INNATE (NON-SPECIFIC) IMMUNITY

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INNATE ( NON-SPECIFIC ) IMMUNITY
Abdul Ghaffar Microbiology and Immunology
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"When the mind is ready,a teacher appears.
Chinese Proverb
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Development of the Immune System

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Cells of the Immune System
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Components of the Immune System
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Balance between Infection and Immunity
infection
immunity
Disease
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Response to Infection
adaptive immunity
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Significance of the Immune System

• Beneficial
• Protection from Invaders
• Elimination of Altered Self
• Detrimental
• Discomfort (inflammation)
• Damage to self (autoimmunity)

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Characteristics of Innate and Adaptive Immunity

• Antigen independent

• Antigen dependent

• No time lag

• A lag period

• Not antigen specific

• Antigen specific

• No Immunologic
• memory

• Development
• of memory

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Components of Innate and Adaptive Immunity
physical barriers
skin, gut Villi, lung cilia,etc
none
soluble factors
many protein and non-protein secretions
Immunoglobulins (antibody)
cells
phagocytes, NK cell eosinophils, K cells
T and B lymphocytes
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Physical Barriers to Resistance
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Effector mechanisms in Innate Immunity -1
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Effector mechanisms in Innate Immunity -2
Nasopharynx and eye
mucus, saliva, tears
flushing, lysozyme
Phagocytes
phagocytosis and intracellular killing
Blood and Lymphiod organs
K, NK LAK cells
direct and antibody dependent cytolysis
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Effector mechanisms in Innate Immunity -3
Serum and other serous fluids
lactoferrin, transferrin
iron deprivation
interferons, TNF-?
antiviral proteins phagocyte activation
lysozyme
peptidoglycan hydrolysis
opsonization, enhanced phagocytosis, inflammation
Fibronectin complement
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Phagocytes are the Most Important Cells
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All phagocytes eat, digest and extrude
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Phagocytes Neutrophils

• phagocytosis, intracellular killing, inflammation
  and tissue damage
• characteristic nucleus, cytoplasm
• granules and CD66 membrane marker.

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PhagocytesMacrophages

• phagocytosis, intracellular and extra-cellular
  killing, tissue repair, antigen presentation for
  specific immune response
• characteristic nucleus and CD14 membrane marker.

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Characteristics of Neutrophil Granules
primary granules
secondary granules
azurophilic characteristic of young neutrophils
specific for mature neutrophils
contain cationic proteins, lysozyme, defensins,
proteases and myeloperoxidase
contain lysozyme, NADPH oxidase, lactoferrin and
B12-binding protein
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Phagocyte Response to Infection

• The SOS Signals
• N-formyl methionine
• Clotting system peptides
• Complement products
• Phagocyte response
• Vascular adherence
• Diapedesis
• Chemotaxis
• Activation
• Phagocytosis and killing

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Initiation of Phagocytosis
Attachment via
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Respiratory Burst
Oxygen Dependent Myeloperoxidase Independent
Reactions
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Respiratory Burst
Oxygen Dependent Myeloperoxidase dependent
reactions

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Pathways of Intracellular Killing
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Mediators of Oxygen Independent Killing in the
Phago-lysosome
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
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Nitric Oxide Dependent Killing
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Non-specific Killer Cells

• NK and LAK cells
• ADCC (K) cell
• Activated
• macrophages
• Eosinophils

• They all kill foreign and altered self targets

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Natural Killer (NK) cells

• also known as large granular lymphocytes (LGL)
• kill infected and malignant cells
• are identified by the presence of CD56 CD16 and
  absence of CD3
• activated by IL2 and IFN-? to become LAK cells

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Lymphokine Activated Killer (LAK) cell
IFN
IFN
IL2
IL2
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Regulation of NK Cell Function
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K Cells

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

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Macrophages

• phagocytose kill intracellularly
• identified by CD14
• adherent of plastic and glass surfaces
• activated by cytokines
• kill both intracellular organisms
• kill malignant and altered self targets

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Elements of Nonspecific ImmunitySummary

• Physical Barriers
• skin, muco-ciliary escalator, secretions,
  peristaltic movement, etc.
• Serous Proteins
• Acute phase proteins, Interferon(s), lysozyme,
  lactoferrin, cationic proteins, etc.

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Elements of Nonspecific ImmunitySummary

• Cells
• pagocytes
• Oxygen-independent killing
• O2-dependent - MPO independent killing
• O2-dependent - MPO dependent killing
• Nitric Oxide mediated killing
• cytotoxic cells
• NK, LAK, K (ADCC)