Infectious diseases
Feb 24, 2016
Infectious diseases
What is a pathogen?
What is a pathogen?
Pathogen- from Greek pathos (emotion/suffering); gene – to give birth toAn agent causing illness or disease in the host/ an infectious particle able to produce disease
Are all pathogens infectious?
• Not necessarily
Infectious agents
• Pathogenic bacteria• Pathogenic viruses (not considered organisms)• Pathogenic fungi• Pathogenic protists (protozoa)• Pathogenic parasites – e.g. helminth worms• Pathogenic prion (not organisms)
What are the top ten infectious diseases?
10. Smallpox9. Typhoid
8. Influenza7. Bubonic Plague
6. Cholera5. Anthrax4. Malaria
3. SARS Coronavirus2. EBOLA or Nanta haemorrhagic virus
1. HIV
WHO
Non-specific defences: External Defences
6.3.3: Outline the role of skin and mucous membranes in defence against pathogens
Routes of infection
Innate Immunity: commensal (non-pathogenic) bacteria
• Of the 100 billioncells in our bodies, only 10 billion are actually human cells!
• The rest are commensal bactseria, fungi, protozoa and even arhropods!
• They perform essential housekeeping functions in our bodies…
Summary of external defences
Anatomical Defences– skin– mucous membranes
Body secretions/excretions– mucous– tears, saliva, urine (wash-out)– Lysozyme (antibacterial
enzymes) in tears/nose/saliva– lactoperoxidase in breast milk– Acidic pH (sweat, urine, gastric
fluid, vaginal secretions)– Zinc and spermine in semen
Normal commensal flora– Inhibitory substances– Compete for nutrients
CiliaMucociliary escalator in respiratory tract
Drug treatment of infection – Antibacterials, Antifungals and antiviral treatments
Antibiotics• Many antibiotics are naturally
produced by saprotrophic organisms (fungi and bacteria) in order to compete for the dead organic matter on which they feed
• Many antibiotics are produced by fungi, to inhibit bacterial growth
• Some antifungals are produced by bacteria to inhibit fungal growth
Organism Antibiotic Mechanism of action
Fungi
Penicillium sp. Penicillin Inhibits cell wall synthesis
Cephalosporium spp. Cepahlosporin Inhibits cell wall synthesis
Streptomyces sp. Tetracycline, Streptomycin Inhibits translation
Saccharopolyspora spp. Erythromycin Inhibits translation
Bacteria
Bacillus spp. PolymyxinBacitracin
Disrupts cell membranesDisrupts Cell wall synthesis
Culture and sensitivity testing
How do antibiotics work?
• Antibiotics block metabolic pathways which are specific to bacterial or fungal cell metabolism/replication (but are absent or different in eukaryotic animal cells):
• Cell wall synthesis• Cell membrane function• DNA replication• Transcription and translation of RNA (remember
that the 70 S prokaryote ribosome differs from the eukaryotic 80 S ribosome)
How do antibiotics work?
• A great wee animation
Antibiotics can be bacteriostatic OR bactericidial
Bacteriostatic drugs inhibit replication and growth of the bacteria (maintain bacteria in a stationary phase of growth):• May act on cell metabolism –
specific prokaryotic enzymes• May inhibit DNA replcation,
transcription or translation• Work in concert with the
immune system• (Chloramphenical,
macrolides, tetracyclins)
Bactericidal drugs KILL bacteria• May disrupt the
integrity of the cell wall• May act on essential
metabolic pathways – specific prokaryotic/fungal enzymes
The definition bacteriostatic/bacteriocidal is an oversimplification
• It depends on the DOSE of drug used• It depends on the efficacy of the host innate
defence system• It depends on ability of the drug to penetrate
the infected tissue (e.g cross the blood brain barrier in meiningitis, penetrate bronchial secretions in pneumonia, penetrate cells for intracellular bacterial infection)
Antibiotics were (once) miracle drugs
• the paradox of the antibiotic miracle drug
Do antibiotics work on viruses?
• Obviously not!!!• This hyperlink introduces the whole complicated world of viral replication…
Antiviral agents
Acyclovir Highly specific for Herpes Viruses – disables viral DNA replication
TamifluSpecific for Flu virusMay accelerate alleviation of symptoms by 12 hResitance has been recorded
Interferon Treatment
• Interferon is a naturally produced protein (cytokine) which is produced in response to viral infection
• It has been used for treatment of HIV, Hepatitis C and certain types of cancer
Innate immunity begins with the inflammatory response
• the inflammatory response
Blood components
Respond to parasitic infections
Involved in allergic reactions
Phagocytes
• Neutrophils (polymorphonuclear neutrophils)(most abundant, 60 – 70%)
• Macrophages: circulating or ‘marginal’ (Big devourers)
• Dendritic Cells
Phagocytes
Macrophages
Neutrophils
• Most common type of white blood cell (50 – 70%)
• Phagocytic – but die immediately!
