Anatomy Of The Immune System Flashcards

1
Q

What is the difference between a WBC count and a differential?

A

WBC count is the total number of WBC/leukocytes

Differential is the amount of neutrophils, basophils, eosinophils, as percentage of the total

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2
Q

What is the most common leukocyte in peripheral blood?

A

neutrophil

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3
Q

For normal blood cell counts, list the WBCs from most to least in the peripheral blood?

A
  1. Neutrophil
  2. Lymphocytes (T, B, NK)
  3. Monocytes
  4. Eosinophils
  5. Basophils
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4
Q

The pluripotent hempatopoeitic cell can derive into two lineages. What are they?

A
  1. Common lymphoid progenitor

2. Common myeloid progenitor

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5
Q

What two lineages does the common myeloid progenitor divide into?

A
  1. Granulocyte/macrophage lineage

2. Megakaryocyte/erythrocyte lineage

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6
Q

What are the five cells that enter the blood from the granulocyte lineage?

A

Neutrophils, eosinophils, basophils, mast cell-precursors, monocytes

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7
Q

When they reach tissue, what do monocytes differentiate into?

A

resident macrophages

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8
Q

What do megakaryocytes make and release to the the blood?

A

Platelets

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9
Q

What are the three lineage of the common lymphoid progenitor?

A
  1. B cell
  2. T cell
  3. NK cell
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10
Q

To what lineage does the dendritic cell arise?

A

unsure, but probably myeloid because it is part of the innate immune system and helps to activate the acquired immune system by presenting antigen in lymph nodes.

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11
Q

What are the two key functions of cells in the macrophage/monocyte lineage?

A
  1. engulf and digest diverse materials

2. process and present antigens to adaptive immune system lymphocytes

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12
Q

Where are monocytes and macrophages located?

A
Monocyte are located in the blood.
Macrophages are located in tissues:
1. Kupffer cells in the liver
2. alveolar macrophages in the lungs
3. splenic macrophages 
4. peritoneal macrophages in the GI
5. Microglia in the brain
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13
Q

When they come into contact with cytokines, what do cells in the monocyte/macrophage lineage trainsition into?

A

APCs

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14
Q

What is the major activated function of :

  1. neutrophil
  2. eosinophil
  3. basophil
  4. mast cell
A
  1. Phagocytize and activate bacteriacidal mechanisms
  2. Kill antibody-coated parasites
  3. ??
  4. Release histamine–> inflammatory response
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15
Q

What type of dendritic cell is present in skin?

A

Langerhan’s cells

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16
Q

Where are immature dendritic cells located?

How do they “sample” the local area for pathogens?

A

Immature dendritic cells are located in the blood circulation and tissues.
They use macropinocytosis to take in a large amount of extracellular fluid to sample for PAMPs.

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17
Q

When do immature dendritic cells mature?

What two major functions do mature dendritic cells perform?

A

When they come into contact with a PAMP.

  1. They secrete cytokines to activate innate and acquired immune systems.
  2. They express surface molecules to activate naive T lymphocytes.
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18
Q

How long do Polymorphonuclear leukocytes (PMNs) persist in the body?
What happens to them during immune response?

A

very short-lived (just a few days)

They increase in number during immune responses

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19
Q

What is the presumed function of the mast cell?

A

It is involved in immune response against parasitic worms and involved in allergic reactions by releasing histamine

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20
Q

Which lymphoid cells have a more stable repertoire of naive cells (B or T)?

A

T cells in the thymus are more constant than B cells in the bone marrow. T cells have a long life span and B cells have a short life span

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21
Q

Why must T-cells have a longer life span than B cells?

A

T cells differentiate in the thymus (2ndary lymphoid organ) and the thymus decreases with age so the cells must be able to persist.
B cells differentiate in bone marrow which doesnt deplete

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22
Q

How long do B cells typically persist in blood circulation?

