Lecture 6 Flashcards

1
Q

The innate immune response is mediated by…

A

PMNS (Type of white blood cell) and Phagocytes

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2
Q

The adaptive immune response is mediated by…

A

Lymphocytes (B and T cells)

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3
Q

ANTIGEN

A

Protein or carbohydrate that engages the immune system and initiates an immune response.

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4
Q

Proteins

A

Majority of antigens, may be pure proteins, glycoproteins or lipoproteins

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5
Q

Polysaccharides

A

Pure polysaccharides or lipopolysaccharides (sugar chains); type of antigen

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6
Q

Lipids

A

Non-immunogenic may assist in antigen-mediated immune activation

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7
Q

Nucleic acid

A

Usually poorly immunogenic, most effective when single-stranded or complexed with proteins

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8
Q

What recognizes antigens?

A

Specific antibody proteins or T-cell receptors

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9
Q

Epitope

A

Antigen determinant; interacts with a single antibody or T-cell receptor (Binds to the antibody)

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10
Q

Types of Epitopes

A

Linear (Short and continuous and formed by a specific sequence; after denaturation, it may still be able to bind to the antibody)
Conformational (3D structure, domains of proteins composed of specific regions of protein chains; after denaturation, it can no longer bind to the antibody)

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11
Q

B-cell epitopes

A

Region of the antigen recognized by immunoglobulins/antibodies 3-20 a.a. or sugar residues

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12
Q

T-cell epitopes

A

Region of the antigen recognized by T-cell receptor
8-15 a.a. long; only recognized after the antigen is processed and presented with an MHC protein

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13
Q

True or False: One antigen can have many different epitodes

A

True

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14
Q

Which are the professional APCs that present antigens to CD4 T-cells

A

Macrophages, dendritic cells, and B-cells

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15
Q

3 stages of APC Sentinels

A

The resting stage, Activated by cytokines or PRR (AP mode), and the attacking mode

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16
Q

Antigen-presenting molecules

A

MHC I/II

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17
Q

What cell is produced when cytokines attract monocytes

A

Dendritic cells

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18
Q

Types of Pattern/Pathogen Recognition Receptors (PRR)

A

TLR-Toll-like receptor, RLR-Rig-like receptor (IFNα/β), NLR-NOD-like receptor (inflammatory), Lectin-like receptors

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19
Q

Which microbes bind with TLRs (extra-cellular and endosomal) and NLRs (cytosolic)

A

Bacterial cell wall lipids

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20
Q

Which microbes bind with RLRs (cytosolic)

A

Viral RNA

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21
Q

Which microbes bind with lectin (extra-cellular)

A

Fungal polysaccharide

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22
Q

Peripheral Dendritic cells role

A

Travel from peripheral site to LN to present antigens to
T cells

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23
Q

Resident/ Follicular Dendritic cells role

A

Stay in LN to sample lymph for opsonized
antigens to present to B cells

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24
Q

Macrophages role

A

Stay at sites of infection/inflammation and support the fight at the site of infection, also re-stimulate T cells that have arrived from LN at peripheral sites of inflammation

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25
Q

B-cell role

A

Stay in LN and stimulate CD4 T cells to support antibody production. They sample antigen specifically through BCR and present it to CD4 T cells.

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26
Q

What are the 2 states of APCs?

A

Immature/quiescent state and the mature state

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27
Q

Characteristics of the immature state of APCs

A

Routinely process and present antigen, Express PRRs, Express low levels of MHC I and II

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28
Q

Characteristics of the mature state of APCs

A

Present antigen to naïve T-cells and activate them, Increase antigen processing and presentation, Increase MHC expression, Express co-stimulatory molecules for T-cells, and produce cytokines

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29
Q

Where do the antigens that MHC I present come from?

A

Intracellularly (present the antigen extracellularly to CD8+ T-Cells)

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30
Q

Where do the antigens that MHC II present come from?

A

Extracellularly (present the antigen extracellularly to CD4 T-cells

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31
Q

MHC II binds with…

A

Macrophages (intravesicular pathogens) and B-cells (extracellular pathogens)

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32
Q

Major Histocompatibility complex (MHC)

A

Control graft rejection and control the immune response to all protein antigens

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33
Q

Polygenic

A

Several different MHC I and II genes, therefore every individual has a set of MHC molecules with different ranges of peptide binding specificities

34
Q

Polymorphic

A

Variability at a gene locus within the population

35
Q

Human Leukocyte antigens (HLA)

A

Called MHC in humans and is controlled by genes located on chromosome 6 (MHC are co-dominantly expressed - half from mother, half from father)

36
Q

HLA in MHC I

A

Bind to CD8+ T-cells; HLA-A, HLA-B, HLA-C

37
Q

HLA in MHC II

A

Bind o CD4+ T-cells; HLA-DR, HLA-DQ, HLA-DP

38
Q

MHC haplotype

A

Set of maternally- and paternally-derived MHC genes on each chromosome (3 MHCI, 3 MHCII from each parent)

39
Q

Parts of a T-cell receptor

A

membrane-bound, a/b chains, disulphide bond, carbohydrate, variable region, constant region, stalk segment, a transmembrane region, cytoplasmic tail (1 antigen binding site)

40
Q

Where does T-cell receptor diversity occur?

A

The thymus

41
Q

Where do Mature and activated T-cells go?

