Biological Products/Agents and Their Impact on Human Cells, Tissue and Their Related Diseases Dr. H. Aziz Djamal MSc.DTM&H.SpMK(K)

Biological Product Induced Human Cells and Tissue Damage : From Inside Human Body :Complement.Antibody.Cytokines

ComplementEx. Extremely painActivate the C3 Complement via alternative pathwaysC3a and othersanaphylatoxinreceptor on capillary endothelialvasodilatation, increase permeabilitymassive leakage of the plasmashock..(anaphylactic shock)

AntibodyEx.Antibody ( mostly IgG) produced inside human body against self antigen, due to similarity structure to the intruder agent (ex. Streptococcus Beta Haemolyticus group A)Antibody attach to related Ag activate complementInflammationTissue injuryEx. Rheumatic Heart Disease

CytokinesMostly activated by biological product from outside human body. Ex. Pro-inflammatory citokines (Interleukin 1 and TNF alpha) in Avian influezae infection.Massive destruction of both side of human lung

B. From Outside Human BodyBiological Product From:Animal ParasiteBacteria FungiVirus

Biological Product from AnimalEx. Venoms produced by Snake, Scorpion,Beevery strong venom, activate Complement C3 via alternate pathwayreceptor on capillary endothelialvasodilatationincrease permeabilitymassive leakage of serumshock ( anaphylactic shock )

Ex. Cats hair (other products), allergenic to some people induced IgE productionat the following contacts. Cytophylic IgE at Mast bound to Allergen sending signal to Mast CellDegranulated Mast CellVasoactive amine release ( Histamine etc ).Target organ.Vasodilatation on capillary and constriction on bronchus.Hypersensitivity type 1.

Biological Products of the ParasitesEx. Ascaris lumbricoides by products ( Slims) and dead body of adult wormallergenic induced IgE production and eosinophilic hypersensitivity.Ex. Larvae of Ascaris lumbricoides, Hook worm ( A.duodenale, N. americanus ) travel to Lungcaused lung tissue damage and Pneumonitis

Bacterial ProductBacterial Product that Penetrate the host Defence:CapsuleComponent of Cells WallEnzymes

EnzymesLeukocidins.HemolysinStreptolysinCoagulase.Bacterial Kinase.Hyalorunidase.Collagenase.Lecithinase.Siderophore.

Bacterial product Damaging the cells and tissue Production of Toxin Exotoxin Endotoxin

Three Principle of ExotoxinCitotoxin a. Shiga toxin. c. Diphtheriae toxin. b. Verotoxin. d. Erythrogenic toxin. 2. Neurotoxin a. Tetanus toxin. b. Botulinum toxin 3. Enterotoxin a. Vibrio enterotoxin. b. Staphylococcal enterotoxin

Viral Structural ProductCPE.Inclusion Body.Syncitia or Giant Cells.Interferon.

Fungi Biological Product Damaged cells and human tissueSclerotia.Ergot.Aflatoxin.Mycotoxin

Bacterial capsulesSome bacteria produced strong capsule consist of polysacharide polymer : Pneumococcus, Klebsiella pneumoniae, Neisseria gonorrhoe , Haemophylus influenzae, Bacillus anthracis etc.

Anti-phagocytic activity.Toxycitic capacity.

Cell Wall Component That Induced Cell and tissue DamageEx. Lipid component ( Polymer of Mycolic acid ) on Mycobacterium tuberculosis cell wall posses a strong anti-phagocitic activity, resist the intracellular digestion.Ex. Lipopolysaccharide component of Salmonella typhi cell wall possesed an endotoxic activity.

Biological activity of Bacterial enzymeCatalyses the hydrolysis of the related component :Hyaluronidase produced by Staphylococcus sp and Streptococcus sp caused hydrolysis of hyalin component of human tissue such on skin and mucose

Leukocidin, Haemolysin, StreptolysinMaking a protein channel on Cytoplasmic membranecause cell death

Viral component that caused cellular damagedCPE : It is due to the burst of the infected cell over load of viral component.Inclusion Body : Unassembly viral components such as in Rabies infection- Negri Body.Syncitial / Giant Cell : Fusion of cytoplasmic membrane of the infected host cell by viral unassembly protein.Interferon : Glycoprotein production by viral infected cell that inhibit the role of the remaining receptor

The Action of an A-B ExotoxinFigure 15.5

Damaging capacity of exotoxinEx. Shiga and Vero toxin. Attach as ligand on the receptor the cell activate thre formation of porinrelease the cytoplasm component death of the cell

The Action of an A-B ExotoxinFigure 15.5

Ex. Neurogenic toxinTetanus toxin : Block the release of relaxing signal from CNS on neurological synapsespasstic , block the release of Glycin on the synapseBotulinum toxin : Block the release of Acetyl choline on the neurological synapse

Action of Tetanus NeurotoxinTetanus causes irreversible muscle _________________ (spastic paralysis or lockjaw)

Action of Botulinum NeurotoxinBotulinum toxin, the most poisonous substance known, causes irreversible muscle _________________ (flaccid paralysis).

Enterotoxin activityEx. Vibrio cholerae enterotoxinAfter bacterial colonization- toxin released-toxin get into the intestinal mucosalcell activate the adenylate enzymatic cascade-produced cyclic -5-AMP- accumulation of cell energy- activate the secretion of water and electrolyte from the to intestinal lumen- produced severe secretoric diarrhea

Action of cholera enterotoxin (cont.)