A&P 300 -- chapter 22 (Lymphatic system) Flashcards

1
Q

what is lymphatic system

A

..

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2
Q

consists of

A

Lymphatic vessels

liquid CT called lymph

Lymphatic organs and tissues
(immune response)

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3
Q

what systems are closely integrated with lymphatic system

A

cardiovascular and gastrointestinal systems

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4
Q

major functions of lymphatic system

A

1) Draining excess interstitial fluid (vessels)

2) Carries out immune responses (organs/nodes/tissues)

3) Transporting dietary lipids absorbed by the gastrointestinal tract to the blood (lacteals/vessels)

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5
Q

1) Draining excess interstitial fluid (vessels)

HOW MUCH (litres)

what other component does lymphatic system return to blood?

A

Approximately 3.5 L per day

Returns lost PLASMA PROTEINS to bloodstream

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6
Q

2) Carries out immune responses (organs/nodes/tissues)

which immune response type?

A

Adaptive immune response (lymphocytes)

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7
Q

3) Transporting dietary lipids absorbed by the gastrointestinal tract to the blood (lacteals/vessels)

INCLUDING WHICH VITAMINS

A

Fat soluble vitamins (A, D, E & K)

ADEK

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8
Q

components of lymphatic system

A

1) Lymph

2) Lymphatic vessels

3) Lymphatic tissues

4) Lymphocytes

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9
Q

what does lymph resemble

A

closely resembles interstitial fluid

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10
Q

lymph vs isf

A

Lymphatic fluid contains lymphocytes, while interstitial fluid contains phagocytes (both are types of white blood cells).

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11
Q

lymph/isf vs plasma

A

Both lymph and interstitial fluid have relatively less protein than plasma. This is because the lymph mainly consists of leaked interstitial fluid. This leak consists of water, cells, smaller proteins but the larger proteins do not leak through.

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12
Q

isf vs plasma

A

Plasma has a much higher protein concentration than interstitial fluid due to the presence of albumin, globulins, and fibrinogen.

Additionally, plasma oxygen levels are significantly higher than those of interstitial fluid, which is largely due to the presence of red blood cells carrying oxygen in the plasma.

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13
Q

lymphatic vessels consist of

A

capillaries, vessels, trunks, ducts

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14
Q

two types of lymphatic tissues

A

Primary and secondary lymphatic tissues

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15
Q

lymphocytes are

A

Cells of the lymphatic system (T-cells and B-cells)

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16
Q

1) lymphatic fluid (lymph)

A

Liquid connective tissue

Formed when excess interstitial fluid enters lymphatic capillaries

Usually clear (exception is in GIT when it appears milky due to absorbed dietary lipids, “lacteal”)

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17
Q

what does lymph contain

A

Contains immune cells

“Lymphatic fluid contains lymphocytes” (?)

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18
Q

2) LYMPHATIC VESSELS ****

A

Often called lymphatics

Carry lymph from peripheral tissues to venous system

Found in close association
with blood vessels

Network begins with lymphatic capillaries (smallest vessels)

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19
Q

lymph vessels: capillaries

A

Differ from blood capillaries:

i) Closed at one end (blind-ended)

ii) Have larger diameters

iii) Have thinner walls —> Basement membrane is incomplete or absent

iv) Typically have a flattened or irregular outline in sectional view

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20
Q

lymph vessels – what is unique about endothelial cells

A

Have overlapping endothelial cells:

i) Region of overlap acts as a one-way valve

ii) Permits entry of fluid and solutes (including proteins)
—-> Also allows entry of viruses, bacteria, cell debris

—-> Prevents return of these materials to the intercellular space

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21
Q

note “one-way flow” of lymphatic vessel wall

(via endothelial cell alignment/structure)

A

“Prevents return of these materials to the intercellular space”

“Pressure changes between the interstitial fluid and lymph cause opening or closing of the endothelial “doors””

I.e.
—> materials can go in, but not back out (?)

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22
Q

note “anchoring filament” of endothelial cells of lymph vessels

A

anchor vessels to surround ISF/cells structures

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23
Q

Lacteals

A

“the lymphatic vessels of the small intestine which absorb digested fats.”

Specialized lymphatic capillaries Located in small intestine

Carry dietary lipids into lymphatic vessels

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24
Q

Chyle

A

Lymph in lacteals appears creamy white because of fat; referred to as CHYLE

Chyle:
“a milky fluid consisting of fat droplets and lymph. It drains from the lacteals of the small intestine into the lymphatic system during digestion.”

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25
Q

where does lymph go from the lymphatic capillaries

A

Lymph from capillaries flow into larger lymphatic vessels that lead toward the body’s trunk

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26
Q

VALVES of lymphatic vessels

A

Vessel bulges at each valve

—> “Series of bulges makes vessel resemble string of pearls”

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27
Q

what feature of lymphatic vessels necessitates presence of valves

A

Low pressure in lymphatic vessels

—> Valves prevent backflow of lymph

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28
Q

what other feature helps movement of lymph in the vessels

A

Contraction of surrounding skeletal muscles aids flow of lymph

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29
Q

superficial vs deep lymphatics

A

..

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30
Q

superficial lymphatics – where?

A

i) Subcutaneous layer deep to skin

ii) Areolar tissues of mucous membranes
(digestive, respiratory, urinary, and reproductive tracts)

iii) Areolar tissues of serous membranes
(pleural, pericardial, and peritoneal cavities)

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31
Q

deep lymphatics – where?

A

Accompany deep arteries and veins supplying skeletal muscles and other organs of the neck, limbs, and trunk, and wall of visceral organs

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32
Q

which direction is lymphatic flow ?

A

Always from periphery to central vasculature

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33
Q

steps in lymphatic flow

A
  1. Begins as interstitial fluid
  2. Enters lymphatic capillaries (forms lymph)
  3. Travels in lymphatic vessels to regional lymph nodes
  4. Enters lymphatic trunks
  5. Drains into either left or right lymphatic ducts
  6. Ducts return lymph to blood stream at subclavian veins
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34
Q

capillaries –> vessels (?) –> trunks –> ducts

A

?

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35
Q

about lymphatic trunks

A

Formed by confluence of many efferent lymph vessels

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36
Q

node meaning of efferent vs afferent in the context of lymphatic vessels

A

Afferent (toward) lymphatic vessels convey unfiltered lymphatic fluid from the body tissues to the lymph nodes,

and efferent (away) lymphatic vessels convey filtered lymphatic fluid from lymph nodes to subsequent lymph nodes or into the venous system.

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37
Q

named lymphatic trunks

A

R/L Lumbar trunks

R/L Intestinal trunks

R/L bronchomediastinal trunks

R/L subclavian trunks

R/L jugular trunks

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38
Q

R/L Lumbar trunks

A

Drain the lower limbs, the wall and viscera of the pelvis, kidneys, adrenal glands and abdominal wall

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39
Q

R/L Intestinal trunks

A

Drain the stomach, intestines, pancreas, spleen, part of the liver

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40
Q

R/L bronchomediastinal trunks

A

Drain the thoracic wall, lung, heart

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41
Q

R/L subclavian trunks

A

Drain upper limbs

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42
Q

R/L jugular trunks

A

Drain head and neck

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43
Q

WHERE DO TRUNKS DRAIN INTO?

A

they drain into

A) THE THORACIC DUCT (Aka Left Lymphatic Duct)

B) RIGHT LYMPHATIC DUCT

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44
Q

which duct drains from most of the body?

A

THORACIC DUCT (LEFT LYMPHATIC DUCT)

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45
Q

1) Thoracic Duct
(Aka left lymphatic duct)

A

Collects lymph from:

—> Entire body inferior to the diaphragm

—> The left side of the body superior to the diaphragm

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46
Q

where does thoracic duct drain?

A

Drains into the left subclavian vein

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47
Q

2) Right Lymphatic Duct

A

Collects lymph from:

—> The right side of the body superior to the diaphragm

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48
Q

where does right lymphatic duct drain?

A

Drains into the right subclavian vein

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49
Q

where does Thoracic (left lymphatic) duct begin?

A

Begins as a dilation called cisterna chyli

@ LEVEL OF L2
(anterior to “)

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50
Q

which trunks does thoracic duct receive lymph from?

A

Right and left lumbar trunks

Right and left intestinal trunks

Left bronchomediastinal trunk

Left subclavian trunk

Left jugular trunk

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51
Q

where exactly does thoracic duct drain lymph into?

A

Drains lymph into venous blood

—> at the junction of the left INTERNAL JUGULAR and left SUBCLAVIAN veins

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52
Q

where does right lymphatic duct receive lymph from?

