Ch. 22: Lymphatic System and Immunity Flashcards
(160 cards)
1
Q
Innate immunity.
A
Non-specific, defences are present at birth, early warning system, prevent microbes from entering body, eliminate microbes that do enter the body.
2
Q
First line of defence of innate immunity.
A
Physical and chemical barriers of skin and mucous membranes. Epidermis has many layers of closely packed keratinized cells, periodic shedding of epidermal cells removes microbes from skin surface, mucous membranes secrete mucous that traps microbes, lacrimal apparatus of eyes produces and drains away tears in response to irritants, washing action of tears dilutes microbes and stops them from settling on eyeball surface, saliva washes microbes from teeth and mouth, cleansing of urethra by flow of urine slows microbial colonization, vaginal secretions expel microbes, vomiting expels microbes, defecation expels microbes, unsaturated FAs in sebum on skin surface inhibit bacteria growth, sweating flushes microbes from skin, gastric juice in stomach destroys bacteria.
3
Q
Second line of defence of innate immunity.
A
Antimicrobial substances, NK cells, phagocytes, inflammation, fever.
4
Q
Adaptive immunity.
A
Specific recognition of microbes, specific response, adapts or adjusts to handle a specific microbe, lymphocytes.
5
Q
Lymphatic system is responsible for which immunity?
A
Adaptive.
6
Q
Lymphatic system contains…
A
Lymph, lymphatic vessels, structures and organs containing lymphatic tissue, and red bone marrow.
7
Q
Lymphatic tissue.
A
Specialized form of reticular connective tissue that contains large numbers of lymphocytes.
8
Q
3 functions of lymphatic system.
A
1) Drains excess interstitial fluid from tissue spaces back into blood
2) Transports dietary lipids from GI
3) Carries out immune responses
9
Q
Lymphatic capillaries.
A
Located between cells, closed at one end, unite to form lymphatic vessels, greater permeability and larger diameter than blood capillaries, one-way structure that permits interstitial fluid to flow into them but not out.
10
Q
Lymphatic vessels.
A
Resemble small veins, thinner walls, more valves.
11
Q
Lymph nodes.
A
Encapsulated bean-shaped organs consisting of masses of B-cells and T-cells. Covered by a capsule of dense connective tissue that extends into the node. Capsular extensions (trabeculae) divide the node into compartments, provide support, and provide a route for blood vessels into the interior of the node. Internal to the capsule is a supporting network of reticular fibres and fibroblasts. Parenchyma of a lymph node is divided into a cortex and medulla, and the cortex consists of an outer cortex and inner cortex.
12
Q
Where are lymphatic vessels in the skin and in the viscera?
A
Skin: Lie in subcutaneous tissue and follow the same route as veins.
Viscera: Follow the same route as arteries and form plexuses around them.
13
Q
Which tissues lack lymphatic capillaries?
A
Avascular tissues (cartilage, epidermis, cornea), parts of spleen, and red bone marrow.
14
Q
Describe the epithelial cell wall of lymphatic capillaries.
A
The cells overlap, and when the pressure is greater in interstitial fluid than in lymph, the cells separate slightly so interstitial fluid enters the lymphatic capillary. When the pressure is greater in the lymphatic capillary, the cells adhere more closely so lymph cannot escape back into interstitial fluid. Pressure is relieved as lymph moves further down the lymphatic capillary.
15
Q
Anchoring filaments.
A
Attach to lymphatic capillaries, contain elastic fibres, extend out from the capillary attaching lymphatic endothelial cells to surrounding tissues. When excess interstitial fluid accumulate and cause tissue swelling, the anchoring filaments are pulled, making the openings between cells even larger so that more fluid can flow into the lymphatic capillary.
16
Q
Lacteals.
A
Specialized lymphatic capillaries, carry dietary lipids into lymphatic vessels and into blood in the small intestine.
17
Q
What colour is lymph?
A
Clear pale yellow. Lymph draining from the small intestine is creamy white.
18
Q
How does lymph travel?
A
Through lymphatic capillaries –> lymphatic vessels –> lymph nodes.
19
Q
Lymph trunks.
A
As lymphatic vessels exit lymph nodes in a particular region of the body, they unite to form lymph trunks.
20
Q
What are the principal lymph trunks?
