0-1 Chapter 21 Lymphatic and immune system Flashcards Preview

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Flashcards in 0-1 Chapter 21 Lymphatic and immune system Deck (277):
1

immune system

not an organ system, but a population of cells that inhabit all of our organs and defend the body from agents of disease

2

lymphatic system

•network of organs and vein-like vessels that recover fluid
•inspect it for disease agents
•activate immune responses
•return the fluid to the bloodstream

3

Lymphatic and Immune Systems

functions

maintain fluid balance
•protect body from infection and disease

4

Functions of Lymphatic System

fluid recovery
immunity
lipid absorption

5

fluid recovery

–fluid continually filters from the blood capillaries into the tissue spaces
•blood capillaries reabsorb 85%
•15% (2 –4 L/day) of the water and about half of the plasma proteins enters lymphatic system and then returned to the blood

6

immunity

excess filtered fluid picks up foreign cells and chemicals from the tissues
•passes through lymph nodes where immune cells stand guard against foreign matter
•activate a protective immune response

7

lipid absorption

lacteals in small intestine absorb dietary lipids that are not absorbed by the blood capillaries

8

Components of the Lymphatic System

lymph
lymphatic vessels
lymphatic tissues
lymphatic organs

9

lymph

–the recovered fluid

10

lymphatic vessels

–transport the lymph

11

lymphatic tissues

composed of aggregates of lymphocytes and macrophages that populate many organs in the body

12

lymphatic organs

–defense cells are especially concentrated in these organs
–separated from surrounding organs by connective tissue capsules

13

lymph

–clear, colorless fluid, similar to plasma, but much less protein
–extracellular fluid drawn into lymphatic capillaries

14

lymphatic capillaries

(terminal lymphatics)
–sacs of thin endothelial cells that loosely overlap each other
–closed at one end
–cells tethered to surrounding tissue by protein filaments
–endothelium creates valve-like flaps that open when interstitial fluid pressure is high, and close when it is low

15

Lymphatic Vessels

larger ones composed of three layers

–tunica interna:
–tunica media:
–tunica externa:
•converge into larger and larger vessels

16

tunica interna

endothelium and valves

17

tunica media

elastic fibers, smooth muscle

18

tunica externa

thin outer layer

19

Route of Lymph Flow

•lymphatic capillaries
•collecting vessels
•six lymphatic trunks:
•two collecting ducts:
•subclavian veins

20

two collecting ducts:

right lymphatic duct
thoracic duct

21

right lymphatic duct

receives lymph from right arm, right side of head and thorax; empties into right subclavian vein

22

thoracic duct

larger and longer, begins as a prominent sac in abdomen called the cisterna chyli; receives lymph from below diaphragm, left arm, left side of head, neck, and thorax; empties into left subclavian vein

23

Mechanisms of Lymph Flow

•lymph flows under forces similar to those that govern venous return, except no pump (heart)
•lymph flows at low pressure and slower speed than venous blood
•moved along by rhythmic contractions of lymphatic vessels
•flow aided by skeletal muscle pump
•arterial pulsation rhythmically squeeze lymphatic vessels
•thoracic pump aids flow from abdominal to thoracic cavity
•valves prevent backward flow
•rapidly flowing blood in subclavian veins, draws lymph into it
•exercise significantly increases lymphatic return

24

natural killer (NK) cells

–large lymphocytes that attack and destroy bacteria, transplanted tissue, host cells infected with viruses or have turned cancerous
–responsible for immune surveillance

25

T lymphocytes (T cells)

–mature in thymus

26

B lymphocytes (B cells)

–activation causes proliferation and differentiation into plasma cells that produce antibodies

27

macrophages

–very large, avidly phagocytic cells of the connective tissue
–develop from monocytes
–phagocytize tissue debris, dead neutrophils, bacteria, and other foreign matter
–process foreign matter and display antigenic fragments to certain T cells alerting the immune system to the presence of the enemy
–antigen presenting cells (APCs)

28

dendritic cells

–branched, mobile APCs found in epidermis, mucous membranes, and lymphatic organs
–alert immune system to pathogens that have breached their surface

29

reticular cells

–branched stationary cells that contribute to the stroma of a lymphatic organ
–act as APCs in the thymus

30

lymphatic (lymphoid) tissue

aggregations of lymphocytes in the connective tissues of mucous membranes and various organs

31

diffuse lymphatic tissue

simplest form
–lymphocytes are scattered, rather than densely clustered
–prevalent in body passages open to the exterior
•respiratory, digestive, urinary, and reproductive tracts

32

MALT

mucosa-associated lymphatic tissue (MALT)

33

lymphatic nodules (follicles)

dense masses of lymphocytes and macrophages that congregate in response to pathogens
–constant feature of the lymph nodes, tonsils, and appendix

34

Peyer patches

dense clusters in the ileum, the distal portion of the small intestine

35

Lymphatic Organs

•lymphatic organs have well-defined anatomical sites
–have connective tissue capsule that separates the lymphatic tissue from neighboring tissues

36

primary lymphatic organs

–red bone marrow and thymus
–site where T and B cells become immunocompetent–able to recognize and respond to antigens

