BLD434 Section 1 Flashcards

Immunology

1
Q

Antigen

A

pathogen component that binds to BCR or TCR

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2
Q

Innate Immunity

A

First line of defense (Non-specific) - Inflammation
- rapid pathogen recognition response (hours)
- fixed - based on the inherited receptors
- limited # of specificities
- constant during response
- neutrophils, eosinophils, basophils, mast cells, monocytes (B)/phagocytes (T), DC, NK cells, ILC

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3
Q

Adaptive Immunity

A

Third line of defense. Antigen-specific
- Slow pathogen recognition response
- Variable (not based on inherited genes)
- Numerous highly selective specificities
- Improves during response and each time infected
- B cells (plasma cells, CD19 and CD20), B-1 forms before birth, B-2 forms after birth
- T cells (CD3) - Helper T cells & T regulatory cells (CD4), Cytotoxic T cells (CD8)

Main advantages: more powerful & long-lasting protection (memory)

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4
Q

CD antigen (marker)

A

“clusters of differentiation” - cell surface molecules that identify immune cells

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5
Q

Sebum

A

Substance secreted by sebaceous glands that contains fatty acids and lactic acids which inhibit bacterial growth at the skin surface.

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6
Q

Lysozyme

A

Enzyme contained in tears and saliva that kills bacteria by degrading their cell walls.

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7
Q

Polymorphonuclear

A

having a nucleus with several lobes and a cytoplasm that contains granules (ex: neutrophils, eosinophils, basophils)

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8
Q

Primary lymphoid tissue

A

Bone marrow - where B & T cells form and multiply. where B cells mature.
Thymus - where T cells mature.

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9
Q

Secondary lymphoid tissue

A

Filters extracellular fluids for antigens and microorganisms. Site for lymphocyte activation by antigens, which develop into effector cells.
- Lymph nodes, spleen, tonsils, Peyer’s patches , appendix.

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10
Q

Lymph

A

fluid and cells (including WBCs) that are transported to the lymphatics and into the bloodstream
- Attack bacteria in the blood and body tissues

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11
Q

Naive lymphocyte

A

Immature B or T lymphocytes that have not been activated by an antigen

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12
Q

PALS (Periarteriolar lymphoid sheath)

A

A portion of white pulp in the spleen that is occupied by T cells.

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13
Q

GALT (Gut-associated lymphoid tissue)

A

Tonsils, adenoids, appendix, Peyer’s patches of the gastrointestinal tract

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14
Q

BALT (Bronchial-associated lymphoid tissue)

A

aggregates of the respiratory epithelium
- mucosal lymphoid tissue in the walls of airways (respiratory tract, bronchi)

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15
Q

MALT (Mucosa-associated lymphoid tissue)

A

Secondary lymphoid tissue that initiates immune responses to specific antigens along mucosal surfaces (ex: vaginal tract)

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16
Q

Mature immune cells from the common Myeloid precursor

A

Monocytes/Macrophages, Neutrophils, Eosinophils, Basophils, Mast cells, DC cells

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17
Q

Mature immune cells from the common Lymphoid precursor

A

B cells, T cells, NK cells, ILC (innate lymphoid cells)

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18
Q

Monocytes vs Macrophages

A

Same cell but is called a monocyte (inactive) when in the blood and a macrophage (active) when in tissue. Macrophages are phagocytic while monocytes are not

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19
Q

Polymorphonuclear leukocytes (granulocytes) of the blood - color of granules & # of lobes

A

Neutrophils (2-5 lobes) - pink/blue/lilac
Eosinophils (2 lobes) - orange-pink
Basophils (2 lobes) - purple-black

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20
Q

How does a naive lymphocytes enter a lymph node?

A

Naïve lymphocyte enters a lymph node via afferent lymphatic vessels and drains through the efferent lymphatic vessel in the medulla

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21
Q

M cell (Microfold cell)

A

Specialized intestinal epithelial cells covering GALT mucosa – Transport antigens to lymphoid follicles to initiate an immune response. Long-lived.

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22
Q

How does an antigen enter a lymph node?

A

Antigen enters lymph node via fluid draining from tissues (due to inflammation) in afferent lymph vessels

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23
Q

Where are B & T lymphocytes primarily located in the lymph node?

A

B cell - Lymphoid follicles in the cortex (circular areas in the outer part)
T cell - Medulla (middle part)/ T-cell area

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24
Q

Where are B & T lymphocytes primarily located in the white pulp of the spleen?

