H2 Biology 20 - Infectious diseases

classified into active immunity/passive immunity >

immunity obtained from

active immunity: development of Ab in response to exposure to Ag(vaccination/infectious disease attack) &

passive immunity: transmission of Ab from mother->fetus through placenta/injection of antiserum >

composes cellular components; lymphocytes(B,T cells);

humoral component; Ab in extracellular fluid >

triggered when innate IS cant eliminate infection; develops > slowly, targets specific pathogen Ag, stimulates long-lasting immunity to repeated exposure to same pathogen >

1o IR; Ag contacts IS for the 1st time, IS learns to recognise Ag, make Ab against it, produce memory B, T cells >

2o IR; same Ag contacts IS again, immunological memory established, start producing Ab immediately >

IR faster, stronger & last longer if exposed to same pathogen

first line of defence - provides resistance through several physical, chemical barriers; pathogens first encounter physical barriers(epithelial layers) that line skin & mucous membranes >

second line of defence - provides resistance through cellular components(macrophages, neutrophils, dendritic cells) >

activated immediately upon infection, response non-specific, diff cell types participate in innate immunity, receptors recognising pathogens limited in specificity; each cell recognise & respond to many diff pathogen types, many can recognise same pathogen >

no immunological memory as receptor structures same over host lifetime >

no clonal expansion

physical barrier

epithelial surfaces act as barriers against pathogens >

pathogen breaches host's physical barriers, other innate immune mechanisms act immediately

chemical barriers

mucus, tears, saliva produced by mucous membranes trap pathogens, provide washing action, inhibit colonisation by fungi, bacteria >

stomach mucus acidic pH prevent microorganism growth >

antimicrobial enzymes cleaves peptidoglycan glycosidic bonds -> bacterial cell lysis >

antimicrobial peptides disrupt bacteria, fungi membranes, membrane envelopes of some viruses

phagocytic cells

inflammation; protective response, eliminate infecting pathogens by delivering immune cells to right place, right time >

histamines(mast cells), cytokines(macrophages) released; increases blood flow to infection site & leakage of fluid, proteins from blood into tissue space, produce redness, swelling

histamine(mast cells), signalling molecule, trigger dilation of blood vessels, results in increased blood flow; recruits > phagocytic cells, increases permeability of blood vessels near infection site to antibacterial peptides(disrupt bacteria membrane) >

cytokines(macrophages), signalling protein, dilates blood vessels, increase blood flow; further recruits, increases movement of > phagocytic cells to infection site >

pathogen binding to receptors embedded in phagocytic cell membrane activates phagocytic cells; engulf pathogens(phagocytosis), digest them w/ lysomal enzymes >

APCs(macrophages, dendritic cells) present Ag(peptide fragments) to B, T cells, activate adaptive IR

development of antibodies in response to exposure to Ag >

latent period b4 response seen as B, T cells activated to respond to antigen; proliferate, differentiate into effector cells >

immunity lasts longer due to lymphocytes, Ab produce & presence of memory B, T cells >

naturally acquired -> exposure to sub-clinical infections

artificially acquired -> vaccination of Ag(attenuated organisms)

immunity produced when individual receives Ab/activated lymphocytes from another individual/immune animal >

immediate protection, individual immune to Ag w/o prior exposure to Ag >

immunity not long-lived, persists only as long as Ab/lymphocytes last; Ab not produced by B cells, regarded as foreign & will be removed from circulation by phagocytes >

risk of hepatitis, AIDs, serum sickness/graft versus host disease

naturally acquired -> transfer of maternal Ab through placenta/breast milk

artificially acquired -> antiserum injection into person bitten to quickly neutralise venom

APCs(macrophages, dendritic cells) link innate IS to adaptive IS when pathogen Ag presented to lymphocytes such as B, T cells to activate adaptive IR

cellular components(cell mediated) - T cells

humoral component(antibody mediated) - Ab produced by B cells

bacterial cell binds receptor on membrane of phagocyte, activate phagocyte >

phagocyte engulfs bacterial cell(phagocytosis), form endocytic vesicle containing bacterial cell >

endocytic vesicle containing bacterial cell fuses w/ lysosome >

bacterial cell digested by lysosomal/hydrolytic enzymes >

bacterial cell processed into short peptides/fragments >

peptides/Ag bind to MHC proteins -> MHC-Ag complexes, transported to CSM of APC(vesicles) >

vacuole containing undigested substances moves to CSM, released out of cell(exocytosis) >

MHC-Ag complex on APC membrane ready for presentation to B, T cells to activate active IR

T_H cell secrete cytokines;

activate B cells to undergo ClEx, dy/dx into plasma cells, memory cells; plasma cells secrete Ab for Ab-mediated response >

stimulate CD8+ T cells to undergo ClEx, dy/dx into cytotoxic T cells >

promote recruitment of > monocytes, macrophages,T_H cells from blood to area of damage