A

Right bronchiomediastinal trunk

Right subclavian trunk

Right jugular trunk

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53
Q

where does right lymphatic duct drain lymph into

A

Drains lymph into venous blood

—> at the junction of the right internal jugular and right subclavian veins

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54
Q

recap of lymphatic flow

A

Blood capillaries  interstitial space  lymphatic capillaries  lymphatic vessels  lymphatic trunks  lymphatic ducts  subclavian veins

 = —>

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55
Q

recall – mechanisms of lymph movement

recall lymph vessels themselves don’t have much pressure
(no/ very little smooth muscle)

A

1) Pressure in the interstitial space

2) ‘Milking’ action of skeletal muscle contractions

3) Pressure changes during inhalation and exhalation (respiratory pump)

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56
Q

recall respiratory pump

A

“The respiratory pump is a mechanism to pump blood back to the heart using inspiration. It aids blood flow through the veins of the thorax and abdomen.”

“During inhalation, the volume of the thorax increases, largely through the contraction of the diaphragm, which moves downward and compresses the abdominal cavity.”

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57
Q

what happens if lymph flow does not occur?

A

Obstruction or malfunction of lymph flow => lymphedema

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58
Q

lymphedema

A

Caused by blocked lymphatic drainage:

—> Interstitial fluids accumulate

—> Affected area becomes swollen and distended

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59
Q

where is lymphedema most often seen?

A

Most often seen in limbs but can
affect other areas

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60
Q

what permanent changes can take place in the CT with excessive / long-term lymphedema?

A

Swelling may become permanent

—> Connective tissue loses elasticity

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61
Q

what other immune-related issues can take place with stagnant ISF that is not being filtered properly??

A

Stagnant interstitial fluids may
accumulate toxins and pathogens

—> Local immune defenses
overwhelmed

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62
Q

3) LYMPHOID TISSUES ****

A

..

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63
Q

lymphoid tissues can either be …

A

A) Lymphoid nodules

B) Lymphoid organs

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64
Q

a) lymphoid nodules

A

Densely packed lymphocytes in an area of areolar tissue

Nodules may cluster together and form larger masses

No fibrous capsule surrounds the masses

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65
Q

lymphoid nodules vs nodes

A

Lymph nodules form in regions of frequent exposure to microorganisms or foreign materials and contribute to the defense against them.

The nodule differs from a lymph node in that it is much smaller and does not have a well-defined connective-tissue capsule as a boundary.

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66
Q

b) lymphoid organs

A

Separated from surrounding tissues by fibrous connective tissue capsule

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67
Q

another way of classifying lymphoid tissues

A

primary vs secondary lymphatic tissues

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68
Q

two ways of classifying?

A

nodules vs organs

primary vs secondary

(?)

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69
Q

primary lymphatic tissues =

A

Red bone marrow and thymus

—> Sites where lymphocytes are made and/or become immunocompetent (mature)

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70
Q

secondary lymphatic tissues =

A

Lymph nodes, spleen, lymphatic nodules

—> Where lymphocytes are activated and cloned

—> Site of most immune responses

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71
Q

SO LYMPHOID NODULES (vs organs) are always (?)

A

Secondary lymphatic tissues

(?)

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72
Q

about red bone marrow

(Primary lymphatic tissue)
and lymphatic organ
= PRIMARY LYMPHOID ORGAN

A

Pluripotent stem cells in red bone marrow give rise to:

—> Mature immunocompetent B cells

—> Pre-T cells
(Migrate to the thymus where they become immunocompetent T cells)

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73
Q

about thymus

(primary lymphatic tissue,
and lymphoid organ)
= PRIMARY LYMPHOID ORGAN

A

..

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74
Q

thymus size/function

A

The thymus is a lymphoid organ that produces functional T cells

Produces several hormones (thymosins) important in functional T cell development

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75
Q

what happens to thymus with age?

A

Size and secretory abilities decline with age:

—> Size is largest (40 g) before puberty

—> Diminishes in size and becomes increasingly fibrous (involution)

—> By age 50, size can be <12 g

—> Correlated with increased susceptibility to disease

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76
Q

Thymus description

A

Located in the mediastinum

—> Posterior to the sternum
(anterior mediastinum)

—> Covered in a capsule that divides it into left and right lobes

Fibrous partitions (septa) divide the lobes into lobules

—-> Each lobule is about 2 mm in diameter

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77
Q

thymus histology

A

Each lobule consists of:

i) Dark outer cortex

ii) Lighter central medulla

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78
Q

i) Dark outer cortex

A

Contains dividing lymphocytes arranged in clusters surrounded by epithelial reticular cells (ERCs)
—> Regulate T cell development and function

Blood vessels in the cortex are also surrounded by epithelial cells
—> Maintain the BLOOD THYMUS BARRIER

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79
Q

epithelial reticular cells

A

“Besides the role of providing a structural support for lymphocytes, epithelial reticular cells are responsible for the secretion of thymic hormones which promote lymphocyte proliferation and maturation.”

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80
Q

blood thymus barrier

A

“The main purpose of the blood thymus barrier is to prevent cortical T lymphocytes from interacting with foreign macromolecules.”

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81
Q

what are the cells of the DARK OUTER CORTEX
(of lobules of thymus)

A

Pre-T cells from red bone marrow

Dendritic cells
—> Assist T cell maturation

Epithelial cells
—> Help educate pre-T cells in a process known as positive selection, produce thymic hormones thought to aid in T cell maturation

Macrophages
—> Help to clear out the debris of dead and dying cells

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82
Q

recall dendritic cells

A

“A dendritic cell is a type of phagocyte and a type of antigen-presenting cell (APC).”

“A special type of immune cell that is found in tissues, such as the skin, and boosts immune responses by showing antigens on its surface to other cells of the immune system.”

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83
Q

what percentage of developing T cells survive?

A

Only about 2% of the developing T cells survive – the remaining cells die via apoptosis

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84
Q

where do the surviving T cells go?

A

The surviving T cells then enter the inner medulla

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85
Q

how long does it take survivng T cells to go to inner medulla of lobules?

A

Developing T cells leave the cortex after about 3 weeks and enter the medulla

NOTE***
No blood thymus barrier in medulla

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86
Q

what are the cells inside the inner medulla?

A

Mature T cells

Dendritic cells

Epithelial cells
—> Create clusters called thymic (Hassall’s) corpuscles
—> Role unknown – may serve as a site of T cell death in the medulla

Macrophages

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87
Q

So what is the major difference between cells of dark outer cortex and light inner medulla of the LOBULES of the thymus?

A

maturity of T cells

outer cortex = pre-T cells
inner medula = mature “

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88
Q

where do T cells go after leaving the thymus?

A

T cells that leave the thymus via the blood travel to

lymph nodes, spleen and other lymphatic tissue.

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89
Q

Thymic (Hassall’s) Corpuscles

A

“one of the small usually concentrically striated bodies in the thymus body representing remains of the epithelial tissue found in early stages of development.”

“Hassall’s corpuscles (also known as thymic bodies) are structures found in the medulla of the human thymus, formed from eosinophilic type VI thymic epithelial cells arranged concentrically.”

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90
Q

LYMPH NODES

SECONDARY (tissue)
Lymphoid organ

A

Small lymphoid organs surrounded by fibrous connective tissue capsule

Shape resembles a kidney bean

Diameter range 1–25 mm (about 1 in.)

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91
Q

large lymph nodes – aka

A

Large lymph nodes (lymph glands) located in neck, groin, axillae

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92
Q

what is function of lymph nodes

A

Function as filters, removing 99 percent of pathogens from lymph before fluid returns to bloodstream

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93
Q

superficial vs deep

A

Superficial and deep lymph nodes

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94
Q

important lymph nodes (HEAD AND NECK)

A

Submental and submandibular lymph nodes

Anterior and posterior cervical lymph nodes

Supraclavicular lymph nodes

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95
Q

important lymph nodes (ARMS)

A

Axillary lymph nodes

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96
Q

important lymph nodes (LEGS)

A

Inguinal lymph nodes

Femoral lymph nodes

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97
Q

lymph node structure

A

Covered by a capsule of dense CT

Capsular extensions (EXTENDING INWAR) called trabeculae
—> Divide the node into compartments
—> Provide support
—> Provide a route for blood vessels

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98
Q

Stroma of lymph node

A

Composed of the capsule, trabeculae, reticular fibers (inside node) and fibroblasts

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99
Q

parenchyma vs stroma

A

a parenchyma is a structure involved directly in the function of a given organ or organelle.

Stroma, on the other hand, is tissue acting as structural support for these parenchyma.