37

secondary lymphatic organs

–lymph nodes, tonsils, and spleen
–immunocompetent cells populate these tissues

38

Red Bone Marrow

red bone marrow is involved in hemopoiesis(blood formation) and immunity
–soft, loosely organized, highly vascular material
–separated from osseous tissue by endosteum of bone
–as blood cells mature, they push their way through the reticular and endothelial cells to enter the sinus and flow away in the blood stream

39

thymus

member of the endocrine, lymphatic, and immune systems
–houses developing lymphocytes
–secretes hormones regulating their activity
–bilobed organ located in superior mediastinum between the sternum and aortic arch

40

reticular epithelial cells

seal off cortex from medulla forming blood-thymus barrier

41

produce signaling molecules

thymosin, thymopoietin, thymulin, interleukins, and interferon

42

lymph nodes

the most numerous lymphatic organs
–about 450 in typical young adult
–serve two functions:
•cleanse the lymph
•act as a site of T and B cell activation

43

parenchyma divided into

cortex and medulla
–germinal centers where B cells multiply and differentiate into plasma cells

44

Lymph Node Locations

cervical lymph nodes
axillary lymph nodes
thoracic lymph nodes
abdominal lymph nodes
intestinal and mesenteric lymph nodes
inguinal lymph nodes
popliteal lymph nodes

45

cervical lymph nodes

–deep and superficial group in the neck
–monitor lymph coming from head and neck

46

axillary lymph nodes

–concentrated in armpit
–receive lymph from upper limb and female breast

47

thoracic lymph nodes

–in thoracic cavity especially embedded in mediastinum
–receive lymph from mediastinum, lungs, and airway

48

abdominal lymph nodes

–occur in posterior abdominopelvic wall
–monitor lymph from the urinary and reproductive systems

49

intestinal and mesenteric lymph nodes

–found in the mesenteries, adjacent to the appendix and intestines
–monitor lymph from the digestive tract

50

inguinal lymph nodes

–in the groin and receive lymph from the entire lower limb

51

popliteal lymph nodes

–occur on the back of the knee
–receive lymph from the leg proper

52

lymphadenopathy

collective term for all lymph node diseases

53

lymphadenitis

swollen, painful node responding to foreign antigen

54

lymph nodes are common sites for

metastatic cancer
–swollen, firm and usually painless

55

metastasis

phenomenon in which cancerous cells break free from the original, primary tumor, travel to other sites in the body, and establish new tumors.

56

tonsils

patches of lymphatic tissue located at the entrance to the pharynx
–guard against ingested or inhaled pathogens
–each covered with epithelium

57

tonsillar crypts

have deep pits –tonsillar crypts lined with lymphatic nodules –tonsillitis and tonsillectomy

58

three main sets of tonsils

palatine tonsils
lingual tonsils
pharyngeal tonsil (adenoid)

59

palatine tonsils

•pair at posterior margin of oral cavity
•most often infected

60

lingual tonsils

•pair at root of tongue

61

pharyngeal tonsil (adenoid)

•single tonsil on wall of nasopharynx
•covered by epithelium
•pathogens get into tonsillar crypts and encounter lymphocytes

62

spleen

the body‟s largest lymphatic organ
spleen highly vascular and vulnerable to trauma and infection

63

parenchyma exhibits two types of tissue:

red pulp
white pulp

64

red pulp

sinuses filled with erythrocytes

65

white pulp

lymphocytes, macrophages surrounding small branches of splenic artery

66

functions

–blood production in fetus
–blood reservoir
–„erythrocyte graveyard‟ -RBC disposal
–white pulp monitors blood for foreign antigens

67

splenectomy

ruptured spleen

68

pathogens

environmental agents capable of producing disease
–infectious organisms, toxic chemicals, and radiation

69

three lines of defenses against pathogens

---

70

first line of defense

external barriers, skin and mucous membranes

71

second line of defense

several nonspecific defense mechanisms
•leukocytes and macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever
•effective against a broad range of pathogens

72

third line of defense

the immune system
•defeats a pathogen, and leaves the body of a „memory‟ of it so it can defeat it faster in the future

73

nonspecific resistance

guards equally against a broad range of pathogens
–their effectiveness does not depend on prior exposure
–skin and mucous membranes
–leukocytes and macrophages, antimicrobial proteins, immune surveillance, inflammation, and fever

74

immunity

specific defense because it results from prior exposure to a pathogen
–usually provides future protection only against that particular one

75

External Barriers

skin
mucous membranes


76

skin

–makes it mechanically difficult for microorganisms to enter the body
–toughness of keratin
–too dry and nutrient-poor to support microbial growth

77

defensins

peptides that kill microbes by creating holes in their membranes

78

acid mantle

thin film of lactic acid from sweat which inhibits bacterial growth

79

mucous membranes

–digestive, respiratory, urinary, and reproductive tracts are open to the exterior and protected by mucous membranes
–mucus physically traps microbes

80

lysozyme

enzyme destroys bacterial cell walls

80

phagocytes

phagocytic cells with a voracious appetite for foreign matter

81

five types of leukocytes

–neutrophils
–eosinophils
–basophils
–monocytes
–lymphocytes

82

Neutrophils

wander in connective tissue killing bacteria
–phagocytosis and digestion
–produces a cloud of bactericidal chemicals

83

killing zone

–degranulation
•lysosomes discharge into tissue fluid
–respiratory burst –neutrophils rapidly absorb oxygen
•toxic chemicals are created (O2.-, H2O2, HClO)
–kill more bacteria with toxic chemicals than phagocytosis