T_C cell kill virally infected cells;

secrete proteins, kills infected cell by forming pores in CSM(perforins), break down cell contents(granzymes) & virus it carries, eventually lyses cell

memory T cell persist long post-infection;

quickly divide by mitosis, undergo ClEx, dy/dx, develop large no. of effector T cells upon re-exposure to same Ag -> provides immunological memory against past infections >

majority T cells die once pathogens cleared; memory T cells persist >

memory T cell no. higher than b4 infection occurred, can be rapidly reactivated upon re-exposure to same Ag >

increased T cell no. increases chances of APC contact >

faster response for 2^o, subsequent IR

secrete Ab for Ab-mediated response

memory B cell persist long post-infection;

quickly divide by mitosis, undergo ClEx, dy/dx to large no. of plasma cells upon same Ag re-exposure -> provides immunological memory against past infections >

majority B cells die once pathogens cleared; memory B cells persist >

memory B cell no. higher than b4 infection occurred, can be rapidly reactivated upon re-exposure to same Ag >

increased B cell no. increases chances of APC contact >

faster response for 2^o, subsequent IR

APCs display peptides bound to MHCs to TcRs on naive T cells, naive T cells whose TcRs can r&b MHC-Ag complexes activated >

activated T cells produce cytokines, undergo ClEx, dy/dx into effector, memory T cells

activation requires 2 signals;

1st activation signal, BcR r&b Ag, activates naive B cell >

BcR+bound Ag endocytosed into B cell, Ag processed into short peptides, attached to MHC proteins, form MHC-Ag complexes >

MHC-Ag complexes transported to CSM of B cell, acts as APC to T_H cells >

T_H cell TcR r&b MHC-Ag complex on B cell CSM >

T_H cell provides 2nd activation signal to B cell, secretes cytokines, activates B cell to undergo ClEx, dy/dx into plasma cells, memory cells

protect indiv against disease by conferring immunity to indiv w/o prior exposure to pathogen >

upon pathogen encounter, memory B T cells ClEx, dy/dx form effector B T cells to provide 2^o IR against pathogen >

confer lifelong immunity; memory B T cells long-lived, contribute to immunological memory to vac indiv >

confer herd immunity to unvac indivs in community >

when infected, immunised indiv wont spread pathogen as readily compared to susceptible indiv >

herd immunity reduces possibility of transmission b/w indivs; unvacc indivs low risk of infection >

contribute to elimination of infectious diseases in human popn if pathogen relies on human host >

herd immunity established, maintained in popn for sufficient time, no disease transmission in popn; if done to whole popn in endemic region, virus eradicated

adverse reactions post-vaccination observed in small no. of indivs, e.g. life-threatening allergic reaction, fainting, rashes >

some indivs > susceptible to vac risks than others, e.g. indivs w/ weaked IS >

for live attenuated vaccine, pathogens used modified to be < virulent; possibility of pathogen regaining virulence, causing disease

globular protein w/ 4^o structure held tgt by intermolecular H, ionic, disulfide bonds, hydrophobic interactions b/w R groups of amino acids >

consists 4 polypeptide chains; 2 identical HC, 2 identical LC >

each chain divided into variable region, constant region >

each LC, HC folded into specific 3^o structure, form part of Ag-binding site of Ab OR

in 4^o structure, one V_H, one V_L brought tgt form Ag-binding site

F_ab region; contains specific Ag-binding site to bind to specific Ag, prevent pathogens attaching to host cell receptor(neutralisation) >

F_c region; binds to Fc receptor on phagocytes/macrophages & activates them so phagocytosis of pathogen occurs, pathogen ingested, killed(opsonisation) >

C_H region; determines diff class of Ab & diff biological fn, determine mechanism used destroy Ag/if Ab secreted or membrane bound >

2 identical Ag-binding sites; bind to 2 same Ag, concentrates Ag tgt(agglutination) >

hinge region; allows indep mvmt of 2 Ag-binding sites, allow both to bind to Ag spaced @ variable dist apart(agglutination) >

disulfide bonds; holds each LC w/ HC, holds 2 HC tgt, maintain Ab as globular protein w/ 4^o structure

form of DNA rearrangement, various gene segments joint tgt randomly, some intervening segments enzymatically removed followed by rejoining of remaining seq >

occurs prior to Ag contact during B cell development in bone marrow >

results in production of naive B cell, expresses BcR specific to particular Ag

RPM in rearranged VDJ/VJ regions in activated B cells >

occurs only in T_H cell-activated B cells, takes place outside bone marrow where activated B cells divide rapidly during ClEx >

RPMs occur in variable regions of HC, LC gene loci when there is prolonged exposure to particular Ag >

each activated B cell w/ mutation acquire slight a.a. diff in variable region of Ig chains >

possesses slightly diff BcRs w/ varying specificity, affinity for particular Ag; results in further diversification of Ab >

altered BcRs bind Ag better than original, B cells selected for dy/dx into plasma, memory cells >

w/ repeated exposure to same Ag, B cells produce Ab of successively greater affinities to Ag(affinity maturation) >

leads to diversity of Ag-binding site, allows IS recognise various Ag

form of DNA rearrangement @ Constant gene segment of HC locus in TH cell-activated B cells >

results in Ab w/ diff constant(Fc) region of Ab HC which can interact w/ diff effector molecules, leads to faster, more ways to eradicate pathogens

genes coding for Ig found @ 3 gene loci > each locus made up of multiple gene segments;

