Infectious Diseases Flashcards
(46 cards)
1
Q
state the characteristics of innate immune system
A
- activated immediately upon infection
- not specific to any pathogen as it relies on recognising only a small group of foreign antigens common to many different types of pathogens
- has not immunological memory as response is the same regardless of whether the same pathogen has been encountered previously
2
Q
describe barrier defence
A
- skin and mucous membranes provide a physical barrier to prevent penetration of microorganisms
- secretions by oil and sweat glands provide the skin with an acidic pH of about 5, serving as a chemical deterrent to the growth of many pathogenic bacteria
- mucous membranes lining the digestive tract also produces mucus which may trap pathogens/foreign particles
- in the trachea, ciliated epithelial cells sweep the mucus and any trapped pathogens upwards away from the lungs, may also be swallowe and killed in acidic environment of lungs
- openings on body surfaces not covered with mucus (eyes) are protected by other types of secretion -> tears contain lysozyme which cleaves glycosidic bonds found in peptidoglycan cell walls of bacteria
3
Q
briefly describe internal defences
A
- pathogens which have evolved strategies to penetrate epithelial cell barrier/enter the body directly through woundds brings about a local inflammatory response that attracts some WBCs of innate immune system (phagocytes and natural killer cells)
- these cells rely on receptors on their CSM that recognise foreign molecules characteristic of a set of pathogens (dsRNA common to some viruses) and are not pathogen-specific
4
Q
state the role of phagocytes
A
- macrophages and dendritic cells
- engulf foreign micro-organisms by phagocytosis
- intracellular digestion of the foreign substances occurs when lysosomes containing hydrolytic enzymes fuse with the phagocytic vesicles
- antigen-presenting cells: present antigen on the CSM where they are recognised by specific antigen receptors of helper T cells, cytotoxic T cells and B cells, resulting in activation of helper T cells, cytotoxic T cells and B cells
5
Q
state the role of natural killer cells
A
- detect viral-infected/cancerous cells
- release cytokines that will trigger apoptosis of abnormal cell
- release perforin which forms pores in cell membrane, disrupting membrane integrity
- releases granzymes, enzymes that break down proteins in cells and induces apoptosis
6
Q
describe the local inflammatory response
A
- an injury triggers mast cells to secrete histamine which triggers the dilation of blood vessels, increasing blood flow to the site and increase the permeability of the blood vessels to othe white blood cells
- macrophages at site of injury secrete cytokines
- histamine and cytokines released leads to recruitment of more phagocytes to the site of injury
- phagocytes engulf and digest pathogens and cell debris at site via phagocytosis
- outcome is accumulation of pus – fluid filled with dead pathogens, cell debris and WBCs
7
Q
what happens during severe inflammatory response
A
- increased production of WBCs (meningitis/appendicitis)
- pyrogens released by pathogens/cytokines released by macrophages trigger fever
- elevated body temperature accelerate tissue repair due to increase in rate of enzymatic reactions, retard pathogen growth and enhance phagocytosis
8
Q
function of antigen representation
A
link between innate and adaptive immune system, helps to activate adaptive immune system
9
Q
state the characteristics of adaptive immunity
A
- develops more slowly and targets specific antigens of a pathogen
- upon secondary infection with the same pathogen, immune response will be faster, stronger and last longer due to immunological memory
10
Q
describe adaptive immune system
A
- during primary response, naive T/B cells are activated when an antigen which is complementary to their cell surface receptors bind to these cells (clonal selection bc an encounter with an antigen selects which lymphocyte will be activated, cells that have antigen receptors specific for other antigens do not respond)
- once activated, a B cell/T cell undergoes multiple cell divisions. for each activated cell, the result of this proliferation is a clone (population of cells that are identical to the original cell) clonal expansion: proliferation/mitotic divisions to give a clonal expansion of thousands of cells specific for a particular epitope
- some cells from this clone become effector cells. naive B cells differentiate into plasma cells which produce large amounts of antibodies (receptor molecules identical to those found on the cell surface in a soluble form that can be secreted, have identical antigen binding sites as the B cell receptor, hence they bind to the same antigen that initially activated the B cells). naive helper T cells/naive cytotoxic T cells differentiate into either effector helper T cells or effector cytotoxic T cells
- remaining cells in the clone become memory cells. upon subsequent encounters with the antigen, these cells may differentiate into effector cells and mediate a secondary response
11
Q
advantages of secondary response
A
- secondary response is faster and stronger
- antigen receptors on memory B and T cells generated in the primary response have higher affinity for the same antigen than the cells from the primary response/affinity maturation due to somatic hypermutation