84

Eosinophils

•found especially in the mucous membranes
•stand guard against parasites, allergens(allergy causing agents), and other pathogens
•kill tapeworms and roundworms by producing superoxide, hydrogen peroxide, and toxic proteins

85

Basophils

secrete chemicals that aid mobility and action of WBC other leukocytes

86

histamine

a vasodilator which increases blood flow
•speeds delivery of leukocytes to the area

87

heparin

inhibits the formation of clots
•would impede leukocyte mobility

88

mast cells

also secrete these substances
–type of connective tissue cell very similar to basophils

89

Lymphocytes

•three basic categories
•circulating blood contains
–80% T cells
–15% B cells
–5% NK cells
•many diverse functions

90

monocytes

emigrate from the blood into the connective tissue and transform into macrophages

91

macrophage system

all the body‟s avidly phagocytic cells, except leukocytes

92

wandering macrophages

actively seeking pathogens
•widely distributed in loose connective tissue

93

fixed macrophages

phagocytize only pathogens that come to them

94

microglia

in central nervous system

95

alveolar macrophages

in lungs

96

hepatic macrophages

in liver

97

Antimicrobial Proteins

proteins that inhibit microbial reproduction and provide short-term, nonspecific resistance to pathogenic bacteria and viruses

98

two families of antimicrobial proteins:

–interferons
–complement system

99

interferons

secreted by certain cells infected by viruses
–of no benefit to the cell that secretes them
–alert neighboring cells and protect them from becoming infected
–bind to surface receptors on neighboring cells
–alerted cell synthesizes various proteins that defend it from infection
–also activates NK cells and macrophages
–activated NK cells destroy malignant cells

100

complement system

a group of 30 or more globular proteins that make powerful contributions to both nonspecific resistance and specific immunity
–synthesized mainly by the liver
–circulate in the blood in inactive form
–activated by presence of the pathogen

101

activated complement brings about four methods of pathogen destruction

•inflammation
•immune clearance
•phagocytosis
•cytolysis

102

three routes of complement activation

•classical pathway
•alternative pathway
•lectin pathway

103

classical pathway

–requires antibody molecule to get started
–thus part of specific immunity
–antibody binds to antigen on surface of the pathogenic organism
•forms antigen-antibody (Ag-Ab) complex
–changes the antibody‟s shape
•exposing a pair of complement-binding sites
•binding of the first complement (C1) sets off a reaction cascade called complement fixation
–results in a chain of complement proteins attaching to the antibody

104

alternative pathway

–nonspecific, does not require antibody
–C3 breaks down in the blood to C3a and C3b
•C3b binds directly to targets such as human tumor cells, viruses, bacteria, and yeasts
•triggers cascade reaction with autocatalytic effect where more C3 is formed

105

lectin pathway

Exists

106

mechanisms of action of complement proteins

•inflammation
•immune clearance
•phagocytosis
•cytolysis

107

inflammation

•C3a stimulates mast cells and basophils to secrete histamine and other inflammatory chemicals
•activates and attracts neutrophils and macrophages
•speed pathogen destruction in inflammation

108

immune clearance

•C3b binds with antigen-antibody complexes to red blood cells
•these RBCs circulate through the liver and spleen
•macrophages of those organs strip off and destroy the Ag-Ab complexes leaving RBCs unharmed
•principal means of clearing foreign antigens from the bloodstream

109

phagocytosis

•neutrophils and macrophages cannot phagocytize “naked” bacteria, viruses, or other pathogens
•C3b assist them by opsonization
–coats microbial cells and serves as binding sites for phagocyte attachment
–makes the foreign cell more appetizing

110

cytolysis

•C3b splits other complement proteins
•bind to enemy cell
•attract more complement proteins –membrane attack complex forms
–forms a hole in the target cell
–electrolytes leak out, water flows in rapidly, and cell ruptures

111

Membrane Attack Complex

complement proteins form ring in plasma membrane of target cell causing cytolysis

112

immune surveillance

a phenomenon in which natural (NK) killer cells continually patrol the body on the lookout for pathogens and diseased host cells.

113

natural killer (NK) cells attack and destroy:

natural killer (NK) cells attack and destroy:
–bacteria, cells of transplanted organs, cells infected with viruses, and cancer cells
•recognizes enemy cell
•NK cells bind to it
•release proteins called perforins
•secrete a group of protein degrading enzymes –granzymes
–enter through pore and degrade cellular enzymes and induce apoptosis

114

perforins

–polymerize a ring and create a hole in its plasma membrane

115

Action of NK cell

-NK cell releases perforins, which polymerize and form a hole in the enemy cell membrane
-Granzymes from NK cell enter perforin hole and degrade enemy cell enzymes.
-Enemy cell dies by apoptosis
-Macrophage engulfs and digests dying cell.

