Flashcards in Phase 1 - Week 2 (Immunology, Bacteria/Viruses) Deck (83):
What type of organisms are bacteria?
Prokaryotes - their genetic information is not localised within a distinct nucleus and no nuclear membrane is present
Describe genetic information in bacteria
- long double-stranded circular molecules of DNA
- either tightly coiled into a region called the nucleoid or extrachromosomal, present as small, circular, self regulating DNA molecules called plasmids
Describe the organelles present in bacteria
Many metabolic functions are carried out by membrane bound organelles - all bacteria except mycoplasmas have a complex cell wall.
List the possible bacterial cell surface structures/appendages
Capsules, flagella + pilli
Long helical filaments extending from the cell surface which enable bacteria to move in their environment
More rigid that flagella - function in attachment either to other bacteria or to host cells
How to bacteria obtain nutrients?
Mainly by taking up small molecules across the cell wall
How are bacteria classified?
Through Gram staining - as Gram positive or Gram negative
Describe the structure of bacterial cell walls and how this allows for Gram staining
The main structural component of the cell wall is peptidoglycan, it can form a thick external layer (Gram positive) or a thin internal layer (Gram negative)
Mixed polymer of hexose sugars and amino acids
The peptidoglycan forms a thick layer external to the cell membrane, when a gram stain is applied to the bacteria the thick cell wall hold the stain in the cell so it will be stained purple
The peptidoglycan layer is thin and is overlaid by an outer membrane, anchored to lipoprotein molecules in the peptidoglycan. When a gram stain is applied the thin layer will not hold the stain in the cell so it is not stained purple - another stain is applied which stains it pink.
When stained, what colours correspond to:
a) Gram positive bacteria
b) Gram negative bacteria
List the classifications for shapes of bacteria
- Spherical (cocci)
- Rods (bacilli)
- Helical (spirilla)
What determines the rate at which bacteria grow and divide?
The nutritional status of their environment
What must a bacterial cell do prior to division?
Duplicate its genomic DNA
Describe duplication of bacterial DNA
- Transcription - may involve single/multiple genes
- The arrangement of promoter + terminal sequences flanking multiple genes forms an operon
Describe horizontal transfer of bacterial DNA
Plasmids may carry genes that affect resistance to antimicrobials or virulence. Genetic material from plasmids can be carried from one bacterium to another in several ways, which can result in the rapid spread of resistance to antimicrobials.
List the methods of transfer of genetic material
- Transformation - genetic material taken into bacterium through membrane
- Transduction - uses a bacteriophage
- Conjugation - pilli connect bacteria allowing for plasmid transfer
How do bacteria cause infection in humans?
Once bacteria enter a new host they multiply (if conditions are favourable) and many produce toxins which cause the development of disease symptoms. Many disease symptoms are cause by the host's immune response to the bacteria.
Why are bacterial infections harmful/difficult to treat?
Bacteria have short lifespans and produce large numbers of offspring so can quickly adapt to changing conditions. They can evolve to adapt to new hosts or become resistant to treatments and medicines such as antibiotics.
Describe the general structure of viruses
- Much smaller than bacteria
- Contain varying types of nucleic acid contained within a coat or capsid
- The complete unit of nucleic acid + capsid = nucleocapsid, which often has distinct symmetry
- The entire virus can only be the nucleocapsid or the nucleocapsid + an outer envelope/membrane
Describe the types of nucleic acid found in viruses
Linear or circular RNA or DNA
List the types of nucleocapsid symmetry
- Icosahedral (spherical)
- Helical (rod)
Describe the outer envelope of a virus
Lipid bilayer or host cell origin, into which virus proteins and glycoproteins are inserted
What effect does the presence of an outer envelope have on a virus?
Viruses without outer envelopes are generally more resistant (e.g. acid/bile resistant, allowing infection in the GI tract), enveloped viruses are more susceptible to environmental factors e.g. drying, gastric acidity and bile.
List the steps in virus infection
1. Attachment - virion attaches to receptors on cell membrane of host cell
2. Penetration - virion enters host cell (by endocytosis/membrane fusion)
3. Uncoating - virion sheds capsid
5. Assembly - capsid forms around nucleic acid
Describe the steps in replication of a virus
- Synthesis of viral messenger RNA (direct or via host machinery)
- Synthesis of viral protein for new capsids
- Synthesis of viral nucleic acid
Describe the methods by which viral particles can be released following assembly
- Budding through cell membrane - will acquire envelope
- Released following cell death
- Released following cell lysis
How is viral messenger RNA synthesised in DNA viruses?
mRNA is formed using the host's RNA polymerase to transcribe directly from the viral DNA
How is viral messenger RNA synthesised in RNA viruses?
