inate immunity
TRANSCRIPT
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•