Lecture 2 - Cells and Tissues of the Immune System Flashcards Preview

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Flashcards in Lecture 2 - Cells and Tissues of the Immune System Deck (100)
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1
Q

What are cytokines?

A

Instructional molecules

2
Q

What are chemokines?

A

Molecules that control cell migration

3
Q

What does immune cell activation require?

A

Cross-linking of at least 2 receptors: signal through their antigen receptor (signal 1), and second signal (signal 2)

4
Q

Are many immune cells plastic? What does this mean?

A

YUP

Their phenotype can change (including CD markers) based on exposure to different cytokines

5
Q

Difference between innate and semi-innate T lymphocyte?

A

An innate T lymphocyte is one that lacks a TCR and has no memory, e.g., NK cell

A semi-innate T lymphocyte has TCR of limited diversity, e.g., iNK T cell (invariant NK T cell)

6
Q

Where does the term antigen come from?

A

Contraction of ANTIbody GENerating

7
Q

Timing of innate immune response?

A

Minutes to hours

8
Q

Timing of adaptive immune response?

A

3-4 (or 7-10) days ??

9
Q

What does the innate immune response target?

A
  1. Patterns of groups of pathogens

2. Conserved microbial motifs

10
Q

What does the adaptive immune response target?

A

Epitopes on specific pathogens

11
Q

Which is more specific: innate or adaptive immune response?

A

Adaptive

12
Q

What are epitopes on antigens?

A

Short AA sequences (10-20)

13
Q

Origin of the innate immune system?

A

Has been conserved throughout evolution and has its origins in unicellular life-forms

14
Q

What does it mean for the innate immune system to be invariant?

A

No matter how many times it encounters a particular agent it responds in the same way

15
Q

What is the innate immune system mediated by?

A
  1. Phagocytic cells

2. Primitive lymphocytes that lack high specificity receptors

16
Q

Origins of adaptive immunity?

A

Arose in the chordates

17
Q

How are T and B lymphocytes distinguished from the other leukocytes?

A

By having antigen receptors

18
Q

Other name for WBCs?

A

Leukocytes

19
Q

How are T and B lymphocytes distinguished from each other?

A

By their sites of differentiation: the thymus (T) and bone marrow (B)

20
Q

3 types of granulocytes?

A
  1. Neutrophils
  2. Eosinophils
  3. Basophils
21
Q

When are dendritic cells activated?

A

After they have encountered a potential pathogen

22
Q

What are dendritic cells derived from?

A

The majority of dendritic cells are derived from the common myeloid progenitor cells, but some may also arise from the common lymphoid progenitor

23
Q

Where do monocytes mature?

A

Monocytes enter tissues, where they differentiate into phagocytic macrophages or dendritic cells

24
Q

Where do mast cells mature?

A

They enter tissues and complete their maturation there

25
Q

What induces hematopoietic stem cells to differentiate?

A
  1. Cytokines
  2. Chemokines
  3. Signal transduction factors
26
Q

What is immunophenotyping?

A

Identification of immune cells to purify them

27
Q

When is a surface molecule called CD? What does CDw mean?

A

Once two specificmonoclonal antibodies(mAb) are shown to bind to the molecule

If the molecule has not been well-characterized, or has only one mAb, it is usually given the provisional indicator “w” (e.g. “CDw186”)

28
Q

What is flow cytology?

A

Clinical application of immunophenotyping in hematology to analyze WBCs by Fluorescence-Activated Cell Sorting (FACS)

29
Q

What does CD stand for?

A

Cluster of Differentiation

30
Q

List the 8 innate immune cells.

A
  1. Macrophages
  2. Dendritic cells
  3. Basophils
  4. Eosinophils
  5. Neutrophils
  6. Mast cells
  7. NK cells
  8. Innate lymphoid cells (ILCs)
31
Q

List the 6 semi-innate immune cells.

A
  1. B-1 cells
  2. Marginal zone B cells (MZB)
  3. γδ T cells
  4. CD8αα T cells
  5. Mucosa-associated invariant T cells
  6. iNKT cells
32
Q

List the 2 adaptive immune cells.