Must use their own polymerase which may be carried in the nucleocapsid
How is viral mRNA translated?
In host cytoplasm using ribosomes to synthesise viral proteins
Describe how retroviruses synthesise new viral DNA
- Virus uses its own reverse transcriptase enzyme to produce DNA from its RNA genome
- DNA is incorporated into the host cell genome by an integrase enzyme
- The host cell then transcribes + translates the viral DNA, producing the components required for new viral particles
Describe the main functional divisions of the immune system
- Innate immune system
- Adaptive immune system
Describe the features of the Innate immune system
1st line defences - physical, chemical + microbiological barriers
2nd line defences - phagocytes, natural killer cells + the complement system
Explain how physical barriers contribute to the 1st line defences of the Innate Immune system
Skin and mucous membranes (epithelial barriers e.g. gut, lungs, eyes/nose) provide a physical barrier which prevents pathogens from entering the body
Explain how chemical barriers contribute to the 1st line defences of the Innate immune system
- Acid secretions in the stomach
- Lysozyme enzyme in tears/saliva
- Low pH of skin due to sweat secreted by eccrine glands
Explain how microbiological barriers contribute to the 1st line defences of the Innate immune system
Normal flora of the gut/skin prevent pathogens from dividing
Describe the phagocytes involved with the 2nd line defences of the Innate immune response
Monocytes which mature into macrophages/neutrophils
How are the Innate and Adaptive immune system linked?
Describe the features of the adaptive immune system
- T lymphocytes: Cytotoxic T cells and Helper T cells
- B lymphocytes
What is the basic function of cytotoxic T cells?
Kill infected cells by apoptosis
What is the basic function of Helper T cells?
Help B cells become activated
What is the basic function of B lymphocytes?
Mature into plasma cells which produce antibodies
Compare the Innate and Adaptive immune response
- No memory
- Immediate standard response
- Recognises pathogen specific molecular patterns
- Heightened response on second exposure
- Clonal expansion
- Unique antigen receptor on each lymphocyte
Name the stains used in Gram staining of bacteria
Crystal violet is used to stain Gram positive bacteria and Safranin is used as a counterstain (stains Gram negative bacteria)
Explain how the immune response starts when a pathogen enters the body
1. Pathogen enters body (e.g. due to break in epithelial barrier due to abrasion of skin)
2. Pathogen is recognised as foreign by pattern recognition receptors (e.g. toll-like receptors) which activate the immune response after recognising the pathogen's specific PAMP (pathogen associated molecular pattern)
3. Inflammatory response is triggered
Describe factors which contribute to the inflammatory response
- Vasodilation - mediators e.g. prostaglandins, capillary widening causes increased blood flow resulting in redness + heat, allows movement of WBCs to injured area
- Increased vascular permeability - mediators e.g. histamine, allows leaking of fluid containing WBCs out of blood vessel to site of injury
- Attraction of WBCs (chemotaxis) - mediators e.g. Leukotriene B
- Systemic response - fever, proliferation of WBCs
List the typical signs of inflammation
1. Redness (rubor) - capillary dilation
2. Heat (calor) - capillary dilation
3. Swelling (tumour) - increased capillary permeability
4. Pain (dolor) - stretching of tissue due to oemdema, mediators e.g. bradykinin, serotonin stimulate pain receptors
5. Loss of function (functio laesa) - movement impaired by pain/swelling
Functions of the inflammatory response
- Helps immune system to coordinate response
- Brings WBC to area
- Protects area from further damage by limiting movement
- Isolates damage
- Promotes healing/tissue repair
Disadvantages of the inflammatory response
- Causes more damage to the body
- Can be triggered unnecessarily (autoimmune, allergies, chronic inflammatory conditions)
- Proteins released by WBCs
- Production stimulated by infection of host cells by pathogens
- Block viral reproduction and stimulate production of antiviral proteins to protect nearby cells from viral infection
- Abundant in blood
- Phagocytise pathogens in acute inflammation
- Contain lysosomes to digest the microbe
- Release soluble mediators
- Short lived
- Contain bacteriostatic and toxic factors
- Mature from monocytes in the blood
- Predominate in chronic inflammation
- Use process of phagocytosis to engulf + digest microbes
- Samples environment
Type of granulocyte which defends the body against multi-cellular parasites
Natural Killer Cells
Induce apoptosis (programmed cell death) in infected cells
List the innate WBCs
- Natural Killer Cells
Release histamine/heparin after they are recruited to the site of injury and inflammation
- Involves a cascade of enzymes
- 3 functions - recruitment of inflammatory cells, opsonisation of pathogens, killing of pathogens
Antigen-presenting cells which have MHC class II proteins. They mature from monocytes in the blood.
