infectious disease Flashcards

Question

(standard qn) STRUCTURE: FUNCTION OF ANTIBODIES

Answer 1

S1 : Antigen binding site of a specific antibody is complementary in shape to a specific epitope of an antigen due to the precise folding of the variable heavy and light chains that gives rise to its unique 3D structure F1 : Hence antibodies can carry out neutralisation** by binding to specific epitope of an antigen*** of pathogen thus preventing pathogen from binding to host cell receptors*** and infecting the host cells S2: Fc region of antibody/constant region of heavy chain has a conformation that is complementary in shape to Fc receptors on phagocytes F2: Hence opsonisation* can occur as once antibodies bind to the pathogen, Fc regions of antibodies bind to Fc receptors of phagocytes********* and promote phagocytosis** S3: Disulfide bridges between heavy and light chains / two heavy chains F3: This gives stability to the quaternary structure by holding the heavy and light chains together / heavy chains together S4: Each antibody has a hinge region** F4: This give antibody flexibility when binding*** to epitopes/antigen/pathogen that are variable distances apart*** S5: Ig G has two antigen binding sites F5: Each IgG can bind to two epitopes**/antigens* at the same time** causing pathogens to aggregate/clump together** to facilitate clearance by macrophages. This is known as agglutination** ``` S6: Constant region of heavy chains F6: Determine the class of antibody*** thus their different functions ```

Answer 2

1. involves 3 genes: 2 genes coding for light chains (kappa and lambda) &1 gene coding for heavy chains 2. due to a. somatic recombination b. somatic hypermutation c. class switching d. combinatorial pairing of heavy & light chains 3. occurs during B cell development Somatic recombination - takes place during B cell maturation in the bone marrow ``` Somatic hypermutation and class switching - takes place after activation of naive b cell in the lymph nodes somatic hypermutation takes place DURING clonal expansion and differentiation ```

Answer 3

1. There are multiple gene segments*** at heavy and light chain genes 2. Somatic recombination** is a form of DNA REARRANGEMENT** where various gene segments are joined together randomly*, and some intervening segments** are enzymatically removed** followed by rejoining of remaining sequences. 3. At the Ig heavy* chain gene locus, one V segment, one D segment and one J segment are randomly joined to form a single VDJ exon 4. At the Ig light* chain gene locus, one V segment and one J segment are randomly joined to form a single VJ exon

Answer 4

VDJ recombination occurs ➔at the heavy chain gene ➔during B cell maturation in the bone marrow ``` 1.During D and J rearrangement, one D segment and one J segment are joined and the intervening sequences are enzymatically removed 2.During V and DJ rearrangement, one V segment is joined to the DJ segment and the intervening sequences are enzymatically removed ``` 3.The DNA segment then undergoes transcription ``` 4.The resulting pre-mRNA undergoes RNA splicing during which the introns are excised and the VDJ exon and C exon are joined ``` ``` 5.The mature mRNA with the VDJC exons joined enters the cytoplasm where it undergoes translation to form the specific heavy chain protein with the specific V, D, J and C domains ```