A
Lumbar trunks, intestinal trunks, bronchomediastinal trunks, subclavian trunks, jugular trunks.
21
Q
Lumbar trunks.
A
Drain lymph from lower limbs, wall and viscera of pelvis, kidneys, adrenal glands, abdominal wall.
22
Q
Intestinal trunks.
A
Drain lymph from stomach, intestines, pancreas, spleen, part of the liver.
23
Q
Bronchomediastinal trunks.
A
Drain lymph from thoracic wall, lung, heart.
24
Q
Subclavian trunks.
A
Drain lymph from upper limbs.
25
Jugular trunks.
Drain lymph from head and neck.
26
Lymph from the upper right quadrant of the body returns to the...
Superior vena cava from the right brachiocephalic vein.
27
Lymph from the upper left side of the body and entire body below diaphragm returns to the...
Superior vena cava from the left brachiocephalic vein.
28
An important function of lymphatic vessels is to...
Return the lost plasma proteins and plasma to the bloodstream.
29
Lymph drains into venous blood through the...
Right lymphatic duct and the thoracic duct at the junction of the internal jugular and subclavian veins.
30
Respiratory pump.
Lymph flow is maintained by pressure changes that occur during inhalation. Lymph flows from the abdominal region (high pressure) to the thoracic region (low pressure). When the pressures reverse during exhalation, the valves in lymphatic vessels prevent back flow.
31
Skeletal muscle pump.
Milking action of skeletal muscle contractions compresses lymphatic vessels and forces lymph toward the junction of the internal jugular and subclavian veins.
32
Primary lymphatic organs.
Sites where stem cells divide and become immunocompetent. Red bone marrow (flat bones, epiphyses of long bones) and thymus.
33
Secondary lymphatic organs and tissues.
Sites where most immune responses occur. Lymph nodes, spleen, lymphatic nodules.
34
Which lymphatic structures are organs and which are tissues?
Organs: thymus, lymph nodes, spleen (each is surrounded by a connective tissue capsule.
Tissue: nodules (lack a capsule).
35
Describe the structure of the thymus.
Located in mediastinum between sternum and aorta. An enveloping layer of connective tissue holds the 2 lobes together, and a connective tissue capsule encloses each lobe separately. Extensions of the capsule (trabeculae) penetrate inward and divide each lobe into lobules.
36
Each thymic lobule consists of a...
Deeply staining outer cortex and lighter staining central medulla.
37
Outer cortex of thymus.
Composed of large numbers of T-cells and scattered dendritic cells, epithelial cells, macrophages.
38
Describe T-cells and the thymus.
Pre-T-cells migrate from red bone marrow to the thymus cortex where they proliferate and mature. T-cells then enter the medulla. T-cells that leave the thymus via the blood migrate to lymph nodes, spleen and other lymphatic tissues where they colonize parts of these organs and tissues.
39
What is the role of thymic macrophages?
Clear out debris of dead and dying cells.
40
Inner medulla of thymus.
Consists of widely scattered mature T-cells, epithelial cells, dendritic cells, macrophages. Some epithelial cells cluster and degenerate and are filled with keratohyalin granules and keratin. These clusters are called thymic corpuscles and they serve as sites of cell death for T-cells in the medulla.
41
Why does the thymus appear red?
High content of lymphoid tissue and rich blood supply.
42
Large groups of lymph nodes are present near the...
Mammary glands, and in the axillae and groin.
43
Stroma of a lymph node.
Capsule, trabeculae, reticular fibres and fibroblasts.
44
Outer cortex of lymphatic node.
Consists of lymphatic nodules.
45
Lymphatic nodules.
Masses of lymphatic tissue that are not surrounded by a capsule. Scattered throughout lamina proprietor of mucous membranes lining the GI, urinary tract, reproductive tract, and respiratory airways. Nodules consisting of mainly B-cells are primary lymphatic nodules, but most of the lymphatic nodules in the outer cortex of nodes are secondary lymphatic nodules which form in response to an antigen and are sites of plasma cell and memory B-cell formation. After B-cells in a primary lymphatic nodule recognize an antigen, the primary lymphatic nodule develops into a secondary lymphatic nodule. The germinal center of a secondary lymphatic nodule contains a region of light staining cells (B-cells, follicular dendritic cells, macrophages). When follicular dendritic cells present an antigen, B-cells proliferate and develop into antibody producing plasma cells or memory B-cells. The region of a secondary lymphatic nodule surrounding the germinal center is composed of dense accumulations of B-cells that have migrated away from their site of origin within the nodule.
