Lecture 2 - Cells and Tissues of the Immune System Flashcards
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
- 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
- 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
- Neutrophils
- Eosinophils
- 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
What induces hematopoietic stem cells to differentiate?
1. Cytokines
2. Chemokines
3. Signal transduction factors
26
What is immunophenotyping?
Identification of immune cells to purify them
27
When is a surface molecule called CD? What does CDw mean?
Once two specific monoclonal 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
What is flow cytology?
Clinical application of immunophenotyping in hematology to analyze WBCs by Fluorescence-Activated Cell Sorting (FACS)
29
What does CD stand for?
Cluster of Differentiation
30
List the 8 innate immune cells.
1. Macrophages
2. Dendritic cells
3. Basophils
4. Eosinophils
5. Neutrophils
6. Mast cells
7. NK cells
8. Innate lymphoid cells (ILCs)
31
List the 6 semi-innate immune cells.
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
List the 2 adaptive immune cells.
1. B cells
| 2. T cells
33
Are all myeloid cells phagocytic?
Yes, except for basophils
34
Activated functions of macrophages?
1. Phagocytosis
2. Activation of bactericidal mechanisms
3. Antigen presentation
35
Activated functions of dendritic cells?
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
Activated functions of neutrophils?
1. Phagocytosis
| 2. Activation of bactericidal mechanisms
37
Activated functions of eosinophils?
1. Phagocytosis
| 2. Killing of antibody-coated parasites
38
Activated function of basophils?
Unknown but involved in anti-parasite immunity
39
Activated function of mast cells?
Release of granules containing histamine and other active agents that act locally on blood vessels
40
What do eosinophils, basophils, and mast cells have in common?
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
What is the most potent phagocytic myeloid cell?
Neutrophil
42
Which 3 myeloid cells are mediator releasing cells?
1. Mast cells
2. Basophils
3. Eosinophils
43
Which 3 immune cells are antigen presenting cells?
1. Macrophages
2. Dendritic cells
3. B cells
44
Which myeloid is the most powerful antigen presenting cell? Why?
Dendritic cells because it is the only myeloid cell that can activate a NAIVE T cell
45
What are the 3 types of ILCs?
1. Type 1
2. Type 2
3. Type 3
46
What are ILCs almost functionally identical to?
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
How are innate lymphoid cells activated?
Signals from injured or infected tissues, typically epithelial cells
48
Role of ILCs?
Help the adaptive system develop by helping helper T cells develop
49
How are NK cells activated?
α and β interferon molecules released by virally infected cells to induce them to kill those cells
50
What do NK cells secrete once activated? Role?
γ interferon = very potent pro-inflammatory cytokine
51
2 roles of iNKT cells?
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
What 6 immune cells do iNKT cells interact with?
1. NK cells
2. Dendritic cells
3. Macrophages
4. Neutrophils
5. T lymphocytes
6. B lymphocytes
53
Why are iNKT cells named that way? What to note?
Because they express an invariant TCR α-chain and one of three different β-chains
54
What are PPRs? How do they work?
= 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
Other name for PAMPS?
Microbe-associated molecular patterns (MAMPS)
56
What is CD14 for? Other name?
Receptor for lipopolysaccharides
= LPS receptor
57
What are 5 examples of signaling pattern-recognition receptors (PPRs)?
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
Where are lipopolysaccharides found?
Alpha-membrane of gram - bacteria
59
Are PPRs intra or extracellular?
BOTH
60
What are DAMPS? Other name?
= 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
2 other names for CD8+ T cells?
Cytotoxic T cells = killer T cells
62
Role of CD8+ T cells?
Kills infected cells
63
Are CD8+ T cells and NK cells the same?
NOPE
64
From where do naive lymphocytes enter lymph nodes and Peyer's patches?
From blood through specialized post-capillary venules of high endothelial venules (HEVs)
65
Where are T lymphocytes found in a lymph node?
Paracortical area
66
Where are B lymphocytes found in a lymph node?
Cortex in primary lymphoid follicles
67
What is found in the medulla of lymph nodes?
Cells exiting the lymphoid tissue: strings of macrophages and antibody-secreting plasma cells known as the medullary cords
68
Does each LN have its own artery and vein?
YUP
69
In which part of the lymph node do dendritic cells enter? What does this mean?
Paracortical area
Means they will first come in contact with T cells
70
Where does the thoracic duct drain into?
Left subclavian vein
71
2 parts of a lymph node? Describe each.
1. Outermost cortex: outer cortex and paracortical areas
| 2. Inner medulla
72
What 2 cells are found in paracortical areas of lymph nodes?
1. T cells
| 2. Dendritic cells
73
What are germinal centers? What is this called?
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
What does the spleen consist of? Describe each part.
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
Where do lymphocytes and antigen-loaded dendritic cells come together in the spleen?
In the peri-arteriolar lymphoid sheath (PALS)
76
Describe secondary follicles in the spleen.
Germinal center surrounded by a B-cell corona
77
Describe the passage of immune cells in blood in the spleen.
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
Describe the organization of a Peyer's patch.
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
Do Peyer's patches have afferent lymphatics? What does this mean?
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
Are basic divisions of cells in all lymphoid tissues?
YUP
81
How do M cells appear on the epithelial surface of the gut?
As a sunken and ruffled area on the epithelial surface
82
How do APCs present extracellular antigens? To what cells?
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
What do all 3 APC cell types express?
Co-stimulatory molecules (B7.1 and B7.2)
84
Which APCs are more efficient at taking up particulate antigens than soluble antigens? What to note?
DCs and MOs (opp is true for B cells)
85
How do APCs present intracellular antigens? To what cells?
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
Which dendritic cells do not process antigens efficiently?
Plasmacytoid DC
87
Do immature and activated DCs have the same surface molecules?
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
What are the chemokynes that bind activated dendritic cells?
Chemokynes secreted by peripheral lymphoid tissues
89
What do we call an activated dendritic cell?
Licensed DC
90
Through what mechanism do DCs take up antigens?
By macropinocytosis, receptor-mediated endocytosis or phagocytosis
91
What stimulates DCs to migrate to lymph nodes?
1. Chemokynes
| 2. Ligation of PAMPS and PRRs
92
Describe the state of DCs when they arrive at a lymph node.
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
What do follicular helper T cells do?
Enter B cell area of the lymphoid tissue and activate B cells by secreting particular cytokines
94
What 3 signals does a T cell need to be activated? What to note?
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
What happens if the only signal a naive T cell receives is binding to an antigen?
It becomes anergic = inactive and dies
96
What CD do iNK T cells have?
May have CD4
97
Why does it take so long to induce acquired adaptive immunity?
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
3 most important costimulatory molecules to activate naive T cells? Others?
```
MOST IMPORTANT:
1. CD28 on T cells
On DC:
2. B7.1
3. B7.2
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OTHERS (T cell:DC):
1. CD27:CD70
2. CD40L:CD40
3. 4-1BB:4-1BBL
4. OX40:OX40L
5. ICOS: ICOSL
99
What signals are needed to activate an effector T cell?
```
Once the naïve T cell has been activated to an effector T cell, it no longer requires
signal 2 (survival signal)
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100
What to note about co-stimulatory signal ICOS:ICOSL?
It does not induce IL-2 but regulates expression of other cytokines produced by CD4 T cells
