6.3 defence against infectious diseases Flashcards
1
Q
what are the surface barriers?
A
- 1st line of defence against infectious disease are the surface barriers that prevent the entry of pathogens into the body
- include both intact skin and mucous membranes
2
Q
compare skin and mucous membranes as surface barriers
A
SKIN
- protects external structures when intact (outer body areas)
- consists of dry, thick and tough region composed predominantly of dead surface cells
- contains biochemical defence agents (sebaceous glands secrete chemicals and enzymes which inhibit microbial growth on skin)
- skin also secretes lactic acid and fatty acids to lower the pH (skin pH is roughly ~ 5.6 – 6.4 depending on body region)
- mitosis of deeper layer of cells, continuously pushes cells outwards; cells slowly gain keratin (structural protein w cytoplasm removed) and squashes together when dead to form impermeable layer
- skin: epidermis (dead skin cells) –> dermis (living cells) –> subcutaneous tissues (not part of skin)
MUCOUS MEMBRANES
- protects internal structures (i.e. externally accessible cavities and tubes – such as the trachea, oesophagus and urethra)
- consists of a thin region of living surface cells that release fluids to wash away pathogens (mucus, saliva, tears, etc.)
- contains biochemical defence agents (secretions contain lysozyme [enzyme found in lysosomes] which can destroy cell walls and cause cell lysis)
- mucous membranes may be ciliated to aid in the removal of pathogens (along with physical actions such as coughing / sneezing)
3
Q
what is clotting (haemostasis)?
A
- mechanism by which broken blood vessels are repaired when damaged
- clotting functions to prevent blood loss from the body and limit pathogenic access to the bloodstream when the skin is broken
- 2 key components of a blood clot – platelets and insoluble fibrin strands
- platelets undergo a structural change when activated to form a sticky plug at the damaged region (primary haemostasis)
- fibrin strands form an insoluble mesh of fibres that trap blood cells at the site of damage (secondary haemostasis)
4
Q
what is the coagulation cascade? outline the steps
A
- process by which blood clots are formed involves a complex set of reactions collectively called coagulation cascade
- coagulation cascade is stimulated by clotting factors released from damaged cells (extrinsic pathway) and platelets (intrinsic pathway)
- platelet cascade (NOT coagulation cascade) that eventually leads to triggering of coagulation cascade:
1. platelets are formed formed from megakaryocytes in the bone marrow
2. when there is a cut, the platelets bind to the collagen in the blood vessels that are now exposed
3. platelets can then become activated, and release many clotting factors
4. some of such clotting factors can also activate other platelets, to release even more clotting factors
5. clotting factors cause platelets to become sticky and adhere to the damaged region to form a solid plug
6. these factors also initiate localised vasoconstriction to reduce blood flow through the damaged region - COAGULATION CASCADE:
1. triggered by either extrinsic pathway or intrinsic pathway
2. clotting factors trigger the conversion of the inactive zymogen (inactive substance that is converted to enzyme when activated by another enzyme) prothrombin into the activated enzyme thrombin
8. thrombin in turn catalyses the conversion of the soluble plasma protein fibrinogen into an insoluble fibrous form called fibrin
9. fibrin strands form a mesh of fibres around the platelet plug and traps blood cells to form a temporary clot
10. when the damaged region is completely repaired, an enzyme (plasmin) is activated to dissolve the clot
5
Q
what are the causes and consequences of coronary thrombosis?
A
- coronary thrombosis: formation of a clot within the blood vessels that supply and sustain heart tissue (coronary arteries)
- occlusion of a coronary artery by a blood clot may lead to an acute myocardial infarction (heart attack)
- blood clots form in coronary arteries when the vessels are damaged as a result of the deposition of cholesterol (atherosclerosis)
- atheromas (fatty deposits) develop in arteries and significantly reduce diameter of lumen (stenosis)
- restricted blood flow increases pressure in the artery, leading to damage to the arterial wall (from shear stress)
- damaged region is repaired with fibrous tissue which significantly reduces the elasticity of the vessel wall
- as smooth lining of artery is progressively degraded, lesions form called atherosclerotic plaques
- if plaque ruptures, blood clotting is triggered, forming a thrombus that restricts blood flow
- if thrombus is dislodged it becomes an embolus and can cause a blockage in a smaller arteriole
- when clot completely blocks blood vessel, occlusion occurs
- blocked blood vessel can result in heart attack if occurs in coronary arteries as part of coronary heart disease
- blood clots can get dislodged and move to block smaller arterioles
- can lead to stroke if occurs in brain
6
Q
what is the innate immune system?