46
Inner cortex of lymphatic node.
Does not contain lymphatic nodules. Consists mainly of T-cells and dendritic cells that enter a lymph node from other tissues. Dendritic cells present antigens to T-cells. Newly formed T-cells migrate from lymph node to other areas of the body.
47
Medulla of lymphatic node.
Contains B-cells, antibody producing plasma cells that have migrated out of cortex, and macrophages.
48
How does lymph enter a lymph node?
Through several afferent lymphatic vessels which penetrate the convex surface of the node, and contain valves that open toward the center of the node. Once inside the node, lymph flows into subcapsular sinuses, then trabecular sinuses, then medullary sinuses.
49
How does lymph exit a lymph node?
Efferent lymphatic vessels contain valves that open away from the center of the lymph node to convey lymph, antibodies secreted by plasma cells, and activated T-cells out of the node.
50
Hilum.
Slight depression on one side of the lymph node where efferent vessels emerge from. Blood vessels can also enter and exit the node here.
51
How does a lymph node act as a filter?
Lymph enters one end --> foreign substances are trapped by reticular fibres within sinuses --> macrophages and lymphocytes destroy foreign substances.
52
Spleen.
Largest single mass of lymphatic tissue. Soft, encapsulated, located between stomach and diaphragm. Splenic artery, splenic vein and efferent lymphatic vessel pass through its hilum. A capsule of dense connective tissue surrounds the spleen and is covered by a serous membrane. Trabeculae extend inward from the capsule.
53
Stroma of the spleen.
Capsule, trabeculae, reticular fibres, fibroblasts.
54
Parenchyma of the spleen consists of 2 different kinds of tissue:
1) White pulp (lymphatic tissue, lymphocytes, macrophages, arranged around branches of splenic artery).
2) Red pulp (blood-filled venous sinuses and cords of splenic tissue, cords consist of RBCs / macrophages / lymphocytes / plasma cells / granulocytes, veins are closely associated with red pulp).
55
What are the roles of B-cell, T-cells and macrophages within white pulp?
B-cells and T-cells carry out immune responses. Macrophages destroy blood borne pathogens.
56
What are the 3 functions of the red pulp related to blood cells?
1) Macrophage removal of ruptured and defective blood cells and platelets.
2) Storage of platelets.
3) Production of blood cells during fetal life.
57
Tonsils.
5 tonsils form a ring at the junction of the oral cavity and oropharynx, and at the junction of the nasal cavity and nasopharynx. Tonsils are strategically positioned to participate in immune responses against inhaled/ingested foreign substances.
58
Single pharyngeal tonsil.
Adenoid. Embedded in the posterior wall of the nasopharynx.
59
Two palatine tonsils.
Posterior region of oral cavity (one on either side). The tonsils commonly removed in a tonsillectomy.
60
Paired lingual tonsils.
Base of tongue. May require removal.
61
Which enzyme is capable of breaking down cell walls of bacteria, and is present in tears, saliva, perspiration, nasal secretions and tissue fluids?
Lysosome.
62
Antimicrobial substances.
Discourage microbial growth. Interferons, complement system, iron-binding proteins, antimicrobial proteins.
63
Interferons.
Lymphocytes, macrophages, and fibroblasts infected with viruses produce IFNs. Once released, they diffuse to uninfected neighbouring cells where they induce synthesis of antiviral proteins that interfere with viral replication.
64
Complement system.
Defensive system made up of 30+ normally inactive proteins produced by the liver and found in blood plasma and on plasma membranes. These proteins enhance immune reactions, causing cytolysis, phagocytosis, inflammation, and prevent excessive damage to body tissues.
65
Iron-binding proteins.
Inhibit growth of bacteria by reducing the amount of available iron.
66
Antimicrobial proteins.
Short peptides that have a broad spectrum of antimicrobial activity, kill a wide range of microbes, attract dendritic cells and mast cells. Microbes exposed to AMPs do not develop resistance.
67
Natural killer cells.