116

fever

an abnormal elevation of body temperature
–pyrexia, febrile
–results from trauma, infections, drug reactions, brain tumors, and other causes

117

fever is an

adaptive defense mechanism, in moderation, does more good than harm
–promotes interferon activity
–elevates metabolic rate and accelerates tissue repair
–inhibits reproduction of bacteria and viruses

118

antipyretic

fever-reducing medications by inhibiting PGE2

119

initiation of fever by exogenous pyrogens

fever producing agents
–glycolipids on bacterial and viral surfaces
–attacking neutrophils and macrophages secrete chemicals, interleukins, interferons, and others that act as endogenous pyrogens
–stimulate neurons in the anterior hypothalamus to secrete prostaglandin E2
–PGE2raises hypothalamic set point for body temperature

120

stages of fever

onset, stadium, defervescence

121

Course of a Fever

-Infection and pyrogen secretion
-Hypothalamic thermostat is reset to highe rset point
-Onset (body temperature rises
-Stadium(body temperature oscillates around new set point)
-Infection ends, set point returns to normal
-Defervescence (body temperature returns to normal)

122

Reye Syndrome

serious disorder in children younger than 15 following an acute viral infection such as chicken pox or influenza
–swelling of brain neurons
–fatty infiltration of liver and other viscera
–pressure of swelling brain
•nausea, vomiting, disorientation, seizures and coma
•30% die, survivors sometimes suffer mental retardation
•can be triggered by the use of aspirin to control fever

123

NEVER give aspirin to

children with chickenpox or flulike symptoms

124

inflammation

local defensive response to tissue injury of any kind, including trauma and infection

125

general purposes of inflammation

–limit spread of pathogens, then destroys them
–remove debris from damaged tissue
–initiate tissue repair

126

four cardinal signs of inflammation

-redness
-swelling
-heat
-pain

127

suffix -itis denotes

inflammation of specific organs: arthritis, pancreatitis, dermatitis

128

cytokines

class of chemicals that regulate inflammation and immunity
–secreted mainly by leukocytes
–alter the physiology or behavior of receiving cell
–act at short range, neighboring cells (paracrines) or the same cell that secretes them (autocrines)
–include interferon, interleukins, tumor necrosis factor, chemotactic factors, and others

129

paracrines

act at short range, neighboring cells

130

autocrines

act on the same cell that secretes them

131

three major processes of inflammation

–mobilization of body defenses
–containment and destruction of pathogens
–tissue cleanup and repair

132

Mobilization of Defenses

most immediate requirement for dealing with tissue injury is to get the defensive leukocytes to the site quickly
•local hyperemia–increasing blood flow beyond normal rate is a way to do this

133

vasoactive chemicals

dilate local blood vessels
–endothelial cells separate increasing capillary permeability
–fluid, leukocytes, and plasma proteins leave the bloodstream
•complement, antibodies, and clotting proteins

134

selectins

cell-adhesion molecules made by endothelial cells that aid in the recruitment of leukocytes
•make membranes sticky and snag leukocytes

135

margination

adhesion of the leukocytes to the vessel wall
•selectins cause leukocytes to adhere to blood vessel walls

136

diapedesisor emigration

leukocytes crawl through gaps in the endothelial cells and enter tissue fluid

137

extravasated

cells and chemicals that have left the bloodstream

138

basis for the four cardinal signs of inflammation

-redness
-swelling
-heat
-pain

139

heat–

results from hyperemia

140

redness

due to hyperemia, and extravasated RBCs in the tissue

141

swelling

(edema) –due to increased fluid filtration from the capillaries

142

pain

from direct injury to the nerves, pressure on the nerves from edema, stimulation of pain receptors by prostaglandins, bacterial toxins, and a kinin called bradykinin

143

Containment and Destruction of Pathogens

•a priority of inflammation is to prevent the pathogens from spreading throughout the body

144

fibrinogen

that filters into tissue fluid clots
•forms a sticky mesh that walls off microbes

145

heparin

prevents clotting at site of injury
•pathogens are in a fluid pocket surrounded by clot
•attacked by antibodies, phagocytes, and other defenses

146

neutrophils

the chief enemy of bacteria, accumulate at the injury site within an hour
–after leaving the bloodstream, they exhibit chemotaxis

147

chemotaxis

attraction to chemicals such as bradykinin and leukotrienes that guide them to the injury site

148

neutrophils are quickest to respond and kill bacteria by

–phagocytosis
–respiratory burst
–secrete cytokines for recruitment of macrophages and additional neutrophils

149

eosinophilia

elevated eosinophil count in allergy or parasitic infection

150

Tissue Cleanup

monocytes the primary agents of tissue cleanup and repair
–arrive in 8 to 12 hours and become macrophages
–engulf and destroy bacteria, damaged host cells, and dead and dying neutrophils

151

edema contributes to tissue cleanup

–swelling compresses veins and reduces venous drainage
–forces open valves of lymphatic capillaries promoting lymphatic drainage
–lymphatics collect and remove bacteria, dead cells, proteins, and tissue debris better than blood capillaries

152

pus

accumulation of dead neutrophils, bacteria, other cellular debris, and tissue fluid form a pool of yellowish fluid

153

abscess

accumulation of pus in a tissue cavity

154

Tissue Repair

platelet-derived growth factor secreted by blood platelets and endothelial cells in injured area
–stimulates fibroblasts to multiply
–synthesize collagen
•hyperemia delivers oxygen, amino acids, and other necessities for protein synthesis
•increased heat increases metabolic rate, speeds mitosis, and tissue repair
•fibrin clot forms a scaffold for tissue reconstruction
•pain makes us limit the use of a body part so it has a chance to rest and heal.