A

5-7 days. They will either see an antigen or go through apoptosis

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23
Q

What is the role of the primary lymphoid organs?

A

It is where the lymphocyte first expresses antigen receptors and attains phenotypic and functional maturity

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24
Q

What is the role of the secondary lymphoid organs?

A

Where lymphocytes respond to foreign antigens

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25
Q

What is the primary lymphoid organ for B cells? T cells?

A

B cells - bone marrow

T cells - thymus

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26
Q

What early events of B cell maturation occur in the bone marrow?

A

They are tested to see if they react to self antigens. If they don’t, they are released to circulation.

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27
Q

What is the general structure of the thymus?

A

It is a bilobed organ in the anterior mediastinum.

Each lobe is broken into multiple lobules with cortex surrounding an inner medulla.

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28
Q

Where do T cell precursors reside in the thymus?

A

In the outer cortex and as they mature, they move in toward the medulla

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29
Q

How many lymphocytes will have a receptor to recognize a particular antigen?

A

1 in 10^5 which shows that selective recruitment is crucial (and which is why lymphocytes need to be constantly circulating)

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30
Q

What are the three major stages of clonal selection of B and T cells and where do they take place?

A
  1. Cognitive phase - lymph nodes/spleen
  2. Activation phase- lymph nodes/spleen
  3. Effector phase- periphery
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31
Q

What happens during the cognitive phase of clonal selection of T and B cells?

A

The naive B or T cell recognizes and antigen

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32
Q

What happens during the activation phase of clonal selection of B and T cells?

A

The cell that recognized the antigen proliferates and differentiates

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33
Q

What happens during the effector phase of clonal selection of B and T cells?

A

All the differentiated cells enter the periphery and become effector cells to attack the infection or memory cells for future response to infection

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34
Q

Where do lymphatic vessels drain?

A

Into the subcapsular sinuses of lymph nodes

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35
Q

What is the major function of the lymphatic system?

What is the draw back of the systme?

A

It brings APCs and dendritic cells into contact with naive lymphoid cells so they can recognize potential pathogens.

The drawback is that they could serve as channels for metastatic spread of cancer

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36
Q

Where are B cells located in lymph nodes?

Where are T cells located?

A

B cells- follicles in the cortex

T cells- paracortex

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37
Q

What are the three layers of a lymph node?

A

capsule, cortex, medulla

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38
Q

Where are dendritic cells located in the lymph node?

A

Paracortex with the T cells

39
Q

When an immune response is initiated, what happens in the lymph node?

A

Germinal centers form in the follicles where there is rapid proliferation of B cells

40
Q

What is the area surrounding the germinal centers?

A

The mantle zone which consists of B cells that are not proliferating because they don’t recognize the antigen

41
Q

What is the other name for a germinal center?

A

Secondary follicles

42
Q

What do proliferating B cells differentiate into?

A

plasma cells that are antibody producing effector cells

43
Q

What is a lymphoma?

A

when B cells proliferate out of control

44
Q

How do T cells in the paracortex get activated?

A

Dendritic cells present them with an antigen

45
Q

What do T cells do when they respond to a DC presented antigen in the lymph node?

A
  1. They interact with B cells in the germinal center to drive proliferation and differentiation
  2. Some differentiate into effector cells, exit lymph node and traffic to the site of infection
46
Q

What is the major role of the spleen?

A

Blood filtration (adaptive immune response to blood-borne antigens)

47
Q

What part of the spleen contains germinal centers?

A

white pulp

48
Q

Describe the structure of the spleen starting with the entrance of the splenic artery.

A

The splenic artery pierces the hilum and branches into smaller arteriolar branches surrounded by trabecula.
White pulp organizes around these arteriolar branches

49
Q

How are B and T cells arranged in the spleen?

A

B cells are in follicles and T cells are in PALS (periarteriolar lymphoid sheaths)

50
Q

Where are antigens delivered in the spleen?