A
  1. B cells

2. T cells

33
Q

Are all myeloid cells phagocytic?

A

Yes, except for basophils

34
Q

Activated functions of macrophages?

A
  1. Phagocytosis
  2. Activation of bactericidal mechanisms
  3. Antigen presentation
35
Q

Activated functions of dendritic cells?

A
  1. Antigen uptake in peripheral sites
  2. Phagocytosis when immature
  3. Antigen presentation in lymph nodes when mature to initiate an adaptive immune response
  4. Produce molecules that enable T cells to be activated by antigens
36
Q

Activated functions of neutrophils?

A
  1. Phagocytosis

2. Activation of bactericidal mechanisms

37
Q

Activated functions of eosinophils?

A
  1. Phagocytosis

2. Killing of antibody-coated parasites

38
Q

Activated function of basophils?

A

Unknown but involved in anti-parasite immunity

39
Q

Activated function of mast cells?

A

Release of granules containing histamine and other active agents that act locally on blood vessels

40
Q

What do eosinophils, basophils, and mast cells have in common?

A
  1. Primarily secretory cells that release the contents of their prominent granules upon activation via antibody during an adaptive immune response
  2. Important in allergic responses
41
Q

What is the most potent phagocytic myeloid cell?

A

Neutrophil

42
Q

Which 3 myeloid cells are mediator releasing cells?

A
  1. Mast cells
  2. Basophils
  3. Eosinophils
43
Q

Which 3 immune cells are antigen presenting cells?

A
  1. Macrophages
  2. Dendritic cells
  3. B cells
44
Q

Which myeloid is the most powerful antigen presenting cell? Why?

A

Dendritic cells because it is the only myeloid cell that can activate a NAIVE T cell

45
Q

What are the 3 types of ILCs?

A
  1. Type 1
  2. Type 2
  3. Type 3
46
Q

What are ILCs almost functionally identical to?

A

Classical T cells:

  1. Type 1 ILC => type 1 helper T cell
  2. Type 2 ILC => type 2 helper T cell
  3. Type 3 ILC => CD4+ TH17+ T cell
47
Q

How are innate lymphoid cells activated?

A

Signals from injured or infected tissues, typically epithelial cells

48
Q

Role of ILCs?

A

Help the adaptive system develop by helping helper T cells develop

49
Q

How are NK cells activated?

A

α and β interferon molecules released by virally infected cells to induce them to kill those cells

50
Q

What do NK cells secrete once activated? Role?

A

γ interferon = very potent pro-inflammatory cytokine

51
Q

2 roles of iNKT cells?

A
  1. Sensors and managers of inflammation by releasing a spectrum of immunoregulatory cytokines and cytotoxic granules upon antibody receptor activation (like the NK cells)
  2. Respond to lipid and glycolipid antigens presented by CD1
52
Q

What 6 immune cells do iNKT cells interact with?

A
  1. NK cells
  2. Dendritic cells
  3. Macrophages
  4. Neutrophils
  5. T lymphocytes
  6. B lymphocytes
53
Q

Why are iNKT cells named that way? What to note?

A

Because they express an invariant TCR α-chain and one of three different β-chains

54
Q

What are PPRs? How do they work?

A

= signaling pattern-recognition receptors

Receptors on professional antigen-presenting cells (APC) (particularly DCs and MOs) and professional phagocytes such as neutrophils, that recognize evolutionarily conserved structures possessed by pathogens, but not by human cells => pathogen-associated molecular patterns (PAMPS)

PPRs ligate PAMPs (or the other way around, but not as common) resulting in the uptake of the pathogen by the cell and the transduction of signals to the cell nucleus => NECESSARY for their activation

55
Q

Other name for PAMPS?

A

Microbe-associated molecular patterns (MAMPS)

56
Q

What is CD14 for? Other name?

A

Receptor for lipopolysaccharides

= LPS receptor

57
Q

What are 5 examples of signaling pattern-recognition receptors (PPRs)?

