Week 102: Swollen Finger Flashcards
Why are abscesses hard to treat?
- No blood supply
- Antibiotics need actively dividing cells to work
- Chemical nature of pus can interfere with antibiotics
⇒ Antibiotics can’t get there, work and can be damaged!
Autocrine cytokines
Work on themselves
Parakryne cytokines
Work on surrounding cells
Endocrine cytokines
Enter the blood stream - e.g. insulin
What are toll-like receptors?
- A class of proteins that play a key role in the innate immune system and digestive system
- Single, membrane-spanning, non-catalytic receptors
- Found in sentinel cells such as macrophages and dendritic cells
- Recognise structurally conserved molecules derived from microbes
- Once these microbes have breached physical barriers such as the skin or intestinal tract mucosa, they are recognized by TLRs, which activate immune cell responses
What are interleukin receptors?
Cytokine receptors for interleukins
What are interleukins?
- A group of cytokines (secreted proteins and signalling molecules) that are expressed by leukocytes (white blood cells)
- Mainly synthesised by helper T cells
- Help development and differentiation of T lymphocytes, B lymphocytes and hematopoietic cells
What are NOD-like receptors?
- Large family of cytoplasmic proteins that contain leucine-rich repeats which bind to bacterial components
- NOD1 and NOD2 recognise fragments of bacterial cell wall proteoglycans, and are found at particularly high amounts in the epithelial cells that line the gut
What is transferrin?
- Takes up iron from environment and blood stream
- Microorganisms need iron so deprives
What are interferons?
- A family of proteins produced rapidly by many cells in response to viral infections, which block the replication of virus in the infected cell and neighbour
- Have a role in communication between immune cells
Fibronectin
- Same as a complement protein, opsonisation (attaches and labels for immune system)
What are defensins?
- Antimicrobial peptides, particularly important in the early protection of the lungs and digestive tract against bacteria
⇒ Innate immune system
What are lysozymes?
- An enzyme secreted by macrophages that attacks the cell wall of some bacteria
⇒ Innate immune system
What is the complement?
- A group of proteins present in serum which when activated produce widespread inflammatory effects, as well as lysis of bacteria etc.
- Some bacteria activate complement directly, while others only do so with the help of antibodies
⇒ Innate immune system
What is lysis?
- Irreversible leakage of cell contents following membrane damage
- In the case of a bacterium this would be fatal to the microbe
⇒ Innate immune system
What is a mast cell?
- Large tissue cell that releases inflammatory mediators when damaged, and also under the influence of antibody
- By increasing vascular permeability, inflammation allows complement and cells to enter the tissues from the blood
⇒ Innate immune system
What is a PMN (polymorphonuclear leucocyte)?
- 80% of the white cells in the human blood
- Short-lived scavenger blood cell whose granules contain powerful bactericidal enzymes
- Peculiar shaped nuclei
- Comes from the bone marrow
⇒ Innate immune system
⇒ Classed as a myeloid cell
What are macrophages?
- Large tissue cell responsible for removing damaged tissue, cells, bacteria, etc
- Comes from the bone marrow
⇒ Innate immune system
⇒ Classed as a myeloid cell
What are dendritic cells?
- Present antigens to T cells
- Initiate all T-cell-dependent immune responses
⇒ Innate immune system
What is phagocytosis?
- ‘Cell eating’
- Engulfment of a particle by a cell
- Macrophages and PMNs are the most important phagocytic cells
- The majority of foreign materials entering the tissues are ultimately disposed of by this mechanism
⇒ Innate immune system
What is cytotoxicity?
- Macrophages can kill some targets (perhaps including tumour cells) without phagocytosing them and there are a variety of other cells with cytotoxic abilities
⇒ Innate immune system
What are natural killer cells?
- A lymphocyte-like cell capable of killing some targets, notably virus-infected cells and tumour cells, but without the receptor or the fine specificity characteristic of true lymphocytes
⇒ Innate immune system
What are antigens?
- A substance that stimulates the production of antibodies
- Term applied to any type of adaptive immune response
- Foreign and either particulate (e.g. cells, bacteria) or large protein or polysaccharide molecules
⇒ Adaptive immune system
What is specificity?
- Denotes the production of an immune response more or less selective for the stimulus, such as a lymphocyte that responds to, or an antibody that fits a particular antigen
⇒ Adaptive immune system
What is a lymphocyte?
- A small cell found in blood, from which it recirculates through the tissues and back via the lymph, policing the body for non-self material
- Its ability to recognise individual antigens through its specialised surface receptors and to divide into numerous cells of identical specificity and long lifespan makes it the ideal cell for adaptive responses
- Two major populations of lymphocytes: T and B cells
⇒ Adaptive immune system
What are B lymphocytes?
- Secrete antibodies, the hum oral element of adaptive immunity
⇒ Adaptive immune system
What is an antibody?
- Major fraction of serum proteins, often called immunoglobulin
- It is made up of a collection of very similar proteins each able to bind specifically to different antigens, and resulting in a very large repertoire of antigen binding molecules
- Antibodies can bind to and neutralise bacterial toxins and some viruses directly but they also act by opsonisation (attachment and labels for immune system) and by activating the complement on the surface of invading pathogens
⇒ Adaptive immune system
What are T lymphocytes?
- T = thymus derived
- Further divided into subpopulations that ‘help’ B lymphocytes, kill virus infected cells, activate macrophages and drive inflammation
⇒ Adaptive immune system
What is opsonisation?