- lag period is absent since antigen presentation, clonal selection and activation of naive cells is not required
- greater concentration of antibodies to neutralise bacterial pathogen by agglutination, opsonisation, neutralisation, activation of complement system
- larger number of cells specific for the pathogen increases chances of encountering pathogens more quickly
- resulting in faster production of plasma cells, helper T cells and cytotoxic T cells specific to the pathogen
- pathogen is removed faster, hence person does not become ill/has no symptoms of infection/pathogen does not spread throughout the body
12
Q
describe cell-mediated immune response
A
- T lymphocytes
- protect against intracellular pathogens by killing host cells that are infected
- protect against extracellular pathogens by helping to activate B lymphocytes to become antibody-secreting plasma cells
13
Q
describe humoral immune response
A
- B cells present antigens
- differentiate to form plasma cells which secrete antibodies that help neutralise or eliminate extracellular pathogens and toxins secreted by pathogens into blood/body fluids
14
Q
role of helper T cells
A
- specific antigen receptors on surface and CD4 proteins of naive helper T cells bind to presented antigen on APC
- both APC and helper T cells stimulated to produce cytokines
- released cytokines activate naive helper T cell, stimulating its proliferation through clonal expansion, large proportion of cells in cloned population will differentiate into effector helper T cells specific to a particular epitope
- activated helper T cells secrete cytokines to allow activation of naive cytotoxic T cells
- activated helper T cells bind to antigen presented by naive B cells and secrete cytokines to allow activation of these B lymphocytes
- can also trigger class switching for plasma cells to produce antibodies of different classes
- a proportion of cells within the cloned population differentiate into memory helper T cells, which persist for a long time in the body. these memory helper T cells are able to proliferate and differentiate faster into effecter helper T cells upon re-exposure to the same antigen, mediating the secondary response
15
Q
role of cytotoxic T cells
A
- specific antigen receptors on surface of naive cytotoxic T cell, together with CD8 proteins, bind to specific complementary antigens presented on infected cell
- naive cytotoxic T cells can be activated under the influence of cytokines released by helper T cells. cytotoxic T cells undergo clonal expansion (multiple mitotic divisions)
- a large proportion of the cells within the cloned population differentiate into effector cytotoxic T cells, while the remaining differentiate into memory cytotoxic T cells
- effector cytotoxic T cells secrete perforin which forms pores in cell membrane, disrupting membrane integrity, and granzymes which break down proteins and induces apoptosis
- death of infected cell exposes released antigens to circulating antibodies
- a proportion of the cells within the cloned population differentiate into memory cytotoxic T cells which persist for a long time in the body. these memory cytotoxic T cells are able to proliferate and differentiate faster into effector cytotoxic T cells upon re-exposure to the same antigen, mediating the secondary response
16
Q
role of B cells
A
- when an antigen binds to B cell receptors on cell surface, antigen taken into B cell by receptor-mediated endocytosis
- B cells present only the antigen to which its receptors specifically bind to, B cells present antigens to activated helper T cells, leading to activation of B cells
- antigen presented to activated helper T cells causes helper T cells to secrete cytokines
- released cytokines activate and stimulate naive B cells to proliferate via mitosis and undergo clonal expansion
- a large proportion of the cloned population of B lymphocytes differentiate into effector plasma cells, while the remaining differentiate into memory B cells
- plasma cells produce and secrete soluble antibodies which have identical binding sites as receptor molecules that were previously expressed
- antibodies neutralise bacterial pathogen by agglutination, opsonisation, neutralisation and activation of complement system
- some B cells within the cloned population differentiate into memory B cells that can persist for a long time in the body. memory B cells can proliferate and differentiate faster into effector cells upon re-exposure to the same antigen, mediating the secondary response
- memory B cells have a higher affinity for the antigen due to affinity maturation as a result of somatic hyper-mutation
17
Q
explain how the size and shape of antibodies relate to their modes of action and functions
A
- antibodies are specific
- antibodies are large due to the presence of several binding sites (2 antigen-binding sites and 1 binding site at Fc region
- antibodies have 2 identical antigen binding sites which allow simultaneous binding to two identical antigens
- unique 3D conformation of the Fab regions/V domains/antigen binding sites of antibody allows complementary binding to specific antigens
- Fc region/C domains provides a specific/complementary site to bind to effector cells and molecules, activating the complement system/stimulate macrophages to carry out phagocytosis of antibody-bound antigens/gives antibody its different class types
