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…