- A phenomenon whereby antibodies bind to the surface of bacteria, viruses and other parasites, and increase their adherence and phagocytosis
- Antibodies also activate complement on the surface of invading pathogens
- Adaptive immunity thus harnesses innate immunity to destroy many microorganisms
What is the complement?
- The complement is often activated by the antibody bound to microbial surfaces
- Binding of a complement to antigen can also greatly increase its ability to activate a strong and lasting B-cell response
- Once activated the complement can damage some cells and initiate inflammation
- Some cells possess receptors for complement which can assist the process of phagocytosis
- An example of reverse interaction between adaptive and innate immune reaction
What is presentation?
- Presentation of antigens to T and B cells by dendritic cells is necessary for most adaptive responses
- Presentation by dendritic cells usually requires activation of these cells by contact with microbial components
- An example of reverse interaction between adaptive and innate immune reaction
What is the ‘help’ provided by T cells?
- Required for many branches of both adaptive and innate immunity
- T-cell help is required for the secretion of most antibodies by B cells for activating macrophages to kill intracellular pathogens and for an effective cytotoxic T-cell response
What is mannose-binding lectin (MBL)?
- MBL binds the surface of bacteria and fungi, and can activate the complement or act directly to assist phagocytosis
⇒ Innate immune system
What are acute phase proteins?
- Complex set of serum proteins
- These proteins are mostly present at very low levels in serum but rapidly produced in high amounts by the liver following infection, where they contribute to inflammation and immune recognition
- Several acute phase proteins also function as PRRs
⇒ Innate immune system
What are pattern-recognition receptors (PRRs)?
- Can be described for every type of pathogen
- Can be broadly divided in terms of cellular localisation, e.g. cell membrane, endosome/phagosome, cytoplasm
- Regulate the innate immune response to infection
- Not all PRRs are found on all types of cell, the majority being restricted to macrophages and dendritic cells
What are virus receptors?
- To enter a cell, a virus has to ‘dock’ with some cell surface molecule
- E.g. CD4 for HIV and the acetylcholine receptor for rabies
What are cytokine receptors?
- They communicate between immune cells is largely mediated by messenger molecules known as cytokines
- To respond to a cytokine, a cell needs to possess a receptor for it
What are hormone receptors?
- Like cytokines, hormones (e.g. insulin and steroids) will only act on cells carrying the appropriate receptor
How do beta-lactam antibiotics work?
Form covalent bonds with penicillin-binding proteins to inhibit final formation of cross-links
How do glycopeptide antibiotics work?
Inhibit the release of building block unit from the cell membrane
What are 3 examples of beta-lactam antibiotics?
Flucloxacillin
Amoxicillin
Cefuroxime
⇒ Penicillins, cephalosporins, carbapenems
How do quinolone antibiotics work?
Inhibit DNA gyrase enzyme to prevent supercoiling of bacterial DNA
What are 2 examples of quinolone antibiotics?
Ciprofloxacin
Levofloxacin
What are 2 examples of glycopeptides?
Vancomycin
Teicoplanin
What would the best antibiotic for a staph/skin infection be?
Flucloxicillin
What would the best antibiotic for strep infection be?
Amoxicillin
What is the best antibiotic for treating anaerobic infections?
Metronidazole
What is the best antibiotic in treating an abscess?
Metronidazole
What would be the best antibiotic for use in penicillin resistant infections?
Coamoxiclav
What is the side effect of penicillin?
Hypersensitivity reaction
What are the side effects of tetracyclines?
Stains teeth and bones in growing people
What is a side effect of rifalprocin?
Orange body excretions (including tears)
What do aminoglycosides and glycopeptides do?
Inhibit cell wall synthesis
What do aminoglycosides and glycopeptides cause?
Nephrotoxicity
Ototoxicity
What are 2 examples of aminoglycosides and glycopeptides?
Gentomycin
Vancomycin
What is best for an eye or ear infection?
Chloramphenicol
What are two examples of antimetabolites?
Suplonamide
Trimethoprim
What is best in treating a kidney infection?
Trimethoprim
What is specificity?
Which bacteria definition - mainly what should be attacked
What does bacteriostatic mean?
Stops bacteria growing
What is bactericide?
Kills bacteria
What is empirical choice?
Based on information
- Based on most likely organism from history
What is minimum inhibitory concentration?
Minimum amount needed to inhibit bacteria
What is the best treatment for strep in skin infections?
Penicillin V
What are two examples of antibiotics used in fungal treatments?
Micanazole
Chlotramazole
What percentage of neutrophils are in circulation?
10%
What are the signs of acute inflammation?
Redness Swelling Heat Pain Loss of function
What does rifampicin do?
Inhibit RNA polymerase to prevent transcription of mRNA
Which categories of antibiotics inhibit protein synthesis?
Macrolides
Tetracyclines
Aminoglycosides
What are two examples of macrolides?
Erythromycin
Clarithromycin
What are two examples of tertracyclines?
Doxycycline
Tetracycline
What are two examples of aminoglycosides?
Gentamicin
Amikacin
What are antimetabolytes?
Folate is required for DNA synthesis
What do sulphonamides do?
Prevent folate synthesis (bacteriostatic)
Enzyme is dihydrofolate synthetase)
What do trimethoprims do?
Prevents dihyfrofolate becoming tetrahydrofolate