Explain how dendritic cells link the innate and adaptive immune system
Antigens from pathogens must be in/on MHC proteins to be recognised by T cells, so dendritic cells take in and present the pathogens and are transported to the lymph nodes via lymph drained from the infected tissue, where they activate specific T cells. Their movement is stimulated by chemokines.
Describe how the structure of lymph nodes allows activation of lymphocytes
Lymph arrives in the node via the afferent vessel and leaves via the efferent vessel. Each node receives lymph draining from tissues - constantly samples the tissue. Nodes contain naive B + T lymphocytes which come into contact with dendritic cells and become activated.
Explain how lymphocytes become activated in the lymph nodes
Dendritic cell presenting the antigen comes into contact with the T cell with the TCR specific to the antigen, binds to it, and causes proliferation of the T cell.
Describe the production of T lymphocytes
- Mature in the Thymus - repertoire of T cells required for life, selection/deletion of autoreactive cells preventing autoimmunity
- Leave Thymus as either CD4 (helper) or CD8 (killer) cells and travel to lymph nodes/spleed to be clonally selected when TCR detects specific antigen.
Explain the mechanism of action of Cytotoxic (CD8) T cells
- Recognise antigens on infected cells
- Induce death of cells - bind, induce cell death (apoptosis) by punching holes in cell membrane using perforin
- Prevent pathogen (e.g. virus) from spreading - sacrifice infected cells
Memory T cells
Can survive for years and allow for rapid response to pathogen if detected in second immune exposure
Describe the action of B cells
- T cell help required for effective proliferation (T:B cooperation)
- Mature into plasma cells which produce antibodies
- Each B cell has specific B cell receptor (BCR) - antibody will have same specificity
- Mature in the bone marrow
- B cell activated, proliferates, produces memory and plasma cells, plasma cells produce antibodies
Describe the structure of antibodies
- Immunoglobin molecules
- Have two heavy chains, two light chains and variable antigen binding sites
- 5 classes - IgG, IgA, IgE, IgM
Describe the action of antibodies
- Secreted into circulation/mucosal surfaces
- Neutralise/eliminate microbes
- Neutralisation - prevent pathogens from entering or damaging cells by binding to them
- Opsonisation - coat pathogen to target it for removal by phagocytosis
- Complement activation - cascade of protein production that either opsonise protein for phagocytosis or lyse it directly by forming a membrane attack complex (MAC)
Why are viruses still a medical problem?
Large population diversity + fast evolution - can exchange genetic material and mutate rapidly.
Gives examples of diseases caused by viruses
- Human papillomavirus
List the classifications of methods by which antibiotics can be used
1. Guided therapy
2. Empirical therapy
3. Prophylactic therapy
- Identify cause of infection and select agent based on sensitivity testing
- Used for mild infections that do not need to be immediately treated/to rationalise therapy in patients already on therapy
- Narrow spectrum - achieve clinical cure with little impact on colonisation + resistance
- Best educated guess therapy based on clinical/epidemiological acumen
- Used when therapy cannot wait for culture - more severe infection (e.g. sepsis, meningitis)
- Need to cover all likely causes
- Broad spectrum - impact on colonisation + resistance may be greater
- Preventing therapy before it begins
- Healthy people exposed to surgery/injury/infected material
- Immunocompromised - HIV, transplantation, splenectomy
Describe the target effects of an antibiotic
- Highly toxic to bacteria causing infection
- Penetrate body area affected by infection
- Limit release of toxins from bacteria
- Convenient administration
Describe the co-lateral damage an antibiotic may cause
- Non-toxic to patient
- Limited effect on colonising bacteria which reduces musosal candida, C. diff infection and selection of resistant bacteria
- Low potential for bacteria to escape treatment through developing resistance
List possible mechanisms of antibiotic action
Acheive sterilisation of the infected site by directly killing bacteria. Lysis of bacteria can lead to release of toxins and inflammatory material.
Suppress growth but does not directly sterilise infected site. Requires additional factors to clear bacteria - immune mediated killing.
Give examples of antibiotic classes
- Penicillins - cell wall agents
- Glycopeptides - cell wall agents e.g. Vancomycin
Describe antibiotic resistance mechanisms
1. Mutation of target site
2. Inactivating enzymes
3. Limit access - reduced permeability, increased efflux
Genes mediating resistance can often by easily trasnsferred