A
  1. Mannose receptor
  2. LPS receptor
  3. Toll-like receptors: TLR-2 and TLR-4
  4. Glucan receptor for glucose
  5. Scavenger receptor for lipids
58
Q

Where are lipopolysaccharides found?

A

Alpha-membrane of gram - bacteria

59
Q

Are PPRs intra or extracellular?

A

BOTH

60
Q

What are DAMPS? Other name?

A

= danger/damage-associated molecular patterns = alarmins

Host molecules that can be recognized by PPRs: elements from nucleus, cytosol, mito, and ER so that when the cell undergoes necrosis and DAMPS are released they can be detected by PPRs

61
Q

2 other names for CD8+ T cells?

A

Cytotoxic T cells = killer T cells

62
Q

Role of CD8+ T cells?

A

Kills infected cells

63
Q

Are CD8+ T cells and NK cells the same?

A

NOPE

64
Q

From where do naive lymphocytes enter lymph nodes and Peyer’s patches?

A

From blood through specialized post-capillary venules of high endothelial venules (HEVs)

65
Q

Where are T lymphocytes found in a lymph node?

A

Paracortical area

66
Q

Where are B lymphocytes found in a lymph node?

A

Cortex in primary lymphoid follicles

67
Q

What is found in the medulla of lymph nodes?

A

Cells exiting the lymphoid tissue: strings of macrophages and antibody-secreting plasma cells known as the medullary cords

68
Q

Does each LN have its own artery and vein?

A

YUP

69
Q

In which part of the lymph node do dendritic cells enter? What does this mean?

A

Paracortical area

Means they will first come in contact with T cells

70
Q

Where does the thoracic duct drain into?

A

Left subclavian vein

71
Q

2 parts of a lymph node? Describe each.

A
  1. Outermost cortex: outer cortex and paracortical areas

2. Inner medulla

72
Q

What 2 cells are found in paracortical areas of lymph nodes?

A
  1. T cells

2. Dendritic cells

73
Q

What are germinal centers? What is this called?

A

Central areas in the follicles of the lymph node cortex where intense B cell proliferation is happening when an immune response is under way

= secondary lymphoid follicles

74
Q

What does the spleen consist of? Describe each part.

A

Red pulp, site of red blood cell destruction, interspersed with the lymphoid white pulp which is arranged around central arterioles surrounded by the peri-arteriolar lymphoid sheath (PALS), made up of T cells

Follicles consist mainly of B cells and are surrounded by a marginal zone of lymphocytes

75
Q

Where do lymphocytes and antigen-loaded dendritic cells come together in the spleen?

A

In the peri-arteriolar lymphoid sheath (PALS)

76
Q

Describe secondary follicles in the spleen.

A

Germinal center surrounded by a B-cell corona

77
Q

Describe the passage of immune cells in blood in the spleen.

A

In each area of white pulp, blood carrying both lymphocytes and antigen flows:

Trabecular artery => central arteriole => smaller blood vessels fan out => eventually terminating in a specialized zone: the peri-follicular zone, which surrounds each marginal zone => cells/antigens pass in open blood-filled spaces in the peri-follicular zone => white pulp

78
Q

Describe the organization of a Peyer’s patch.

A
  1. Germinal centers with numerous B-cell follicles
  2. T-cell dependent areas in between follicles with T cells
  3. Subepithelial dome: layer between the surface epithelium and the follicles containing dendritic cells, T cells, and B cells
79
Q

Do Peyer’s patches have afferent lymphatics? What does this mean?

A

NOPE

The antigen enters directly from the gut across a specialized epithelium made up of so-called microfold (M) cells which do not have microvilli

80
Q

Are basic divisions of cells in all lymphoid tissues?

A

YUP

81
Q

How do M cells appear on the epithelial surface of the gut?

A

As a sunken and ruffled area on the epithelial surface

82
Q

How do APCs present extracellular antigens? To what cells?