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100
Q

Parenchyma of lymph node

A

i) Cortex

ii) Medulla

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101
Q

Cortex of lymph node (parenchyma)

A

Outer cortex
—> Consists mostly of B cells

Inner cortex
—> Consists mainly of T cells and dendritic cells that enter a lymph node from other tissue

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102
Q

Medulla of lymph node (parenchyma)

A

Contains B cells, plasma cells and macrophages

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103
Q

lymph nodes general function

A

Type of filter:

Foreign substances are trapped by the reticular fibers within the sinuses

—> Macrophages destroy by phagocytosis

—> Lymphocytes create immune responses

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104
Q

Path of lymph through a lymph node
(afferent vessels/lymphatics)

A

Afferent (afferens, to bring to) lymphatics bring lymph into the node on the opposite side
from the hilum (indentation)

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105
Q

hilum

A

“another term for hilus.”

“an indentation in the surface of a kidney, spleen, or other organ, where blood vessels, ducts, nerve fibers, etc. enter or leave it.”

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106
Q

Path of lymph through a lymph node —> all the steps

A
  1. Afferent (afferens, to bring to) lymphatics bring lymph into the node on the opposite side
    from the hilum (indentation)
  2. Through the subcapsular space
    —> Network of fibers and dendritic cells (involved in immune response)
  3. Into the outer cortex
    —> Contains B cells within germinal centers
  4. Through lymph sinuses in the paracortex
    —> Contains T cells
  5. Into the medullary sinus at the core
    —> Contains B cells and plasma cells
  6. Out of the lymph node in efferent (efferens, to bring out) lymphatics at the hilum and into venous circulation
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107
Q

path of lymph through lymph node – RECAP

A

afferent lymphatics
—> Subcapsular space
—> Outer cortex
—> Paracortex
—> Medullary Sinus
—> efferent lymphatics (via hilum)

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108
Q

Spleen

A

lecondary lymphatic tissue
lymphoid organ

Contains the largest mass of lymphoid tissue in the body

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109
Q

spleen function

A

Performs same function for blood that lymph nodes do for lymph (filter)

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110
Q

spleen function..

A

Removes abnormal red blood cells and other blood components by phagocytosis

Stores iron recycled from red blood cells

Initiates immune response by B cells and T cells in response to antigens in circulating blood

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111
Q

liver vs spleen RBC breakdown (???)

A

““The liver, not the spleen, is the major on-demand site of red blood cell elimination and iron recycling,” according to Filip Swirski, PhD, of the Massachusetts General Hospital Center for Systems Biology, and his colleagues.”

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112
Q

spleen diaphragmatic surface

A

Smooth and convex

Conforms to the shape of the diaphragm and the body wall

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113
Q

spleen gross anatomy

A

Lies along the curving lateral border of the stomach on the left side

Attached to lateral border of the stomach by the gastrosplenic ligament (broad band of mesentery)

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114
Q

other gross anatomy facts about spleen

A

About 12 cm (5 in.) long and weighs ~160 g (5.6 oz.)

Deep red when dissected
(Due to large amounts of blood it contains)

Soft texture
–> Shape molded by structures around it

Visceral (medial) surface has two indentations:
—> Gastric area (near stomach)
—> Renal area (near kidney)

Hilum (indentation where blood and lymphatic vessels communicate)

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115
Q

spleen structure

A

Outer capsule of collagen and elastic fibers

—> Fairly easily ruptured by impact
—> Spleen tissue too fragile to repair surgically
—> Damage can necessitate removal (splenectomy)

Trabeculae
Fibrous partitions that radiate (INWARD) from the capsule
(similar to nodes)

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116
Q

parenchyma of spleen

A

Parenchyma is made up of pulp:
Cellular components within the capsule

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117
Q

two types of pulp within spleen (within capsule)

A

RED pulp

WHITE pulp

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118
Q

Red pulp

A

Consists of blood filled venous sinuses and cords of splenic tissue called splenic (Billroth’s) cords

—> Consist of many red blood cells and macrophages

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119
Q

Billroth’s cords

A

“WThe cords of Billroth (also known as splenic cords or red pulp cords) are found in the red pulp of the spleen between the sinusoids, consisting of fibrils and connective tissue cells with a large population of monocytes and macrophages.”

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120
Q

White pulp

A

Lymphatic tissue: mostly lymphocytes and macrophages

Arranged around branches of the splenic artery called central arteries

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121
Q

function of red pulp

A
  1. Removal by macrophages of ruptured, worn out or defective blood cells and platelets
  2. Storage of platelets (up to 1/3rd of body’s supply)

3.Production of blood cells (hematopoiesis) during fetal life

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122
Q

function of white pulp

A

Splenic arteries carry blood to central arteries of white pulp

—> B cells and T cells carry out immune functions in white pulp

—> Spleen acts like an ‘immune filter’ of the blood

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123
Q

ruptured spleen

A

Spleen tears easily and is difficult to repair surgically

Treatment is a splenectomy: removal of spleen

—> Without a spleen, person has increased risk for bacterial infection

—> Liver and bone marrow can take over some functions

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124
Q

Lymphoid nodules
(secondary tissue)

A

Lymphoid nodules are egg-shaped masses of lymphatic tissue

Differ from lymph nodes because they are NOT surrounded by a capsule (NODULES, not organs)

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125
Q

where are lymphoid nodules

A

Scattered throughout the lamina propria (CT) of mucous membranes lining the gastrointestinal, urinary and reproductive tracts and respiratory airways

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126
Q

why? (lymphoid nodules)

A

“Lymph nodules form in regions of frequent exposure to microorganisms or foreign materials and contribute to the defense against them.”

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127
Q

(Lymphoid nodule locations)

Mucosa-associated lymphoid tissue (MALT)

A

Mucosa-associated lymphoid tissue (MALT)

—> Protect epithelia of digestive, respiratory, urinary, and reproductive tracts from pathogens and toxins

Examples of MALT
E.g.
—> GALT (gut-associated lymphoid tissue)
—> Peyer’s Patches (small intestine)
—> Tonsils

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128
Q

note tonsils

A

Large lymphoid nodules in the walls of the pharynx

—> Pharyngeal tonsil (or the adenoid)
Located on posterior superior wall of the nasopharynx

—> Palatine tonsils (left and right)
Located at posterior, inferior margin of the oral cavity along the boundary of the pharynx

—> Lingual tonsils
Pair of tonsils located deep to the epithelium covering the base of the tongue

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129
Q

Tonsillitis

A

inflammation of tonsils

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130
Q

clinical disorders (related to lymphatic nodules)

A

MALT defends exposed epithelia in multiple tracts exposed to the exterior environment

Infection and/or inflammation of MALT components can cause variety of clinical disorders
*
E.g.
—> Tonsillitis (inflammation of the tonsils)
—> Appendicitis (inflammation of the lymphoid tissue in the appendix)

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131
Q

lecture 2

A

..

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132
Q

immunity

A

The ability to fight infection, illness, and disease

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133
Q

two mechanisms – work independently and together

A

​1. Innate (nonspecific) immunity

  1. Adaptive (specific) immunity
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134
Q

Innate (nonspecific) immunity

A

Present at birth (innate)

Does not distinguish one type of threat from another (non-specific)

Response is the same regardless of type of invading agent

Prevents the approach, denies the entry, limits the spread of microbes or other environmental hazards

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135
Q

Adaptive (specific) immunity (Acquired immunity)

A

Utilizes adaptive defenses

Develops over time (acquired)

Protects against particular threats (specific)

Depends on the activities of specific lymphocytes

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136
Q

1st line defense (part of innate IS)

A

skin

mucous membranes

secretions of skin and MM

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137
Q

2nd line defense

A

phagocytes

antimicrobial proteins (other than complement & IFNs)

inflammation

fever

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138
Q

3rd line defense

A

lymphocytes

antibodies

memory cells

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139
Q

cells of innate (MONONUCLEAR PHAGOCYTES)

A

macrophage (APC)
&monocyte
dendritic cells (APC)

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140
Q

macrophage vs monocyte (recall)

A

Macrophages are monocytes that have migrated from the bloodstream into any tissue in the body.

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141
Q

cells of innate IS (granulocytes)

A

basophils
eosinophils
neutrophils

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142
Q

cells of innate IS (lymphocyte?)

A

NK cells

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143
Q

innate IS other

A

mast cells?

complement protein system

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144
Q

innate IS

A

macrophage (APC)
&monocyte
dendritic cells (APC)

basophils
eosinophils
neutrophils

mast cells?

NK cells

complement protein system

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145
Q

component of innate IS

A

Physical barriers and chemical barriers

Phagocytes

Immune surveillance

Interferons

Complement

Inflammation

Fever

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146
Q

Physical barriers and chemical barriers

A

skin and mucous membranes

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147
Q

Phagocytes

A

cells that engulf pathogens and cell debris

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148
Q

Immune surveillance

A

destruction of abnormal cells by natural killer (NK) cells

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149
Q

Interferons

A

chemicals against viral infections

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150
Q

Complement

A

circulating proteins that assist antibodies

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151
Q

Inflammation

A

localized tissue-level response to limit spread of infection

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152
Q

Fever

A

elevation of body temperature

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153
Q

interferons??? PROTEINS

A

A natural substance that helps the body’s immune system fight infection and other diseases, such as cancer.