Lack membrane molecules that identify B-cell and T-cells. Attack any body cell that displays abnormal or unusual plasma membrane proteins. NK binding to a target cell releases granules containing toxic substances. Some granules contain perforin which inserts into PM of target cell and creates perforations in the membrane, ECF flows into target cell and it bursts. Other granules contain granzymes which are protein-digesting enzymes that induce the target cell to undergo apoptosis.
68
Phagocytes.
Neutrophils and macrophages. Ingest microbes and cellular debris. When an infection occurs, neutrophils and monocytes migrate to infected area. Monocytes enlarge and develop into wandering macrophages.
69
Describe the steps involved in phagocytosis.
1) Chemotaxis: chemically stimulated movement of phagocytes to site of damage.
2) Adherence: attachment of phagocyte to microbe.
3) Ingestion: PM of phagocyte extends pseudopods that engulf microbe into a phagosome.
4) Digestion: phagosome enters cytoplasm and merges with lysosomes to form a phagolysosome.
5) Killing: lysozyme, digestive enzymes and oxidants within a phagolysosome kills microbe.
70
Inflammation.
Produced by pathogens, abrasions, chemical irritants, cell distortions or disturbances, extreme temperatures. Attempt to dispose of microbes at the site of injury to prevent their spread and prepare for tissue repair.
71
Describe PRISH in relation to inflammation.
P: Pain (release of chemicals and injury to neurons)
R: Redness (blood is rushed to affected area)
I: Immobility (loss of function in inflamed area)
S: Swelling (accumulation of fluids)
H: Heat (blood is rushed to affected area)
72
What are the 3 major events during inflammation?
1) Vasodilation and increased blood vessel permeability
2) Emigration of phagocytes from blood to interstitial fluid
3) Tissue repair
73
Vasodilation and increased blood vessel permeability during inflammation.
Defensive proteins enter damaged area from blood, more blood can flow through damaged area, remove toxins and dead cells from area. Histamine, kinins, prostaglandins, leukotrienes.
74
Histamine.
Released by mast cells, basophils, platelets, neutrophils, macrophages. Causes vasodilation and increased permeability.
75
Kinins.
Polypeptides formed in blood by inactive precursors. Cause vasodilation and increased permeability. Serve as chemotactic agents for phagocytes. Affect some nerve endings, causing much of the pain associated with inflammation.
76
Prostaglandins.
Released by damaged cells. Intensify the effects of histamine and kinins. Stimulate emigration of phagocytes through capillary walls. Intensify and prolong the pain associated with inflammation.
77
Leukotrienes.
Produced by basophils and mast cells. Cause increased permeability. Work as chemotactic agents to attract phagocytes.
78
Emigration of phagocytes from blood to interstitial fluid during inflammation.
Phagocytes appear at damaged area within an hour. As blood accumulates, neutrophils stick to the inner surface of endothelium of blood vessels and squeeze through the wall to reach the damaged area. This emigration depends on chemotaxis. A steady stream of neutrophils is ensured by the production and release of cells from red bone marrow. Neutrophils predominate in early stages of infection and die off quickly. Monocytes follow neutrophils to damaged area and transform into wandering macrophages. Within a few days, a pocket of dead phagocytes and damaged tissue forms (pus). Pus formation occurs in most inflammation responses and usually continues until the infection subsides. Pus reaches the surface of the body or drains into an internal cavity and is dispersed.
79
Acute inflammation.
Signs and symptoms develop rapidly and last for a few days to weeks. Principal defensive cells are neutrophils.
Examples: sore throat, appendicitis, cold, flue, bacterial pneumonia, skin scratch.
80
Chronic inflammation.
Signs and symptoms develop slowly and last for months to years. Principal defensive cells are monocytes and macrophages.
Examples: mononucleosis, peptic ulcers, tuberculosis, rheumatoid arthritis, ulcerative colitis.
81
Fever.
Occurs because the hypothalamic thermostat is reset. Bacterial toxins elevate temperature to trigger release of fever-causing cytokines (IL-1). Elevated body temperature intensifies effects of interferons, inhibits growth of microbes, and speeds up reactions that aid repair.
82
T-cells and B-cells develop in...
Primary lymphatic organs from pluripotent stem cells that originate in red bone marrow.
83
T-cell maturation.