• First immune cells to reach a site of infection – attracted by chemotaxis
• PUS is made of dead neutrophils (that’s what makes pus white…)
Dendritic Cells
A dendritic cell slide show…
• Dendritic Cells are beautiful...
Phagocytosis (1)
Phagocytosis (2)
The process of phagocytosis
Begins with chemotaxis (attraction by chemicals:– inflammatory mediators, chemicals released by the
damaged cell membrane– ‘foreign’ proteins produced by the pathogen and
recognised by ‘Toll like receptors’
Phagocytosis
• Animation• Endocytosis• phagosomes• Lysosome organelles• Eventual exocytosis of
debris• Antigen presentation to
the immune system
Natural Killer CellsThe NK releases "perforin" molecules onto the target
cell, which punches holes in its plasma membrane. The
NK cell then releases cytotoxins which will induce apoptosis (programmed cell
death) in the target cell. Nasty!! )
Watch them in action…
‘Adaptive’ Immune response: disease-specific cellular and humoral response
Adaptive Immunity: Lymphocytes and the antigen-antibody complex
Humoral response: Antibodies
Cellular response: T cells and B cells
Distinguish between antigens and antibodies…
Antigen (Epitope)Any ‘non-self’
substanceA substance or molecule, often found on the surface of a cell or virus, that stimulates antibody formation
AntibodyA special protein synthesised in the shape of a Y, whose top contains an antigen-binding site
Antigens and antibodies in blood
Lymphocytes: The ‘cellular’ immune response
• Lymphocytes are essential for both cell mediated (phagocyte attraction) and humoral (antibody mediated) immunity• T and B lymphocytes have different functions!
• Both types originate in the bone marrow• T cells mature in the Thymus• B cells mature in the bone marrow• Lymphocytes are selective for just ONE antigen. When a new
invading organism arrives, the correct lymphocyte must be chosen to multiply and produce many identical lymphocytes, specific for the infection. This is clonal selection
There are several types of T cells1. T ‘helper’ cells (also called CD4+)2. Memory T cells3. Cytotoxic T cells (also called CD8+)
• T helper cells activate macrophages and other phagocytes; some are involved in B-lymphocyte differentiation
• Cytotoxic T cells attach cells, releasing destructive enzymes, inducing apoptosis (programmed cell death)
• MEMORY cells remain in the body for years, and will multiple if the same antigen is presented a second time
What do T cells do?
• They have special receptors that recognise antigen fragments on the surface of infected or cancerous cells
• Some T cells regulate and direct the imune response (attract phagocytes, stimulate B cells to produce antibodies)
• Some T cells are KILLERS – directly attach infected or neoplastic cells
The central role of HELPER T cells
• Secrete active chemicals called ‘cytokines’, which stimulate the non-specific immune response, and stimulate appropriate specific immune responses
• ‘Conductors’ of the immune system: co-ordinate activity of the other cells involved in immune response
• ‘Generals’ of the immune system – they call up armies of B cells, TH cells and cytotoxic cells to join the battle…
HIV glycoprotein GP120 binding to CD4 receptor
Cytotoxic T cells attack specific pathogens
There are two types of B Cell• B cells are stimulated to produce
antibodies• They are powerless to attack
infected or damaged cells• Each B cell is programmed to
make one specific type of antibody• When triggered, it gives rise to
many large plasma cells, which synthesise antibodies
• B memory cells remember an infection, so that the second immune response to an infection will be faster and stronger
Mounting an immune repsonse1. A specific antigen type is identified (e.g. proteins on flu virus)2. A specific B lymphocyte responds and is able to produce an
antibody that can bind to the antigen(e.g. proteins on flu virus)3. The B lymphocyte matures into a plasma cell and clones itself (by
mitosis) into plasma cells 4. The new army of plasma cells produce hugwe quantities of antibody5. Newly released antibodies circulate in the bloodstream and locate
their antigen match (the proteins on the flu virus)6. The antibodies help to eliminate the infection7. Some of the cloned antibody-producing lymphocytes remain in the
bloodstream as memory cells. If the infection occurs, they will mount a rapid, specific, powerful immune response
How does an immune response work?
• Burnett's Clonal Selection Theory• Simple animation• Antibodies at work
How do antibodies work?• Antibodies are proteins. They bind to a
specific target and lead to destruction of the pathogen through various mechanisms
• This link will tell you more…