Answer 5

``` VJ recombination occurs ➔at the light chain gene ➔during B cell maturation in the bone marrow 1.During V and J rearrangement, one V segment and one J segment are joined and the intervening sequences are enzymatically removed 2.The segment then undergoes transcription 3.The resulting pre-mRNA undergoes RNA splicing during which the introns are excised and the VJ exon and C exon are joined 4.The mature mRNA with the VJC exons joined enters the cytoplasm where it undergoes translation to form the specific light chain protein with the specific V, J and C domains ```

Answer 6

1. Somatic hyper-mutations are RANDOM POINT MUTATIONS** that occur in the rearranged VDJ / VJ regions in activated B cells*** 2. They are called ‘hypermutations’ as they occur at a much higher rate than normal mutations 3. This further diversifies the variable regions** of antibody for antigen binding (due to slight amino acid differences which result due to the mutation) 4. It occurs during* clonal expansion** of the activated B cells (i.e. after naïve mature B cells have been activated by an antigen) 5. Some point mutations result in the B cells expressing low affinity Ig chains*** on their cell surface membrane and some point mutations result in the B cells expressing higher affinity Ig chains*** on their cell surface membrane 6. B cells that express higher affinity BCR on their cell surface membrane are selected for*** clonal expansion & differentiation. This is called affinity maturation*** 7. The resulting plasma cells and memory B cells will have BCRs with higher affinity antigen binding sites for a specific antigen. The plasma cells will also produce antibodies with higher affinity antigen binding sites for a specific antigen.

Answer 7

Class switching is DNA REARRANGEMENT** at the CONSTANT* gene segment of the heavy chain gene locus in activated* B cells - Allows for production of antibodies with the same antigen binding site*** but different function ``` Heavy chain gene ➔ VDJ recombination complete ➔ occurs after B cell activation 1. Before class switching, VH DNA linked to Cµ. Hence Ig M antibodies are produced. 2. During class switching, DNA rearrangement occurs and VH DNA becomes linked to another constant gene segment of the heavy chain gene locus, for example, Cγ Hence Ig G antibodies are produced 3. Only the constant region of the heavy chain (CH ) of the antibody changes, due to the change of C gene segment from Cµ to Cγ. Hence Ig G is produced instead of Ig M. ```

Answer 8

What is alters: SR alters teh heavy and light gene loci; Meiosis alters any gene locus* Gene segments: SR involves removing and joining of gene segments* ; Crossing over in meiosis involves exchange of equivalent segments Chromosomes involved: SR occurs on a single chromosome; meiosis involves non-sister chromatids on a pair of homologous chromosomes

Answer 9

Immune response: Yes (AI) vs No (PI) Antibody production: (AI) Produced by individual's own immune system in response to antigens vs (PI) transferred to recipient without the participation of the recipient's immune system Duration: (AI) long term immunity conferred since memory cells are formed after primary immune response vs (PI) short-lived since there is no formation of memory cells

Answer 10

1) RATE OF RESPONSE: Primary immune response: Response is SLOWER: presence of lag period**: 3-6 days between encountering antigen and production of antibody (more time required for clonal expansion and differentiation of T cells to effector T cells and then B cells to plasma cells) VS Secondary immune response: Response is FASTER: within hours (as memory B and T cells undergo faster clonal expansion and differentiation in response to re-exposure to the same pathogen) 2) STRENGTH OF RESPONSE: Primary immune response: Response is weaker: antibody concentration rises gradually and peaks at a lower level ➔ FEWER antibodies produced and they are produced for a SHORTER time Secondary immune response: Response is stronger: antibody concentration rises sharply and peaks at much higher level ➔ MORE antibodies produced (as there is a pool of memory B cells that can form antibody-producing plasma cells) and they are produced for a LONGER time (as long-lived memory B cells can continue to differentiate into antibody producing plasma cells) Shorter lag period: the memory B cells take a shorter Yi,e to differentiate into plasma cells 3) MEMORY Primary immune response: NO memory Secondary immune response: Has memory: confers long term immunity*** to the SAME pathogen** if it is encountered again

Answer 11

(I) shorter lag period : The memory B cells take a shorter time to differentiate into plasma cells which will go on to produce igG (ii) concentration reaches a higher level : Pool of memory B cells differentiate** to form more plasma cells which produce more antibodies (iii) sustained antibody concentration for a longer period of time As the long-lived * memory B cells can continue to proliferate and differentiate into plasma cells

Answer 12

The intentional administration of an antigen****, usually a harmless form of a pathogen*** in order to induce* a specific adaptive** immune response** that protects* the individual against later exposure to the SAME pathogen** due to the production of memory cells*. The individual should not develop disease symptoms

Answer 13

➔ The vaccine may contain a live attenuated OR a heat killed inactivated form of pathogen ➔ The modified pathogen is no longer able to cause disease but it still retains its immunogenic effect (ability to elicit an immune response) because characteristic surface antigens of the pathogen are retained and can be recognised by APCs ➔ Adaptive immune response occurs: specific naïve B and T cells are activated to become effector and memory B and T cells respectively (i.e. primary immune response is triggered)

