Innate Immunity

Part 1 Date :04-01-2012

Dr. Durgadas G. Naik

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In Immunology You Study :

Defense system in humans, organs and cells involved
Different defense mechanisms Role of defense cells, antigen, antibodies, complement and cytokines in immunity. Different types of antigen and antibodies Innate and acquired immunity- humoral and cell mediated. Different types of hypersensitivity reactions and mechanisms involved. Role of MHC in antigen recognition and transplantation Importance of vaccines and immunization Different types of antigen antibody reactions and their application

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Immunity - Classification

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Innate Immunity (Native/Natural/Nonspecific)

Present in all normal healthy individuals right from birth because of genetic make-up. May differ at 1. 2. ----Species Level : Plant pathogens donot cause diseases in humans Individual level : Extreme age group Malnourished Physiological imbalance Immunocompromised or Immunosuppressed state
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1. Active Immunity - Immune system involvement, - Antigen required to induce immune response - Immunological memory present a. Natural By infection/disease b. Artificial By Vaccination 2. Passive Immunity - No Immune system involvement, - Antigen not required to induce immune response Immunological memory absent a. Natural Mother to foetus b. Artificial administration of Readymade Antibodies
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Innate Immunity : Mechanism

1. External Defense ( Extracellular)

Skin: a. b. c. d. e. Intact skin acts like physical barrier, Sweat glands sweat Sebaceous glands secretion Low pH not favourable to pathogens Commensal flora

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Respiratory Tract
a. Architecture of nose b. Nasal hairs c. Nasal mucosa muco-polysaccharides neutralize viruses d. Respiratory epithelial cells e. Sneezing, Coughing mechanisms f. Alveolar macrophages -Phagocytosis

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Digestive tract
a. Saliva Antimicrobial, mouth wash
(Saliva with Lysozyme, myeloperoxidase Peroxidase, Lactoferrin molecules)

b. Stomach acidic pH c. Intestine - mucosa - Peristalsis - Commensal Flora - Colicins

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Urogenital tract:
a. Flushing action of urine b. Spermine in Semen c. Acidic pH of vagina

Eye & Ear ( Minor Routes)

a. Eyelids b. Tears Lysozyme enzyme c. Ear wax- antimicrobial in action
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Antibacterial substances in blood & Tissue

1. Complement in Blood 2. Acute Phase Proteins C- Reactive Protein ( CRP) Mannose binding proteins Endotoxin binding protein Activate Complement by Alternate Pathway

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Phagocytosis :
Carried out by Phagocytes Neutrophils(Blood), Macrophages (tissue)( major or potential)

Eosinophils, Monocytes (minor or less effective)

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Neutrophil

Monocyte

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Eosinophil

Lymphocyte

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Ingestion
Phagocytosis Invagination of cell membrane - Phagosome formation , organism is taken in

3. Killing
a. Respiratory Burst Superoxide radical Weak bactericidal Hydrogen Peroxide (H2O2) Strong bactericidal b. Nitric Oxide (NO)production Reactive Nitrogen Intermediates

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Neutrophils 2 types of granules 1. Primary granules Azurophilic granules large granules (15%) Myeloperoxidase & Lysozyme

2. Secondary granules Specific Small granules (85%) Lactoferrin , Proteases, Nucleases, Lipases

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Myeloperoxidase catalizes reaction between Chloride ion + H2O2 ClO (hypochlorite) Hypochlorite damage cell wall and Singlet Oxygen damage cells

Lysozyme acts on bacterial cell wall peptidoglycan Lactoferrin Iron chelating protein. Deprives bacteria of Iron Lipase, Nuclease, Protease destroy organisms molecules

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Macrophages act similarly like Neutrophils with some differences

1. Lysosome contains lysozyme, lactoferrin, NO MYELOPEROXIDASE ENZYME Therefore No Production of Hypochlorite 2. Macrophages ingest certain bacteria like M.tuberculosis, Brucells, Toxoplasma. 3. Macrophages present Antigen 4. Macrophages have MHC Class II

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Interferons :
Glycoproteins 1. Alpha 2. Beta 3. Gamma (Produced by White Blood cells) - Alpha & Beta induced by Virus infection - Gamma by Antigen - Virus infected cells secrete Interferon molecules - Interferon molecules induce other healthy cells to produce TIP Translation Inhibiting Protein (TIP)Mixture of 3 different enzymes Protein kinase, Oligonucleotide synthetase and Ribonuclease TIP blocks translation of Viral mRNA into proteins Produced within one hour,( Antibodies 5-7 days ) Species specific
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Inflammation :
Presence of foreign bodies Inflammatory response Inflammatory response Redness, Swelling, Warmth and Pain -Increased capillary permeability, increased blood flow. Acute : Pyogenic Bacteria + Antibody Classical C C5a attracts neutrophils proteases damage endothelium edema Bacterial surface Alternate C C3a, C5a triggers mediators (histamine, Prostaglandins, Leukotrienes) release -Vasodilation Capillary Permeability Increased- (erythema), -Bradykinin important mediator of pain. Chronic : Intracellular bacteria Helper T cells release IL2, Gamma IFN Activated macrophages, helper T cells Delayed Hyper sensitivity -Induration & Erythema.

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FEVER

Protective mechanism higher temperature Phagocytes are very active at 38 C

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Null cells Natural killer cells.: (5 % of Lymohocytes)

Large granular lymphocytes 1. These cells lack T cell receptor, CD 3 and IgM/IgD 2. They do not pass through thymus They have no immunological memory

Functions of NK cells:
Specialized in killing virus infected cells and tumor cells by secreting cytotoxins (perforins and granzymes) similar to those of cytotoxic T cells and participating in Fas- Fas ligand mediated apoptosis. NK cells kill without antibody, but antibody (IgG) enhances their effectiveness, by antibody dependent cellular cytotoxicity (ADCC) NK cells detect the presence of cancer or tumor cells by recognizing a protein called MICA that is found on the surface of many cancer cells but NOT on normal cells.

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Lymphoid System
Lymphoid Organs Central
Thymus ( T lymphocytes) Bone Marrow ( Bursa of Fabricius)- (B lymphocytes)

Peripheral
Lymphnodes Spleen Malt - Mucosa Asociated Lymphoid Tisse Galt Gut Associated Lymphoid Tissue Balt Bronchus Associated Lymphoid Tissue Blood

Cells in Immune System

Lymphocytes T cells, B cells, Natural Killer cells Neutrophils, Eosinophils, Basophils, Mast cells, Monocytes, Macrophages, Dendritic cells

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