Recurrente Infections With Catalase Positive Organisms In Chronic Granulomatose Disease (CGD)

Medically Important Fungi

Dr Warhol’s Periodic Table of Microbes

56. Ba. Bacillus

There are more than 300 species of Bacillus, which is a whole whopping load of microbes. Just to wrap your head around that number, if you talked about each one for 1 minute you’d be talking nonstop for 5 hours! Take that TedTalks!

Starting with the basics, these organisms found all over the world, predominantly in soil but microbes go where they please, so they have been found in undersea hydrothermal vents as well as in the stratosphere. They are rod-shaped and form spores.

Just to list a few of the most noteworthy and awesome Bacillus species:

Abyssalis: found more than a mile and a half down at the bottom of the South China Sea.

Anthracis: causative agent of Anthrax, the disease, not the band; death, disease, toxins, yahoo!

Azotofixans: fixes nitrogen.

Canaveralius: StarFleet Academy space bacteria living on the walls of the Kennedy Space Center!

Cereus: you get to play with this in General Microbiology, a pathogen causing foodborne illness.

Decolorationis: for you art history majors, isolated from decaying parts of a mural in the Roman necropolis in Carmona, Spain.

Megaterium: it can consume cave paintings.

Stratosphericus: found in high concentrations orbiting the Earth with satellites around 6 miles up!

Subtilis: the grass bacillus; used for industrial enzyme secretion.

Thuringiensis: absolutely famous for producing the BT toxin used as a natural insecticide.

Bacillus cells are Gram positive rods that measures about 1 micron wide by 4 to 10 microns long, but with more than 300 species you will see a range of sizes.

Everyone needs their own Periodic Table of Microbes from https://www.etsy.com/no-en/shop/WarholScience.

Copyright 2016 Warhol.

Innate Immunity - intro

First line of defence + first to act

A primitive response (exists in animals and some plants)

Non-specialised and without ‘memory’

Consists of:

Physical barriers (eg skin and mucosa//tight junctions, airflow)

Chemical barriers (eg enzymes, lung surfactant, antimicrobals)

Soluble mediators of inflammation (eg cytokines)

Microbal defence (eg commensal competition, secreted antimicrobals)

Cells (eg phagocytes)

Receptors to recognise presence of pathogen/injury - results in inflammation

Soluble Mediators

Complement Proteins

liver-derived 

circulate in serum in inactive form

activated by pathogens during innate response

functions include lysis, chemotaxis and opsonisation

Auxiliary Cells

Mediate inflammation as part of the immune response. The main auxiliary cells involved in the immune response are Basophils, Mast cells and Platelets.

Basophils 

Leukocyte containing granules 

on degranulation release histamine + platelet activating factor

causing increased vascular permeability and smooth muscle contraction

also synthesise and secrete other mediators that control the development of immune system reactions

Mast Cells

Also contain granules 

However they are not circulating cells - found close to blood vessels in all types of tissue especially mucosal and epithelial tissues.

rapidly release inflammatory histamine but this is IgE dependant so not innate

Platelets 

normally function in blood clotting

also release inflammatory mediators

Cytokines and chemokines

Produced by many cells but especially mØ (macrophages), initiate inflammatory response and act on blood vessels 

interferons - antiviral protection

chemokines - recruit cells

interleukines - fever inducing, IL-6 induces acute phase proteins 

IL-1 - encourages leukocytes to migrate to infected/damaged tissue

as does tumour necrosis factor (TNFa)

Acute phase proteins

Liver derived proteins 

plasma concentrations increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation

called the acute-phase reaction 

triggered by inflammatory cytokines ( IL-1, IL-6, TNFα)

help mediate inflammation ( fever, leukocytosis, increased cortisol, decreased thyroxine, decreased serum iron, etc)

activate complement opsonisation 

Inflammation 

Cells

Cytotoxic Cells

Eosinophils/natural killer cells, cytotoxic T cells

kill target via release of toxic granules 

dendritic cell derived IL-12 helps activate NK cells

Phagocytes

mono-nuclear = long-lived; polynuclear = short-lived

engulf, internalize and destroy 

phagosome forms around microbe

enzyme filled with lysosomes fuses to form phagolysosome

organism is digested

fragments are either ‘presented’ or exocytosed

phagocytosis requires recognition of microbe via receptors for

PAMPs (pathogen associated molecular patterns - eg flagella or capsule) - recognised by toll-like receptors 

activated complement

antibody

The innate immune response primes for the adaptive 

B-cells are primed by activated complement

Th1 cell differentiation needs pro-inflammatory cytokines

MORE MIXED MNEMONICS

It’s Medical Mnemonics Monday!

Renal Papillary Necrosis is a form of nephropathy characterized by coagulative necrosis of the renal medullary pyramids and papillae.  

Causes of Papillary Necrosis can be remembered by the mnemonic “POSTCARDS”.

P yelonephritis

O bstruction of the urogenital tract

S ickle cell disease

T uberculosis

Chronic liver disease,

A nalgesia /A lcohol abuse,

R enal transplant rejection

D iabetes mellitus

S ystemic vasculitis

Check out the list of the previous Medical Mnemonics here.

Passive Immunotherapy

Active immunotherapies:

Cytokines (TNFa IL-2, IFNs)

Cancer vaccines

tumour CTL and APC

DC priming

Passive immunotherapy:

Administration of monocolnal (clone derived asexually from a single individual or cell) antibodies which target either tumour-specific or over expressed antigens

Generally comprised of antibodies made outside of the body (in a lab)

administered to patients to provide immunity against a disease, or to help fight existing disease

do not stimulate a patient’s body to ‘actively’ respond to a disease the way a vaccine does

immunogen is given several times to induce a strong secondary response

blood serum contains many different antibodies to the immunogen

most immunogens have multiple antigenic epitopes 

each stimulates a different B cell clone/receptor –> polyclonal antibody (PAb) response 

Monoclonal antibody (mAb) therapy is the most widely used form of cancer immunotherapy. Monoclonal antibodies cannot be purified from a polyclonal sample and are derived from a single clone/specific for a single epitope.

Antibodies in cancer therapy:

Trigger immune system to attack cancer cells 

Block molecules that stop the immune system working (checkpoint inhibitors)

 Block signals telling cancer cells to divide 

Carry drugs or radiation to cancer cells

Checkpoint inhibitors

Immune system uses particular molecules to stop it being over activated and damaging healthy cells  - these are known as checkpoints

some cancers make high levels of checkpoint molecules to switch of immune system T cells which would normally attack cancer cells

examples of targets include CTLA-4, PD-1 and PD-L1 (programmed death ligand 1)

Blocking cell division signals 

Cancer cells often express large amounts of growth factor receptors on their surface –> rapid cell division when growth factors stimulate them

some monoclonal antibodies stop growth factor receptors working

either by blocking the signal or the receptor itself 

cancer no longer gets signal to divide

Carrying drugs/radiation

drugs or radioisotopes can be attached to monoclonal antibodies

the mAB binds to the cancer cell, delivering directly

known as conjugated MABs

Yesterday’s notes featuring actual winter sunshine!!