T-cells develop from pre-T-cells that migrate from red bone marrow into the thymus where they mature. Most T-cells arise before puberty, but they continue to mature and leave the thymus throughout life. T-cells develop immunocompetence before they leave the thymus.
84
B-cell maturation.
B-cells complete their development in red bone marrow. B-cells develop immunocompetence before they leave the red bone marrow.
85
B-cells and T-cells begin to make several proteins that...
Are inserted into their plasma membranes. Some of these proteins function as antigen receptors which are capable of recognizing specific antigens.
86
CD4 T-cells.
Helper T-cells. Their plasma membranes include antigen receptors and a protein CD4. Aid the immune responses of cell-mediated and antibody-mediated immunity. Recognize exogenous antigen fragments associated with MHC-II molecules at the surface of an APC.
87
CD8 T-cells.
Cytotoxic T-cells. Their plasma membranes include antigen receptors and a protein CD8. Recognize foreign antigens combined with MHC-I molecules on the surface of body cells infected by microbes, tumour cells, and cells of a transplanted tissue.
88
Cell-mediated immunity.
Cytotoxic T-cells directly attack invading antigens. Effective against intracellular pathogens (viruses, bacteria, fungi inside cells), cancer cells, foreign tissue transplants. Triggered by antigens.
89
Antibody-mediated immunity.
Humoral immunity. B-cells transform into plasma cells which synthesize and secrete antibodies. Effective against extracellular pathogens (viruses, bacteria, fungi in body fluids). Triggered by antigens.
90
How can an antigen provoke both cell-mediated and antibody-mediated immunity?
When an antigen enters the body, there are many copies made. Some copies may be present inside body cells, and other may be present in body fluids outside body cells.
91
Clonal selection.
Once helper T-cells, cytotoxic T-cells, and B-cells encounter a copy of the antigen and receives stimulatory cues, they undergo clonal selection. The lymphocyte will proliferate and differentiate in response to the specific antigen. Result of this is the formation of a population of identical cells that can recognize the same specific antigen as the original lymphocyte.
92
Where does clonal selection occurs?
Secondary lymphatic organs and tissues.
93
Swollen tonsils or lymph nodes in the neck during sickness are usually caused by...
Clonal selection.
94
A lymphocyte that undergoes clonal selection gives rise to...
Effector cells and memory cells.
95
Effector cells.
Carry out immune responses that result in the destruction or inactivation of an antigen. Die after the immune response is complete.
Examples: helper T-cells, cytotoxic T-cells, plasma cells.
96
Memory cells.
If the same antigen enters the body again, these cells initiate a faster reaction. Respond to the antigen by proliferating and differentiating into more effector and memory cells. Do not die at the end of the immune response.
Examples: memory helper T-cells, memory cytotoxic T-cells, memory B-cells.
97
Immunogenicity.
Antigen characteristic. Ability to provoke immune response by stimulating production of antibodies and/or proliferation of T-cells.
98
Reactivity.
Antigen characteristic. Ability to react specifically with the antibodies or cells it provokes.
99
Complete antigen.
Possess both immunogenicity and reactivity.
100
Nonmicrobial antigens.
Chemical components of pollen, egg white, incompatible blood cells, transplanted tissues and organs.
101
Epitopes.
Antigenic determinants. Small parts of a large antigen molecule that act as the triggers for immune responses.
102
Antigens that get past the innate defences follow 1 out of 3 routes into lymphatic tissue:
1) Antigens that enter the blood are trapped as they flow through the spleen.
2) Antigens that penetrate the skin enter lymphatic vessels and lodge in lymph nodes.
3) Antigens that penetrate mucous membranes are trapped by MALT.
103
What is MALT?
Mucosa-associated lymphatic tissue.
104
Why can plastic materials be used in artificial heart valves or joints?
Because large molecules with simple repeating subunits (like plastics) are not antigenic.
105
Hapten.
Small substance that has reactivity but lacks immunogenicity. It can stimulate an immune response only if it is attached to a larger carrier molecule.
106
Why can B-cells and T-cells recognize so many epitopes?
Genetic recombination increases the diversity of the antigen receptors on these cells. This occurs as the B-cells and T-cells are developing from stem cells in primary lymphatic organs.
107
MHC antigens.
