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BS127: Agents of Infectious Disease > Introduction to Immunology (Lecture 9-14) > Flashcards

Introduction to Immunology (Lecture 9-14) Flashcards

1
Q

What are the 3 major classes of phagocyte?

A
  • Neutrophil
  • Eosinophil
  • Macrophage
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2
Q

Describe characteristics of a neutrophil

A
  • Short-lived cells
  • Abundant in blood
  • Not present in normal healthy tissues
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3
Q

Describe a neutrophil’s defense mechanism

A

Phagocytose and destroy microrganisms esp bacteria

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4
Q

How are neutrophils recruited to sites of infections?

A
  • Release of cytokines by activated macrophages
  • Presence of peptide fragments of cleaved complement proteins
  • Recognition of PAMPs by PRRs
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5
Q

Describe characteristics of macrophages

A
  • Larger than neutrophils
  • Longer-lived than neutrophils
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6
Q

Describe a macrophage’s defense mechanism

A
  • Recognize and remove senescent, dead and damaged cells in tissues
  • Able to ingest large microorganisms (e.g. protozoa)
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7
Q

Describe a macrophage’s defense mechanism

A
  • Recognize and remove senescent, dead and damaged cells in tissues
  • Able to ingest large microorganisms (e.g. protozoa)
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8
Q

What do eosinophils help to do?

A
  • Destroy parasites
  • Modulate allergic inflammatory responses
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9
Q

What are granules?

A

Dense membrane-bound lysosomal derivatives

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10
Q

Describe a granule’s defense mechanism

A

They fuse w the phagosome membrane and release their contents (lysozyme acid hydrolase) to digest the pathogen’s cell walls
Also contain defensins → destabilize the pathogen’s membranes

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11
Q

Describe shock

A

Widespread inflammation

Swelling and blood clotting

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12
Q

What does shock lead to?

A

Significant decrease in blood pressure → blood supply to vital organs (e.g. brain, heart and kidney) is reduced

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13
Q

What does the innate immune system rely on?

A
  • Recognition of CpG motifs in viral DNA by TLR9
  • Recognition of viral dsRNA that is an intermediate in the life-cycle of many viruses
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14
Q

Describe TLRs

A
  • Usually found on the plasma membrane
  • Active on internal membranes, where they aid in detecting internal pathogens
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15
Q

Describe how IFN limits viral replication

A
  • Limit viral spread by promoting apoptosis (programmed cell death) of the infected cell
  • Make the virally infected cell and its neighboring into much less efficient factories for making new viruses
  • Warn neighbouring cells of infection and indue expression of other cytokines → communication b/w cells is increased
  • Activate a ssRNA nuclease → degrades host ssRNA non-specifically, reducing host protein synthesis
  • Activate other mechanisms that shut down host cell synthesis in neighbouring cells by inhibiting the process of translation
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16
Q

Describe other processes done by IFNs apart from limiting viral replication

A
  • Upregulate display of viral peptides on the outer membrane of the infected cell → provides signals for recognition by activated T cells
  • Stimulate expression of the immunoproteasome to process and destroy viral proteins
  • Provide a call for help, attracting natural killer cells and also activate macrophages
  • Fight cancers
  • Inflame the tongue and cause dysfunction in taste bud cells
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17
Q

Describe how natural killer cells operate

A
  • Recognize their targets by monitoring the level of expression of these molecules at the cell surface
  • Attracted to virally-infected cells by IFNs
  • Persuade such cells to commit suicide → the target cells die apoptosis
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18
Q

How do NK cells persuade their clients to apoptose?

A

Kill by triggering apoptosis of the infected/ transformed cells

Apoptotic bodies left behind are typically engulfed and destroyed by phagocytes

Method of persuasion is the same as that of cytotoxic T cells

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19
Q

Describe characteristics of the adaptive immune system

A
  • Destroy/eliminate invading organisms or toxins
  • Raise immune system responses against pathogens that hv never been encountered before by host organisms
  • Highly specific to a particular pathogen
  • Long-lasting protection (memory)
  • Recruited and trained by the innate immune system
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20
Q

What is an antigen?

A

Substance capable of generating an adaptive immune response

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21
Q

Describe immunization experiments

A
  • Antigen is injected into the animal in the form of a suspension containing adjuvant
  • Adjuvant activates innate immunity responses
    • It comprises immunological stimulants such as inactivated mycobacterial proteins and irritants (e.g. aluminum hydroxide)
  • Activated innate response also responds to the antigen in the vaccine
  • Innate immune response trains adaptive immune response
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22
Q

Where do lymphocytes develop?

A
  • Central / primary lymphoid organs
    • Bone marrow
    • Thymus
  • They then migrate to the peripheral or secondary lymphoid organs
    • Adenois
    • tonsils
    • Lymph nodes
    • Spleen
    • Peyer’s patches
    • Appendix
    • Skin
    • Respiratory tract
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23
Q

Describe how experiments established that lymphocytes were responsible for adaptive immune responses

A
  • Rats were injected w antigen in the presence of the adjuvant
    • Antigen is part of the disease pathogen that we want the immune response to
    • Adjuvant is used to activate innate immune response
  • Normally, there is a stimulation of the adaptive immune response
  • Other group was heavily irradiated to cause tissue damage
    • Resulted in mice being unable to develop adaptive immune response
    • Could still react via some innate immune response
  • Result suggest that radiation must hv killed some of the adaptive immune response’s cells that were required to initiate and maintain it
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24
Q

What do activated DC do?