155

immune system

composed of a large population of widely distributed cells that recognize foreign substances and act to neutralize or destroy them

156

two characteristics distinguish immunity from nonspecific resistance

specificity
memory

157

specificity

immunity directed against a particular pathogen

158

memory

when re-exposed to the same pathogen, the body reacts so quickly that there is no noticeable illness

159

two types of immunity

cellular (cell-mediated) immunity:
humoral (antibody-mediated) immunity

160

cellular (cell-mediated) immunity:

(T cells)
•lymphocytes directly attack and destroy foreign cells or diseased host cells
•means of ridding the body of pathogens that reside inside human cells, where they are inaccessible to antibodies
•kills cells that harbor them

161

humoral (antibody-mediated) immunity

(B cells)
•mediated by antibodies that do not directly destroy a pathogen
•indirect attack where antibodies assault the pathogen
•can only work against the extracellular stage of infectious microorganisms

162

natural active immunity

–production of one‟s own antibodies or T cells as a result of infection or natural exposure to antigen

163

artificial active immunity

–production of one‟s own antibodies or T cells as a result of vaccination against disease

164

vaccine

consists of dead or attenuated (weakened) pathogens that stimulate the immune response without causing the disease

165

booster shots

periodic immunizations to stimulate immune memory to maintain a high level of protection

166

natural passive immunity

–temporary immunity that results from antibodies produced by another person
•fetus acquires antibodies from mother through placenta, milk

167

artificial passive immunity

–temporary immunity that results from the injection of immune serum (antibodies) from another person or animal
•treatment for snakebite, botulism, rabies, tetanus, and other diseases

168

antigen

any molecule that triggers an immune response
–large molecular weights of over 10,000 amu
•complex molecules with structures unique to the individual
•proteins, polysaccharides, glycoproteins, glycolipids
•can distinguish „self‟ molecules from foreign

169

epitopes

(antigenic determinants) –certain regions of an antigen molecule that stimulate immune responses

170

haptens

too small to be antigenic in themselves
–must combine with a host macromolecule
–create a unique complex that the body recognizes as foreign
–cosmetics, detergents, industrial chemicals, poison ivy, and animal dander
–penicillin binds to host proteins in allergic individuals

171

major cells of the immune system

–lymphocytes
–macrophages
–dendritic cells
•especially concentrated in strategic places such as lymphatic organs, skin, and mucous membranes

172

three categories of lymphocytes

–natural killer (NK) cells –immune surveillance
–T lymphocytes (T cells)
–B lymphocytes (B cells)

173

Life Cycle of T cells

involves three stages and three anatomical stations in the body

174

„born‟

•„born‟ in the red bone marrow
–descendant of the pluripotent stem cells (PPSCs)
–released into the blood as still-undifferentiated stem cells that colonize the thymus

175

mature

maturein thymus
–thymosins stimulate maturing T cells to develop surface antigen receptors
–with receptors in place, the T cells are now immunocompetent –capable of recognizing antigens presented to them by APCs
–reticuloendothelial cells in the thymus test T cells by presenting „self‟ antigens to them
–two ways to fail the test:
•inability to recognize the RE cells, especially their MHC antigens
–would be incapable of recognizing a foreign attack on the body
•reacting to the self antigen
–T cells would attack one‟s own tissues

176

negative selection

T cells that fail either test must be eliminated

177

two forms of negative selection

clonal deletion
anergy

178

clonal deletion

self-reactive T cells die and macrophages phagocytize them

179

anergy

self-reactive T cells remain alive but unresponsive

180

self-tolerance

–negative selection leaves the body in a state of self-tolerance in which the surviving T cells respond only to foreign antigens, and tolerating our own

181

2% of the T cells that reach the thymus leave as

immunocompetent T cells
•move to thymus medulla and undergo positive selection –they multiply and form clones of identical T cells programmed to respond to a specific antigen

182

naïve lymphocyte pool

immunocompetent T cells but have not yet encountered the foreign antigens

183

deployment

naïve T cells leave thymus and colonize lymphatic tissues and organs everywhere in the body

184

B Lymphocytes (B cells)
•site of development

–group fetal stem cells remain in bone marrow
–develop into B cells

185

B cell selection

–B cells that react to self antigens undergo either anergy or clonal deletion same as T cell selection

186

self-tolerant B cells

synthesize antigen surface receptors, divide rapidly, produce immunocompetent clones
•leave bone marrow and colonize same lymphatic tissues and organs as T cells

187

Antigen-Presenting Cells (APCs)

are required to help
–dendritic cells, macrophages, reticular cells, and B cells function as APCs
•T cells can not recognize their antigens on their own

188

function of APCs depends on

major histocompatibility complex (MHC) proteins
–act as cell „identification tags‟ that label every cell of your body as belonging to you
–structurally unique for each individual, except for identical twins

189

antigen processing

–APC encounters antigen
–internalizes it by endocytosis
–digests it into molecular fragments
–displays relevant fragments (epitopes) in the grooves of the MHC protein

190

antigen presenting

antigen presenting
–wandering T cells inspect APCs for displayed antigens
–if APC only displays a self-antigen, the T cell disregards it
–if APC displays a nonself-antigen, the T cell initiates an immune attack
–APCs alert the immune system to the presence of foreign antigen
–key to successful defense is to quickly mobilize immune cells against the antigen
–with so many cell types involved in immunity, they require chemical messengers to coordinate their activities –interleukins