Human leukocyte antigens (HLA). Self-antigens located in the plasma membrane of body cells, and they mark the surface of each of your body cells (except RBCs). They reject transplanted tissue, and help recognize that an antigen is foreign.
108
MHC-I
Built into plasma membranes of all body cells except RBCs.
109
MHC-II
Appear on the surface of antigen-presenting cells (APCs).
110
B-cells recognize and bind to antigens in...
Lymph, interstitial fluid, blood plasma.
111
T-cells recognize and bind to...
Fragments of antigenic proteins that are processing and presented in a specific way.
112
Antigen processing.
Antigenic proteins are broken down into peptide fragments that associate with MHCs, and the antigen-MHC complex is inserted into the plasma membrane of the body cell (antigen presentation).
113
When a peptide fragment comes from a self-protein...
T-cells ignore the antigen-MHC complex.
114
When a peptide fragment comes from a foreign protein...
T-cells recognize the antigen-MHC complex as an intruder, and an immune response takes place.
115
Antigen processing and presentation occur in...
2 days. Depends on if the antigen is intracellular or extracellular.
116
Processing of exogenous antigens.
Bacteria, bacterial toxins, parasitic worms, inhaled pollen/dust and viruses that have not yet infected a body cell. APCs process and present exogenous antigens.
1) Ingestion of antigen: APCs ingest exogenous antigens by phagocytosis or endocytosis.
2) Digestion of antigen into peptide fragments: protein-digesting enzymes split large antigens into short peptide fragments within the phagosome or endosome.
3) Synthesis of MHC-II: APC synthesizes MHC-II molecules at ER.
4) Packaging of MHC-II: into vesicles.
5) Fusion of vesicles: vesicles containing antigen peptide fragments and MHC-II merge and fuse.
6) Binding of peptide fragments to MHC-II.
7) Insertion of antigen-MHC-II into PM: combined vesicle undergoes exocytosis and the complexes are inserted into the PM.
The APC then migrates to lymphatic tissue to present the antigen to T-cells.
117
Antigen-presenting cells.
Dendritic cells, macrophages, B-cells. Strategically located in places where antigens are likely to penetrate the innate defences and enter the body.
118
Processing of endogenous antigens.
Viral proteins produced after a virus infects the cell and takes over metabolic processes, toxins produced from intracellular bacteria, and abnormal proteins synthesized by cancerous cells.
1) Digestion of antigen into peptide fragments: within infection cell protein-digesting enzymes split endogenous antigen into short peptide fragments.
2) Synthesis of MHC-I: infected cell synthesizes MHC-I molecules at ER.
3) Binding of peptide fragments to MHC-I: antigen peptide fragments enter ER and bind to MHC-I.
4) Packaging of antigen-MHC-I: into vesicles.
5) Insertion of antigen-MHC-I into PM: vesicles that contain antigen-MHC-I complexes undergo exocytosis and are inserted into PM.
119
Cytokines.
Small protein hormones that stimulate or inhibit normal cell functions.
120
Which cells release cytokines?
Lymphocytes, APCs, fibroblasts, endothelial cells, monocytes, hepatocytes, kidney cells.
121
Describe the brief process of cell-mediated immunity.
Specific antigen --> T-cell activation --> clonal selection --> clone cell formation --> effector and memory cells --> eliminate intruder.
122
How are T-cells activated?
TCRs recognize and bind to specific foreign antigen fragments that are presented in antigen-MHC complexes.
123
What is the first signal in activation of a T-cell?
Antigen recognition by a TCR with CD4 or CD8 proteins.
124
What is a costimulation?
A T-cell only becomes activated if it binds to the antigen at the same time it receives a second signal. The need for costimulation can prevent immune responses from occurring accidentally. Different costimulators affect the activated T-cell in different ways.
125
Recognition without costimulation leads to...
A prolonged state of inactivity in T-cells and B-cells = anergy.
126
How are helper T-cells activated?
With the help of the CD4 protein, the helper T-cell and APC interact with each other, costimulation occurs, and it is activated. Once activated, the helper T-cell undergoes clonal selection, and a clone of active helper T-cells and memory helper T-cells is produced. Active helper T-cells secrete cytokines (IL-2). IL-2 binds to IL-2 receptors on the PM of the cell that secreted it, which stimulators cell division. More helper T-cells are produced, leading to more IL-2 secretion and more cell division.