A

Mature: Lymphoid organs
Activated: Sites of infection

42
Q

VDJ Recombination - segments

A

V: Variable, J: Joining, D: Diversity

43
Q

a-chain gene rearrangement

A

Germline DNA –>(recombination) rearranged DNA –>(transcription splicing translation)–> protein T-cell receptor

44
Q

b-chain gene rearrangement

A

Protein T-cell receptor (translation splicing transcription) <–rearranged DNA (recombination) <–germline DNA

45
Q

How does germline DNA produce genetic diversity in the antigen binding site of the receptor?

A

Use of different gene segments and the addition of nucleotides when forming the antigen receptor mRNAs

46
Q

How are T-cells activated?

A

High-affinity TCR engagement with MHC/ peptide
Complexes through Receptor activation: CD4/TCR: MHC class II and co-stimulation through Co-receptor activation: CD28:CD80/86

47
Q

Licensing

A

Promotes CD8 T cell activation and promotes survival
of the dendritic cell. CD40L:CD40, cytokines

48
Q

The signals for T-cell activation

A

Signal 1: MHC-peptide-TcR recognition (naïve and memory T-cells)
Signal 2: co-stimulation recognition (naïve T-cells)
Signal 3: cytokine signalling recognition (naïve and memory T-cells)

49
Q

Immunological Synapse

A

Adhesion molecules bring APC and CD4 T-cells together. Rearrangement of cytoskeleton and
polarization of cell (4-10 hours)

50
Q

What does the TCR/co-receptor binding result in?

A

Activating a signalling cascade and the activation of genes that promote cell cycle, survival and activation (inadequate co-activation signals results in cell death or anergy - abnormal immune response)

51
Q

How can a NAÏVE antigen-specific lymphocyte manage to contact its specific antigen, or encounter a helper cell with the appropriate antigen specificity?

A

The “dating bars of the body”– the Lymph nodes

52
Q

Parts of the Lymphatic System

A

Cervical nodes, lymph nodes(2dary), thymus, axillary nodes, diaphragm, lymph vessels, spleen(2dary), inguinal nodes

53
Q

GALT (gut-associated lymphoid tissue)

A

Lamina propria, Peyer’s patches

54
Q

BALT (bronchial-associated lymphoid tissue)

A

Respiratory epithelium

55
Q

MALT (mucosal-associated lymphoid tissue)

A

Other diffuse mucosal sites, ex reproductive tract, small and large intestine

56
Q

How many lymphocytes enter lymph nodes?

A

About 10,000 lymphocytes enter the lymph nodes each second

57
Q

Langerhans cell

A

Immature dendritic cells are found in the skin.

58
Q

Lymph node

A

A specialized organ that facilitates the presentation of foreign antigens to the immune system.

59
Q

Lymph node: Structure and function

A

T-cells and activated APC enter and leave through lymphatic vessels, lymph filter (lined with macrophages that can devour pathogens as they enter the lymph node)

60
Q

High Endothelial Venule (HEV)

A

Doorway to enter LN from the blood – special columnar endothelial cells that allow entry.

61
Q

Paracortex

A

T-cell suppression

62
Q

Afferent (substance going in)

A

Lymphocyte immigration

63
Q

Cortex

A

B-cell activation

64
Q

Medulla

A

Lymphocyte emigration

65
Q

Paracortex

A

T-cell activation

66
Q

Naïve cells (LN Trafficking)

A

Surface adhesion molecules for any secondary lymphoid organs (remain in circulation until a match is made; if no match = death by apoptosis)

67
Q

Activated cells (LN Trafficking)

A

Surface adhesion molecules that are expressed depending on where they were activated – tend to return to compartments they encountered antigen

68
Q

Activated CD4 T-cells

A

Exit LN and recirculate; promote the function of other T-cells and LN stimulates B-cells and CD8 T-cells

69
Q

Activated CD8 T-cells

A

Exit LN and go to sites of inflammation and destroy target cells

70
Q

Activated B cells

A

Remain in the LN and cycle between germinal and follicular zones; some will mature to plasma cells to produce anti-bodies (locate in intestinal lamina propria)

71
Q

How is the movement of cells (T & B cells) regulated?

A

Up and down regulation of receptors that act as “passports” to various compartments

72
Q

MALT

A

Gut surveillance

73
Q

Lamina propria

A

Connective tissue containing lymphocytes and some
germinal centers

74
Q

Peyer’s patches

A

Lymph node-like nodules in ILEUM, have HEV lymphatic drainage, but no incoming lymphatics (recieve antigens sent from endosomes through M-cells)

75
Q

Spleen

A

Filters blood (collects antigen from the blood and disposes of old red blood cells)

76
Q

Th1

A

CD4 T-cell; Cell-mediated immunity and inflammation, attacks intracellular pathogens, autoimmunity (IL-2, IFN-y, TNF-a)

77
Q

Th2

A

CD4 T-cell; Antibody-mediated immunity, extracellular parasites, asthma, allergy (IL-4, IL-5, IL-6, IL-10, IL-13)

78
Q

Th1 response outcome (cell-mediated)

A

Microbes (IFN-y)–> Macrophage activation
B-cell (IFN-y)–> Complement-binding and opsonizing antibodies
Neutrophil(LT, TNF)–> Neutrophil activation

79
Q

Th2 response outcome (humoral)

A

B-cells (IL-4) –> Production of neutralizing IgG antibodies + IgE
Eosinophil (IL-5) –> eosinophil activation
Activated macrophage (IL-10, IL-4) –> suppression of macrophage activation

80
Q

Regulatory T-cells function (T-reg)

A

Control/ dampen the immune response, Maintain tolerance to self-antigens, Prevent autoimmune disease

81
Q

True or False: CD4 cells are terminal and cannot respond to dynamic change in the immune system

A

False; They are not terminal and can change with the course of the infection to respond to the needs of the immune system dynamically