191

interleukins

•chemical signals from one leukocyte to another

192

cellular (cell-mediated) immunity

a form of specific defense in which the T lymphocytes directly attack and destroy diseased or foreign cells, and the immune system remembers the antigens and prevents them from causing disease in the future

193

cellular immunity involves four classes of T cells

cytotoxic T (TC) cells
helper T (TH) cells
regulatory T (TR) cells –T-regs
memory (TM) cells

194

cytotoxic T (TC) cells

killer T cells
•the „effectors‟ of cellular immunity
•carry out attack on enemy cells

195

helper T (TH) cells

GENERAL MANAGER OF IMMUNITY SYSTEM
•help promote TC cell and B cell action and nonspecific resistance

196

regulatory T (TR) cells –T-regs

•inhibit multiplication and cytokine secretion by other T cells
•limit immune response

197

memory (TM) cells

•descend from the cytotoxic T cells
•responsible for memory in cellular immunity

198

both cellular and humoral immunity occur in three stages:

–recognition
–attack
–memory

199

thought of as the „three Rs of immunity

–recognize
–react
–remember

200

T Cell Recognition

recognition phase has two aspects: antigen presentation and T cell activation

201

antigen presentation

–APC encounters and processes an antigen
–migrates to nearest lymph node
–displays it to the T cells
–when T cell encounters its displayed antigen on the MHC protein, they initiate the immune response

202

T cells respond to two classes of MHC proteins

MHC–I proteins
MHC–II proteins (human leukocyte antigens –HLAs)

203

MHC–I proteins

–occur on every nucleated cell in the body
–constantly produced by our cells, transported to, and inserted on plasma membrane
–normal self antigens that do not elicit a T cell response
–viral proteins or abnormal cancer antigens do elicit a T cell response
–infected or malignant cells are then destroyed before they can do further harm to the body

204

MHC–II proteins (human leukocyte antigens –HLAs)

–occur only on APCs and display only foreign antigens

205

TC cells respond only to

MHC–I proteins

206

TH cells respond only to

MHC–II proteins

207

T cell activation

–begins when TC or TH cell binds to a MHC protein displaying an epitope that the T cell is programmed to recognize
–T cell must then bind to another APC protein related to the interleukins
–T cell must check twice to see if it is really bound to a foreign antigen –costimulation

208

T cell activation

Sequence

-antigen recognition
-costimulation
-clonal selection
-lethal hit

209

successful costimulation will trigger

•activated T cell undergoes repeated mitosis
•gives rise to a clone of identical T cells programmed against the same epitope
•some cells of the clone become effector cells and carry out the attack
•other cells become memory cells

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Attack : Role of Helper T (TH) Cells

•helper and cytotoxic T cells play different roles in the attack phase
•helper T cell necessary for most immune responses
•play central role in coordinating both cellular and humoral immunity

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when helper T cell recognizes the Ag-MHC protein complex

secrete interleukins that exert three effects:

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secrete interleukins that exert three effects:

•attract neutrophils and NK cells
•attract macrophages, stimulate their phagocytic activity, and inhibit them from leaving the area
•stimulate T and B cell mitosis and maturation

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Attack : Cytotoxic T (TC) Cells

•cytotoxic T (TC) cell are the only T cells directly attack other cells
•when TCcell recognizes a complex of antigen and MHC–I protein on a diseased or foreign cell it „docks‟ on that cell

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delivers a lethal hit of toxic chemicals

•perforin and granzymes–kill cells in the same manner as NK cells
•interferons–inhibit viral replication
–recruit and activate macrophages
•tumor necrosis factor (TNF) –aids in macrophage activation and kills cancer cells
–goes off in search of another enemy cell while the chemicals do their work

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Memory

•immune memory follows primary response
•following clonal selection, some TC and TH cells become memory cells
–long-lived
–more numerous than naïve T cells
–fewer steps to be activated, so they respond more rapidly

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T cell recall response

upon re-exposure to same pathogen later in life, memory cells launch a quick attack so that no noticeable illness occurs
–the person is immune to the disease

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Humoral Immunity

•humoral immunity is a more indirect method of defense than cellular immunity
•B lymphocytes of humoral immunity produce antibodies that bind to antigens and tag them for destruction by other means
–cellular immunity attacks the enemy cells directly

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works in three stages like cellular immunity

–recognition
–attack
–memory

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Humoral Immunity


•recognition

–immunocompetent B cell has thousands of surface receptorsfor one antigen
–activation begins when an antigen binds to several of these receptors
•links them together
•taken into the cell by receptor-mediated endocytosis
•small molecules are not antigenic because they cannot link multiple receptors together
•B cell processes (digests) the antigen
•links some of the epitopesto its MHC–II proteins
•displays these on the cell surface

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usually B cell response goes no further unless

a helper T cellbinds to this Ag-MHCP complex
•bound THcell secretes interleukins that activate B cell

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triggers clonal selection

•B cell mitosis gives rise to an entire battalion of identical B cells programmed against the same antigen
•most differentiate into plasma cells
•larger than B cells and contain an abundance of rough ER
•secrete antibodies at a rate of 2,000 molecules per second during their life span of 4 to 5 days
•antibodies travel through the body in the blood or other body fluids
–first exposure antibodiesIgM, later exposures to the same antigen,IgG

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attack

–antibodies bind to antigen, render it harmless, „tag it‟ for destruction

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memory

some B cells differentiate into memory cells

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immunoglobulin (Ig)

an antibodyis a defensive gamma globulin found in the blood plasma, tissue fluids, body secretions, and some leukocyte membranes