- hinge region on the heavy chain between the V and C domains provides flexibility when binding
18
Q
explain how somatic recombination during development results in millions of different antibody molecules
A
- in an immature B cell, there are many V(D)J gene segments
- during development, V(D)J recombinase deletes the DNA between randomly selected V(D)J segments, and then joins the selected V(D)J segments
- results in different combinations of V(D)J segments which are transcribed and translated to different V domains
- different V domains result in antibodies with different antigen binding sites
- random pairing of different V domains of light and heavy chains during the formation of the receptors further generates diversity
19
Q
after antigenic stimulation, a B cell can further rearrange its DNA to allow synthesis of a different class of antibody. state the significance of this process
A
- different daughter cells from the same activated B cell can produce antibodies of different class types/isotypes to allow interaction with different effector molecules
- same antigen specificity allows the antibody to retain affinity for the same antigens
20
Q
explain somatic hyper-mutation
A
- introduction of random point mutations into the gene segments coding for V domains of both light and heavy chains
- occurs only in activated B cells
- upon B cell activation, enzyme activation-induced cytidine deaminase (AID) catalyses deamination of cytosine to uracil in DNA
- due to resulting base mismatch, DNA repair is initiated where mismatched nucleotides are excised. however, DNA synthesis in B cells is error-prone and tends to introduce mutations in repaired DNA. mutations introduced throughout rearranged V domain exons at a very high rate
- some point mutations may result in B cells expressing receptors with higher affinity for antigen
- B cells expressing mutant antibodies which bind to the antigen better than the original activated B cells will survive and divide more than the other b cells. these B cells are preferentially selected to undergo clonal expansion, giving rise to affinity maturation of the antibody population
21
Q
explain class switching
A
- during class switching, gene segments coding for C domains are removed irreversibly, and intact gene segments coding for V domains are rejoined to a different gene segment coding for C domains
- recombination of gene segments coding for C domains of heavy chain affects Fc region of antibody, leading to class switching
- class switching provides antibodies with the same antigen specificity but allow them to interact with different effector cells/molecules
- stimulated in the presence of cytokines released by helper T cells
22
Q
why is IgG better than IgM?
A
- IgG has greater effectiveness in neutralisation and opsonisation of pathogen, and is capable of transport across placenta to provide passive immunity from a pregnant mother to her fetus
- secreted in greater quantities as compared to IgM during secondary immune response
23
Q
explain how influenza virus causes diseases in humans
A
- NA on viral envelope helps virus to penetrate mucus layer, breaching body’s barrier defences
- HA on viral envelope allows virus to bind to specific sialic-acid containing receptors on epithelial cells lining respiratory tract and infect these cells. once virus has entered host cells, viral replication occurs
- expression and insertion of viral glycoproteins on host CSM causes epithelial cells to be recognised as foreign and targeted by body’s immune defences, leading to a local inflammatory response induced by release of histamine by mast cells, causing symptoms like runny nose, blocked nose, sore throat and coughing
- cytokines released during inflammatory response recruit more WBCs to site of infection, migration of epithelial cells to infected epithelial cells may cause damage to epithelial tissue. build-up of dead epithelial cells and WBCs in airways result in accumulation of pus
- systemic inflammatory response may occur, where release of pyrogens can lead to fever and body aches
24
Q
severe side effects of influenza
A
- inflammation may be harmful when it is a result of over-reaction of immune system agaisnt novel flu strains
- infected individuals usually due as a result of a surge in cytokine release, which laeds to excessive fluid accumulation in lungs, causing respiratory issues
- infection by influenza may cause damage to ciliated epithelium, making respiratory passage more susceptible to secondary bacterial infections leading to diseases like pneumonia
25
explain how HIV causes diseases in humans
* selectively infects macrophages and helper T cells
* due to the expression and insertion of viral glycoproteins on host CSM, infected helper T cells may bind to adjacent uninfected CD4+ cells and fuse together, forming giant multinucleated cells/syncytium. syncytium may lyse/recognised and killed by cytotoxic T cells
* HIV infection can induce apoptosis of infected helper T cells after these infected cells are targeted by cytotoxic T cells, resulting in a significant depression of the adaptive immune response and an increased susceptibility to opportunistic infections by other pathogens