Interferons are made in the body by white blood cells and other cells

“Interferons are a group of signaling proteins made and released by host cells in response to the presence of several viruses.”

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154
Q

interferon types

A

There are three types of interferons (IFN), alpha, beta and gamma.

IFN-alpha is produced in the leukocytes infected with virus,

while IFN-beta is from fibroblasts infected with virus.

IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen
or non-sensitized lymphocytes with mitogens.

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155
Q

mitogen

A

a substance that induces or stimulates mitosis.

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156
Q

1st line of defense (PHYSICAL)… 1)

A

1) Integumentary system:

Stratified squamous epithelium

Secretions

Hair

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157
Q

Stratified squamous epithelium

A

Multiple layers of epithelial cells with keratin that are connected with desmosomes

158
Q

Secretions

NOTE LYSOZYMES

A

From sebaceous and sweat glands wash away microorganisms and chemical agents

May also contain bactericidal chemicals, destructive enzymes (lysozymes), and antibodies

159
Q

Hair

A

Provides protection from physical abrasion

Prevents hazardous materials or insects from contacting skin

160
Q

1st line of defense (PHYSICAL)… 2)

A

2) Mucous Membranes (Line body cavities):

Mucous

Hairs

Cilia

161
Q

Mucous

A

A viscous fluid that lubricates, moistens and traps microbes and foreign substances

162
Q

Hairs

A

Trap and filter microbes, dust and pollutants

Found in the mucous membrane of nose

Initiate sneezing, coughing and vomiting reflex

163
Q

Cilia

A

Waving action helps propel inhaled dust and microbes towards the throat

Found in the mucous membrane of upper and lower respiratory tract

164
Q

1st line of defense consists of

A

PHYSICAL barriers

and

CHEMICAL barriers

165
Q

first line of defense (CHEMICAL) … 1)

A

Lysozyme

Lacrimal apparatus

Saliva

Flow of urine, vaginal secretions, defecation and vomiting

Sebum

Perspiration

Vaginal secretions

166
Q

Lysozyme

A

Enzyme capable of breaking down the cell walls of certain bacteria

167
Q

where lysozymes found

A

Found in

tears,
saliva,
perspiration,
nasal secretions,

tissue fluids

168
Q

Lacrimal apparatus

A

Found in the eyes

Manufactures and drains away tears in response to irritants

169
Q

Saliva

A

Produced by salivary glands in the mouth

Washes microbes from teeth and mucous membranes of mouth

170
Q

Flow of urine, vaginal secretions, defecation and vomiting

A

Helps move microbes out of the body

171
Q

Sebum

A

From sebaceous (oil) glands

172
Q

Gastric juices

A

Very low pH inhospitable to most organisms

173
Q

Vaginal secretions

A

Mechanical (trapping and removal),

antimicrobial proteins,

antibodies,

immune cells

174
Q

about CHEMICAL BARRIERS – what do they all (or most?) have in common?

(physical/chemical feature that discourages bacterial growth)

A

All are ACIDIC which helps to discourage bacterial growth

175
Q

SECOND LINE OF DEFENSE: PHAGOCYTES

A

Phagocytes are specialized cells that perform phagocytosis

Engulf and destroy foreign substance, pathogens, and cellular debris

First line of cellular defense against pathogenic invasion

176
Q

which cells do phagocytes outpace in quickness to detect pathogens?

A

Can attack and remove microorganisms even before lymphocytes detect their presence

177
Q

how can different phagocytes differ?

A

Different types target different threats

All function in the same basic way

178
Q

3 major types of phagocytes

A

Monocytes/macrophages
Neutrophils
Dendritic cells

also?
eosinophils?
basophils?

179
Q

basophils and eosinophils as phagocytes –

a comparison to 3 major phagocytes

A

Among the White blood cells (WBCs) four cells have the phagocytic ability. The neutrophils, monocytes, eosionophils and basophils.

The basophils and the eosinophils have much less phagocytic ability when compared to the phagocytic ability of neutrophils and monocytes.

“Eosinophils and basophils are broadly referred to as non-professional phagocytes, in that they can use phagocytosis, but don’t primarily”

“Basophils, a type of white blood cell, can be phagocytic, but this is not their main function.”

180
Q

about neutrophils

A

Neutrophils (in bloodstream and tissues)

Abundant, mobile, fast-acting

Phagocytize cellular debris or bacteria

181
Q

Monocyte–macrophage system

A

Macrophages (derived from monocytes)

Fixed macrophages (scattered among connective tissues; immobile within those tissues)

Free macrophages (travel throughout body)

182
Q

what can macrophages function as

A

Function as antigen presenting cells (APCs)

183
Q

3 main APC cell types

A

dendritic cells

macrophages

B cells

184
Q

Dendritic cells

A

foundin tissue that has contact with the outside environment (ie. resp. mucosa, skin, GI tract)

Function as antigen presenting cells (APCs)

185
Q

Eosinophils (less abundant than neutrophils)

— NOT ONE OF THE 3 MAJOR PHAGOCYTE TYPES

A

Phagocytize foreign compounds and antibody-coated pathogens

186
Q

5 steps of phagocytosis

A
  1. Chemotaxis
  2. Adherence
  3. Ingestion
  4. Digestion
  5. Killing
187
Q

chemotaxis

A

movement of the phagocyte due to the attraction of chemicals

“Chemotaxis is defined as the unidirectional movement of a cell in response to a chemical gradient in the direction from a low to a high … “

“The ability of somatic cells, bacteria, other single-celled organisms and multicellular organisms to move in a particular direction in response to a chemical stimulus is known as chemotaxis”

“the directed movement of cells in a gradient of chemoattractant—allows leukocytes to seek out sites of inflammation and infection”

188
Q
  1. Adherence
A

attachment of the phagocyte to the target cell

189
Q
  1. Ingestion
A

pseudopods –“false feet” are formed and engulf the target cell forming a phagosome

190
Q
  1. Digestion
A

lysozymes, proteasomes, &/or peroxisomes bind with the phagosome

191
Q

proteasome

A

a protein complex in cells containing proteases; it breaks down proteins that have been tagged by ubiquitin.

192
Q

peroxisome

A

“Peroxisomes are small, membrane-enclosed organelles (Figure 10.24) that contain enzymes involved in a variety of metabolic reactions, including several aspects of energy metabolism.”

193
Q
  1. Killing
A

death of target cell (or pathogen??) & release of debris

194
Q

SECOND LINE OF DEFENSE: IMMUNE SURVEILLANCE

A

Constant monitoring of normal tissues (immune surveillance) by natural killer (NK) cells

Normal cells are generally ignored by immune system

195
Q

what do cancer cells often contain that is detected by IMMUNE SURVEILLANCE of NK cells

A

Cancer cells often contain tumor-specific antigens

NK cells recognize as abnormal and destroy

196
Q

Tumor-specific antigens (TSAs)

A

A protein or other molecule that is found only on cancer cells and not on normal cells. Tumor-specific antigens can help the body make an immune response

197
Q

what can NK cells (immune surveillance cells) recognize?

A

NK cells recognize

bacteria,
foreign cells,
virus-infected cells,
cancer cells

198
Q

Steps of NK recognition and destruction

A
  1. Presence of unusual plasma membrane activates NK cell
  2. Golgi apparatus moves within NK cell near target cell
  3. Perforins are released from NK cell and arrive at target cell
  4. Perforins create pores in target cell membrane
199
Q

what do NK cells do

A

NK cell adheres to target cell

200
Q

what does Golgi apparatus in NK cells produce

A

Produces many secretory vesicles containing perforins

201
Q

what happens to target cell after pores are created in its plasma membranes by perforins?

A

Target cell can no longer maintain its internal environment and disintegrates

202
Q

SECOND LINE OF DEFENSE: ANTIMICROBIAL SUBSTANCES

A

Interferons (proteins)

Complement system

Iron-binding proteins

Antimicrobial proteins

203
Q

1) Interferons (IFNs)

A

Small proteins released by activated lymphocytes, macrophages, and virus-infected tissues

204
Q

WHAT CAN RELEASE IFNs

A

activated lymphocytes,

macrophages,

virus-infected tissues

205
Q

what can IFNs do when released?

A

Trigger production of ANTIVIRAL PROTEINS (?) in cytoplasm of nearby cells

—> (Do not prevent entry of viruses but interfere with viral replication)

Also stimulate activities of macrophages and NK cells

206
Q

IFNs are an example of a broader category of proteins called

A

Example of a CYTOKINE

CYTOKINES

207
Q

cytokine define

A

any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells.