HC gene contains Variable, Diversity, Joining, Constant gene segments >

LC gene contains V, J, C segments >

2 types LC; kappa chain encoded by IgK locus on chr 2, lambda chain encoded by IgL locus on chr 22

def; process whereby vaccine administered to indiv, stimulate long lasting, active immunity against infectious diseases >

3 types of vaccine; attenuated/dead pathogen, non-disease causing pathogen w/ same Ag, fragment of pathogen >

non-pathogenic, immunogenic >

generates memory B, T cells specific to pathogen; confers immunological memory >

provide 2^o IR faster, stronger than 1^o IR upon actual exposure to same pathogen; indiv protected from disease >

vaccination of high enough proportion confers herd immunity to unvac indivs; breaks disease transmission cycle

virus didnt mutate frequently, same vaccine used for whole programme/need not be changed >

cow pox virus harmless, allow use of 'live' virus vaccine, results in stronger IR >

vaccine heat stable, suitable for hot countries/isolated areas/rural areas >

one dose enough to give life-long immunity, no boosters required >

few/no symptomless carriers, no animal reservoir as virus infects humans, infected ppl easy to identify & isolate to prevent spread of disease >

mandatory for each country run their own mass vac campaigns & eradicate disease within own borders, confers herd immunity to unvac indivs & vac of high enough proportion of popn can break disease transmission cycle

rapid repn of influenza virus in epithelial cells of RT disturbs cellular fn, damages tissue >

excessive budding of newly synthesised influenza virions depletes epithelial cells CSM >

cells produce >> mucus, secrete cytokines -> inflammation to activate IS; causes typical flu symptoms(fever,chills,fatigue,cough,body aches) >

causes epithelial lining of upper, lower RT to be lost >

causes cell damage, death within host's RT >

if virus reaches lower RT, leads to > severe complications(viral pneumonia)

enters bloodstream, targets cells w/ CD4 proteins on surface(T_H cells) >

activated T_H cells req in development, activation of AIR >

HIV infects T_H cells, viral DNA integrate into T_H cell chr, remain dormant evading AIS, attacks only actively replicating viruses >

random insertion of viral DNA in host cell chr disrupt T cell fn >

over long time period, untreated HIV infection leads to repn of new virus, triggers T_H cell destruction; excessive budding of new virions from T_H cells disrupts plasma membrane permeability, fn >

T_H cell count declines below critical level, cell mediated immunity lost, AIS weakened >

host susceptible to opportunistic infections >

immunodeficiency+uncontrolled opportunistic infections -> AIDS occurs

transmitted from person to person via fine, aerosol droplets in which bacterial cells carried within >

infected person sneezes, coughs out aerosol droplets; droplets inhaled by uninfected person

once in lungs, alveolar macrophages phagocytose bacteria, form phagosomes w/ MTB >

inside phagosome, MTB inhibits fusion of phagosome w/ lysosomes; no lysosomal enzymes available kill MTB >

MTB survives, continues multiply inside macrophages >

tubercle formed, consists of macrophages in tight ball-like formation >

@ center of tubercle, cell death by necrosis occurs -> macrophage cell membrane ruptures, releases cell contents to surroundings, tubercle remains intact; disease arrested, remain latent for years >

TB active when tubercle ruptures, MTB released into bronchiole, infection spreads in lungs, productive cough develops; facilitates aerosol MTB spread >

lungs progressively destroyed by cavity formation as tubercles rupture

bacteriostatic; inhibits growth of bacteria(no. of bacteria remains constant)

bactericidal; kills bacteria(no. of bacteria decreases)

inhibit peptidoglycan synthesis, component of bacterial cell wall essential for maintaining structural integrity of bacterial cell >

inhibits enzyme transpeptidase, prevents formation of cross-links b/w adjacent chains of peptidoglycans >

indiv peptidoglycan chains remain separated, cross-links cant be formed >

BCWs of dividing bact cells weakened, osmotic lysis occurs due to high osmotic pressure within bact cells

antibiotics; natural substances obtained from microorganisms, kill/inhibit growth, replication of bact by disrupting metabolism >

limit bacteria growth to level where host IS can eliminate pathogen >

antibiotics effective to bact, usually builds up antibiotics within cytoplasm >

cell wall synthesis(refer to flashcard 32)

protein synthesis

streptomycin; binds to SRS of bact ribosome, itRNA cant bind to SRS >

as unstable mRNA-ribosome complex formed, N-Formylmethionine(fMet)-tRNA cant bind SRS >

leads to codon misreading, eventual protein synthesis inhibition >

tetracycline; inhibit protein synthesis, blocks entry of aminoacyl-tRNA to A site of bacterial ribosome

nucleic acid synthesis

rifampin; inhibit RNA syn by binding to bact RNA pol, prevent t/c >

quinolones; inhibit bact DNA gyrase/topoisomerase, inhibit DNA repn, t/c