ETA Infectious diseases Flashcards

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1
Q

Somatic recombination

A
  • happens during B cell development in bone marrow
  • process in which recombination happens in the heavy and light chain genes in the V region of antibody
  • V, (D), J segments are present in multiple copies in B cells
  • different V, D, J in heavy chains / different V, J in light chains
    are selected randomly during V(D)J rearrangement
  • deletion of intervening seq and re-ligation of remaining gene segments
  • by V(D)J recombinase
  • multiple combinations of light and heavy chains to form different V regions during development
    => create a large diversity of antibody molecules (with diff antigen binding sites)
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2
Q

significance of somatic recombination

A
  • reduces no of genes needed to code for large no of different antibody molecules
  • variety of antibody molecules -> able to bind to wide variety of pathogens
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3
Q

Class switching

A
  • after exposure to antigen
  • process where same V region of heavy chain is rearranged
  • to associate with different C regions of heavy chain
    • e.g. lgM -> lgE: C region of heavy chain of lgM gene is removed, retaining only that of lgE gene
  • DNA recombination in the heavy chain between switch regions
  • result in the generation of antibodies of different isotopes
  • also has ability for subsequent switching with any downstream C region of heavy chain
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4
Q

somatic hypermutation

A
  • after exposure to antigen
  • V regions of heavy and light chain genes undergo mutations
  • allowing coding for antibodies with increased affinity for binding to antigen
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5
Q

significance of class switching

A
  • diverse responses to the same antigen
    -> antigen specificity retained due to same V region of heavy chain
    -> but different effector activity through different combinations of C region of heavy chain
  • allows for specific response at different times in the course of an infection
    -> e.g. different classes of lg for different functions, ability to continue switching to respond to later infections
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6
Q

possible deductions about effector functions of different antibodies based on info given

A
  • presence of antigen-binding sites
    -> have a role in neutralisation / opsonisation / agglutination of viruses / enhancing phagocytosis by phagocytes
    -> the antibody with a large no of antigen-binding sites (e.g. 10) is best used for agglutination of viruses
  • when the antibody is produced (produced early vs later on)
    -> if antibody persists in the body, it provides sustained immunity to virus
  • where antibody is secreted into
    -> if antibody is secreted into external fluids (e.g. tears, mucus), antibody prevents entry of pathogen via eyes or nose
  • whether antibody can cross the placenta
    -> if antibody can cross the placenta, it can provide immunity to the fetus
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7
Q

reason why antibody acts against antigen A but not antigen B

A
  • antibody has a specific antigen-binding site
  • with each antibody having a different 3d conformation
  • this particular antibody has a complementary shape to antigen A
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8
Q

justification for why antibodies could be useful for prevention and treatment of disease

A
  • (in context of qn) block mode of action of bacteria/virus
    • e.g. agglutination of bacteria prevents them from colonising intestine, bacteria release less toxin
  • needs to be given at early stages
  • considered passive immunity
  • which acts beside the immune system
  • leading to a quicker recovery
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9
Q

how size and shape of antibodies relate to their modes of actions and functions

A
  • antibodies have 2 antigen-binding sites
  • which has a shape that is complementary to antigen
    => thus allowing it to bind to antigen
  • antibodies are **large*
    => thus allowing it to have several binding sites / interact with other cells
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10
Q

how size and shape of antibiotics relate to their modes of actions and functions

A
  • has a a shape complementary to active site of enzyme
  • has a small size, which allows them to interfere with enzymes
    => thus allowing them to function as enzyme inhibitors,
    and prevent growth/protein synthesis/cell wall synthesis
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11
Q

1st line of defence of immune system

A

non-specific external barriers
- natural physical and chemical surface barriers that limit the entry of microorganisms into the body
- operates regardless of exact nature of invader

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12
Q

2nd line of defence of immune system

A

innate immunity
- functions
- mediates initial immediate protection against infections
- instructs adaptive immunity system to respond to diff microbes in ways that are effective for combating these microbes

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13
Q

inflammatory response (innate immunity)

A

1a. mast cells at site secrete histamine and other mediators that
- dilate surrounding blood vessels -> increase in local blood flow
- make vessels more permeable -> exudation of plasma proteins
(i.e. proteins like complement system can leak out of blood vessels into surrounding tissue)
b. Injured tissues and macrophages at the site release chemokines, which recruit immune system cells to site
2a. Recruitment of Natural Killer (NK) cells
-> destroy virus-infected cells
b. Recruitment of neutrophils and macrophages (phagocytes)
-> remove pathogens via phagocytosis
-> release chemokines which …
c. Recruitment of dendritic cells (phagocytes)
-> remove pathogens by phagocytosis
-> act as antigen-presenting cells (APCs) to activate helper T cells, cytotoxic T cells and B cells by showing the antigens to the adaptive lymphocyte populations
note: all these cells release chemokines, thus recruit more immune system cells to site