“Cytokines are a broad and loose category of small proteins important in cell signaling.”

208
Q

cytokine – class notes

A

Cytokines are chemicals released by cells to coordinate local activities

209
Q

2) Complement system

why called complement system

A

Name refers to the fact that the system complements the action of antibodies

210
Q

how many proteins in complement system

A

Over 30 special proteins form this system

211
Q

what do proteins do – how do they interact w/ each other

A

Proteins interact with one another in chain reactions or cascades (similar to blood clotting system)

212
Q

what are three possible pathways of complement system

A

​Classical pathway

​Lectin pathway

​Alternative pathway

213
Q

CLASSICAL PATHWAY

A

Most rapid and effective complement activation method

Complement proteins attach to antibody molecules already bound to a pathogen

Attached protein activates and initiates cascade to activate and attach other complement proteins

Membrane attack complex (MAC)—destroys integrity of target cell

214
Q

LECTIN PATHWAY

A

Activated by mannose-binding lectin (MBL) protein

—> Binds to carbohydrates on bacterial surfaces

Activates an inflammatory response

Also enhances phagocytosis (opsonization)

215
Q

mannose define

A

a sugar of the hexose class which occurs as a component of many natural polysaccharides.

216
Q

mannose binding lectin define

A

Mannose-binding lectin (MBL) is a pattern recognition molecule of the innate immune system.

It belongs to the collectin family of proteins in which lectin (carbohydrate-recognition) domains are found in association with collagenous structures.

217
Q

ALTERNATIVE PATHWAY

A

Important defense against bacteria, some parasites, and virus-infected cells

—> Interaction triggered by exposure to foreign substances

End result is attachment of activated complement protein

effect?
enhances phagocytosis?
& induces inflammation?

218
Q

properdin define

A

a protein present in the blood, involved in the body’s response to certain kinds of infection.

219
Q

properdin etymology

A

properdin etymology:
pro = before
perdere = destroy

220
Q

ALL THREE PATHWAYS =

A

Regardless of the pathway, the effects are the same

The split of inactive C3 complement protein into C3a and C3b leads to:

221
Q

what are the effects of complement protein system

A
  1. Pore formation and cell lysis (MAC)
  2. Enhanced phagocytosis
  3. Histamine release
222
Q
  1. Pore formation and cell lysis (MAC)
A

Pore formed in cell membrane by many complement proteins

Destroys integrity of target cell

223
Q
  1. Enhanced phagocytosis
A

Attracts phagocytes and makes target cells easier to engulf

Process called OPSONIZATION

224
Q
  1. Histamine release
A

By mast cells and basophils

Increases inflammation and blood flow to region

225
Q

opsonization

A

Opsonization is an immune process which uses opsonins to tag foreign pathogens for elimination by phagocytes.

Without an opsonin, such as an antibody, the negatively-charged cell walls of the pathogen and phagocyte repel each other.

226
Q

3) IRON-BINDING PROTEINS

A

Inhibit the growth of certain bacteria by reducing the amount of available iron

i.e. transferrin, lactoferrin, ferritin

227
Q

3) ANTIMICROBIAL PROTEINS

A

Short peptides that have a broad spectrum of antimicrobial activity

—> Includes killing and assisting other cells in targeting and neutralizing microbes

228
Q

antimicrobial proteins E.g.

A

dermicidin, defensins, catherlicidins, thrombocidin

229
Q

SECOND LINE OF DEFENSE: INFLAMMATION

A

Localized tissue response to injury, producing the cardinal signs and symptoms of inflammation:

Local redness
Swelling
Heat
Pain
Sometimes lost function

230
Q

SHARP

A

Sis for swelling caused by an accumulation of fluids

His for heat which is also due to more blood rushed to the affected area

Ais for altered function or loss of function that results in severe inflammation

Ris for redness because more blood is rushed to the affected area

Pis for pain due to the release of certain chemicals

231
Q

inflammation caused by

A

Caused by various stimuli that kill cells, damage connective tissue fibers, or injure tissue

Cause a change in chemical composition of the interstitial fluid

232
Q

(inflammation) what do damaged cells release

A

Damaged cells release prostaglandins, proteins, and potassium ions

Foreign proteins or pathogens may have been introduced

—> trigger complex inflammation response

233
Q

THREE STAGES OF INFLAMMATION RESPONSE

A
  1. Vasodilation and increased permeability of blood vessels
  2. Emigration of phagocytes from the blood to interstitial fluid
  3. Tissue repair
234
Q
  1. Vasodilation and increased permeability of blood vessels
A

VIA WHICH SUBSTANCES?

235
Q

vasodilation / permeability of BV

VIA WHICH SUBSTANCES?

A

KININS

HISTAMINE

PROSTAGLANDINS

LEUKOTRINES (LTs)

COMPLEMENT

236
Q

histamine – which cells release?

A

mast cells, basophils and platelets

237
Q

histamine – which cells STIMULATE its release

A

Neutrophils and MO (monocytes?)

238
Q

a) histamine

A

Histamine:

—> Released by mast cells, basophils and platelets

—> Neutrophils and MO (monocytes?) stimulate its release

—> Causes vasodilation and increased permeability

239
Q

b) KININS

A

Polypetides (e.g. bradykinin)

Induce vasodilation and increased permeability

Serve as chemotactic agents for phagocytes

240
Q

bradykinin define

A

“a compound released in the blood in some circumstances that causes contraction of smooth muscle and dilation of blood vessels. It is a peptide comprising nine amino-acid residues.”

241
Q

histamine vs kinins?

A

The action of the kinins on the microvasculature is similar to that of histamine, that is, potent vasodilatation. =

Kinins are rapidly destroyed by tissue proteases, suggesting their importance is limited to the early inflammatory stage of wound healing.

242
Q

histamine quicker than kinins (??)

A

..

243
Q

c) Prostaglandins (PGs)

A

Lipids released by damaged cells

Intensify the effects of histamine and kinins

Stimulate emigration of phagocytes (chemotaxis?)

244
Q

d) Leukotrienes (LTs)

A

Produced by basophils and mast cells

Cause increased permeability

Adherence of phagocytes to pathogens

Chemotactic agents that attract phagocytes

245
Q

e) Complement

A

Stimulate histamine release, attract neutrophils by chemotaxis, promote phagocytosis, same can destroy bacteria

246
Q

what cells release LTs

A

basophils and mast cells

247
Q

what do basophils and mast cells release

A

LTs

Histamine
(also via platelets)

248
Q

what stimules HISTAMINE release

A

Neutrophils
monocytes (?)

complement proteins

249
Q

which of 5 inflammation substances are CHEMOTACTIC

all?

A

complement

LTs

PGs

Kinins

histamine (?)

250
Q

which one enhances effect of histamine/kinins?

A

PGs

251
Q

INFLAMMATION

  1. EMIGRATION OF PHAGOCYTES
A

A process, dependent on chemotaxis, in which phagocytes migrate to the area of tissue damage and squeeze through holes in the endothelium of the blood vessel wall

252
Q

NOTE THAT SAME SUBSTANCES THAT INCREASE BV PERMEABILITY/DILATION

ALSO ARE CHEMOTACIC (trigger emigration of phagocytes)

A

..

253
Q

leukocytosis

A

Increased production and release of WBCs in red bone marrow

“Leukocytosis is a high white blood cell count. It can occur when you have infection or inflammation in your body.”

254
Q

INFLAMMATION

  1. TISSUE REPAIR
A

Once the inflammation & edema subsides, fibroblasts bring in ground substance that contains protein aggregates to help with tissue repair

New collagen, elastin, & fibrin are brought in, and new blood vessels and neuronal synapses are formed

255
Q

**SECOND LINE OF DEFENSE: FEVER

A

Body temperature > 37.8ºC (100ºF)
—> 38 C
—> either 100.0 F (37.8 C) or 100.4 F (38 C).

37ºC is normal body temperature
—> (36.4 C) to 99.6 F (37.6 C)
—> between 97 F (36.1 C) and 99 F (37.2 C)

256
Q

low vs moderate vs high fever

A

low = to 38.0 C

moderate = 38.1 to 39.0

high = 39.1 to 41 C

257
Q

Pyrogens

A

Circulating fever-inducing proteins

Reset temperature thermostat in hypothalamus

—> Raise body temperature

258
Q

what is function of fever

A

Can be beneficial within limits

—> May inhibit some viruses and bacteria

—> Increases metabolic rate, which may accelerate tissue defenses and repair process

259
Q

SUMMARY OF INNATE IMMUNITY

A

Physical barriers and chemical barriers

—> Prevent approach of pathogens and deny them access

Phagocytes
—> Remove debris and pathogens

Immune surveillance
—> Destroys abnormal cells

Interferons
—> Increase resistance of cells to viral infections
—> Slow the spread of disease

Complement system
—> Attacks and breaks down surfaces of cells, bacteria, and viruses
—> Attracts phagocytes
—> Stimulates inflammation

Fever
—> Mobilizes defenses
—> Accelerates repairs
—> Inhibits pathogens

260
Q

adaptive (specific) immunity

A

Not present at birth

Specific response to a particular antigen

Exposure to antigen (natural or vaccine)
—> Active immunity

Receiving antibodies
—> Passive immunity

261
Q

passive immunity

A

receiving antibodies (injection?)

