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Biochemistry > Activation of Innate Immunity > Flashcards

Activation of Innate Immunity Flashcards

1
Q

Neutrophils vs macrophages/dendritic cells

A

Neutrophils only kill microbes

Macrophages/dendritic cells kill microbes and present the antigen to T-helper cells

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2
Q

PRR’s of innate immune system

A

Pattern-recognition receptors

Recognize a PAMP (pathogen-associated molecular pattern) that is on pathogens but not human cells

Bridge between innate and adaptive

PRR’s cause activation and maturation of APC → antigen is presented to naive T cell →secreted cytokines assist development and maturation of T-cell

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3
Q

Where are Toll-like receptors (TLRs) found?

A

On surface of macrophages, dendritic cells, mast cells

They recognize pathogens, activate TF’s that enhance pro-inflammatory cytokines

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4
Q

What determines the type of immune response?

A

The cytokines made by macrophages determine the PRR (pattern recognition receptor) that is used

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5
Q

Which cells are considered to be the sentinel (resident) cell of innate immunity?

A

Tissue macrophages

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6
Q

What happens when bacteria enters and encounters effector cell?

A

Bacteria enters, activate EFFECTOR CELLS which secrete CYTOKINES→ ↑ vasodilation and permeability → helps inflammatory cells to enter tissue from blood → infected tissue becomes inflamed, causing redness, heat, swelling, pain

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7
Q

Which mediator causes vasodilation and increased vascular permeability?

A

Histamine

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8
Q

Complement

A

Lysis of pathogen (make holes in cell)

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9
Q

Cytokines

A

Activation of immune cells

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10
Q

Lysozyme

A

Bacterial wall destruction

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11
Q

Leukotrienes and prostaglandins

A

Vasodilation and vascular permeability

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12
Q

What is in respiratory tract and eyes that prevents infection?

A

Lysozyme (nasal secretions) and in tears

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13
Q

What are some leukocytes?

A

Neutrophils, monocytes, tissue macrophages, eosinophils

Innate immune system

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14
Q

NK cells are lymphocytes

A

True

Innate immune system

Kill via PERFORIN

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15
Q

Neutrophils

A

First to arrive at tissue damage → release granules to control bacterial growth

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16
Q

Macrophages

A

Release inflammatory mediators

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17
Q

Eosinophils

A

Contain cationic granule proteins, fight parasites

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18
Q

Neutrophils and monocytes enter tissue through what?

A

Through post-capillary venules except parenchymal tissues (liver, lungs, kidney) where all blood cells enter through capillaries

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19
Q

How Neutrophils Come to Tissue

A

Inflammation-activated ENDOTHELIAL CELLS cause → ↑ E-selectin (ES) and P selectin (PS) adhesion molecules

  • Neutrophils have receptors for these two (ES and PS)
    1. Neutrophils slow down and roll along endothelium (the ligand of neutrophil and selectin of endothelial cells interact)
    2. Tight binding-integrins (leukocyte) and Integrin ligands (endothelial cells)
    3. Diapedesis- transmigration through endothelium
    4. Chemoattractant (IL-8) controls migration of neutrophils to inflammatory site
20
Q

Integrin Activation (like riding bike through fresh cement which slows you down)

A
  • Integrins on blood leukocytes are normally in a low-affinity state (bent)
  • When leukocytes are rolling, chemokines on endothelial surface bind to the chemokine receptors on the leukocyte and they signal, which activates the leukocyte integrins
  • This ↑ affinity of integrins (extended conformation) and their ligands on endothelial cells
21
Q

Steps in getting Leukocytes through endothelial cell wall

A
  1. Capture (Selectins e.g. E-selectin)
  2. Rolling ( “ “ )
  3. Activation (Chemokines e.g. IL-8, MCP-1)
  4. Arrest (Adhesion molecules e.g. VCAM-1, ICAM-1)
  5. Firm adhesion ( “ “ )
  6. Transmigration
22
Q

What is involved in the activation of integrins on monocytes?

A

IL-8

23
Q

What does the following neutrophil granule (there are several) do?

Cathepsin G

A

Cathepsin G

-Ser protease that digests collagen and proteoglycans

24
Q

What does the following neutrophil granule (there are several) do?