Answer 14

1.attenuated measles virus still retains its ability to stimulate an immune response** because the specific surface antigens** of the pathogen* are retained*; 2. Antigen presenting cells(APCs)such as macrophages / dendritic cells take up the virus by phagocytosis, process antigen and present it as a peptide:MHC complex; 3. Each naïve T cell has a specific T cell receptor (TCR) that specifically binds to the complementary peptide:MHC complex on APC;4. APC secretes cytokines that activates naïve T cell which will undergo clonal expansion and differentiation to form helper T cells, cytotoxic T cells and memory T cells; 5. T helper cells* bind to the secrete cytokines that activate specific naïveB cells* to undergo clonal expansion and differentiation and form antibody-secreting plasma cells* and memory B cells*;6. Memory B and T cells* when re-exposed to the same measles virus, will recognise it and mount a faster and stronger secondary immune response;7. Where more antibodies are produced for a longer period of time;8. A booster shot is given at age 4 to further stimulate memory cell formation Hence prevent the child from developing measles.

Answer 15

Advantages: Closest thing to a natural infection ➔ will elicit a strong immune response***with just a small dosage **& confer longer-term protection*** (i.e. effective vaccine) Disadvantages: • Possibility of reversion to virulent*** form by mutation ➔ can then cause disease • Needs to be refrigerated* to stay potent

Answer 16

• Vaccines protect individuals against disease • Deaths due to illness can be prevented • Long-term disabilities (e.g. infertility, deafness, blindness) due to diseases can be prevented • Herd immunity** - If a large number of individuals*** in a population (e.g. 95%) are immunised *due to vaccinations, transmission of the disease ***in a community is less likely** due to the low chance** of a an individual who is not vaccinated** (e.g babies, elderly) coming into contact with an infected individual****. Hence the unvaccinated are protected** because transmission is prevented.*** • Some diseases may be completely *eradicated *by vaccination, reducing human suffering & future costs of treatment e.g. Smallpox (unique circumstances) - Human was the only host - Virus did not mutate - Infected people easily identified & isolated, no symptomless carriers - Compulsory live, attenuated vaccine that was also heat stable; no boosters required (note: some people are unsuitable for vaccines)

Answer 17

* While live, attenuated vaccines are more effective than inactivated vaccines, they pose the risk of reversion to virulence*** to cause disease * Some people may be allergic* to components in vaccines * Immunitydevelopedaftervaccination may not be as effective*** as natural immunity** due to a real infection. (Hence booster shots may be needed.) * Some pathogens mutate very quickly*** and a new vaccine is need every year (as the immune system will not recognize the new mutant form of the pathogen) * Excessive vaccination may reduce effectiveness of immune system to respond to new infections

Answer 18

1. Vaccine and vaccination programme - Compulsory smallpox vaccination programme in many countries resulted in herd immunity - Smallpox vaccine was a live, attenuated vaccine and could elicit a strong immune response - The vaccine was heat stable vaccine this allowed for the delivery of the vaccine to rural/hot areas thus ensures effectiveness of vaccine; - One dose of vaccine was enough to give life-long immunity so no boosters were required 2. Nature of smallpox - stable/ did not mutate and so the vaccine remained effective for a long period of time - no animal or insect vectors/human was the only host for small pox limiting transmission - no symptomless carrier state hence easy to identity infected persons which leads to ease of isolation of cases to prevent spread

Answer 19

- natural substances obtained from microorganisms (e.g fungi and bacteria) Role: - Prevent spread of bacteria within the body and hence aid recovery - Prevent death as consequences may be fatal without treatment - Prevent transmission of disease from individual to individual in a population

Answer 20

1. Bacteriostatic: inhibits cell division of bacteria | 2. Bactericidal: kills bacteria when bacteria are in process of undergoing cell division by binary fission

Answer 21

1. Disrupting cell wall synthesis 2. Disrupt nucleic acid synthesis: - ribosomes of prokaryotes are 70S while ribosomes of eukaryotes are 80s - e.g. streptomycin: binds to small subunit(30s) of bacterial ribosome such that initiation tRNA cannot bind to small subunit - e..g tetracycline: blocks aminoacyl-tRNA from attaching to the A site of bacterial ribosome 3. Disrupting protein synthesis - enzymes used are different in conformation e..g bacterial RNA polymerase is not the same as human RNA polymerase E.g. Rifampin: inhibits RNA synthesis by binding to bacterial RNA polymerase ➔ preventing transcription

Answer 22

• Virus / phage is very specific and will only attack a particular bacterial strain (vs. antibiotics which kill different types of bacteria, including useful ones) • As bacteria evolve resistance, viruses can also evolve to overcome resistance (vs. bacteria evolve resistance to antibiotics over time) • Viruses can replicate once they infect the bacteria - Only a small quantity of virus needed, as it can replicate once in the host to produce more viruses (vs. antibiotics are metabolised and eliminated from the body) • Viruses stop reproducing once specific target bacteria are destroyed • Less likely to cause side effects/ allergies to patient