A
  • Phagocytose and degrade invading microorganisms
  • Peptides from the degraded organism are displayed on the cell surface of these dendritic cells
  • DC then migrates to the nearest lymphoid organs and activate adaptive immune response
    • Train them to recognize the peptides on its surface
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25
Q

Describe what happens when a bacteria breaches the cell tissue

A
  • Bacteria cells breach the tissue, causing an infection
  • DC hv PAMP then bind n engulf the bacteria
  • DC mature to APC
    • Present the antigen on cell surface
  • As they’re maturing, they roll to lymphoid organs where T cells are present
  • T cells hv T cell receptors
    • Activated when they find a matching antigen
26
Q

Describe how T cells develop

A
  • In adults, they arise from bone marrow
  • In fetus, they arise from liver
  • Within the bone marrow, there are haemopoietic stem cells which develop into common lymphoid progenitor
    • These cells migrate to the thymus by the blood and the lymph
    • They then develop further into a thymocyte
      • T[hymocyte]-cell
  • Initial training in the thymus result in being able to recognize foreign material
    • Inappropriate responses (e.g. attacking own tissues) will result in killing by apoptosis
      • Important in the prevention of autoimmune disease
    • Once they pass the “training”, they will migrate to the peripheral lymphoid organs where they mature to become T cells
      • T cells do not respond to self antigen but can respond to foreign antigens
27
Q

How does DC activate T cells?

A
  • DC present peptides to TC in the lymphoid organs
  • T cell TCR recognizes non-self antigen: activation, mitosis and clonal expansion of specific TC
28
Q

Why do APC only present to TC?

A
  • Highly specific interaction b/w the groove w the peptide on its surface and the TCR
  • To stop similar proteins from activating T cells, there is a second interaction (co-stimulatory molecules)
    • Present in the antigen presenting cell and on T cell
    • 2 step process: both hv to interact
      • If it can bind n the protein in the groove can interact w the TCR, this leads to T cells being activated n clonal expansion occurring
      • No recognition leads to no action, cells undock
29
Q

Why does the innate immune system need to kick in first?

A

Activation and clonal expansion takes time

30
Q

What do Helper T cells do?

A

Activate macrophages, DC, B cells and maintain cytotoxic TC activity by secreting a variety of cytokines

31
Q

What do regulatory T cells do?

A

Inhibit the function of Th, Tc and DC

32
Q

What do cytotoxic T cells do?

A

Kill infected host cells by persuading them to commit suicide apoptotically

33
Q

How do cytotoxic T cells kill?

A
  • Cytotoxic TC that has been trained by the innate immune system to recognize n target cells which could be virally infected
    • Recognizes the peptides that hv been shown in the lymphoid organ (“trained”)
  • Upon recognition of the foreign antigen, CT binds specifically to the target cell
    • This forms an immunological synapse
34
Q

Describe the 2 methods cytotoxic T cells use

A
  • B/w the 2 cells are an immunological synapse

First method
- T cell wants to cause apoptosis to remove target cell n program cell death
- Apoptosis will cause target cell to break into membrane bound blebs so pathogens are removed as well
- Perforins form channels thru the target cell plasma membrane (punches holes essentially)
- Opens up spaces for granzymes
- Granzyme is a portease (good at chewing up proteins)
- Has a specific target protein called caspase
- Granzyme will cleave caspase to activate it
- Caspase will bind n cleave the substrate
- Often part of the cytoskeleton
- Caspase will chew up cytoskeleton molecules, which triggers apoptosis

Second method
- T cell binds receptors on the target cell that send a signal that activates caspases (the effector proteins of apoptosis)

35
Q

Where are T and B cells derived from?

A

Common lymphoid progenitor cells

These cells are derived from hemopoietic stem cells, which originate from the liver or bone marrow

36
Q

Describe what happens once a B cell is activated

A
  • Once B cells are activated, they differentiate into a plasma cell
  • Hv the ability to secrete antibodies into the surrounding environment
  • Recognize specific antigen using membrane bound antibodies
  • Massive expansion in ER
    • Important for entry point of secretion
    • Helps cell to become a secretory machine
    • Don’t last v long bc of high lvl of activity
37
Q

Describe an antibody’s basic structure

A
  • Tetrameric structure
    • 4 polypeptide chains
    • 2 identical heavy chains (H)
    • 2 identical light chains (L)
  • Chains are held together by covalent disulfide bonds at the hinge
  • Antigen binding site is made up of a combination of N terminal domain of both the heavy n light chain
38
Q

How does the basic structure of an antibody allow for multiple antibody interactions?

