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Biochemistry > Introduction to Immune System > Flashcards

Introduction to Immune System Flashcards

1
Q

PAMPs

A

Lipids or sugars on surface of antigen

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2
Q

Humoral vs Cell-Mediated Immunity

A

Humoral: acts through molecules (antibodies or complements) circulating in fluid. Primary target are extracellular pathogens (bacteria)

Cell-Mediated: acts through cell to pathogen contact (phagocytosis or cytotoxicity). Primary targets are intracellular pathogens (viruses)

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3
Q

Neutrophils

A

Early phagocytosis and killing of microbes

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4
Q

Macrophages

A

Efficient phagocytosis and killing of microbes, secretion of cytokines that stimulate inflammation

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5
Q

NK cells

A

Lysis of infected cells, activation of macrophages

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6
Q

Complement

A

Killing of microbes, opsonization of microbes, activation of leukocytes

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7
Q

Mannose-binding lectin (collectin)

A

Opsonization of microbes, activation of complement (lectin pathway)

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8
Q

C-reactive protein (pentraxin)

A

Opsonization of microbes, activation of complement

Opsonization: marking a pathogen for destruction

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9
Q

TNF, IL-1, chemokines

A

Inflammation

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10
Q

IFN-α, β

A

Resistance to viral infection

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11
Q

IFN-γ

A

Macrophage activation

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12
Q

IL-12

A

IFN-γ production by NK cells and T-cells

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13
Q

IL-15

A

Proliferation of NK cells

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14
Q

IL-10, TGF-β

A

Anti-inflammatory

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15
Q

PAMPs

A

Pathogen-associated molecular patterns

Molecules that are recognized by cells of the innate immune system

PAMPs have no structural similarity with self Ags

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16
Q

Cell receptors that recognize PAMPs are called what?

A

PRRs (pattern recognition receptors)

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17
Q

2 different kinds of PRRs (pattern recogniztion receptors):

A

Mannose-tailed glycans are essential surface molecules of bacteria and viruses

Germ-line encoded refers to sequences that are found in gamete producing cells

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18
Q

Toll-like Receptors (TLRs)

A

On the cell surface they recognize pathogens and activate inflammation

Other TLR’s are in the endosome (where microbes are ingested). These only respond to nucleic acids

Once they bind they activate transcription factors

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19
Q

TLR-1; TLR-2 (cell surface) recognize what?

A

Bacterial lipopeptides

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20
Q

TLR-2 (cell surface) recognizes what?

A

Bacterial peptidoglycan (gram-positive bacteria)

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21
Q

TLR-4 (cell surface) recognizes what?

A

LPS (gram-negative bacteria)

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22
Q

TLR-5 (cell surface) recognizes what?

A

Bacterial flagellin

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23
Q

TLR-2; TLR-6 (cell surface) recognize what?

A

Bacterial lipopeptides

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24
Q

TLR-3 (endosome) recognizes what?

A

double stranded RNA

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25
Q

TLR-7 and TLR-8 (endosome) recognize what?

A

single stranded RNA

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26
Q

TLR-9 (endosome) recognizes what?

A

CpG DNA

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27
Q

Can multiple TLR’s can cause the same response

A

True

28
Q

NF-κB

A

The actual TF that is activated by Toll-like receptors→activation of immune cells

Plays a key role in regulating the immune response to infection

Incorrect regulation of NF-κB has been linked to cancer, inflammatory, and autoimmune diseases, septic shock, viral infection, and improper immune development.

29
Q

TLR-4

A
  1. A complex of TLR-4, MD2, CD14 and LPS is assembled at the macrophage surface
  2. MyD88 binds TLR4 and activates IRAK4 to phosphorylate TRAF6, which leads to the phosphorylation and activation of IKK
  3. IKK phosphorylates IκB, leading to its degradation and the release of NFκB, which enters the nucleus
  4. NFκB activates transcription of genes for inflammatory cytokines, which are synthesized in the cytoplasm and secreted via the ER
30
Q

Role of PRRs in Phagocytosis

A
  1. Microbes bind to phagocyte receptors
  2. Phagocyte membrane zips up around microbe and microbe ingested into phagosome
  3. Fusion of phagosome with lysosome
  4. Killing of microbes by lysosomal enzymes in phagolysosomes
  5. Killing of phagocytosed microbes by ROS and NO
31
Q

Innate Immunity: Complement

A

Complement system is made up of serum proteins which are normally soluble, inactive precursors

When activated they are cleaved into more pieces

Large fragments activate downstream components resulting in formation of “Membrane Attack Complexes (MACs)-disrupt the membranes of certain pathogens

32
Q

What do small fragments of broken-up Complements do?

A

Serve as:

  • Opsonins: deposited on microbes and enhance their uptake by phagocytes bearing complement receptors
  • Chemotactic factors: attract immune cells
  • Anaphylatoxins: cause degranulation of mast cells/basophils and release vasoactive substances.
33
Q

How can Complements be activated? (3 pathways)

A
  1. Classic pathway is activated by antigen-antibody (Ag-Ab) complexes
  2. Alternative pathway activated by microbial-cell walls
  3. Lectin pathway by the interaction of microbial carbohydrates with mannose-binding protein in the plasma
34
Q

Complement activation occurs in 2 phases:

A
  • activation of C3 component
  • activation of C5 component

Formation of the “attack” or lytic sequence=Membrane Attack Complex (MAC)…perforation of bacterial membrane

35
Q

Proteins that are induced rapidly by cytokines after infection (acute-phase proteins)

A

Plasma mannose-binding lectin (MBL) is a protein that recognizes microbial carbohydrates. MBL activates the complement cascade through the lectin pathway

-C-reactive protein (CRP) binds to surface of bacteria and activates complement which can kill the bacteria.