262
Q

adaptive immunity coordinated and produced by

A

Coordinated and produced by T cells and B cells

263
Q

acitve immunity

A

1) Naturally acquired

2) artificially induced

264
Q

naturally acquired active immunity

A

Develops after natural exposure to antigens in the environment

Example: contracting the measles gives immunity against future infection by that specific pathogen

265
Q

artificially induced active immunity

A

Develops after administration of an antigen

Example: vaccination (immunization)

266
Q

vaccines

A

Vaccines contain dead or inactive pathogens, antigens derived from those pathogens, or simulated antigens

Stimulate immune response to produce antibodies against that specific pathogen

267
Q

passive immunity tpes

A

1) Naturally acquired

2) Artificially induced

268
Q

naturally acquired passive immunity

A

Example: transfer of maternal antibodies across placenta or breast milk

269
Q

artificially induced passive immunity

A

Example: administration of antibodies to a patient

270
Q

properties of adaptive immunity

A

1) ​Specificity

2) ​Versatility

3) Memory

4) ​Tolerance

271
Q

1) ​Specificity

A

T cells and B cells have receptors for only one specific antigen

Responses of activated T cell or B cell are also specific (do not affect any other antigens)

272
Q

2) ​Versatility

A

Millions of lymphocytes, each sensitive to a different antigen

When activated, a lymphocyte divides

Produces more lymphocytes with same specificity

All cells produced by the division of an activated lymphocyte constitute a clone

273
Q

3) Memory

A

Activated lymphocytes produce two groups of cells

a) Groups that attack invaders immediately

b) Group that remains inactive unless exposed to the same antigen later

—> These memory cells “remember” antigens, making future attacks faster, stronger, and longer lasting

274
Q

4) ​Tolerance

A

Immune response ignores “self” but targets abnormal and foreign “nonself” cells and toxins

Can develop over time in response to chronic exposure to an antigen

275
Q

Types of Adaptive Immune Cells

A

The adaptive immune response is produced and coordinated by lymphocytes (T cells and B cells)

276
Q

Types of B cells:

A

Plasma cells: create antibodies

Memory B cells

277
Q

Types of T cells:

A

a) Cytotoxic (suppressor) T cells (CD8+ cells)
—> Kill infected cells

b) Helper T cells (CD4+ cells)
—> Help activate immune cells (T and B)

c) Regulatory T cells

d) Memory T cells

278
Q

CD marker define

A

CD is an abbreviation “for cluster of differentiation”. CD molecules are cell surface markers which are very useful for the identification and characterization of leukocytes and the different subpopulations of leukocytes.

The cluster of differentiation (also known as cluster of designation or classification determinant and often abbreviated as CD) is a protocol used for the identification and investigation of cell surface molecules providing targets for immunophenotyping of cells

279
Q

T Cell CD markers

A

Membrane proteins
involved in antigen
recognition

CD stands for “cluster of differentiation”

Two classes associated with T cell:
CD4 & CD8

280
Q

Two classes associated with T cell:

A

​CD8 markers
(on CD8 T cells: cytotoxic and regulatory T cells)

​CD4 markers
(on CD4 T cells: helper T cells)

281
Q

Overview of the immune response

A

Antigens either infect cells or are “processed” by phagocytes

Antigens or antigenic fragments are then displayed on the plasma membrane

Called antigenic presentation
—> (PHAGOCYTE, DENDRITIC CELLS, B CELLS)

Triggers an immune response

282
Q

presentation of specific antigens stimulates

A

a) Cell-mediated immunity (T cells)

b) Antibody-mediated immunity (B cells)

2 types both triggered by antigens

Both of these types of responses are aided by helper T cells

283
Q

a) Cell-mediated immunity

A

Cytotoxic T cells directly attack cells

284
Q

b) Antibody-mediated immunity

A

Activated B cells transform into plasma cells, which synthesize and secrete specific proteins called antibodies (Abs) / immunoglobulins (Igs)

Antibodies bind to and inactivate specific extracellular antigens

285
Q

which cell type aids in both Cell-mediated immunity & antibody-mediated immunity

A

Both of these types of responses are aided by helper T cells

286
Q

Cell-mediated immunity is effective against:

A

Intracellular pathogens: viruses, bacteria, fungi

Some cancer (tumour) cells

Foreign tissue transplants

287
Q

Antibody-mediated immunity is effective against:

A

Extracellular pathogens

—> Viruses, bacteria, fungi that are in extracellular fluids

288
Q

in other words, T cells…

A

attack infected cells

289
Q

in other words, B cells…

A

attack invaders outside cells (via antibodies they release)

290
Q

Antigens

A

any substance that causes the body to make an immune response against that substance

291
Q

antigen =

A

antibody generator

292
Q

antigen may be

A

Bacteria or virus

Chemicals or toxins

Pollen

Self-protein (autoimmune)

Abnormal cellular protein (E.g. cancer cells)

293
Q

small portion of the antigen that interacts with immune receptors

A

The small portion of the antigen that interacts with immune receptors on T cells or antibodies is called an EPITOPE

294
Q

epitope

A

upon + place

“the part of an antigen molecule to which an antibody attaches itself.”

“An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope.”

295
Q

Antigens have 2 important characteristics:

A

Antigenicity

Immunogenicity

296
Q

Antigenicity

A

the ability of antigen to combine specifically with immune cells or antibody

297
Q

Immunogenicity

A

The ability to provoke an immune response by stimulating the production of specific antibodies, the proliferation of specific T cells, or both

298
Q

Hapten

A

a small molecule which, when combined with a larger carrier such as a protein, can elicit the production of antibodies which bind specifically to it (in the free or combined state).

299
Q

Haptens

A

Have antigenicity but lack immunogenicity

Can stimulate an immune response only if it is attached to a larger carrier molecule

Example: poison ivy (reacts with skin proteins to generate immune response)

300
Q

epitope aka

A

antigenic determinant site (?)

301
Q

bacterium can contain millions of…

A

A bacterium can contain millions of antigenic determinant sites

Can become carpeted with antibodies

302
Q

which routes do antigens follow when they get past innate immune system?

A

Antigens that get past our innate defenses generally follow one of three routes into lymphatic tissue:

a) Via blood stream to the spleen

b) Via skin through lymphatic vessels to lymph nodes

c) Via mucous membranes to MALT

303
Q

Clonal Selection

A

The process by which lymphocytes proliferate (divide) and differentiate (form more highly specialized cells) in response to a specific antigen

304
Q

result of clonal selection

A

Formation of a population of identical cells, called clones, that can recognize the same specific antigen as the original lymphocyte

305
Q

where does clonal selection occur?

A

Occurs in secondary lymphatic organs

306
Q

secondary lymphatic organs

A

lymph nodes, spleen, tonsils (MALT?), …

307
Q

Lymphocytes that undergo clonal selection give rise to 2 major cell types:

A

a) Effector cells

b) Memory cells

308
Q

a) effector cells

A

Carry out immune responses that ultimately result in the destruction or inactivation of the antigen

Die after immune response is completed

E.g.
active helper and cytotoxic T cells, plasma cells

309
Q

b) memory cells

A

Do not actively participate in the initial immune response to the antigen

Do not die at the end of an immune response

Result in a quicker response to any subsequent exposures

E.g.
memory helper T cells, memory cytotoxic T cells, memory B Cells

where?
lymph nodes, MALT, spleen (?)

310
Q

Major histocompatibility complex (MHC) proteins

A

aka Human Leukocyte Antigens (HLA)

Genetically determined membrane glycoproteins

MHC proteins display antigens that were processed inside the cell

Placement of the antigen-glycoprotein combination on the plasma membrane is called antigen presentation

311
Q

what is the function of antigen presentation

A

Capable of activating T cells

“the functioning of both cytotoxic and helper T cells is dependent on APCs”

312
Q

Two classes of MHC proteins

A

a)​ Class I MHC proteins (MHC I)

b) Class II MHC proteins (MHC II)

313
Q

a)​ Class I MHC proteins (MHC I)

A

Present in all nucleated cells

Triggered by viral or bacterial infection of a body cell

MHC I display intracellular or endogenous antigens

314
Q

b) Class II MHC proteins (MHC II)

A

Present only in antigen-presenting cells (APCs)
—> Examples: monocyte–macrophages, dendritic cells, B cells

Appear only when the cell is processing antigens

MHC II display extracellular or exogenous antigens

315
Q

recall, what else is related to intracellular/extracellular antigens?

