Infectious Diseases Flashcards
Non-specific / innate immune system
Impermeable anatomical barriers such as intact skin and mucous membrane prevents pathogens from entering the organism.
Chemical barriers that include secretions of antimicrobial substances such as lysozyme that cleaves glycosidic bonds in peptidoglycal cell wall of bacteria or acidic pH that denatures proteins in pathogens.
Phagocytes such as neutrophils, macrophages and dendritic cells that make up cellular component of innate immune system that engulf pathogens by phagocytosis.
Macrophages are also responsible for inflammatory responses by secreting chemokines to recruit neutrophils to the site of infection and secreting cytokines to increase permeability of blood vessels allowing neutrophils to migrate into tissue from blood.
Phagocytosis
Antigen presenting cells (macrophages) take up bacteria by phagocytosis, where pseudopodia are formed and extended outwards to engulf the bacteria. When the ends of the pseudopodia fuse, a vesicle containing the bacteria is pinched off and enters the cytoplasm as a phagosome.
Phagosomes fuse with lysosomes, forming phagolysosomes. Hydrolytic enzymes from lysosome break down bacteria into short peptides. (Lysozyme hydrolyses glycosidic bonds in the peptidoglycan cell wall of bacteria. Nuclease in lysozyme hydrolyses phosphodiester bonds in bacterial nucleic acids. Bacteria are also killed by hydrogen peroxide/free radicals.
Antigens on the bacteria are processed into short peptides of antigens to be loaded onto MHC protein to form peptide:MHC complex, presented on the cell surface membrane for binding by naive T cells.
Non-self antigen
A non-self antigen is a foreign molecule that stimulates an immune response / the production of antibodies.
How B-lymphocytes recognise non–self antigens
B-lymphocytes has immunoglobulin on its cell surface membrane that acts as a B-cell receptor, which has antigen-binding sites complementary in shape and charge to specific epitope of an antigen.
Role of memory B cells
Memory B cells are involved in secondary response when re-exposed to the same antigen, will recognise it and undergo faster clonal expansion and differentiation into antibody-secreting plasma B cells, which will result in production of more antibodies for a longer period of time, preventing person from falling ill.
Helper T cells
Secrete cytokines that activate B cells and stimulate macrophages.
Cytotoxic T cells
Cytotoxic T cells secrete perforins which makes pores in cell membrane of infected cells, and also secrete granzymes which enter the cell via the pores and activate the enzymes which trigger apoptosis of the infected cells.
Antibody molecule structure and functions
- An antigen-binding site is made of one variable heavy chain and one variable light chain, and is complementary in shape and charge to a specific epitope of an antigen due to folding of heavy and light chains giving rise to unique 3D conformation.
- IgG has two antigen binding sites, allowing agglutination of antigens as it can bind to two antigens at the same time, pathogens clump to facilitate clearance.
- Neutralisation of pathogen by antibody prevents pathogen entry: prevents antigen from binding to host cell surface receptor on host cell surface membrane and prevents receptor-mediated endocytosis from occurring.
- Opsonisation, when Fc region / constant region of heavy chains of antibodies binds to Fc receptors on phagocytes, promoting phagocytosis.
- Hinge region gives flexibility when binding to epitope of antigen
- Disulfide bridges hold heavy and light chains together, giving stability to the quaternary structure.
Antibody diversity
1) Somatic Recombination
There are multiple gene segments at heavy and light chain genes.
Somatic recombination, occurring in precursor B cells in the bone marrow, 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.
At the Ig heavy chain gene locus, 1 V segment, 1 D segment, and 1 J segment are randomly joined to form a single VDJ exon.
At the Ig light chain gene locus, 1 V segment and 1 J segment are randomly joined to form a single VJ exon.
2) Somatic hypermutation
Random point mutations in the rearranged VDJ region of heavy chain locus and rearranged VJ region of light chain gene locus in activated B cells carried out at a much higher rate than normal.
Diversifies the variable regions of antibody for antigen binding. Occurs during clonal expansion of the activated B cells.
Some point mutations result in B cells expressing low affinity Ig chains on their cell surface membrane and some mutations result in B cells expressing higher affinity Ig chains on their cell surface membrane, the latter of which are selected for clonal expansion and differentiation, known as affinity maturation.
Resulting plasma cells and memory B cells will have BCRs with higher affinity antigen binding sites for a specific antigen and lasma cells will also produce antibodies with higher affinity antigen binding sites for a specific antigen.
3) Class switching
DNA rearrangement at the constant gene segment of the heavy chain gene locus in activated B cells allows for the production of antibodies with same antigen binding site, but different function.
The genetic variation in Somatic recombination vs meiosis
- Somatic recombination only alters the heavy and light chain gene loci while genetic variation in meiosis can alter any gene locus on an organism.
- Somatic recombination involves the removing and joining of gene segments while crossing over in meiosis involves exchange of equivalent segments.
- Somatic recombination occurs on a single chromosome while crossing over in meiosis occurs between non-sister chromatids of homologous chromosomes.
How plasma cells produce antibody molecules
and release them
DNA undergoes transcription to form pre-mRNA in the nucleus. Pre-mRNA undergoes alternative splicing where introns are excised and exons are joined. Mature mRNA leaves nucleus and associates with ribosomes for translation at the rough endoplasmic reticulum, formation of peptide bonds between amino acids thus forming a polypeptide.
Polypeptide enters the RER and folds into its tertiary conformation, then is transported in transport vesicles to cis face of Golgi apparatus and fuses with it. Further modification of the protein occurs in Golgi apparatus such as glycosylation or formation of quaternary structure with formation by disulfide bridges.
Secretory vesicles containing antibody molecules bud off from the trans face of the Golgi apparatus and fuse with the cell surace membrane, releasing antibodies via exocytosis. Exocytosis requires ATP.
Antibiotics cannot treat viral infections
Antibiotics act at a cell structure not possessed by a virus, like cell wall
Viruses are inside host cells out of reach of antibiotics
Antibiotics only work on living, growing cells.
Antibiotics do not work on capsid, viral envelope
How antibiotic resistance arises as a result of mutation
Mutation involves change in sequences of bases of nucleotides of DNA. Gene mutation leads to base substitution, deletion, addition or inversion, thus leading to altered mRNA which will be translated to form different proteins with different 3D conformation resulting in range of proteins with different functions some of which may result in antibiotic resistance.
Incomplete dosage of antibiotics
Incomplete treatment where dose of antibiotic is not finished can lead to some bacteria surviving.
Spontaneous mutation in bacterial population may produce strains that are resistant to antibiotic and transfer of antibiotic resistance genes from bacteria to bacteria via conjugation/transduction/transformation can occur.
When antibiotic is applied and serves as selection pressure, those with resistance gene survive and reproduce, passing on allele to daughter bacterial cells while those that are susceptible die.
Over time, microevolution occurs as there is increase in frequency of antibiotic resistance allele in bacteria population.
Vaccination
Vaccination is the administration of harmless form of a pathogen to induce a specific adaptive immune response, to protect individual against later exposure to the same pathogen by production of memory cells.
Vaccine is an artificial active immunity.