A
- 2nd line of defence
- non-specific in its response
- a principle component of this line of defence are phagocytic white blood cells that engulf and digest foreign bodies
- other components of innate immune system include inflammation, fever and antimicrobial chemicals (complement proteins)
innate immune system has 2 key properties:
- does not differentiate between different types of pathogens (non-specific)
- responds to an infection the same way every time (non-adaptive)
7
Q
how do white blood cells operate in the innate immune system?
A
- phagocytosis is the process by which solid materials (such as pathogens) are ingested by a cell (i.e. cell ‘eating’ via endocytosis)
- phagocytic leukocytes circulate in the blood and move into body tissue (extravasation) in response to infection
- damaged tissues release chemicals (e.g. histamine) which draw white blood cells to site of infection (via chemotaxis)
- pathogens are engulfed when cellular extensions (pseudopodia formed by phagocytes) surround the pathogen and then fuse to form an internal vesicle
- vesicle is then fused to a lysosome (forming a phagolysosome) and pathogen is digested
- antigens left over from digestion carried back to cell surface membrane, where antigens are presented for recognition and response from antibody producing cells
- pathogen fragments (antigens) may be presented on the surface of the phagocyte in order to stimulate the 3rd line of defence
8
Q
what is the adaptive immune system?
A
- 3rd line of defence
- specific in its response
- can differentiate between particular pathogens and target a response that is specific to a given pathogen
- can respond rapidly upon re-exposure to a specific pathogen, preventing symptoms from developing (immunological memory)
- coordinated by lymphocytes (a class of leukocyte) and results in the production of antibodies
9
Q
what are the different lines of defence in the body?
A
- surface barriers (skin and mucous membrane)
- innate immune system (phagocytic white blood cells)
- adaptive immune system (T(subscript)H cells and B lymphocytes)
10
Q
how do lymphocytes (class of leukocytes) operate in the adaptive immune system?
A
- adaptive immune system is coordinated by lymphocytes (a class of leukocyte) and results in production of antibodies
- B lymphocytes (B cells) are antibody-producing cells that recognise and target a particular pathogen fragment (antigen) [produced in bone marrow]
- mount the humoral immune response –> secrete antibodies into blood and lymphatic fluid
- T lymphocytes produced in bone marrow but developed further in thymus
- carry out cell-mediated immune response where they attack and destroy the bacterial / viral infected human cells
- helper T lymphocytes (T(subscript)H cells) are regulator cells that release chemicals (cytokines) to activate specific B lymphocytes; also promote phagocytosis of other wbc
- when phagocytic leukocytes engulf a pathogen, some will present the digested fragments (antigens) on their surface
- these antigen-presenting cells (dendritic cells) migrate to the lymph nodes and activate specific helper T lymphocytes
- helper T cells then release cytokines (proteins important in cell signalling) to activate the particular B cell capable of producing antibodies specific to the antigen
- activated B cell will divide and differentiate to form short-lived plasma cells that produce high amounts of specific antibody
- antibodies will target their specific antigen, enhancing the capacity of the immune system to recognise and destroy the pathogen
- small proportion of activated B cell (and activated TH cell) will develop into memory cells to provide long-lasting immunity
11
Q
how do antigens and antibodies interact?