A

They load fragments of the antigen into major histocompatibility (MHC) class II receptors which traffic to the cell membrane and are displayed to CD4+ T cells

83
Q

What do all 3 APC cell types express?

A

Co-stimulatory molecules (B7.1 and B7.2)

84
Q

Which APCs are more efficient at taking up particulate antigens than soluble antigens? What to note?

A

DCs and MOs (opp is true for B cells)

85
Q

How do APCs present intracellular antigens? To what cells?

A

They load fragments of the antigen into major histocompatibility (MHC) class I molecules and present them on the cell surface to cytotoxic CD8+ T cells

86
Q

Which dendritic cells do not process antigens efficiently?

A

Plasmacytoid DC

87
Q

Do immature and activated DCs have the same surface molecules?

A

NOPE

Immature: numerous PPRs, including most of the Toll-like receptors (TLRs)

Mature: PPRs (more of them), cell adhesion molecules (LFA-1, CD58), co-stimulatory molecules, MHCs, chemokyne receptors

88
Q

What are the chemokynes that bind activated dendritic cells?

A

Chemokynes secreted by peripheral lymphoid tissues

89
Q

What do we call an activated dendritic cell?

A

Licensed DC

90
Q

Through what mechanism do DCs take up antigens?

A

By macropinocytosis, receptor-mediated endocytosis or phagocytosis

91
Q

What stimulates DCs to migrate to lymph nodes?

A
  1. Chemokynes

2. Ligation of PAMPS and PRRs

92
Q

Describe the state of DCs when they arrive at a lymph node.

A

Fully mature non-phagocytic dendritic cells that express both antigen and the co-stimulatory molecules necessary to activate a naive T cell that recognizes the antigen

93
Q

What do follicular helper T cells do?

A

Enter B cell area of the lymphoid tissue and activate B cells by secreting particular cytokines

94
Q

What 3 signals does a T cell need to be activated? What to note?

A
  1. Antigen on MHC binding to TCR and CD4 or CD8
  2. SURVIVAL SIGNAL: ligation of co-stimulatory molecules delivered by APCs
  3. Cytokines from the APC

NOTE: signals 1 and 2 (the antigen-specific and the co-stimulatory signals) MUST be
delivered to the naïve T cell from the same cell => CRUCIAL in preventing autoreactive T cells that escaped from the thymus from mounting an autoimmune responses

95
Q

What happens if the only signal a naive T cell receives is binding to an antigen?

A

It becomes anergic = inactive and dies

96
Q

What CD do iNK T cells have?

A

May have CD4

97
Q

Why does it take so long to induce acquired adaptive immunity?

A
  1. Pathogen antigen has to be taken up by antigen-presenting cells (APCs), notably the dendritic cell (DC), taken to draining lymph nodes where peptides derived from the pathogen are presented by DCs bound in the groove of MHC I or MHC II molecules
  2. The DCs must wait for a T lymphocyte bearing a T-cell receptor (TCR) that recognizes the pathogen-derived peptide and the MHC molecule to enter the lymph node
  3. If and when this occurs the T cell must undergo clonal expansion to develop a population of effector cells or the T cell must interact with a B cell in the lymph node that is bearing the same peptide in its MHC molecules
  4. Once this happens the B cell undergoes clonal expansion and a portion of them become effector B cells by terminally differentiating into plasma cell populations that secrete antibody
98
Q

3 most important costimulatory molecules to activate naive T cells? Others?

A
MOST IMPORTANT:
1. CD28 on T cells
On DC:
2. B7.1
3. B7.2

OTHERS (T cell:DC):

  1. CD27:CD70
  2. CD40L:CD40
  3. 4-1BB:4-1BBL
  4. OX40:OX40L
  5. ICOS: ICOSL
99
Q

What signals are needed to activate an effector T cell?

A
Once the naïve T cell has been activated to an effector T cell, it no longer requires
signal 2 (survival signal)
100
Q

What to note about co-stimulatory signal ICOS:ICOSL?

A

It does not induce IL-2 but regulates expression of other cytokines produced by CD4 T cells