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antibody monomer

the basic structural unit of an antibody
–composed of four polypeptide chains linked by disulfide (-S-S-) bonds
–two larger heavy chains about 400 amino acids long
•heavy chains have a hinge region where antibody is bent
–two light chains about half as long
–variable (V) region in all four chains
•gives the antibody its uniqueness

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antigen binding site

formed from the V regions of the heavy and light chain on each arm
•attaches to the epitope of an antigen molecule

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constant (C) region

has the same amino acid sequence within one person and determines mechanism of antibody action

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Five Classes of Antibodies

named for the structure of their C region
IgA
IgD
IgE
IgG
IgM

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IgA

monomer in plasma; dimer in mucus, saliva, tears, milk, and intestinal secretions
•prevents pathogen adherence to epithelia and penetrating underlying tissues
•provides passive immunity to newborns

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IgD

monomer; B cell transmembrane antigen receptor
•thought to function in B cell activation by antigens

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IgE

monomer; transmembrane protein on basophils and mast cells
•stimulates release of histamine and other chemical mediators of inflammation and allergy
–attracts eosinophils to parasitic infections
–produces immediate hypersensitivity reactions

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IgG

monomer; constitutes 80% of circulating antibodies
•crosses placenta to fetus, secreted in secondary immune response, complement fixation

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IgM

pentamer in plasma and lymph
•secreted in primary immune response, agglutination, complement
fixation

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Antibody Diversity

human immune system capable of as many as 1 trillion different antibodies
•accustomed to „one gene, one protein‟ thinking
•35,000 genes in human genome

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somatic recombination

–DNA segments shuffled and form new combinations of base sequences to produce antibody genes

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somatic hypermutation

–B cells in lymph nodules rapidly mutate creating new sequences

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Humoral Immunity -Attack


4

neutralization
complement fixation
agglutination
precipitation

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neutralization

–antibodies mask pathogenic region of antigen

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complement fixation

–antigen binds to IgM or IgG, antibody changes shape, initiates complement binding which leads to inflammation, phagocytosis, immune clearance, or cytolysis
–primary defense against foreign cells, bacteria, and mismatched RBCs

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agglutination

–antibody has 2-10 binding sites; binds to multiple enemy cells immobilizing them from spreading

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precipitation

–antibody binds antigen molecules (not cells); creates antigen-antibody complex that precipitates, phagocytized by eosinophils

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Humoral Immunity -Memory

primary immune response

immune reaction brought about by the first exposure to an antigen
–appearance of protective antibodies delayed for 3 to 6 days while naïve B cells multiply and differentiate into plasma cells

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as plasma cells produce antibodies

the antibody titer (level in the blood plasma) rises
•IgM appears first, peaks in about 10 days, soon declines
•IgG levels rise as IgM declines, but IgG titer drops to a low level within a month
–primary response leaves one with an immune memory of the antigen
•during clonal selection, some of the clone becomes memory B cells
•found mainly in germinal centers of the lymph nodes
•mount a very quick secondary response

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secondary (anamnestic) response

if re-exposed to the same antigen
–plasma cells form within hours
–IgG titer rises sharply and peaks in a few days
–response is so rapid that the antigen has little chance to exert a noticeable effect on the body
–no illness results
–low levels of IgM also secreted and quickly declines
–IgG remain elevated for weeks to years
•conferring long lasting protection
•memory does not last as long in humoral immunity as in cellular immunit

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immune response may be:

–too vigorous
–too weak
–misdirected against wrong targets

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hypersensitivity

an excessive immune reaction against antigens that most people tolerate

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alloimmunity

reaction to transplanted tissue from another person

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autoimmunity

abnormal reactions to one‟s own tissues

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allergies

reactions to environmental antigens (allergens) –dust, mold, pollen, vaccines, bee and wasp venom, poison ivy and other plants, foods such as nuts, milk, eggs, and shellfish, drugs such as penicillin, tetracycline, and insulin

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four kinds of hypersensitivity

based on the type of immune agents involved (antibodies or T cells) and their method of attack on the antigen

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Type I

acute (immediate) hypersensitivity –very rapid response

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Type II and Type III

subacute –slower onset (1 –3 hours after exposure)
•last longer (10 –15 hours)
•Types I, II, and III are quicker antibody mediated responses

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Type IV -

delayed cell-mediated response

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Type I (acute) Hypersensitivity

•includes most common allergies
•IgE-mediated reaction that begins within seconds of exposure
•usually subsides within 30 minutes, although it can be severe to fatal

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Type I (acute) Hypersensitivity

signs

•clinical signs include:
–local edema, mucus hypersecretion and congestion, watery eyes, runny nose, hives, and sometimes cramps, diarrhea and vomiting
•examples: food allergies and asthma–local inflammatory reaction to inhaled allergens

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Type I (acute) Hypersensitivity

anaphylaxis

–immediate, severe reaction Type I reaction
–local anaphylaxis can be relieved with antihistamines

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Type I (acute) Hypersensitivity

anaphylactic shock

–severe, widespread acute hypersensitivity that occurs when an allergen is introduced to the bloodstream of an allergic individual
–characterized by bronchoconstriction, dyspnea (labored breathing), widespread vasodilation, circulatory shock, and sometimes death
–antihistamines are inadequate by themselves
–epinephrine relieves the symptoms by dilating bronchioles, increasing cardiac output, and restoring blood pressure
–fluid therapy and respiratory support are sometimes required