A
- antigen: substance that body recognises as foreign and will elicit an immune response
- antibody: protein produced by B lymphocytes (and plasma cells) that is specific to a given antigen
- antibodies are made of 4 polypeptide chains that are joined together by disulphide bonds to form Y-shaped molecules (2 light chains 2 heavy chains)
- ends of the arms are where the antigen binds – these areas are called the variable regions and differ between antibodies
- rest of the molecule is constant across all antibodies and serves as a recognition site for the immune system (opsonisation)
- each type of antibody recognises a unique antigen, making antigen-antibody interactions specific (like enzymes and substrates)
12
Q
how do antibiotics work?
A
- antibiotics: compounds that kill or inhibit growth of microbes (specifically bacteria) by targeting prokaryotic metabolism
- metabolic features that may be targeted by antibiotics include key enzymes, 70S ribosomes and components of the cell wall
- because eukaryotic cells do not possess these features, antibiotics will target pathogenic bacteria and not infected host
- antibiotics may either kill the invading bacteria (bactericidal) or suppress its potential to reproduce (bacteriostatic)
- viruses do not possess a metabolism (they are not alive) and instead take over the cellular machinery of infected host cells
- thus they cannot be treated with antibiotics and must instead be treated with specific antiviral agents
- antiviral treatments target features specific to viruses (e.g. viral enzymes like reverse transcriptase or components of the capsid)
13
Q
how are viruses treated?
A
- viruses do not possess a metabolism (they are not alive) and instead take over the cellular machinery of infected host cells
- thus they cannot be treated with antibiotics and must instead be treated with specific antiviral agents
- antiviral treatments target features specific to viruses (e.g. viral enzymes like reverse transcriptase or components of the capsid)
14
Q
how does antibiotic resistance come about?
A
- antibiotics can be narrow spectrum (effective against specific bacteria) or broad spectrum (effective against many bacteria)
- some strains of bacteria have evolved with genes that confer resistance to antibiotics and some strains have multiple resistance
- genes may confer resistance by encoding traits that degrade the antibiotic, block its entry, increase its removal or alter the target
- because bacteria reproduce at a rapid rate, resistant strains of bacteria can proliferate very quickly following the initial mutation
- additionally, resistant strains can pass resistance genes to susceptible strains via bacterial conjugation (horizontal gene transfer)
- prevalance of resistant bacterial strains is increasing rapidly with human populations due to a number of factors:
1. antibiotics are often over-prescribed (particularly broad-spectrum drugs) or misused (e.g. given to treat a viral infection)
2. many antibiotics are freely available without a prescription and certain antibiotics are commonly included in livestock feed
3. multi-drug resistant bacteria are especially common in hospitals (i.e. nosocomial infections) where antibiotic use is high - example of an antibiotic resistant strain of bacteria is Golden Staph (MRSA – Methicillin Resistant Staphylococcus aureus)
summary of steps:
- high number of bacteria; few of them are resistant to antibiotics
- antibiotic kills pathogenic bacteria as well as good bacteria in body (probiotics)
- antibiotic resistant bacteria now proliferates without competition
- bacteria can transfer antibiotic-resistance gene to other bacteria via plasmids (conjugation)
15
Q
how did florey and chain test penicillin?
A
- 1st chemical compound found to have antibiotic properties was penicillin, identified by Alexander Fleming in 1928
- discovery of penicillin was a fortuitous accident (serendipitous), resulting from the unintended contamination of a dish containing S. (staphylococcus) aureus
- penicillium mould began to grow on the plate and a halo of inhibited bacterial growth was observed around the mould
- fleming concluded that the mould was releasing a substance (penicillin) that was killing the nearby bacteria
- medical applications of penicillin as an antibiotic were demonstrated by an Australian scientist, Sir Howard Florey, in 1940
- working with another scientist (Ernst Chain) and a team of researchers, Florey tested penicillin on infected mice
- 8 mice were injected with pathogenic bacteria (hemolytic Streptococcus) and 4 of these mice were subsequently injected with doses of penicillin
- untreated mice died of bacterial infection while those treated with penicillin all survived – demonstrating its antibiotic potential
- following chemical determination of penicillin structure in 1945, several synthetic derivatives have since been created
- these derivatives (including methicillin) offer many benefits including a broader spectrum, more stability and greater tolerance
