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 :

A. From Inside Human Body : 1. Complement. 2. Antibody. 3. Cytokines

Complement
Ex. Extremely painActivate the C3 Complement via alternative pathwaysC3a and othersanaphylatoxinreceptor on capillary endothelialvasodilatation, increase permeabilitymassive leakage of the plasmashock..(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 complementInflammationTissue injuryEx. 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: A. Animal B. Parasite C. Bacteria D. Fungi E. Virus

Biological Product from Animal

Ex. 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 Parasites

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

Enzymes
1. 2. 3. 4. 5. 6. 7. 8. 9. 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

1. 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

1. 2. 3. 4. CPE. Inclusion Body. Syncitia or Giant Cells. Interferon.

Fungi Biological Product Damaged cells and human tissue

1. Sclerotia. 2. Ergot. 3. Aflatoxin. 4. 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 membranecause 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 porinrelease 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 synapsespasstic , 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 releasedtoxin get into the intestinal mucosalcell activate the adenylate enzymatic cascadeproduced cyclic -5-AMP- accumulation of cell energy- activate the secretion of water and electrolyte from the to intestinal lumenproduced severe secretoric diarrhea

Action of cholera enterotoxin (cont.)

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