36
Q

What is the general function of a cytokine?

A

Mediate inflammation, immunity and hematopoiesis (make blood cell components)

Function is dependent upon the cell that they bind to

37
Q

What are the 2 types of innate immunity cytokines?

A

Pro-inflammatory and Anti-inflammatory

38
Q

Chemokines

A

Small protein chemoattractants that are important for trafficking of immune cells

39
Q

Most of the cytokines are derived from macrophages besides which one?

A

Interferon-γ (IFN-γ): it activates macrophages. Stimulation of some antibody responses

40
Q

Local vs Systemic Cytokine Effects

A

On sensing microbial products, macrophages secrete a variety of pro-inflammatory cytokines

Local effects: lymphocyte activation and ↑ antibody production

Systemic effects: Fever, shock

41
Q

B cell receptors (BCR’s) can recognize what kinds of things?

A

Antigens-proteins, carbs, lipids, nucleic acids

42
Q

T cells can’t “see” antigens without help from what?

A

APC

43
Q

T-helper cells produce what?

A

Cytokine called IFN-γ→stimulates MΦ to destroy microbes

44
Q

Professional APCs

A

Dendritic cells, MΦ, B cells

Activate both T-helper cells and Cytotoxic T cells

(Non-professional=any nucleated cell and show to cytotoxic T cell)

45
Q

Capture of antigens by Dendritic cells

A

Epithelium:

  1. Microbes enter and are captured by DCs
  2. DCs transport antigen to lymph nodes and B and T cells can recognize antigen and mature

Blood:
1. Antigen enters and are captured by APCs in spleen

46
Q

What MHC complexes do professional APCs use?

A

Both class 1 and 2

Non-professional: only MHC class 1

47
Q

CD4+ and CD8+

A 
CD4+ = T helper (use MHC class 2)
CD8+= Cytotoxic (use MHC class 1)
48
Q

T cells express what?

A

TCR and MHC class 1

49
Q

B cells express what?

A

BCRs and both MHC complexes

50
Q

Granulocytes (neutrophils, mast cells, eosinophils and basophils) express what?

A

MHC class 1

51
Q

How TCR recognizes antigen

A

TCR recognizes a complex of a peptide antigen displayed by a MHC

Peptides bind to MHC by anchor residues

52
Q

Phagocytosis vs endocytosis

A

Phagocytosis: MΦ
Endocytosis: DCs and B cells

53
Q

Antibody structure

A

Tetramer of 2 pairs of identical heavy and light chains

Both chains have variable and constant domains

Variable region=antigen specific

Heavy chain contains ‘hinge’ (flexibility to allow optimal Ag binding)

Fc=constant. Determines effector property of antibodies. Give distinct biological activities

54
Q

How are antibodies classified?

A

According to heavy chains

Constant region of heavy chain gives function and represents 5 different classes: IgM, IgD, IgG (1-4), IgE, IgA (1-2)

55
Q

Acute phase proteins

A

They are circulating proteins that fight infections. They are plasma proteins that are induced rapidly by cytokines after infection and called “Acute-Phase Proteins”

E.g. Mannose-binding lectin (MBL) is a protein that recognizes microbial carbohydrates. MBL activates the complement cascade through the lectin pathway

C-reactive protein (CRP): binds to phosphorylcholine on microbes and coats the microbes for phagocytosis by macrophages

56
Q

IL-8

A

Neutrophil migration

57
Q

MIP-1α and MIP-1β

A

Chemoattractants for monocytes

58
Q

TGF-β

A

Anti-inflammatory. Inhibits activation of T cells. Increases isotype switching to IgA

Wound repair, fibrosis

59
Q

IL-1

A

Helps activate CD4

60
Q

IL-2

A

Activates CD8 cell to attack virus-infected cells

61
Q

IL-4/5

A

Induce B cell to differentiate into plasma cell → produce antibodies

62
Q

IL-4 and IL-13

A

Macrophage activation (M2)

63
Q

IFN-γ

A

Enhances killing by macrophages

Macrophage activation (M1). Secreted by NK cells to activate macrophages

64
Q

IL-12

A

Secreted by M1 cells to activate NK cells

65
Q

IL-6

A

Production of acute-phase proteins (produced by hepatocytes in response to inflammation)

Inc Ab production

66
Q

HOT T-Bone stEAk

A

IL-1: fever (hot)
IL-2: stimulates T cells
IL-3: stimulates Bone marrow
IL-4: stimulates IgE production (B cell antibody)
IL-5: stimulates IgA production (B cell antibody)

67
Q

What are the pro-inflammatory cytokines?

A

IL-1,6 and TNF

Anti: IL-10, TGF-β

Biochemistry (41 decks)

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