Dr. H. Aziz Djamal MSc.DTM&H.SpMK(K) 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

Complement Ex. Extremely pain……Activate the C3 Complement via alternative pathways…C3a and others…anaphylatoxin…receptor on capillary endothelial…vasodilatation, increase permeability…massive leakage of the plasma…shock..(anaphylactic shock)

Antibody Ex.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 complement…Inflammation…Tissue injury…Ex. Rheumatic Heart Disease

Cytokines Mostly 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 Body Biological Product From: Animal Parasite Bacteria Fungi Virus

Biological Product from Animal Ex. Venoms produced by Snake, Scorpion,Bee…very strong venom, activate Complement C3 via alternate pathway…receptor on capillary endothelial…vasodilatation…increase permeability…massive leakage of serum…shock ( anaphylactic shock )

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

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

Bacterial Product Bacterial Product that Penetrate the host Defence: Capsule Component of Cells Wall Enzymes

Enzymes Leukocidins. Hemolysin Streptolysin Coagulase. Bacterial Kinase. Hyalorunidase. Collagenase. Lecithinase. Siderophore.

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

Three Principle of Exotoxin Citotoxin 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 Product CPE. Inclusion Body. Syncitia or Giant Cells. Interferon.

Fungi Biological Product Damaged cells and human tissue Sclerotia. Ergot. Aflatoxin. Mycotoxin

Bacterial capsules Some 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 Damage Ex. 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 enzyme Catalyses 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, Streptolysin Making a protein channel on Cytoplasmic membrane…cause cell death

Viral component that caused cellular damaged CPE : 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 Exotoxin Figure 15.5

Damaging capacity of exotoxin Ex. Shiga and Vero toxin. Attach as ligand on the receptor the cell… activate thre formation of porin…release the cytoplasm component… death of the cell

The Action of an A-B Exotoxin Figure 15.5

Ex. Neurogenic toxin Tetanus toxin : Block the release of relaxing signal from CNS on neurological synapse…spasstic , block the release of Glycin on the synapse Botulinum toxin : Block the release of Acetyl choline on the neurological synapse

Action of Tetanus Neurotoxin Tetanus causes irreversible muscle _________________ (‘spastic paralysis’ or ‘lockjaw’)

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

Enterotoxin activity Ex. Vibrio cholerae enterotoxin After 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.)

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