Defensins

A

Defensins: highly positively charged (i.e. cationic). Create pore in bacteria membrane (effective against all gram +/- bacteria, fungi, enveloped viruses)

Located primarily in GI and lower respiratory tracts (neutrophils contain defensin)

25
Q

What does the following neutrophil granule (there are several) do?

BPI

A

BPI (bactericidal permeability increasing protein)

↑ permeability of bacterial membrane

26
Q

What does the following neutrophil granule (there are several) do?

Lysozyme and lactoferrin

A

Lysozyme and lactoferrin

Bactericidal or bacteriostatic proteins

27
Q

Transmigration of Monocytes

A

Steps 1-3 (rolling, firm adhesion, diapedesis) are same as neutrophils

Chemoattractants for monocytes are macrophage inflammatory protein-1α (MIP-1α) and MIP-1β

Monocytes mature into tissue macrophages

Macrophages and neutrophils are phagocytic cells

28
Q

Classically Activated Macrophages (MΦ) are induced by what? (2)

A

Induced by TLRs and by cytokine IFN-γ

29
Q

What do classically activated MΦ do?

A

Called M1

Inflammation and destroy microbes

30
Q

Alternatively Activated Macrophages (MΦ) are induced by what? (2)

A

Induced by IL-4 and IL-13

31
Q

What do alternatively activated MΦ do?

A

Called M2

Tissue repair and control inflammation

32
Q

What do phagocytes use to help distinguish self from non-self?

A

PRR (pattern recognition receptor)

N-formylmethjionyl peptide (fMet) is in prokaryotes but NOT in eukaryotes

33
Q

What happens when Toll-like receptors are triggered in phagocytes?

A

→ production of cytokines and ROS → kill microbes

34
Q

What happens when Mannose receptors are triggered in phagocytes?

A

→ production of ROS and cytokines OR phagocytosis → killing

35
Q

What activates NK cells?

A

IL-12 (made by macrophages)

36
Q

What do NK cells secrete that activates phagocytosis and killing of pathogens by macrophages?

A

IFN-γ

37
Q

NK cells use what kind of MHC?

A

MHC class 1

Inhibitory receptor is “ON” if cell is normal (no changes in class 1 MHC)

In virus-infected cell, the level of class 1 MCH is decreased b/c virus inhibits class 1 MCH expression

38
Q

Complements

A

30 proteins (C1, C2, C3 etc)

3 distinct pathways. All pathways → C3b→ activates C5 → cascade → MAC (membrane attack complex) → kills pathogen by creating holes in membrane

39
Q

C3 convertase formation

A

Classical formation initiated by binding of IgM or 2 IgG’s on microbial surface

  1. C1 binds to IgM or IgG on bacteria
  2. C1 cleaves C2 and C4
  3. C4b can covalently attach to microbial surfaces
  4. C2a binds to C4b and creates → C3 CONVERTASE
40
Q

What is role of C3b?

A

Formation of C5 convertase

41
Q

What is role of C3a?

A

Inflammation and chemotaxis

42
Q

Formation of C5 convertase

A
  1. C3 convertase activates C3 → C3a and C3b
  2. C3b put onto bacteria surface (think star wars on crater)
  3. C3b serves as opsonin (“tag”) and ↑ phagocytosis
  4. C3b + C3 convertase → complex→C5 convertase (C4b, 2a, 3b)
  5. C5 convertase→C5→C5a (enhance inflammation) or C5b (MAC complex)
43
Q

What does C5a do?

A

anaphylatoxin

Enhance inflammation

44
Q

What does C5b do?

A

MAC complex

45
Q

Formation of Membrane Attack Complex (MAC)

A

C5→C5a (enhance inflammation) or C5b (MAC complex)

MAC complex: C5b, C6, C7, C8, lots of C9

Purpose: makes transmembrane channels that lead to cell lysis

C5 convertase → C5b → +C6,C7,C8 → C5b678 + C9 (x10-16) → MAC

*How complements protect body from pathogens

46
Q

Acute Phase Proteins (APP)

A
  • Systemic acute-phase response
  • Accompany inflammation
  • Made by hepatocytes
  • Production is regulated by cytokines (IL-6)
  • Functions: highly variable and diverse
47
Q

What regulates Acute Phase Proteins? (APP)

A

IL-6

Biochemistry (41 decks)

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