Immunology T1C3

• first line of defense; response is quick
• includes physical, chemical and cellular barriers
• no immunological memory
• found in all multicelllar plants and animals

• skin
• mucous membranes

• acidity of the stomach contents
• specialized soluble molecules that possess antimicrobial activity

• epidermis - consists of several tiers of tighly packed epithelial cell (mostly dead) filled with keratin
• dermis - thicker layer composed of connective tissue, blood vessels, hair follicles, sebaceous glands, sweat glands

psoriasin (prevents colonization of E. coli)

• alimentary tracts
• trespiratory tracts
• urinogenital tracts
• eyes

• saliva
• tears
• mucous secretion

• influenza virus - attach firmly to the cells in the mucous membrane or respiratory tract
• gonorrhea producing bacteria - surface projections that bind to the epithelial cells of hte urogenital tract
• adherence of bacteria to a mucous membrane is mediated by fimbriae or pilli
• pilli can interact with certain glycoproteins or glycolipids specific to the epithelial cells of the mucous membrane of a particular tissue

• detection (detected by sensors- where the host must deciminate whether it is itself or a nonself aka pathogen)
• attack (attaked by various mechanisms)

• PRRs = Pattern Recognition Receptors
• PAMPs = Pathogen-Associated Molecular Patterns

• recognize particular molecular pattern; also present in host
• membrane-bound toll-like receptors (TLR)
• each TLR reacts with specific microbial product

such patterns are found in pathogens; NOT in the host

• Mannose-binding lectin (MBL)
• C-reactive protein (CRP)
• --these soluble mediators are able to activate complement system
• --when a pathogen bears PAMP recognized by these mediators (MBL or CRP), the complement system will be activated and the pathogen will be targeted

is the collection of proteins that makes a hole in the cell membrane of the targeted microbees and kills the pthogen by lysis; also promotes uptake of microorganisms by phagocytosis

the activation cascase of complements can be activated by mannose-binding lectin (MBL) and C-reactive protein (CRP) that recognize PAMPs

adtibodies bind to specific foreign antigens and activates complement

contain TLRs which allow them to detect a broad spectrum of pathogens

• phagocyic activity (innate immunity)
• and the activated macrophages also secrete cytokines (also innate immunity)

internalize antigen, processed, and then present to T cells (adaptive immunity) and also secrete cytokines (innate immunity)

• swelling, redness, heat, pain
• there is an increase in vascular diameter (vasodilation), rise of blood volume in the area, heat, and redden the tissue
• accumulation of fluid swells the tissue (edema)

• come to inflamed region
• phagocytose
• release molecular mediators

• neutrophils
• they must recognize the inflamed endothelium
• they must adhere strongly (because blood cells are always moving)

extravasation

• rolling: attach loosely to the endothelium
• activation by chemoattractant stimulus
• arrest and adhesion
• transendothelial migration

• vascular endothelium
• (selectin and mucin)

• defensins
• cathelicidins
• interferons

complement and acute phase proteins

• disrupting microbial membranes
• by inhibiting the synthesis of DNA, RNA and proteins of the invaders

• a groups of serum proteins that increase in concentration in response to inflammation (some complements, MBL, interferons)
• LIVER is one of the most important sites

the increase of acute phase protein after infection (innate immune system)

Cytokines (TNF-alpha, IL-1, and IL-6)

• TLR
• MBL and CRP (soluble PRR, bind to microial surfaces, promoting phagocytosis, making the invader ready for complement-mediated lysis)
• Lypopolysaccharide-binding protein (LBP - recognizes and signals a response to lipopolysaccharide)
• Nucleotide-binding oligomerization domain (NOD - cytosolic, two members NOD1 and NOD2, recognize products derived from bacterial peptidoglycans
• Scavenger receptors (present in the macrophages and many types of dendritic cells, involved in binding and internalization of gram-positive and gram-negative bacteria, phagocytose apoptic host cells)

membrane-spanning proteins, share a common structual element called leucine-rich repeats or LRR in the extracellular region

TLR

TIR (I= IL-1) which has 3 highly conserved domain (boxes 1,2,3)

• dimmers
• monomers
• or partners yet to be discovered! O_o

a complete set of TLRs

found in the cell walls of gram-negative bacteria

• Neutrophils - in blood
• Macrophages - in tissues
• NK cells - in blood
• Dendritic cells - in lymph

• 1st to migrate from the blood to the sites of infection
• phagocytosis
• TLRs and other pattern recognition receptors are present on their surfaces (TLR2 detects peptidoglycans; TLR4 detects LPS)
• able to attack by both oxidative and nonoxidative
• able to express high levels of inducible nitric oxide synthetase (iNOS)

• phagocytic activity, increased ability to kill ingested microbes, secrete mediators of inflammation
• express high levels of class II MHC molecules
• promote acute phase response
• secrete cytokines and complement proteins
• produce both ROS and RNS
• express high levels of iNOS

• provide 1st line of defense against many viral infection
• able to produce cytokines (INF-gamma and TNF-alpha)

• recognize pathogens
• mature DCs expressed both MHC class I and MHC class II molecules
• capable of generating reactive oxygen species and nitric oxide
• capable to produce antimicrobial peptides
• phagocytic activity

transmission of the signal to the inside of the cell

• signal: a microbial product
• receptor: a PRR on a leukocyte
• signal transduction: by the interactions of specific intracelluar molecules
• the effector mechanism: the action that takes place as a consequence of the signal
• result: the clearance of the invading organism

a system of immunity protects all multicellular organisms from microbial infection and exploitation

progressive accumulation of lipids and fibrous elemments in the arteries

cardiovascular events

• IL-6
• TNF-alpha
• the actue phase response protein CRP

• cholesterol
• LDL
• HDL

monocytes attached to the arterial walls migrate through endothelial cells and differentiate into macrophage

bind lipoprotein particles, internalize them, accumuating lipid droplets and assuming a "foamy" appearance

foamy macrophages

degrade the local extracellular matrix which undergoes some remodeling during repair process

they accumulate more cells and lipids into the newly forming plaque; as a result the artery is narrowed and more susceptible to blackage

blocked arteries in the heart

• an agent of innate immunity
• a mediator of inflammation is also associated with high risk of coronary heart disease

drugs that are able to inhibit cholesterol biosynthesis as well as inflammation

CRP