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Type I (acute) Hypersensitivity

asthma

–most common chronic illness in children

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allergic (extrinsic) asthma

is most common form
•respiratory crisis triggered by inhaled allergens
•stimulate plasma cells to secrete IgE
•binds to most cells in respiratory mucosa
•mast cells release a complex mixture of inflammatory chemicals
•triggers intense airway inflammation

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asthma

effects

•bronchospasms within minutes
–severe coughing, wheezing, and sometimes fatal suffocation

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asthma

treatment

•epinephrine and other β-adrenergic stimulants to dilate airway and restore breathing, and with inhaled corticosteroids to minimize inflammation and long term damage

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Type II Hypersensitivity (Antibody-Dependent Cytotoxic)

•occurs when IgG or IgM attacks antigens bound to cell surfaces
–reaction leads to complement activation
–and lysis or opsonization of the target cell
–macrophages phagocytize and destroy opsonized platelets, erythrocytes, or other cells
•examples: blood transfusion reaction, pemphigus vulgaris, and some drug reactions

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Type III Hypersensitivity (Immune Complex)

occurs when IgG or IgM form antigen-antibody complexes
–precipitate beneath endothelium of blood vessels and other tissues
–at site, activate complement and trigger intense inflammation
–examples: autoimmune diseases -acute glomerulonephritis and in systemic lupus erythematosus, a widespread inflammation of the connective tissues

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Type IV Hypersensitivity (Delayed)

•cell-mediated reaction in which the signs appear 12 to 72 hour after exposure
–begins with APCs in lymph nodes display antigens to helper T cells
–T cells secrete interferon and cytokines that activate cytotoxic T cells and macrophages
–result is a mixture of nonspecific and immune responses
•examples: haptens in cosmetics and poison ivy, graft rejection, TB skin test, beta cell destruction that causes type I diabetes mellitus

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autoimmune diseases

failures of self-tolerance
•immune system fails to distinguish self-antigens from foreign ones
–produces autoantibodies that attack the body‟s own tissues

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three reasons why self-tolerance

cross-reactivity
abnormal exposure of self-antigens in the blood
self-reactive T cells

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cross-reactivity

•some antibodies against foreign antigens react to similar self-antigens
•rheumatic fever -streptococcus antibodies also react with heart valves

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abnormal exposure of self-antigens in the blood

•some of our native antigens are not exposed to blood
•blood-testes barrier isolates sperm from blood

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self-reactive T cells

–not all are eliminated in thymus and are normally kept in check by regulatory T (TR) cells

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Immunodeficiency Diseases

immune system fails to react vigorously enough

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Severe Combined Immunodeficiency Disease (SCID)

–hereditary lack of T and B cells
–vulnerability to opportunistic infection and must live in protective enclosures

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Acquired Immunodeficiency Syndrome (AIDS)

nonhereditary diseases contracted after birth
•group of conditions that involve and severely depress the immune response
•caused by infection with the human immunodeficiency virus (HIV)

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nonhereditary diseases contracted after birth
•group of conditions that involve and severely depress the immune response
•caused by infection with the human immunodeficiency virus (HIV)

–HIV structure (next slide)
–invades helper T cells, macrophages and dendritic cells by “tricking” them to internalize viruses by receptor mediated endocytosis
–reverse transcriptase (retrovirus) uses viral RNA as template to synthesize DNA
•new DNA inserted into host cell DNA (may be dormant for months to years)
•when activated, it induces the host cell to produce new viral RNA, capsid proteins, and matrix proteins
•they are coated with bits of the host cell‟s plasma membrane
•adhere to new host cells and repeat the process

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AIDS

by destroying THcells, HIV strikes at the central coordinating agent of nonspecific defense, humoral immunity, and cellular immunity
•incubation period ranges from several months to 12 years
•signs and symptoms
–early symptoms: flulike symptoms of chills and fever
–progresses to night sweats, fatigue, headache, extreme weight loss, lymphadenitis
–normal THcount is 600 to 1,200 cells/L of blood, but in AIDS it is less than 200 cells/L
–person susceptible to opportunistic infections (Toxoplasma, Pneumocystis, herpes simplex virus, cytomegalovirus, or tuberculosis)
–Candida (thrush): white patches on mucous membranes
–Kaposi sarcoma: cancer originates in endothelial cells of blood vessels causes purple lesions in skin

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HIV Transmission

through blood, semen, vaginal secretions, breast milk, or across the placenta
•most common means of transmission
–sexual intercourse (vaginal, anal, oral)
–contaminated blood products
–contaminated needles
•not transmitted by casual contact
•undamaged latex condom is an effective barrier to HIV, especially with spermicide nonoxynol-9

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Treatment Strategies

prevent binding to CD4 proteins of THcells
•disrupt reverse transcriptase to inhibit assembly of new viruses or their release from host cells
•medications
–none can eliminate HIV, all have serious side-effects
–HIV develops drug resistance
•medicines used in combination
–AZT (azidothymidine)
•first anti-HIV drug -inhibits reverse transcriptase
–protease inhibitors
•inhibit enzymes HIV needs to replicate
–now more than 24 anti-HIV drugs on the market