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Immune system protects body against pathogen External barriers prevent microorganism entry to the body Immune system performs immune response resulted in immunity Classification
Innate immune response Adaptive immune response
Innate immunity
Immediate Short protection Non specific Elimination: phagocytosis & killing activity Cells: granulocyt, macrophage, NK cell (natural killer) Humoral: complement
Adaptive immunity
Induced immune response Long term protection Memory Specific Cells: lymphocyte (B and T) Humoral: antibody
Non-Specific or natural Immune system Immediate response (0-4 hours) Function: provide the initial defense against infections: Prevent infections Eliminate microbes : depends on the presence of cells that recognize and kill pathogens and foreign materials directly
Humoral
Acute phase protein Complement
Intact epithelial form physical barriers Produces peptides that have antimicrobial properties
Defensins (epithel/paneth cell, neutrophil, NK cells, Tcytotoxic,) direct toxicity to microbes Cathelicidins (neutrophil, skin, GI mucosal cells, respiratory mucosal cells) direct toxicity
Steps:
Recruitment to sites of infection Recognition of pathogens Ingestion of microbes Destruction
Integrin stabilize adhesion of leucocyte to endothelium Cytoskeleton alter the shape of cells Extracellular matrix
The innate immune system distinguishes infectious microbes from self cells by recognizing molecular structures which expressed by microbes Pathogen has non-self structures : PathogenAssociated Molecular Patterns (PAMPs) Part of the innate immune cells which bind to PAMPs known as Pattern-recognition receptors
Anionic polymers Broad spectrum of ligands LPS (in gram negative bacteria)
Mannose binding lectin Macrophage mannose receptor Scavenger receptor Toll-like receptor (TLRs)
PAMPS in pathogens
PRR in phagocytes
Phagocytic receptor : stimulate ingestion of pathogen Chemotactic receptor : binds to special peptide on bacteria
O2 dependent degradation (ROS) O2-independent degradation (ex: NO) Opsonins: protein that coat pathogen easy to be ingested
Antibodies Complements Lectins
Other mechanism
CRP Mannose binding protein Serum amyloid P component 1 acid glycoprotein, etc
Substance that interfere with viral replication 14 class of IFN Infected cell secretes IFN to the extracelullar fluid bind to uninfected cell cordon of uninfected cell around site of infection inhibits viral reproduction between cells
Some mediator resets thermal setpoints in the hypothalamus induce heat formation fever Mediator = pyrogen Can be endogenous ( PG, IL-1) or exogenous (bacterial toxin, etc)
Inflamare: to set on fire Complex biological response of vascular & tissues to harmful stimuli Objection: to remove the injurious stimuli initiate the healing process for the tissue Terminology:
Organ + -itis
Deliver additional effectors molecule and cells to sites of infection augment killing of invading microorganism Induce blood clotting physical barrier to the spread of infection in blood stream Promote the repair of injured tissue
Increase in vascular diameter increase local blood flow increase the metabolic rate heat and redness
Endothelial cells lining the blood vessels are activated to express cell-adhesion molecules promote binding of circulating leukocytes
Increase in vascular permeability exit of fluid and protein from blood accumulate in the tissue swelling and pain
Clotting in microvessels in the site of infection prevents the spread of pathogen via the blood
Macrophage activation by pathogen lead to cytokine; chemokine release & local mediators Various cytokine can lead to fever & interferon response Various chemokine attract other cell to come to site of infection Local mediators make blood vessels dilate & increase vascular permeability redness & heat
Leukocyte in blood circulation has receptor for chemokine come to blood vessel near the site of infection Blood vessel express cell adhesion molecule bind leucocyte
Margination Rolling adhesion Tight adhesion Diapedesis Migration
Leucocyte migration/extravasation together with fluid & protein increase interstitial volume swelling Accumulation can activate free nerve endings pain Inflammatory mediators can also induce pain sensation More accumulation loss of function
Lymphocytes derived from lymphoid progenitor. Circulate in the blood Contain cytolytic granules Important in the defense from certain lymphoid tumor cell lines and from virally infected cells. Innate immune response Act without prior activation
NK cell has 2 receptors: killing receptors & inhibiting receptors allow NK cells to kill infected cells, while sparring uninfected cells.
Activation of NK cell is regulated by a balance between signal from activating receptor and inhibitory receptors Activating receptor recognize
stressed cell Virus infected cell Malignant cell
Activation
release of cytotoxic granule contents production of the cytokines IFN- and TNF-
NK
cells are activated through Killer Activating Receptors (KARs). Ex: NKp46, NKp30, NKp44 of these receptors contain a (+) charge in their transmembrane domain associated with adaptor to internalize external signals stimulates granule release
Each
Perforin or cytolysin can insert into cell targets membrane Polymerize form transmembrane pore Release of granzymes through transmembrane pore Granzymes consists of serine protease activate apoptosis reaction cell target death NK cell contain Fas Ligand bind with receptor (Fas) apoptosis
Infected cells can inhibit the synthesis of all proteins decreases the amount of MHC-I produced. Viruses can also selectively prevent the export of MHC-I molecule number of MHC class I molecules on the cell surface is decreased Decreased MHC-I expression decrease in the number of KIR/MHC-I interactions reduces inhibition signaling killing activity of NK cell
Macrophage produces cytokine IL-12 activates NK cell NK cell produces cytokine IFN- activates macrophage
Complement : heat-labile component of normal plasma that augments the opsonization and killing of bacteria by antibodies. Complement= the ability to assist or complement the antimicrobial activity of antibodies The complement system may be activated by microbes in the absence of antibody as part of innate immune response to infection, and by antibodies attached to microbes