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14
Q

fever (innate immunity)

A
  • function: occurs to combat large-scale infections
  • key steps:
    • results in elevated body temp
      -> increased activity of phagocytes
    • stimulates virus-infected cells to ** produce interferon**
      -> stimulation of **NK cells **
    • causes cells to multiply more quickly
      -> faster onset of adaptive immune response
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15
Q

3rd line of defence of immune system

A

adaptive immunity
- function
- specific immune response that functions to greatly enhance the antimicrobial mechanisms of innate immunity

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16
Q

types of adaptive immunity

A
  • hummoral immunity
    • principle defence mechanism against extracellular microbes and their toxins
    • mediated by antibodies produced by B lymphocytes
  • cell-mediated immunity
    • defence against intracellular microbes
    • mediated by T lymphocytes which recognise antigens produced by intracellular microbes
17
Q

function of T lymphocytes (by type)

A
  • helper T cells
    • release cytokines that stimulate B cells to divide, develop into plasma cells and secrete antibodies
    • release cytokines that stimulate macrophages to carry out phagocytosis more vigorously
  • cytotoxic T cells
    • recognise antigens from pathogens displayed on cell surface membranes of infected cells,
      attach themselves to surface
      and secrete toxic substances that kill the cells and pathogens inside
18
Q

development (“life cycle”) of T lymphocytes

A
  1. T lymphocytes (Th and Tc) are generated in bone marrow
    (immature)
  2. migrate to thymus, where they mature
    (naive -> mature but unspecialised)
    - mature via production of T cell receptors, which serve as antigen receptors
  3. enter bloodstream and circulate through peripheral lymphoid tissues
    - sites where mature naive T lymphocytes are maintained and adaptive immune responses are initiated when lymphocytes interact with corresponding antigen
    (activated)
  4. clonal selection
    - the small numbers of T lymphocytes with receptors complementary to antigen are stimulated to divide by mitosis
  5. clonal expansion
    - the small clone of cells divides repeatedly by mitosis
  6. some become effector Th or Tc cells,
    while others become memory cells which remain circulating in the body for a long time
19
Q

development (“life cycle”) of B lymphocytes

A
  1. B lymphocytes are generated in bone marrow
    (immature)
  2. mature in bone marrow
    (naive -> mature but unspecialised)
    - gains the ability to make just one type of antibody
    - mature through production of the antibody, which serves as antigen receptor
  3. enter bloodstream and circulate through peripheral lymphoid tissues
    - sites where mature naive B lymphocytes are maintained and adaptive immune responses are initiated when lymphocytes interact with corresponding antigen
    (activated)
  4. clonal selection
    - the small numbers of B lymphocytes with receptors complementary to antigen are stimulated to divide by mitosis
  5. clonal expansion
    - the small clone of cells divides repeatedly by mitosis
  6. some become plasma cells,
    while others become memory cells which remain circulating in the body for a long time
20
Q

function of B lymphocytes

A
  • express membrane forms of antibodies that serves as the receptors that recognise antigens,
    thus initiating process of B cell activation
  • which leads to the production of antibodies
21
Q

function of antibodies

A
  • definition:
    • a type of glycoprotein molecule
    • also called immunoglobulin (lg)
    • which are produced by B lymphocytes
    • and binds antigens
  • functions:
    • (a) bind specifically to toxins, and
      (b) neutralise and
      (c) eliminate microbes and microbial toxins that are present outside of host cells
    • stop microbes that are present as mucosal surfaces and in blood from
      (d) gaining excess to and colonising host cells and connective tissues, thus
      (e) preventing infections from ever being established
22
Q

Antigen-Presenting Cells (APCs)

A
  • functions:
    • capture antigens,
    • transport them to peripheral lymphoid organs
    • and display them to lymphocytes
  • include dendritic cells and macrophages
    • for dendritic cells,
      • antigen is ingested via phagocytosis
      • enzymes in cell break down antigen proteins into peptide fragments
      • which are then displayed
    • for macrophages,
      • antigen is digested into smaller pieces through phagocytosis
      • which are then displayed
23
Q