A

Via dendritic cells in the marginal sinus (blood) or by macrophages in the marginal zone (tissue)

51
Q

What is in the red pulp of the spleen?

What occurs in the red pulp?

A

1 vascular sinusoids

  1. macrophages
  2. dendritic cells
  3. lymphocytes

The red pulp is where the blood is cleared of microbes and damaged RBC by splenic macrophages

52
Q

Where are the majority of antibody-coated microbes opsonized?

A

the spleen

53
Q

Why are patients that lack a spleen especially susceptible to gram + bacterial infections like streptococcus, meningococcus, pneumonococci, etc?

A

This is where most antibody-coated microbes are opsonized and these bacteria are encaspulated

54
Q

What cells in the epidermis participate in host defense?

A
  1. Keratinocytes
  2. Langerhans cells
  3. Resident macrophages
  4. T lymphocytes
55
Q

What is the role of keratinocytes in the skin?

A

They produce cytokines to contribute to innate immune response and inflammation

56
Q

What is the role of Langerhans cells in the skin?

A

They are immature dendritic cells of the cutaneous immune system that capture antigens that enter the skin via PRRs.

57
Q

When a PAMP binds a PRR of a langerhans cell, what happens?

A

It loses its adhesion to the epidermis and migrates to the regional lymph node

58
Q

What type of T cell is found in the dermis?

A

Memory T cells so they can guard against reinfection by recognized pathogens

59
Q

Where are cells of the immune system found in the mucousal epithelia?

A
  1. Scattered throughout the lamina propria (skin equivalent of dermis)
  2. In Peyer’s Patches
60
Q

What are Peyer’s patches?

A

They are in the small intestine and consist of B cell rich regions with germinal centers and interfollicular regions with T cells

61
Q

How do antigens enter Peyer’s patch?

A

Via M cells which transport macromolecules from the intestinal lumen into the subepithelial tissue via transcytosis.
The antigen is taken up by immature dendritic cells that go into peyer’s patch to initiate T cell response

62
Q

What type of antibody is specific for mucousal immune response?

A

IgA

63
Q

What are the three ways that antigens are trafficked into secondary lymphoid organs?

A
  1. activated dendritic cells
  2. flow of lymph through channels
  3. M cells in mucosa of GI and respiratory tract
64
Q

What is lymphocyte trafficking?

A

lymphocytes constantly circulate from blood to lymph nodes, through lymphatics to the thoracic duct back to the blood stream then back to the lymph nodes, etc.

This occurs because there is a 1 in 10^5 chance that the lymphocyte has the receptor for a specific antigen.

65
Q

How do lymphocytes enter lymph nodes and by what process?

A

The enter by diapedesis through high endothelial venules

66
Q

What happens if a B or T cells meets an antigen in the lymph node?

A

It is activated and retained in the lymph node to initiate adaptive immune response

67
Q

If a lymphocyte is not activated in the lymph node what happens?
What happens if it IS activated?

A

It flows out the efferent lymphatic vessel to move to the next lymph node.
It will differentiate into an effector cell and exit the lymph node via the efferent lymphatic vessel to flow to the thoracic duct to enter the blood stream and then it will home to the site of infection.

68
Q

How are lymphocytes trafficked?

A

The lymphocyte has a homing receptor and the target epithelia has an addressin.

69
Q

What homing receptor on the naive lymphocyte will traffic it toward the HEV of lymph node or the surface of mucousal epithelium?

A

L-selectin

70
Q

What are the two areas that L-selectin can traffic a lymphocyte to?

A
  1. HEV of lymph node

2. mucousa of the gut or respiratory tract

71
Q

What are the two addressins that L-selectin can bind on the HEV of lymph nodes?

A
  1. CD34

2. GlyCAM-1

72
Q

What is the addressin on mucosal epithelium?

A
  1. MAdCAM-1
73
Q

When L-selectin on a lymphocyte binds to MAdCAM, GlyCAM1 or CD34, what happens?