A

cell-mediated immunity is against INTRACELLULAR PATHOGENS (via T cells)

antibody-mediated immunity is against EXTRACELLULAR PATHOGENS (via B cells)

316
Q

antigen-MHC complex

A

Antigenic proteins are broken down into peptide fragments and attached to either an MHC I or MHC II protein depending on the cell

Antigen–MHC complex is inserted into the plasma membrane of the cell (antigen presentation)

317
Q

peptide fragment source vs response

A

If peptide fragment comes from:

—> a self protein, then lymphocytes ignore it

—> a foreign protein, then lymphocyte initiates immune response

318
Q

Processing Extracellular or Exogenous Antigens

A

Extracellular or exogenous antigens exist outside of cells

Examples:
bacteria and bacterial toxins
viruses
parasites
inhaled pollen and dust

319
Q

APCs vs exogenous antigens

A

Antigen-presenting cells (APCs)

–> Process and present exogenous antigens

–> Include: dendritic cells, macrophages and B cells

–> Located in areas where antigens are likely to penetrate innate defenses

–> After processing and presentation of antigen they migrate from tissues via lymphatic vessels to lymph nodes

320
Q

how are extracellular antigens displayed

A

EXTRACELLULAR OR EXOGENOUS ANTIGENS ARE DISPLAYED ON MHCII PROTEINS

321
Q

what happens after exogenous antigen is displayed by apc

A

APCs process antigens and present them to T cells. Antigen presentation stimulates immature T cells to become either mature “cytotoxic” CD8+ cells or mature “helper” CD4+ cells.

“Lymph tissue and bloodstream: Fully mature T-cells travel to tissue and organs in your lymph system, like your spleen, tonsils and lymph nodes. They may also circulate in your bloodstream.”

“…. The dendritic cell is then a fully mature professional APC. It moves from the tissue to lymph nodes, where it encounters and activates T cells.”

322
Q

Processing Intracellular or Endogenous Antigens

A

Intracellular or endogenous antigens exist inside cells

Examples:
–> viruses
–> bacterial toxins
–> abnormal protein synthesis by a cancerous cell

INTRACELLULAR OR ENDOGENOUS ANTIGENS ARE DISPLAYED ON MHCI PROTEINS

323
Q

Cytokines

A

Small protein hormones that stimulate or inhibit many normal cell functions, such as cell growth and differentiation.

Secreted by lymphocytes, APCs, fibroblasts, endothelial cells, monocytes, and more

Examples include;
Interleukins (ILNs), Tumor Necrosis Factor (TNFs), Granzymes, Perforin, Interferons (IFNs)

324
Q

cytokine define

A

any of a number of substances, such as interferon, interleukin, and growth factors, which are secreted by certain cells of the immune system and have an effect on other cells.

325
Q

interleukin define

A

any of a class of glycoproteins produced by leukocytes for regulating immune responses.

326
Q

interferon define

A

a protein released by animal cells, usually in response to the entry of a virus, which has the property of inhibiting virus replication.

327
Q

**ACTIVATING CELL-MEDIATED IMMUNITY

The surface of cytotoxic T cells have:

A

a) T cell receptors (TCRs)

b) CD8 co-receptor

Antigen binding by a TCR with CD4 or CD8 proteins is the first signal in activation of a T cell

328
Q

a) T cell receptors (TCRs)

A

Antigen receptors on the surface of T cells that recognize and bind to specific foreign antigen fragments that are presented in antigen-MHC complexes.

329
Q

b) CD8 co-receptor

A

help maintain the proper TCR-MHC coupling

330
Q

Activation of CD8 T cells

(Activating Cell-mediated Immunity)

A

1) Antigen recognition

2) Costimulation

3) Activation and cell division

331
Q

Activation of CD8 T cells

(Activating Cell-mediated Immunity)

Step 1)
“Antigen recognition”

A

Occurs when CD8 T cell encounters specific antigen bound to a class I MHC protein on the surface of another cell

—> Body cells infected by microbes (usually APCs)

—> Some tumor cells

—> Cells of a tissue transplant
(antigen within cell, non-self proteins)

332
Q

Activation of CD8 T cells

(Activating Cell-mediated Immunity)

Step 2)
“Costimulation”

A

Physical or chemical stimulation of T cell in addition to the class I MHC molecule

More that 20 known costimulators
—> Some cytokines (e.g. interleukin-2)
—> Pairs of plasma membrane molecules

Like the safety on a gun: prevents T cells from mistakenly attacking normal cells

Recognition with no costimulation leads to a prolonged state of inactivity called ANERGY

333
Q

anergy define

A

absence of the normal immune response to a particular antigen or allergen.

“without” + “work”

334
Q

IL-2

A

Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein[5] that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity.

335
Q

Activation of CD8 T cells

(Activating Cell-mediated Immunity)

Step 2)
“activation and cell division”

A

Three different types of
CD8 T cells produced
(all sensitive to the same antigen):

-> ​Cytotoxic T cells

-> ​Memory T (cytotoxic?) cells

-> ​Regulatory T cells (T reg cells)

336
Q

Activated Cell-Mediated Immunity

A

Activation and Clonal Selection of Cytotoxic T cells

A) Active Cytotoxic T cells
—> Leave secondary lymphatic organs and tissues and migrate to seek out and destroy infected target cells, cancer cells, and transplanted cells

B) Memory cytotoxic T cells
—> Act quickly during a second encounter with the same antigen

337
Q

cytotoxic T cell action after Cell-mediated immunity activated

A

Cytotoxic T cells are like ‘assassins’ – they leave the secondary lymphatic organ to hunt down their victims (which have a specific antigen in a MHC I molecule).

338
Q

which cells are cytotoxic T cells similar to

A

Cytotoxic T cells kill much like NK cells

a) Granzymes

b) Perforin and/or granulysin

c) Release lymphotoxin

339
Q

a) Granzymes

A

Protein-digesting enzymes that trigger apoptosis (microbes are then killed by phagocytes)

340
Q

b) Perforin and/or granulysin

A

Pierces the cell (cytolysis)

341
Q

c) Release lymphotoxin

A

Activates enzymes in the target cell

342
Q

Activating Antibody-Mediated Immunity

A

Antigen-presenting cells can stimulate activation of CD4 T cells, producing helper T cells that promote B cell activation and antibody production

343
Q

Activation of CD4 T cells

A

First must be exposed to antigens bound to class II MHC proteins

Costimulation completes activation

Next step involves series of divisions
—> Daughter cells differentiate into active helper T cells (TH cells) and memory TH cells

Active helper T cells secrete cytokines
—> Stimulate both cell-mediated and antibody-mediated immunity

344
Q

B cell sensitization

A

Preparation for activation is called SENSITIZATION

—> Antigens are brought into cell through endocytosis and then placed on surface of cell bound to class II MHC proteins

inactive B cell –> sensitized B cell –> activated B cell (via helper T cell)

345
Q

B cell activation

A

Full activation requires helper T cell

—> Helper T cell must have been activated by exposure to the same antigen

—> Helper T cell binds to MHC complex of sensitized B cell
= Secretes cytokines to promote B cell activation

346
Q
A
347
Q

B cell division, differentiation, and antibody production

A

Stimulation by cytokines causes series of cell divisions in B cells

Two types of daughter cells
A) Memory B cells
B) Plasma cells

348
Q

A) Memory B cells

A

Inactive until second exposure to antigen

Respond then by differentiating into plasma cells

349
Q

B) Plasma cells

A

Activated B cells, each capable of secreting up to 100 million antibody (immunoglobulins) molecules per hour

Unlike Cytotoxic T cells which leave lymphatic tissues to seek out and destroy a foreign antigen, B cells remain in lymphatic tissue

350
Q

WHERE DO B CELLS REMAIN??