T DAAAB S

Steps of adaptive immune system

A
  1. Threat
    - adaptive immune system begins invader evades first 2 lines of defence and enters body
  2. Detection
    - macrophage encounters, engulfs and digests invader into smaller pieces through phagocytosis
  3. Alert
    - presents antigen to a Th cell with the specific complementary T cell receptor to alert it that an antigen is present
    - upon binding to a Th cell, macrophage secretes cytokines that activates other immune cells
  4. Alarm
    - activated Th cell begins to secrete cytokines, which
    • activates macrophages
    • activates Tc cells
      - activated Th cell also binds to B lymphocytes and promote their differentiation into plasma cells and memory B cells
  5. Building specific defences
    - clonal selection -> clonal expansion -> effector and memory cells
  6. Surveillance
    - memory cells remain -> secondary immune response to any future encounters
24
Q

NOA

mode of action of antibodies

A
  • Neutralisation
    • antibodies bind to proteins on surface of a virus
      -> thus preventing infection of a host cell
      -> neutralising the virus
  • Opsonisation
    • antibodies bind to antigens on surface of bacteria
      -> thus presenting a readily recognised structure for macrophages or neutrophils
      -> promoting phagocytosis
  • Activation of complement system
    • antibodies bind to antigens on surface of foreign cell, which then binds to a complement protein
      -> generation of a membrane attack complex
      -> which forms a pore in membrane of cell
      -> ions and water rush into cell
      -> causing it to swell and lyse
25
Q

mode of action of Tc cells

A
  • effector Tc cells release cytotoxic pore-forming molecules called perforins
    -> causes water to enter cell
    -> cell swells and burst
    as well as granzymes
    -> activate enzyme cascade that induces cell to undergo apoptosis
26
Q

TCR and co-receptor

antigen recognition by T cells

A
  • membrane-bound protein composed of an a-chain and a B chain,
    each chain containing one variable (V) region and one constant (C) region
  • V regions of a and B chains together form a single antigen-binding site
  • TCR binds only to antigen fragments displayed by APCs
  • when TCR binds to antigen fragments, co-receptor also binds to it,
    thus strengthening the molecular interactions bet the cells
    and enhancing activation of the T cell
27
Q

antigen recognition by B cells

A
  • first Igs made by B cell are inserted into plasma membrane to serve as B cell receptor (BCR)
  • Structure:
  • Y shaped, with 2 identical antigen-binding sites, one at the tip of each arm of the Y
  • consists of 4 pp chains, 2 identical light (L) chains and 2 identical heavy (H) chains,
    with each chain having a variable (V) region and a constant (C) region
    • H and L chains interact via intra- and inter-disulfide linkages
    • H chain also contains a hinge domain that confers flexibility to allow optimal binding to antigen
  • parts of the V regions of a H chain and a L chain come together to form asymmetric antigen-binding site
    => V region confers antigen recognition
  • constant region interacts with cell surface receptors or cell itself directly
    • eg: C region of lgE interacts with mast cell to activate it and elicit a cellular response, in this case an allergy respoonse towards lactose
28
Q

antigen recognition by antibodies

A
  • the soluble Ig secreted by effector B cell (i.e has undergone clonal selection and expansion), which is now called an antibody
  • Structure:
  • Y shaped, with 2 identical antigen-binding sites, one at the tip of each arm of the Y
  • consists of 4 pp chains, 2 identical light (L) chains and 2 identical heavy (H) chains,
    with each chain having a variable (V) region and a constant (C) region
    • H and L chains interact via intra- and inter-disulfide linkages
    • H chain also contains a hinge domain that confers flexibility to allow optimal binding to antigen
  • parts of the V regions of a H chain and a L chain come together to form asymmetric antigen-binding site
    => V region confers antigen recognition
  • constant region interacts with cell surface receptors
29
Q

difference between C and V regions of antibody

A

Amino acid sequences
- C region: amino acid seq vary little among receptors on diff B cells
- V region: amino acid seq vary extensively from one B cell to another

30
Q

primary immune response

A
  • an adaptive immune response that occurs after the 1st exposure of an individual to a foreign antigen
  • relatively slow kinetics and small magnitude
    • peaks 10-17 days after initial exposure
  • mediated by naive lymphocytes
31
Q

secondary immune response

A
  • immune response that occurs with subsequent encounters with the same antigen
  • more rapid, larger and better able to eliminate antigen
  • mediated by memory B and T cells, which are activated
32
Q

characteristics of adaptive immune responses

A
  • specificity and diversity
  • specialisation
  • immunological memory
  • contraction and homeostasis
  • immunological tolerance