Answer 23

1. Attachment 2. Replication 3. Important virus-specific enzymes/ proteins

Answer 24

Drug that binds to specific host cell plasma membrane receptor ➔ prevents virus from binding and entering via endocytosis

Answer 25

1. Drug that carries antisense RNA that will bind to viral RNA to form dsRNA ➔ ribosome cannot bind ➔ translation cannot occur to replicate viral RNA 2. Nucleoside analogs (resemble nucleosides): impair virus’s ability to extend its RNA during replication as incorporating analog into RNA prevents addition of next nucleotide

Answer 26

1. Drugs that inhibit RNA-dependent RNA polymerase (in influenza) ➔ prevents viral replication 2. Drugs that inhibit viral reverse transcriptase/ integrase (in HIV) ➔ prevents integration of viral genome into host cell chromosomes ➔ prevents viral replication 3. Drugs that inhibit viral protease (in HIV) ➔ cannot hydrolyse polyproteins into smaller functional protein components 4. Drugs that bind to viral polyproteins (in HIV) ➔ cannot be cleaved by viral protease

Answer 27

1. DNA undergoes transcription* to form pre mRNA in nucleus; 2. The pre mRNA then undergoes splicing where introns are excised and exons joined; 3. Mature mRNA leaves nucleus and associates with ribosomes* for translation* at rough endoplasmic reticulum* (RER); 4. formation of peptide bonds* between adjacent amino acids thus forming a polypeptide; 5. polypeptide enters RER where it folds into its tertiary conformation and are then transported in transport vesicles to cis face of Golgi apparatus* and fuses with it; 6. [What type of modification] further modification of the protein occurs in Golgi apparatus e.g. glycosylation / formation of quaternary structure with formation of disulfide bridges ; 1. vesicles containing antibodies bud off from trans face of Golgi apparatus; 2. fuse* with cell surface membrane and releases antibodies via exocytosis*; (R: active transport) 3. exocytosis requires ATP; Note: must have point 2

Answer 28

1. Papain consists of a single polypeptide chain extensively folded into specific 3D conformation, held by 2. Tertiary structure is maintained by bonds between R-groups of amino acids e.g. hydrophobic interactions, hydrogen bonds, ionic bonds and disulfide bonds*; 3. Most of its hydrophilic R groups are on external surface / facing surrounding, and most of its non-polar / hydrophobic R are buried in interior / away from the aqueous surrounding; [Must have point 3]

Answer 29

1. The bacteria, Mycobacterium tuberculosis* are transmitted from person to person in fine, aerosol droplets; 2. When an infected person with the active TB disease sneezes or coughs; 3. and an uninfected person inhales the droplets/ fine, aerosol droplets which contains the bacteria;

Answer 30

1. One antibody molecule is made up of 2 heavy and 2 light chains / two different types of polypeptides; 2. Each type of chain/polypeptide is coded by a different gene / 2 genes;

Answer 31

1. HIV/AIDS leads to weak immune system/reduced immunity due to reduced number of helper T cells ; 2. Bacteria, M. tuberculosis can multiply faster/ are not destroyed by the immune system; 3. More likely to reactivate dormant bacteria, M. tuberculosis (Note: HIV infection is most powerful known risk for reactivating TB bacteria); 4. Idea that important organs (e.g. lungs) in the body may not be functioning well/may be down with other diseases (e.g. influenza)as a consequence of HIV/AIDS; 5. Treating both conditions at the same time can be challenging because of side-effects, drug interactions etc.

Answer 32

Describe the action of penicillin on bacteria. [8] 1. Bacterial cell wall is made of peptidoglycans*; 2. (Penicillin is only effective) when bacterium is growing/making new cell wall; 3. Penicillin is an antibiotic that inhibits bacterial cell wall synthesis/disrupts peptidoglycan synthesis; 4. This is done by penicillin acting as a competitive inhibitor and binding to active site of transpeptidase; 5. to inhibit formation of cross-links between adjacent chains; 6. As a result, weakening bacterial cell wall of dividing bacterial cells; 7. Because of high osmotic pressure inside the bacterium / when bacteria take in water by osmosis; 8. the increased turgor pressure against weakened cell wall causes bacterium to swell and lyse;

Answer 33

1. combination treatment of antibiotics act on different parts of the bacterial replication cycle 2. bacteria that are resistant due to mutations* to a single antibiotic are unlikely to be resistant against all the antibiotics 3. hence some of the antibiotics should still be effective and all bacteria will be killed leaving no bacteria behind to develop resistance

Answer 34

1. Impermeable anatomical barriers such as intact skin and mucous membrane that prevents pathogens from entering the organism; 2. Chemical barriers that include secretions in that has antimicrobial substances such as lysozyme that cleaves glycosidic bonds of peptidoglycan cell walls of bacteria, or acidic pH that denature proteins in pathogens; 3. Phagocytes such as neutrophils, macrophages and dendritic cells that make up the cellular component of the non-specific immune system that engulf pathogens by phagocytosis; 4. Macrophages are also responsible for the inflammatory response as they secrete chemokines to recruit neutrophils to the site of infection to carry out phagocytosis; 5. Macrophages secrete cytokines that increases permeability of blood vessels allowing neutrophils to migrate into tissue from the blood;