A
  • Antibodies hv identical antigen binding sites so they can cross link antigens
  • Antigens w 2 identical antigenic determinants can form large 3D lattices that readily precipitate out of solution
  • Most antibodies hv many different antigenic determinants and different antibodies that recognize different determinants can cooperate in cross linking the antigen into large 3D lattices
39
Q

What characteristics of an antibody allow for different spatial geometries of antigen binding?

A
  • Ability to cross-link antigens
  • Flexible hinge region
40
Q

What is the benefit of these large networks?

A

Make it easier for phagocytes to engulf pathogens or soluble antigens, which can then be degraded and re-presented into T cells thus amplifying the immune response

41
Q

Describe the structure of IgM

A
  • Pentamer of basic tetrameric unit
  • Held together by a J chain, which is thought to aid polymerization of the complex
42
Q

What is the valency of IgM

A
  • Valency (how many antigens it can bind to): 10
    • 2 antigen binding sites
    • 5 antibodies in IgM
43
Q

What is the valency of IgM

A
  • Valency (how many antigens it can bind to): 10
    • 2 antigen binding sites
    • 5 antibodies in IgM
44
Q

What is the difference between IgM and IgD?

A

IgM can be secreted while IgD cannot

45
Q

What pathway does IgM trigger?

A

Classical pathway via their tail regions

Starts w the activation of C1 that goes onto cleave and activate C2, which does the same for C4

46
Q

Explain the maturation and activation of naive B cells

A
  • Immature naïve B cell in bone marrow expresses surface IgM
  • It migrates to the lymphoid tissue and expresses IgD
    • IgD can be developmental marker to show
      more mature B cell
  • Once the B cell has both IgM and IgD, it can now respond to soluble antigens
    • Process helped by T helper cells, which aid
      clonal expansion and differentiation of B cells
      and conversion to plasma cells
  • Plasma cells hv an increase in ER
    • Able to secrete antibodies
    • Hv an IgM receptor so antibodies they are
      secreting will also be IgM
    • IgM binding site will be specific to the
      antigen that activated the B cell
47
Q

Define an opsonin

A

Molecule that targets antigens for phagocytosis

Complement is also an opsonin

48
Q

Define opsonization

A

Coating of a target w IgM (or other antibodies) or complement

49
Q

Describe the structure of IgG

A

Standard tetrameric structure

2 heavy chains n 2 light chains

50
Q

Functions of IgG

A
  • Toxin neutralization
  • Binding to microorganisms n opsonization thus leading to phagocytosis
  • Provision of passive immunity to fetuses n newborns
51
Q

What region of IgG is able to interact w FC receptors?

A

Tail region

52
Q

Describe the process in which IgG crosses the placenta (passive immunity)

A
  • Placental cells take up maternal IgG by pinocytosis
  • Placental endosomes hv receptors (FcRn receptors) that recognize n bind the tail region (Fc) of IgG antibodies
  • IgG molecules are transported across the placental cells in vesicle carriers (transcytosis)
  • IgG is released into the fetal circulation
53
Q

Describe how IgG is secreted into maternal milk

A
  • FcRn receptors on neonatal gut cells (enterocytes) recognize n bind the tail region (Fc) of IgG antibodies
  • IgG molecules are transported across the enterocytes in vesicle carriers (transcytosis)
  • IgG is released into the neonatal circulation
54
Q

Describe the process of opsonization by IgG

A
  • Bacterium is coated in IgG
    • Macrophages n neutrophils express the FC receptor hence can interact w IgG
  • Macrophage binds to the bacterium due to the IgG
  • This activates the macrophage to start phagocytosis
    • Movement of cytoskeleton out to engulf the pathogen
55
Q

Describe IgA’s structure

A
  • Dimer of 2 tetrameric structures
  • Held together by a J chain n S (secretory component) chain
    • S chain allows secretion into saliva, tears, milk n mucus
56
Q

Function of IgA

A

Protects our mucosal surfaces n provides some passive immunity to newborns via milk

57
Q

Function of IgA

A

Protects our mucosal surfaces n provides some passive immunity to newborns via milk

58
Q

Describe how IgE triggers mast cell/basophil degranulation

A
  • Mast cell is full of secretory vesicles, which contain histamine
  • Mast cells hv FC receptors which are IgE specific
    • Can capture IgE antibodies, which effectively act as a receptor on the surface
  • Mast cell has a receptor, which binds to IgE
    • IgE that it binds is specific to a certain antigen
  • Once the antibodies hv managed to come across the antigen which it’s originally activated by, cross-linking by the 2 IgE antibodies
  • Mast cell becomes activated, which leads to degranulation (massive release of histamine)
59
Q

Describe how IgE acts as a receptor of eosinophils

A

The IgE-specific Fc receptors on mast cells, basophils and eosinophils allow these cells to be targeted to different antigens/pathogens

Antibody arm of the adaptive immune system can direct parts of the innate immune system

60
Q

Describe how IgE acts as a receptor of eosinophils

A

The IgE-specific Fc receptors on mast cells, basophils and eosinophils allow these cells to be targeted to different antigens/pathogens

Antibody arm of the adaptive immune system can direct parts of the innate immune system

BS127: Agents of Infectious Disease (4 decks)

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