* HIV infection associated with a progressive decrease of CD4+ T cell count and an increase in viral load
* upon initial viral infection, a period of rapid viral replication ensues, leading to a high viral load in blood. acute infection lasts for several weeks and may include fever, swollen lymph nodes, sore throat
* clinical latency stage involves few/no symptoms and can last from 2 weeks to twenty years. HIV provirus is integrated in DNA of infected host cells and remains dormant. viral replication may occur at a low rate as immune system keeps infection under control
* increasing loss of helper T cells leads to impaired immune response in affected individual
* AIDS is defined by low CD4+ T cell counts
* death usually results from secondary infections
* virus mutates at a very high rate during replication resulting in altered viral glycoproteins
* virus prevents recognition and elimination by antibodies allowing it to evolve rapidly to form new viral strains
26
explain the mode of transmission of Mycobacterium tuberculosis
* Mycobacterium tuberculosis causes lung disease, tuberculosis (TB)
* TB is an airborne disease
* when an infected person with active TB sneezes/coughs, the bacteria are transmitted in fine aerosol droplets to an uninfected person who inhales the droplets
* each one of these droplets may transmit the disease, since infectious dose of TB is very small
27
explain the mode of infection of Mycobacterium tuberculosis
* bacteria colonise host cell macrophages inside lungs
* inhibit phagosome fusion with lysosome thereby avoiding killing and allowing sustained survival in these cells
* provide signal for recruitment of more phagocytes/macrophages
* together with lymphocytes, these macrophages aggregate to form tubercles/granulomas
* granulomas allow bacteria to avoid destruction by host's immune system
* macrophages and dendritic cells in granulomas are unable to present antigen to lymphocytes thus immune response is suppressed
* necrosis occurs, death of macrophages leading to formation of granulomas with caseous centre
* bacteria inside the granuloma can become dormant, resulting in latent infection in an immunocompetent person
* in an immunocompromised person, immune system is unable to contain the pathogen and primary infection may progress into active TB after a few weeks
* granuloma ruptures, resulting in liquefaction hence releasing the pathogen into the airways
28
define disease
abnormal condition/abnormal state/disorder/ill-health having an adverse effect on an organism which reduces the effectiveness of functions and is associated with signs and symptoms
29
explain how a parasite can cause increased body temperature and pain
* repeated release of parasites stimulates innate immune response
* increased body temperature is caused by pyrogens which may retard pathogen growth
* pain is due to damage to tissue/inflammation/histamine release
30
suggest why it is extremely difficult to design an effective vaccine against malaria
* parasite evades immune system/mostly stays inside host cells
* host CSM helps to disguise parasite as "self"
* there is a need to stimulate cytotoxic T-lymphocyte/cell-mediated response to kill infected host cells/without free antigens or antigen presentation it is difficult to generate a large enough B-lymphocyte response/antibody production is not enough
* large degree of variation/change in parasite antigens due to short replication time (higher rate of mutation due to higher rate of DNA replication, errors can occur during DNA replication)
31
outline some factors that led to the successful eradication of smallpox (smallpox virus only)
* smallpox virus was stable/did not mutate as rapidly
* allows the same vaccine to be used for the whole programme/vaccine needs not be changed
* few/no symptomless carriers of the virus/infected people are easy to identify
* no animal reservoir/only in humans
* isolation of cases to prevent spread
32
outline how vaccine led to the successful eradication of smallpox
* mass vaccination/many countried have mandatory vaccination resulting in herd immunity
* one dose was enough to give life-long immunity/no boosters required
* vaccine was live/effective/gave a strong immune response
* heat stable/freeze dried vaccine makes it suitable for hot countries/isolated/rural areas
* bifurcated/steel needle, could be re-used/easier delivery
* comparatively low cost/qualified/many volunteers became vaccinators
33
explain how a vaccine consisting of an attenuated (weakened) form of the virus can provide long-term immunity against the virus
* vaccine which comprises the attenuated virus has the antigens which stimulates the immune response
* macrophages, acting as APCs, engulf virus by phagocytosis and present antigen on the CSM
* specific receptors on naive helper T cells bind complementarily to antigen presented by APCs and are activated/clonal selection
* helper T cells proliferate by mitosis/undergoes clonal expansion and release cytokines to activate cytotoxic T cells and B cells
* forming memory T and B cells and antibodies which are specific with a higher affinity to the antigen
* booster is used to further stimulate memory cells formation to increase strength of the immune response/immunological memory
* on infection by the virus, faste, stronger and longer-lasting response as higher levels of antibody are formed/patients shows on symptoms
34
