Infectious Diseases Flashcards
Innate immune system
Barriers:
1. skin
2. mucous membrane
–> contain antimicrobial proteins (e.g. lysozyme, break down bacterial cell wall
3. acidic pH of the stomach
–>denatures proteins in pathogens
Cellular components:
- phagocytes
–> macrophages, dendritic cells, neutrophils
- non-specific, no memory, rapid
Adaptive immune system
- cell mediated response –> mediated by cytotoxic T cells that kill cells infected with intracellular pathogens
- humoral response –> mediated by antibodies, which target extracellular pathogens
- specific, shows memory, takes time to develop
role of T lymphocytes
- when a specific naive T cell is. activated, it undergoes clonal expansion and differentiation to form cytotoxic T cells, helper T cells, and memory T cells
- helper T cell: activate naive B cells so that it can undergo clonal expansion and differentiation
- cytotoxic T cells: kill intracellular pathogens by secreting perforins and granzymes, involved in cell mediated response
- memory T cells: when re-exposed to the same antigen, it will recognize it to undergo faster clonal expansion and differentiation to mount a stronger and faster immune response –> confers. long term immunity
role of B lymphocytes
- when a specific naive B cell is activated by specific T helper cell, it undergoes clonal expansion and differentiation to form antibody-secreting plasma B cells and memory B cells
- plasma B cells secrete antibodies that initiates the humoral response to target extracellular pathogens
- memory B cells: when re-exposed to the same antigen, it will recognize it to undergo faster clonal expansion and differentiation to mount a stronger and faster immune response –> confers long term immunity
How naive cells become activated, the adaptive immune response and immunological memory
- B cell receptor on a naive B cell is complementary in shape to an antigen of the pathogen and binds to it, the cell surface membrane invaginates and pinches off to form an endocytotic vesicle via receptor-mediated endocytosis.
- The pathogen is processed when vesicle fuses with. lysosome to form an endolysosome and the pathogen is cut up into short peptides
- A peptide of the antigen binds to an MHC protein to form peptide-MHC complex which is then presented on the cell surface membrane for presentation to T helper cell.
- An antigen presenting cell forms pseudopia around the pathogen, engulfs and wraps around to form a phagosome, known as phagocytosis.
- The pathogen is processed.
- The peptide of the antigen binds to an MHC protein to form peptide-MHC complex, which is then transported to the cell surface membrane for presentation to naive T cell.
- The specific naive T cell has a specific T cell receptor that can recognise and bind to complementary peptide-MHC complex of APC, APC secretes cytokines and activates it, triggering clonal expansion and differentiation to form cytotoxic T cells, helper T cells and memory B cells.
- The helper T cells with specific T cell receptor
binds to complementary peptide-MHC complex on naive B cells. - Helper T cell secretes cytokines and. activates the specific B cells to undergo clonal expansion and differentiation to form naive B cells, memory B cells.
- The antibodies then destroy extracellular pathogens via opsonisation, neutralisation and agglutination.
- Cytotoxic. T cells kill infected cells by secreting perforins and granzymes.
- If the body is reexposed to the same pathogen, memory B and T cells can recognise it to mount a stronger and faster immune response
Humoral response
- neutralisation
–> antigen binding sites of antibodies bind to the antigen to prevent entry into host cell by preventing binding to host cell receptor - opsonisation
–> after binding of antigen binding site of antibody to pathogen, binding of Fc portion of antibody to Fc receptors on phagocyte –> promotes phagocytosis - agglutination
–> each antibody has two antigen binding sites –> can bind to two pathogens simultaneously –> clumping of pathogens –> promote phagocytosis
cell mediated response
- perforins created pores in the cell membrane
- granzymes activate enzymes in the cell that trigger apoptosis of the virus infected cell
antibody structure and function
- two antigen binding sites in one antibody molecule
–> facilitates agglutination where two pathogens can bind to antibody at one time, promotes clumping of pathogens hence facilitates phagocytosis - Fc region of the antibody complementary to the Fc receptors of the phagocytes –> facilitates opsonisation
- antigen binding site is complementary in shape to a specific antigen due to precise folidng of variable heavy and light chains that give rise to unique 3D conformation
–>antibodies can carry out neutralisation by binding to specific epitope of antigen of pathogen thus preventing pathogen from binding to host cell receptors and infecting other host cells - disulfide bridges linking heavy and light chains
–> maintain its specific quaternary structure - hinge region on each antibody
–> can bind to antigens that are variable distances apart - constant region of heavy chains
–> class of antibody thus their functions determined
Somatic recombination
- a form of DNA rearrangment where various gene segments are joined randomly and some intervening. segments are enzymatically removed followed by rejoining of remaining sequences
- at the heavy chain, V, D and J segment randomly joined tgt to form VDJ exon
- at the light chain, V and J segment joined to form VJ exon
somatic hypermutation
- random point mutations that occur in the rearranged VDJ and VJ regions of the DNA in activated B cells
- occurs during clonal expansion of the activated B cells
- some point mutations result in B cells expressing lower affinity lg chains while some have higher affinity lg chains on the csm
- B cells that express higher affinity BCR are selected for clonal expansion and differentiation –> affinity maturation
- the resulting plasma 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
class switching
- DNA rearrangement at the constant gene segment of the heavy chain locus in activated B cells
- allow for the production of antibodies with same antigen binding site but different function
active vs passive immunity, natural vs artificially acquired
active, natural: when infected by a pathogen
passive, natural: antibodies passed from mom to child via breast milk
active, artificial: vaccination
passive, artificial: antiserum with antibodies received from another host
active: produced by individual’s own immune system in response to antigens
passive: transferred to recipient without the participation of recipient’s immune system
vaccination
- intentional administration of a harmless form of pathogen to induce a specific adaptive immune response
- a form of artificial active immunity to initiate a primary immune response and specific naive B and T cells are activated to become effector and memory B and T cells respectively
- upon reexposure to the same pathogen, memory B and T cells will quickly recognise the surface antigen of pathogen and mount a stronger and faster immune response
- memory B and T cells rapidly undergo clonal expansion and differentiation and develop into antibody-secreting plasma B cells and effector T cells respectively
- vaccines confer long term immunity
benefits and risks of vaccinations
Benefits:
- protects individuals against diseases
- increase herd immunity
–> if many individuals in a population are vaccinated, transmission of diseases is less likely
- can completely. eradicate some diseases
Risks:
- pose the risk of reversion to virulence to cause disease
- allergic to components in vaccine
- immunity developed may not be as effective as natural immunity
- some pathogens mutate very quickly, new vaccine needed every year
- excessive vaccinations may reduce effectiveness of immune system to respond to new infections
treatment of bacterial infections with antibiotics
penicillin
–> bactericidial, only effective when bacteria are growing and making new cell wall as it disrupts peptidoglycan cell wall
–> penicillin acts as a competitive inhibitor and binds to active site of transpeptidase
–> inhibition to formation of crosslinks between tetrapeptides of adjacent chains of peptidoglycans
–> bacterial cell wall becomes weakened
–> high osmotic pressure inside the cell when water enters, increases turgor pressure against the weakened cell wall cause bacteria to swell and lyse
