelium Physical barrierDesquamation

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 pHLysozyme and phospholipase A

Defensins (respiratory & GI tract)

Antimicrobial

Sufactants (lung) Opsonin

Humoral ComponentsComponent Mechanism

Complement Lysis of bacteria and some virusesOpsoninIncrease in vascular permeabilityRecruitment and activation of phagocytic cells

Coagulation system Increase vascular permeabilityRecruitment of phagocytic cellsΒ-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 killingInflammation and tissue damage

Macrophages Phagocytosis and intracellular killingExtracellular killing of infected or altered self targetsTissue repairAntigen presentation for specific immune response

NK and LAK cells Killing of virus-infected and altered self targets

Eosinophils Killing of certain parasites

PHAGOCYTOSISAND

INTRACELLULAR KILLING

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

• Characteristic nucleus, cytoplasm

• Granules

• CD 66 membrane marker

Phagocytes - Neutrophils (PNMs)

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

• Characteristic nucleus

• Lysosomes

• CD14 membrane marker

Phagocytes - Macrophages

PHAGOCYTOSIS

• CHEMOTACTIC FACTORS• CONTACT AND INGESTION

(PHAGOSOME FORMATION)• FORMATION OF PHAGOLYSOSOME• KILLING, DIGESTION OF MICROBES• RELEASE OF DEBRIS

Attachment via Receptors:

IgG Fc R

Scavenger R

Complement R

Toll-like R

Initiation of Phagocytosis

Phagocytosis

• Attachment

•Pseudopod extension

•Phagosome formation

•Granule fusion

•Phagolysosome formation

Intracellular Killing Pathways

Intracellular Killing

OxygenDependent

OxygenIndependent

MyleoperoxidaseDependent

MyleoperoxidaseIndependent

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

NON-SPECIFIC KILLER CELLS

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

Lymphokine Activated Killer (LAK) cell

IL2

IFNIFN

IL2

kills malignant

cells

kills transformed

and malignant cells

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)

Opsonization by IgG Ab by phagocyte

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

ACTION OF INTERFERONACTION OF INTERFERON

Mechanism of alpha and beta Interferon

Ant-viral activity of Interferon

Effects of IFN gamma

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•