127
IL-2
Needed for all immune responses. The prime trigger of T-cell proliferation. Can act as a costimulator for resting helper T-cells or cytotoxic T-cells. Enhances activation and proliferation of T-cells, B-cells and NK cells.
128
How are cytotoxic T-cells activated?
To be activated, cytotoxic T-cells require costimulation by IL-2 or other cytokines produced by active helper T-cells that have already become bound to copies of the same antigen. Maximal activation requires presentation of antigens associated with MHC-I and MHC-II molecules. Clonal selection occurs to produce a clone of active cytotoxic T-cells and memory cytotoxic T-cells.
129
How do cytotoxic T-cells eliminate invaders?
They leave secondary lymphatic organs and tissues and migrate to seek out and destroy infected target cells, cancer cells and transplanted cells.
A) Cytotoxic T-cells recognize and bind to infected target cells that have microbial antigens displayed on their surfaces --> release granzymes which are protein-digesting enzymes that trigger apoptosis --> infected cell is destroyed --> released microbes are killed by phagocytes.
OR
B) Cytotoxic T-cells bind to infected body cells --> release perforin and granulysin --> perforin creates channels in the PM of target cell allowing ECF to flow in and the target cell bursts --> granulysin enters through the channels and destroys microbes by creating holes in the PM. Cytotoxic T-cells can also release lymphotoxin which activates enzymes in the target cell to cause DNA fragmentation and cell death. Cytotoxic T-cells can also release gamma-interferon which attracts and activates phagocytic cells. Cytotoxic T-cells can also release macrophage migration inhibition factor which prevents migration of phagocytes from the infection site.
130
Immunological surveillance.
When a normal cell transforms into a cancerous cell, it often displays novel cell surface components which are rarely displayed on the surface of normal cells. If the immune system recognizes a tumour antigen as non-self, it can destroy any cancer cells carrying that antigen. These immune responses are carried out by cytotoxic T-cells, macrophages and NK cells. Most effective in eliminating tumour cells due to cancer-causing viruses.
131
Transplant recipients who are taking immunosuppressive drugs have an increased incidence of...
Virus-associated cancers.
132
Describe the brief process of antibody-mediated immunity.
A specific B-cell in a lymph node, spleen or MALT becomes activated in the presence of a foreign antigen --> clonal selection --> a clone of plasma cells and memory cells.
133
Plasma cells.
Effector cells of a B-cell clone. Secrete specific antibodies which circulate in lymph and blood to reach invasion site.
134
How are B-cells activated?
An antigen binds to BCRs --> antigen is taken into B-cell --> broken down into peptide fragments --> combined with MHC-II --> moved to B-cell PM --> helper T-cells recognize antigen-MHC-II complex and deliver costimulation needed for B-cell proliferation and differentiation --> helper T-cell produces IL-2 and other cytokines that function as costimulators for B-cells.
135
IL-4 and IL-6.
Also produced by helper T-cells. Enhance B-cell proliferation, B-cell differentiation into plasma cells, and secretion of antibodies by plasma cells.
136
Antibodies.
An antibody can combine specifically with the epitope on the antigen that triggered its production.
137
Plasma cells can secrete as many different antibodies as there are different BCRs because...
The same recombined gene segments code for both the BCR and the antibodies eventually secreted by plasma cells.
138
Describe the chains in an antibody.
An antibody contains 4 polypeptide chains. 2 of the chains are identical to each other and have short CHO chains attached to them = heavy chains. 2 other chains are also identical to each other = light chains. A disulphide bond holds each L chain to a H chain. Two disulphide bonds also link the mid-region of the 2 H chains (hinge region). Because the antibody arms can move as the hinge region bends, an antibody can assume either a T-shape or Y-shape. Beyond the hinge region, parts of the 2 H chains form the stem region.
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Neutralizing antigen.
The reaction of antibody with antigen blocks/neutralizes bacterial toxins and prevents attachment of viruses to body cells.
140
Immobilizing bacteria.
If antibodies form against antigens on the cilia/flagella of motile bacteria, the antigen-antibody reaction causes the bacteria to lose their motility limiting their spread.
141
Agglutinating and precipitating antigen.