A

Active B cell - Germinal center
Inactive B cell - lymphoid follicles
T cell - PALS (periarteriolar lymphoid sheath)

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25
Q

C (Complement proteins)

A

soluble zymogens (inactive enzymes) in the blood that are part of the innate immune system
First line of defense against infection

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26
Q

Defensins

A

small amphipathic proteins inserted into pathogenic membranes to cause lysis. Defend against bacterial, viral, and fungal infections

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27
Q

Opsonization

A

Coating or binds to the surface of a pathogen to help phagocytosis.

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28
Q

Complement fixation

A

Opsonization where C3b is the opsonin.
- C3b is covalently bonded to the pathogen’s surface to mark it as a target for destruction by a phagocyte

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29
Q

Anaphylatoxin

A

Complement fragments that float away (C3a, C4a, C2b)
- Substance that activates blood vessel endothelial cells to initiate inflammation by: causing degranulation, increasing vascular permeability and vasodilation.

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30
Q

Chemoattractant

A

A chemical substance that creates a gradient to attract cells (from low to high concentration) towards an infection

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31
Q

4 Main Functions of complement proteins in immune system

A
  • opsonization
  • anaphylatoxin
  • chemoattraction
  • direct lysis (pore formation - C9)
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32
Q

List the 3 Complement Pathways and what initiates them

A
  • Classical (Antibody-initiated, C1 binds)
    • CRP initiates without antigen binding
  • Lectin (MBL binds)
  • Alternative (spontaneous hydrolysis of C3, Factor B binds)
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33
Q

C3 covertase (Classical and Lectin)

A

C4b2a

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34
Q

C3 convertase (Alternative)

A

C3bBb

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35
Q

C5 convertase (Classical and Lectin)

A

C4b2a3b

36
Q

C5 convertase (Alternative)

A

C3bBb3b

37
Q

Major advantage that complement has compared to antibody in tagging pathogens for disposal?

A

Complement binds covalently (strong and permanent) to pathogen surface, while antibody binds non-covalently (not as strong and can be reversible)

38
Q

Explain the similarities and differences between iC3 vs iC3b and iC3Bb vs C3bBb.
Identify which are enzymatically active and which have been inactivated.

A

iC3
- inactive
- soluble
- can bind Factor B to be cleaved into
iC3b
iC3b:
- inactive (C3b, by Factor I)
- opsonin
- bind to Factor D to be cleaved into
iC3bBb
iC3Bb:
- active
- soluble
- C3 convertase of alternative
pathway
C3bBb:
- active
- fixed (covalently bonded to pathogen
surface)
- C3 convertase of alternative
pathway

39
Q

Which complement component fragment provides the greatest amount of amplification of the complement cascade, and why (i.e, C2b, C3b, C4b, C5b?)?

A

C3b - provides a way to activate the alternative pathway and add exponential activation of complement proteins.

40
Q

Complement proteins of the MAC

A

C5b, C6, C7, C8, C9

41
Q

Which complement component polymerizes a pore in the pathogen membrane?

A

C9

42
Q

What protein can amplify complement activation? Which complement pathway? What mechanism?

A

Properdin (Factor P) binds to C3bBb (alternative C3 convertase) bound to a pathogen surface and protects it from protease degradation (Bacteria and parasites secrete proteases around their surface). Amplifies the alternative pathway.

43
Q

List the two points at which complement activation can be inhibited, and identify the product of C3b cleavage produced by Factor I.

A
  • Inactivate C3 convertase
  • Prevent MAC formation
    Product = iC3b
44
Q

Describe how a2-macroglobulins, pentraxins and defensins function in innate immune system protection of the body.

A
  • a2-macroglobulins inhibit proteases
  • Pentraxins enhance phagocytosis
  • Defensins are antimicrobial peptides that disrupt microbial membranes & cause lysis
45
Q

Neutrophils

A
  • short-lived
  • highly mobile
  • crucial in early stages of infection
  • die after they phagocytize by apoptosis
  • enter inflammatory site when called upon
46
Q

Macrophages

A
  • Long-lived
  • Tissue residents
  • First to respond
  • Detect danger infection signal using inflammatory cytokines
  • Clean up mess after pathogen is killed
  • Help in tissue repair
  • Function as sentinels (guards)
47
Q

IL-1B

A

inflammatory cytokine released by macrophages that enhances the effects of TNF-a and IL-6
- Activates vascular endothelium and lymphocytes; local tissue destruction, increases access of effector cells