A

The lymphocyte is pulled out of the blood stream and starts rolling on the surface of the HEV (or mucosa)

74
Q

After the lymphocyte starts rolling on the HEV, what is the next step to happen?

A

LFA-1 is activated by the chemokine CCL21 being released from the lymph node to CCR7 (a chemokine receptor on the surface of the lymphocyte)

75
Q

What are chemokines?

A

Small molecules that influence the adhesion and movement of lymphocytes in a tissue

76
Q

When LFA1 is activated by CCL21 binding to CCR7, what will it bind to?

A

LFA1 binds to ICAM-1 on the surface of the HEV which initiates diapedesis.

77
Q

What are the steps necessary for the lymphocyte to enter the HEV of a lymph node?

A
  1. L-selectin binds GlyCAM1 or CD34
  2. The lymphocyte starts rolling along the HEV
  3. CCL21 chemokine released from the lymph node binds to CCR7, a chemokine receptor on the lymphocyte.
  4. LFA1 is activated and binds to ICAM-1
  5. Diapedesis begins allowing the lymphocyte to enter the lymph node.
78
Q

What mediates the change in trafficking pattern from a naive lymphocyte and mature lymphocyte?

A

the homing receptors and chemokine receptors on the mature lymphocyte are different from the naive

79
Q

What are the specific changes in homing receptors from the naive to effector lymphocyte?

A

The effector lymphocyte no longer expresses L-selectin but instead has VLA-4 and increased LFA1 to bind VCAM1 and ICAM1 on peripheral vascular endothelium at the site of infection

80
Q

What addressin does VLA4 bind? On what cells?

A

VCAM1 on peripheral vascular endothelium near the site of infection

81
Q

What homing receptors and addressins allow lymphocytes to enter Peyers patches in the mucosal immune system?

A

CCR7 and L-selectin are what localize the naive lymphocyte to Peyer’s patches.

82
Q

What homing receptors are on effector cells destined to go to the lamina propria of the intestine?

A

L-selectin and CCR7 get replaced by alpha4:beta7 integrin homing receptor and CCR9 chemokine receptor

83
Q

What homing receptor and chemokine receptor localize a lymphocyte to the skin?

A

CLA and CCR4 on the lymphocyte bind to addressin E-selectin and respond to chemokine CCL17

84
Q

What chemokine is expressed by keratinocytes? What receptor does it bind to on the skin-homing effector T cell?

A

CCL27 chemokine binds to the CCR10 receptor

85
Q

What two chemokine receptors and what homing receptor are located on the mature skin-homing effector cell?

A

CCR4 and CCR10

CLA

86
Q

What vascular addressins does L-selectin bind to?

A

GlyCAM1, MAdCAM1, CD34

87
Q

What cell expresses L-selectin?

A

naive lymphocyte being localized to HEV of lymph nodes or Peyer’s patches in gut mucosa

88
Q

What cell expresses alpha4-beta7 integrin?

A
  1. Naive lymphocytes to Peyer’s patches

2. Effector T cells to lamina propria in GI

89
Q

What addressins do a4;b7 integrin bind?

A

MAdCAM1 for peyer’s patches

VCAM1 for lamina propria of GI tract

90
Q

What cell expresses CLA? Where does it get localized to? What does it bind?

A

Skin homing effector cells that bind E-selectin or P-selectin

91
Q

What cells express VLA4 and LFA1?
To what do they bind?
Where do they localize to?

A

effector cells to the vascularture near the site of infection that bind VCAM1 or ICAM1

92
Q

Which two homing receptors on lymphocytes are used in the primary and secondary phase of adhesion?

A

a4b7 integrin and VLA4

93
Q

What does it mean that the innate and adaptive immune system have cross-talk?

A

Innate immunity cells release cytokines that influence B and T cell localization and trafficking to the infection.
B cell antibodies and T cell cytokines then feedback to influence the innate immune systems effector cells.