Because antibodies have 2+ sites for antigen binding, the antigen-antibody reaction crosslinks pathogens to one another causing agglutination. Phagocytic cells ingest agglutinated microbes more readily, and soluble antigens may come out of solution and form a more easily phagocytize precipitate when cross linked by antibodies.
142
Activating complement.
Antigen-antibody complexes initiate the classical pathway of the complement system.
143
Enhancing phagocytosis.
Stem region acts as a flag that attracts phagocytes once antigens have bound to the antibody. This enhances phagocytic activity by causing agglutination and precipitation by activating complement and coating microbes so that they are more susceptible to phagocytosis.
144
What are the actions of an antibody?
Neutralizing the antigen, immobilizing bacteria, agglutination and precipitating the antigen, activating complement, and enhancing phagocytosis.
145
C1-C9
Complement proteins. Become activated when split by enzymes into active fragments.
146
How may complement activation occur?
Via 3 different pathways. All end up activating C3.
147
Classical pathway of complement activation.
Antibodies bind to antigen --> antigen-antibody complex binds and activates C1 --> activates C3.
148
Alternative pathway of complement activation.
Interaction between lipid-CHO complexes on the surface of microbes and complement protein factors B, D and P --> activates C3.
149
Lectin pathway of complement activation.
Macrophages that digest microbes release chemicals that cause the liver to produce lectin proteins --> bind to CHO on surface of microbes --> activates C3.
150
What happens once C3 is activated?
1) Inactive C3 splits into activated C3a and C3b.
2) C3b binds to surface of microbe --> receptors on phagocyte attach to C3b --> C3b enhances phagocytosis by coating a microbe (opsonization).
3) C3b initiates a series of reactions that bring about cytolysis (C3b splits C5 --> C5b binds C6 and C7 --> C6 and C7 attach to PM of invading microbe --> C8 and C9 join other complement proteins and together form a cylinder-shaped membrane attack complex which inserts into PM).
4) Membrane attach complex creates channels in PM that result in cytolysis.
5) C3a and C3b bind to mast cells and cause them to release histamine that increases blood vessel permeability during inflammation. C5a also attracts phagocytes to the site of inflammation.
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What happens once activated C3 activates the complement system?
It is broken down so its destructive capabilities are minimized.
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Immunological memory.
Due to the presence of long-lasting antibodies and and long-lived lymphocytes that arise during clonal selection and antigen-stimulated B-cells and T-cells.
Primary response: After an initial contact with an antigen, no antibodies are present for a few days, then a slow rise in the antibody titer occurs, followed by a gradual decline.
Secondary response: After subsequent encounters, the antibody titer increases and consists mainly of IgG antibodies.
Antibodies produced during a secondary response have an even higher affinity for the antigen than those produced during a primary response.
This provides the basis for immunizations by vaccination.
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Antibody titer.
The amount of antibody in serum.
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Self-recognition.
Possessed by T-cells. The ability to recognize self MHC proteins.
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Self-tolerance.
Possessed by T-cells and B-cells. Lack reactivity to peptide fragments of self proteins.
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How do autoimmune diseases develop?
The loss of self-tolerance.
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How do T-cells develop self-recognition?
Pre-T-cells develop this in the thymus via position selection. During positive selection, some pre-T-cells express TCRs that interact with self-MHC proteins in epithelial cells in the thymic cortex. Because of this interaction, the T-cells can recognize the MHC part of an antigen-MHC complex. Other pre-T-cells that fail to interact with thymic epithelial cells are not able to recognize self-MHC proteins and they undergo apoptosis.
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How do T-cells develop self-tolerance?
Occurs via negative selection in which the T-cells interact with dendritic cells located at the junction of the thymic cortex and medulla. T-cells with receptors that recognize self-peptide fragments or other self-antigens are eliminated or inactivated. T-cells selected to survive do not respond to self-antigens. Negative selection occurs via deletion and anergy.
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What percentage of pre-T-cells in the thymus receive the proper signals to survive positive and negative selection?
1-5%.
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How do B-cells develop self-tolerance?
While B-cells are developing in red bone marrow, those cells exhibiting antigen receptors that recognize common self-antigens are deleted. Once B-cells are released into blood, anergy appears to be the main mechanism preventing responses to self-proteins. When B-cells encounter an antigen not associated with an APC, the necessary costimulation signal often is missing, and the B-cell is likely to become anergia rather than activated.