48
Q

TNF-a

A
  • inflammatory cytokine produced by macrophages
  • makes blood vessels more permeable so cells, fluid, and soluble effectors can enter infected tissue.
  • Can cause septic shock if produced in abundance
49
Q

IL-6

A
  • inflammatory cytokine produced by macrophages
  • induces metabolism of fat and muscle cells –> heats infected tissue
  • Induces the production of acute-phase proteins CRP and MBL to activate complement opsonization
50
Q

CXCL8

A
  • chemokine released by macrophages
  • recruits neutrophils from the blood into infected tissue
51
Q

CCL2

A
  • chemokine released by macrophages
  • recruits monocytes from the blood to infected tissue
52
Q

IL-12

A
  • recruits and activates NK cells to secrete cytokines to strengthen macrophage response to infection
53
Q

TLR

A

Toll-like receptors
- activate immune cells in innate immunity and are involved in cell signaling & the production of inflammatory cytokines

54
Q

TLR subfamily I

A
  • TLR 1, 2, 4, 6, 10
  • Located in plasma membranes of immune cells (mostly granular sites, DC, and some B)
  • Recognize lipid components in the membranes of pathogens (bacteria, parasites, fungi) to activate macrophage or DC response
55
Q

TLR subfamilies II & III

A

II = TLR 7, 8, 9, III = TLR 3 homodimer
- Located in endosomal membranes
- Virus release viral DNA/RNA when phagocytized, and then these TLR will have access, activating immune cells to produce cytokines and other mediators

56
Q

TLR subfamily IV

A

TLR 5
- Expressed on intestinal epithelial cells in their plasma membrane to recognize bacterial flagellin protein
- Activates intestinal epithelium to send immune signals to call in help

57
Q

TLRs located in plasma membrane

A

TLR subfamilies 1 and 4
- recognize extracellular pathogens
- target antigen: bacteria

58
Q

TLRs located in endosomes

A

TLR subfamilies 2 & 3
- recognize intracellular pathogens
- target antigen: viruses (attack gene irregularities

59
Q

NFKB

A

Protein transcription factor that initiates inflammatory cytokine production and secretion to regulate innate immunity.
- Activates transcription of genes for inflammatory cytokines, which are synthesized in the cytoplasm and secreted from the ER

60
Q

IRF3 & IRF7

A
  • phosphorylated and travel to nucleus to
    act as transcription factors
  • they induce Type I interferon production
    and secretion (IFN-a & IFN-B)
    IRF3 = for single-stranded RNA
    IRF7 = for double-stranded RNA
61
Q

Type I Interferons

A

IFN-a and IFN-B, which fight viral infections

62
Q

What is the outcome of activation of MAVS receptors?

A

MAVS = Mitochondrial antiviral-signaling proteins
Type I interferon (IFN-a & IFN-B) production by the cell

63
Q

Plasmacytoid dendritic cells

A

Dendritic cells specialized in secreting high levels of Type I interferons - response to viral nucleic acid during early infection

64
Q

Respiratory burst

A

the consumption of O2 by phagocytes, pumping H+ ions out of the phagolysosome, raising the pH and activating neutral proteases to digest the microbes consumed.

65
Q

Chronic Granulomatous Disease - identify the immune system defect

A

Caused by a mutation of the genes encoding subunits of the NADPH oxidase enzyme complex.
Leads to:
- Defective respiratory burst
- Reduced ability of phagocyte to kill pathogens
- Infected cell forms a granuloma, a wall, around itself to prevent infection spread

66
Q

Identify the major macrophage cytokine that triggers the “acute phase” response and the proteins that are produced as a part of the acute phase response.

A

IL-6 - by inducing liver hepatocytes to produce acute phase proteins (CRP, MBL, LPS-binding protein).

67
Q

Importance of an acute phase reaction (response) and which tissues/organs of the body are primarily responsible?

A

Response to a pathogen by creating a hospitable environment for pathogens and trying to kill the pathogen until the adaptive immune system can step in.