discuss the benefits of vaccination
* allows possible eradication of disease
* reduced suffering/cost of treatment
* prevention of death/immunity from the disease
* long-term disabilities reduced (sterility from mumps/congenital defects from rubella)
* prevent epidemics/spread of infections
* herd immunity conferred as the vaccination of a significant portion of a population provides a measure of protection for individuals who have not developed immunity
35
discuss the risks of vaccination
* people may contract disease from vaccine due to possible risk of pathogen to revert to virulence/virulent form
* can cause serious infections in immunocompromised/immunodeficient individuals
* immunity may not be life-long
* vaccination may cause allergic reactoin to egg proteins as a consequence of viral vaccines produced in eggs
* takes some time for the production of memory T and B cells to confer immunity, hence infection occurring just before/after vaccination may still result in symptoms
36
describe naturally acquired immunity
* occurs through contact with a disease-causing agent, when the contact was not deliberate
* occurs as a result of infection (memory cells and antibodies are produced after first exposure to pathogen. re-exposure/secondary infection with same pathogen, immune response will be more effective -- faster, stronger and last longer)
* occurs when antibodies from a mother cross the placenta and enter her foetus, providing a temporary protection for the baby until his/her own immune system is fully functional, no immunological memory is involved
37
describe artificially acquired immunity
* occurs via non-natural means, with the help of technology
* achieved by administration of vaccines, to induce adaptive immune response that protects individual against later exposure to pathogens due to production of memory cells
* occurs when antibodies which have been formed in one individual/animal are extracted and injected into the blood of another individual which may/may not be of the same species
* used to confer immunity immediately, no immunological memory involved
38
explain how the size and shape of antibiotics relate to their modes of action and functions
* antibiotics are specific
* can be enzyme inhibitors, their small size allows them to interfere with enzymes activity/function
* has a 3D conformation complementary to the active site of enzyme/a site other than the active site, to allow specific binding
* prevent bacterial growth/protein synthesis/cell wall synthesis/DNA replication
39
suggest two ways in which antibiotics act at ribosomes to inhibit protein synthesis (assuming they bind to ribosomes)
* prevent binding of tRNA hence no anticodon-codon pairing/peptide bond formation prevented
* prevent mRNA attachment to small ribosomal subunit
* inhibition of enzyme peptidyl transferase involved in translation
* prevent/restrict ribosome translocation along mRNA
* inhibits association of large and small ribosomal subunits
40
explain how antibiotics target bacterial cell wall
* penicillin inhibit bacterial growth by interfering with the transpeptidation reaction of bacterial cell wall synthesis
* penicillin-binding protein (PBP) is an enzyme which catalyses the formation of peptide cross-links betwen adjacent peptides, giving cell wall its structural rigidy
* penicillins are competitive inhibitors which bear structural simmilarity to the natural substrate of PBP and covalently bind to the active site of PBP, inhibiting the transpeptidation reaction, halting peptidoglycan synthesis, cell undergoes osmotic lysis
41
explain how antibiotics target bacterial cell membrane
* amphipathic substances which possess both polar and non-polar functional groups
* after binding to membrane of some bacteria, they disrupt the phospholipid bilayer
* increased permeability of the cell membrane which leads to a leakage of cellular contents and subsequently cell death
42
explain how antibiotics target DNA replication
* inhibit synthesis of nucleotides
* inhibit action of enzymes involved in DNA replication (e.g. inhibit bacterial topoisomerase, preventing relaxation of supercoiled DNA that is required for normal replication)
43
explain how antibiotics target protein synthesis
* inhibit bacterial RNA polymerase
* binding of antibiotics to RNA polymerase inhibits formation of phosphodiester bonds between adjacent ribonucleotides during transcription
44
explain how reducing number of T-lymphocyes reduces effectiveness of an immune response
* reduction in helper T cell count leads to a less effective activation of cytotoxic T cells and B cells
* with fewer activated cytotoxic T cells, infected/cancerous cells are less likely to be induced to undergo apoptosis
* with fewer activated B cells/plasma cells, less antibody secreted
* little/no/slower/weak immune response, resulting in high susceptibility to infectious diseases
45
explain how some pathogens being covered in CSM from their host reduces effectiveness of an immune response
antigens of pathogen are not recognised by host antibodies/phagocytosis of these intracellular pathogens cannot take place
46
explain how B-lymphocytes not maturing properly and not recognising any pathogens reduces effectiveness of an immune response
* B cells not able to present antigens
* no plasma cells hence antibodies not produced
* no humoral immune response