A

B cells remain in lymphatic tissue

351
Q

Antibodies

A

Antibodies are small soluble proteins that bind to specific antigens and whose abundance increases upon later antigen exposure

352
Q

antibody molecule structure

A

Consists of two parallel polypeptide chains
—> One pair of heavy chains
—> One pair of light chains

**

Each pair contains:
—> Constant segments
(On heavy chains, form the base of antibody molecule)

—> Variable segments
(Free tips are antigen binding sites)
(Differences in amino acid sequences produce variability needed for different antibodies)

353
Q

Classes of antibodies, or immunoglobulins (Igs) – determined by…

A

Class determined by
differences in structure of
the heavy-chain constant
segments

354
Q

There are five classes of antibodies:

A

IgG
IgE
IgD
IgM
IgA

355
Q

IgG

A

Most numerous of the 5 types (75 percent of all antibodies in the bloodstream)

Found in blood, lymph and the intestines

Responsible for resistance against many viruses, bacteria, and bacterial toxins

Only one to cross placenta from mother to child*****************

356
Q

Only one to cross placenta from mother to child

A

IgG

357
Q

IgE

A

Least common of 5

Attaches to basophil and mast cell surfaces

Involved in allergic, parasitic, & hypersensitivity reactions

358
Q

​IgD

A

On B cell surface, where it binds antigens in extracellular fluid

Plays role in B cell SENSITIZATION

359
Q

IgM

A

First class of antibody secreted after antigen encountered

Production declines as IgG production increases

Therefore, indicates recent infection

Anti-A and anti-B antibodies are examples
(BLOOD CELL ANTIGENS/Ab)

360
Q

Anti-A and anti-B antibodies

A

IgM

361
Q

biggest Immunoglobulin

A

IgM

“IgM is the largest antibody and the first one to be synthesized in response to an antigen or microbe, accounting for 5% of all immunoglobulins present in the blood”

362
Q

IgA

A

Found primarily in glandular secretions, such as mucus, tears, saliva, breast milk, and semen

Attack before pathogens gain internal access

363
Q

Antigen-antibody complex

A

Formed when a specific antibody molecule binds to its corresponding antigen molecule

Binds to specific portions of the exposed surface called ANITGENIC DETERMINANT SITES or EPITOPE on an antigen

(Bacteria may contain millions of antigenic determinant sites)

364
Q

Antibody Mechanisms

(Methods of eliminating antigens)

A

1) ​Neutralization

2) Prevention of pathogen adhesion

3) Activation of complement

4) ​Stimulation of inflammation

5) Attraction of phagocytes

6) Opsonization

7) ​Precipitation and agglutination

365
Q

1) ​Neutralization

A

Antibodies occupy binding sites on viruses and bacterial toxins, preventing them from affecting body cells

366
Q

2) Prevention of pathogen adhesion

A

IgA antibodies in glandular secretions cover bacteria or viruses, preventing adhesion and infection of body cells

367
Q

3) ​Activation of complement

A

After antigen binding, complement also can bind to the antibody, accelerating the complement cascade

368
Q

4) Stimulation of inflammation

A

Stimulate basophil and mast cells to release chemicals

369
Q

5) ​Attraction of phagocytes

A

Attached antibodies attract eosinophils, neutrophils, and macrophages

370
Q

6) Opsonization

A

Coating of pathogen with antibodies allows phagocytes to bind more easily

371
Q

7) ​Precipitation and agglutination

A

Antibodies can bind to antigenic determinant sites on adjacent antigens

The linking of multiple pathogens by antibodies creates an IMMUNE COMPLEX

—> Formation of insoluble complexes (too large to stay in solution) is called PRECIPITATION

—> Formation of an immune complex from surface antigens is called AGGLUTINATION
E.g.
clumping of RBCs in a transfusion reaction

372
Q

AGGLUTINATION
(immune complex?)

A

—> Formation of an immune complex from surface antigens is called AGGLUTINATION
E.g.
clumping of RBCs in a transfusion reaction

373
Q

PRECIPITATION
(immune complex?)

A

—> Formation of insoluble complexes (too large to stay in solution) is called PRECIPITATION

374
Q

LEAST COMMON IMMUNOGLOBULIN

A

IgE

375
Q

Immunological Memory

A

Due to the presence of long lasting antibodies and very long-lived lymphocytes (memory cells) which arise during clonal selection of activated B and T cells

376
Q

Primary response

A

Antibody-mediated response to initial antigen exposure

Takes time to develop
—> Appropriate B cells must be activated then differentiate into antibody-secreting plasma cells

377
Q

antibody TITER

A

Antibody titer (level of antibodies in the blood) peaks 1–2 weeks after initial exposure

Levels decline if no longer exposed to the antigen

378
Q

Secondary response

A

Triggered when antigen is encountered again

More extensive and lasts longer than primary response

–> Antibody titers increase more rapidly and reach higher concentrations

Result of immediate response by memory B cells for specific antigen

Appears even if second exposure is years after the first

379
Q

how long can memory cells potentially survive?

A

—> Memory cells may survive 20 years or more

380
Q

immunization / vaccines

A

Provides the basis for immunization by vaccination against certain diseases.

—> Originally discovered by Edward Jenner in early 1796 working with cowpox

—> Redeveloped in 1950 by Jonas Salk working with polio

381
Q

Types of vaccines

A

Inactivated vaccines
—> Killed whole pathogen

Live-attenuated vaccines
—> Weakened whole pathogen that can no longer replicate and cause disease

Subunit, recombinant, polysaccharide, and conjugate vaccines
—> Specific portion of pathogen

mRNA
—> Genetic material coded for specific pathogen antigen

382
Q

Integrated Immune Response

A

Responses to bacterial and viral infection

Overcoming a bacterial infection
—> Most effective defenses involve phagocytosis and antigen presentation by APCs

Overcoming a viral infection
—> Cytotoxic T cells and NK cells can be activated by direct contact with virus-infected cells
—> Process also involves antigen presentation and subsequent responses

383
Q

pathologies

A

Type I (anaphylactic)
—> Most common, occurs due to immediate hypersensitivity due to re-exposure to an allergen (mainly IgE)

Type II (cytotoxic)
—> Antibodies (IgG or IgM) directed against antigens on a person’s blood or tissue cells (basis of some autoimmune diseases)

Type III (immune-complex)
—> Ag/Ab complexes that escape phagocytosis leading to inflammation (IgA or IgM) (eg. RA)

Type IV (cell mediated)
—> aka delayed hypersensitivity
—> 12-72 hrs post exposure to an allergen, activated T-cells move to the site of initial antigen entry and stimulate an inflammatory response (eg. contact dermatitis)

384
Q

Acquired Immunodeficiency Syndrome (AIDS)

A

Caused by human immunodeficiency virus (HIV)

Virus binds to CD4 proteins and infects helper T cells:

Infected cells synthesize and release new viral proteins

Helper T cells are destroyed by virus or immune defenses

Impairs both cell-mediated and antibody-mediated responses

Suppressor T cells not affected

385
Q

HIV –> AIDS — what happens

A

Body more vulnerable to microbial invaders, opportunistic infections, and cancer

Spread by contact with body fluids

Infects 33 million people worldwide, with 2 million deaths each year

386
Q

Infectious Mononucleosis

A

Mono or kissing disease

Contagious disease caused by Epstein-Barr Virus (EBV)

No cure, runs its course in a few weeks

Symptoms:
Fatigue
Headache
Dizziness
Sore throat
Enlarged, tender lymph nodes
Fever

387
Q

Systemic Lupus Erythematosus (SLE)

A

Chronic, autoimmune, inflammatory disease that affects multiple body systems

Cause unknown

Affects many tissues around the body leading to wide ranging symptoms

Characterized by periods of active disease and remission (relapsing-remitting)

Develops between ages of 15-44 (mainly females)

Most common symptom is a ‘butterfly rash’

Arthritis is also very common

388
Q

Rheumatoid Arthritis

A

Autoimmune and inflammatory disease creating severe joint pain

Body produces antibodies that recognize joints as foreign and attacks them causing severe pain, inflammation and joint deterioration

Risk factors include family history, being female and a smoker

389
Q

(RA) Severe joint inflammation can lead to joint deformities such as:

A

Boutonniere deformity:The middle finger joint bends toward the palm while the outer finger joint may bend opposite the palm.

Swan-neck deformity:The base of the finger and the outermost joint bend, while the middle joint straightens.

Hitchhiker’s thumb:The thumb flexes at the metacarpophalangeal joint and hyperextends at the interphalangeal joint below your thumb nail. It is also called Z-shaped deformity of the thumb.

Claw toe deformity:The toes are either bent upward from the joints at the ball of the foot, downward at the middle joints, or downward at the top toe joints and curl under the foo

390
Q

Myasthenia Gravis

A

Body produces antibodies that recognize the NMJ (neuromuscular junction) as foreign

Produces Abs that block Ach receptors on the motor end plate side and thus decrease the number of functional receptors

Causes progressive muscle weakness and atrophy

391
Q

Lymphomas

A

Idiopathic cancers of the lymphatic organs.

Hodgkin’s Lymphoma (Hodgkin’s Disease)
—> Ages 15-35 and those over 60, males > females.
—> Painless, nontender enlargement of one or more lymph nodes in the neck, chest and axilla
—> better prognosis with early detection

**

Non-Hodgkin’s Lymphoma
—> All age groups; more common and more fatal
—> Starts the same way as HD but include an enlarged spleen, anemia and general malaise

392
Q
A