  • Liver
    Acute-phase proteins (CRP and MBL)
    activate complement opsonization
  • Bone marrow
    Neutrophil mobilization (5-day supply) causes phagocytosis
  • Hypothalamus
    Increases body temperature via shivering –> decreasing viral and bacterial replication
  • Fat and muscle cells
    Metabolism increases body temperature via fever –> decreasing viral and bacterial replication
68
Q

Necrosis

A

cell death by trauma (inflammation, damage, osmotic pressure) - releases inflammatory cytokines

69
Q

Netosis

A

Neutrophils get overstimulated and extrude their DNA and granule contents (NETs) to trap extracellular bacteria

70
Q

Trogocytosis

A

Neutrophils extend membrane to take a “bite” out of a cell (parasite) that is too large to phagocytose.

71
Q

Apoptosis

A

NK cells and Tc cells induce another cell to digest itself from the inside out.
- Virus-infected cells, cancer, damaged cells

72
Q

Pyroptosis

A

Inflammatory cell death - Macrophages get highly activated and inflammasomes form, leading to the release of inflammatory cytokines (IL-1B)
- ALL infections

73
Q

Phagocytosis

A

Neutrophil and macrophage cell receptors bind to target and wrap its plasma around pathogen and engulfs it in a phagosome.

74
Q

LTi (Lymphoid Tissue inducers)

A

Responsible for creating lymphoid tissues (lymph nodes and white pulp organization in spleen)

75
Q

NK cells

A

Cytotoxic ILC of lymphoid lineage
- circulate blood & kill infected cells (virus, bacteria, protozoa)
- Perforin mediator creates a hole in an infected cell, allowing granzymes in to induce apoptosis. IFN-Y further activates macrophages

76
Q

ILCs (Innate Lymphoid Cells)

A
  • Facilitates the development of secondary lymphoid structures
  • Secrete cytokines that help to activate the effector cells of innate immunity (e.g. macrophages, granulocytes) & phagocytosis
  • ILC1, ILC2, ILC3 (Tissue residents - for immediate response)
77
Q

ILC1

A
  • Respond to intracellular infections to any invading pathogen
  • Either stops the infection or limits its spread until NK cells are recruited from the blood (by IL-12)
78
Q

ILC2

A
  • Present at mucosal surfaces
  • Respond to large extracellular parasites (i.e. worms)
79
Q

ILC3

A
  • Respond to extracellular bacterial or fungal infections
  • Abundant in mucosal tissues
80
Q

Type 1 Immunity

A
  • Intracellular bacteria and viruses
  • Mediated by IFN-Y, NK cells, ILC1,
    neutrophils
  • Cell-mediated toxicity (NK cells) & inflammatory activation of macrophages
81
Q

Type 2 Immunity

A
  • Parasites in the gut
  • Mediated by ILC2, IL-4, IL-5, IL-13, mast cells, eosinophils, and basophils
  • Non-inflammatory activation of macrophages
82
Q

Type 3 Immunity

A
  • Extracellular bacterial or fungal infections
  • Mediated by ILC3, which produces IL-17 and IL-22
  • Promotes phagocytosis and secretion of antimicrobial peptides
83
Q

How do Type I interferons activate NK cells to combat infections?

A

(IFN-a and IFN-B) by promoting NK cell maturation and recruitment into virally-infected cells

84
Q

How do Type II interferons activate NK cells to combat infections?

A

(IFN-Y)
- Macrophages produce IL-12 and IL-15, causing NK cells to proliferate and differentiate
- NK cells secrete IFN-Y, which binds to and activates macrophages to increase phagocytosis and secretion of inflammatory cytokines to kill ingested viruses

85
Q

Macrophage and NK cell interaction

A

Synergistic
1. Virus activates macrophage, which then secretes cytokines:
- CXCL8 recruits the NK cell
2. IL-12 & IL-15 activate the NK cell via the
synapse
3. NK cells proliferate into effector cells and secrete IFN-Y
4. IFN-Y binds to macrophage to increase phagocytosis and cytokine secretion

86
Q

What are the three types of interactions that can occur between DC cells and NK cells?

A
  1. DC cells drive NK cells activation, proliferation, and differentiation
    • Immature DC cell takes up antigen,
      gets activated, and secretes IL-15 to
      drive NK cell proliferation
    • This produces effector NK cells that
      secrete cytokines and kill virus-
      infected cells
  2. Abundance of NK cells
    • NK cells outnumber and kill DC cells
    • There are enough NK cells to
      terminate the viral infection, so
      there’s no need to activate adaptive
  3. Scarcity of NK cells
    • NK cells signal DC cells to mature and
      initiate an adaptive immune response
    • DC cells move to secondary lymphoid
      tissues to present antigen
    • Innate immunity fails; need adaptive