Infectious Diseases Flashcards
What is an infectious disease?
a disease aka. abnormal funciton of body caused by pathogen invading the body, which can be transmitted from one organism to another uninfected person
What is meant by a non-self antigen?
Foreign molecule that stimulates an immune response
Describe the non-specific/innate immune system: barriers
Anatomical barriers: intact skin & mucous membrane→ prevent pathogens from entering organism
Chemical barriers:
- secretions w antimicrobial substances e.g. lysozyme (cleave glycosidic bonds of bac’s peptidoglycan cell wall)
- acidic pH (denature proteins in pathogens)
Describe the non-specific/innate immune system: cellular component
Role: phagocytosis; induce inflammation; APC
- Phagocytes engulf pathogens by phagocytosis
- Macrophages and dendritic cells are APCs
- Macrophages
> Secrete chemokines to recruit neutrophils to site of infection→ inflammatory response
> Secrete cytokines that increase permeability of blood vessels→ neutrophils can migrate into tissue from blood
Compare the innate and adaptive immune system
Non-specific vs specific
Rapid vs takes time to develop
No memory vs shows memory
Compare T cells and B cells
- Differentiate in thymus vs bone marrow
- Naive cell’s TCR/BCR recognises and bind to specific, complementary processed peptide of peptide MHC complex on APC/unprocessed antigen of pathogen
- Naive T/B cells–> activation by APC/helper T cell–> clonal expansion and differentiation–> effector T/B cells (helper, cytotoxic, plasma) & memory cells
- S: has a specific T/B CR on its surface
- S: memory T/B cells confer long term immunity
What is in the cell-mediated and humoral response of adaptive immunity?
Cell-mediated: cytotoxic T cells
Humoral response: antibodies target extracellular pathogens
Compare active immunity and passive immunity
Immune response antibody production duration E.g. natural E.g. artificial
What happens during a secondary immune response:
Re-exposure to the same sf antigen→ specific memory T/B cells quickly recognise it→ memory B/T cell faster clonal expansion and differentiation into effector T/B cells→ faster & stronger secondary immune response; plasma cells produce high conc of antibody which prevent further infection by neutralisation, agglutination & opsonisation
Compare primary and secondary immune response
Slower response and lag period VS faster response
Weaker/Stronger response: [antibody] rises gradually/sharply and peaks at a lower/much higher level–> fewer/more antibodies produced, produced for a shorter/longer time
No memory VS has memory hence confers LT immunity to same pathogen
Describe phagocytosis and antigen-presentation
- Phagocytes/APC engulf pathogen via phagocytosis
> Pseudopodia extends outwards to engulf bac→ ends of pseudopodia fuse→ vesicle pinched off→ phagosome - Phagosome fuse w lysosome→ phagolysosome
- Bac antigen broken down by hydrolytic enzymes in lysosome into short peptides
> Nuclease hydrolyses phosphodiester bonds in bac nucleic acids
> Bac also killed by hydrogen peroxide/free radicals; - , which bind to MHC protein (major histocompatibility complex)→ peptide:MHC complex→ ready for presentation to naïve T cells
Why must antigen be processed before being presented?
epitopes of antigen recognised by TCR are buried. Antigen must be processed into short peptides, so that epitope can bind to MHC for presentation
Very briefly outline the adaptive portion of the immune response
- clonal selection
- activation of T cells–> memory cells & effector cells: cytotoxic and helper T cells
- activation of B cells–> plasma cells and memory cells
- action of antibodies
- immunological memory
Describe clonal selection and the activation of T cells (w/o details of roles of each effector cell)
- Clonal selection: specific naive T cells w specific TCR binds to complementary peptide-MHC complex on APC→ APC secretes cytokines that activates naive T cell
- T cell undergoes clonal expansion & differentiation into effector T cells (cytotoxic, helper) and memory T cells
What is the role of the cytotoxic T cells?
kill cells infected w intracellular pathogens like viruses→ prevent reproduction of intracellular pathogens
- Infected host cells display same peptide-MHC complex presented earlier→ cytotoxic T cells recognise it, TCR complementary in shape and binds to peptide-MHC complex on target cells→ produce perforins (make pores in infected cell’s cell membrane; may lyse) and granzymes (diffuses in via pores & activate enzymes→ apoptosis)
- Also kills tumour cells
Describe the activation of B cells and the role of helper T cells (w/o role of plasma cells)
- Clonal selection & receptor-mediated endocytosis: Specific naive B cell has a BCR w antigen binding site that’s complementary in shape and binds to antigen of pathogen→ cell sf membrane invaginates, pinches off, endocytic vesicle
- Pathogen processed, peptide of antigen binds to MHC protein→ peptide-MHC complex, transported to sf membrane for presentation
- Specific TCR on specific T helper cell binds to complementary peptide-MHC complex on specific naive B cell→ helper T cell secretes cytokines→ activates B cell→ clonal expansion and differentiation into effector B cells/plasma cells and memory B cells
Describe the role of plasma cells and antibodies
Plasma cells secretes antibodies, which destroy extracellular pathogens and toxins
Antigen-binding site of antibodies bind to antigens of pathogen/bac toxin→
- Neutralisation: prevents antigen from binding to host cell sf receptor & prevents receptor-mediated endocytosis→ prevent entry
- Agglutination: each antibody has 2 antigen binding site→ 2 pathogen binds to 1 antibody simultaneously→ aggregation of pathogens→ promote phagocytosis
- Opsonisation: Fc portion of antibody binds to Fc receptors on phagocyte→ recruits macrophages/ phagocytes→ increase feq of phagocytosis (tag it for uptake by phagocytosis)
Link the structure of IgG to its function
- Globular protein→ Soluble, transported in blood
- Folding of VH and VL chains→ unique 3D conf→ antigen binding site complementary in shape to specific epitope of antigen
> Can carry out neutralisation by binding to specific epitope of antigen→ prevent pathogen from binding to host cell receptor and infecting host cell - IgG has 2 antigen binding sites per antibody mlc
> Each IgG can bind to 2 antigens simultaneously→ pathogens aggregate→ allows agglutination - Fc region of antibody is complementary in shape to Fc receptors on phagocytes
> Fc bind to Fc receptors on phagocytes→ tag/promote phagocytosis→ opsonisation - Constant region of H chain determines class of antibody and hence their different functions
- Disulfide bridges between H and L chain/2 H chains hold them tgt
> Stability to quaternary struc - Hinge region–> flexibility when binding to antigens that are variable distances apart
Where and when does somatic recombination, HC and LC combinatorial pairing, somatic hypermutation and class switching occur?
In bone marrow, during B cell maturation: somatic recombination and HC and LC combinatorial pairing
In lymph nodes after activation of B cells: somatic hypermutation and class switching
Describe somatic recombination in both H and L chains
V(D)J recombination: DNA rearrangement, where various gene segments joined tgt randomly, some intervening segments are enzymatically removed, followed by rejoining of remaining seq
- HC gene: 1 V gene segment, 1 D segment, and 1 J segment randomly joined→ 1 VDJ exon, coding for VH
- D & J rearrangement: 1 D and 1 J segment joined (intervening seq enzymatically removed)
- V & DJ rearrangement: 1 V segment and DJ segment joined (intervening seq enzymatically removed)
- LC gene: 1 V gene segment and 1 J segment randomly joined→ 1 VJ exon, coding for VL
- V & J rearrangement: 1 V segment and 1 J segment joined (intervening seq enzymatically removed)
- Then, transcription→ pre-mRNA→ RNA splicing: V(D)J exon and C exon joined→ mature mRNA→ translation→ specific H/L chain protein with specific VH/L and C domains
