Module 15 Flashcards
1
Q
The Blood
A
Blood is a Connective Tissue:
- Cells and Formed Elements (WBCs, RBCs, platelets)
- Extracellular Fluid Matrix (Plasma)
Functions:
- Transportation for oxygen, carbon dioxide, hormones, and nutrients
- Regulation of body temperature and pH
- Protection
Blood is a very important part of maintaining homeostasis
2
Q
Characteristics of the Blood
A
Blood has a number of physical characteristics that give it its functional properties:
- Viscosity: Thicker than water due to the amount of solutes, colloids, & suspended formed elements.
- Temperature: 38 degrees C (100.4 degrees F)
- pH: 7.35-7.45 (slightly alkaline)
- Color: Variable shades of red depending on oxygen content
- Volume: 4-6 liters depending on gender and body mass
3
Q
What are the 2 main components of blood?
A
1. Cells
4
Q
Cells
A
Blood Component:
Cells make up 45% of Blood
- More specifically formed-elements
- White Blood Cells, Red Blood Cells, and Platelets (thrombocytes)
5
Q
Plasma
A
Blood Component:
Plasma makes up 55% of Blood
- Typically a clear, yellow liquid
- 92% Water
- 8% solutes: 7 of the 8% are the plasma proteins Albumin, globulins, and fibrinogen
- 1% miscellaneous solutes
6
Q
Hematopoiesis
A
Hematopoiesis is the development of the formed elements of the blood:
- Red Bone Marrow
- Blood Cells are formed in red bone marrow from pluripotent stem cells and mature in the bone marrow or lymphoid tissue (spleen, tonsils, lymph nodes, thymus, etc.) under the influence of vaious cytokines
7
Q
Cytokines
A
Proliferation and maturation of blood cells depends of specific cytokines: chemical signals from one group of cells to stimulate another. Under the influence of these cytokines (growth factors, colony-stimulating factors, and interleukins) cells differentiate into the various cell types. The stem cells differentiate into either:
- the myeloid group or
- the lymphoid group
8
Q
The Myeloid Group
A
The immature myeloid (bone marrow) cells differentiate and become red blood cells, platelets, and many types of white blood cells.
9
Q
The Lymphoid Group
A
The lymphoid cells mature in the lymphatic system and give rise to a specific group of white blood cells called lymphocytes.
10
Q
What are the 3 types of Cytokines?
A
The three types of cytokines, chemical signals, are:
- Erythropoietin (EPO): Increases number of early red blood cells in the bone marrow
- Thrombopoietin (TPO): Increases the formation of platelets
- Colony-stimulating factors (CSFs) and interleukins: Increases the production and differentiation of white blood cells.
11
Q
Red Blood Cells (RBCs)
A
- Red cells are bi-concave discs: give high surface-to-volume rations.
- Red cells demonstrate reversible-deformity: able to squeeze through small spacese
- Mature red cells do not have a nucleus: provides maximum cytoplasmic space. Before the nucleus is lost, it provides instructions to produce hemoglobin, the oxygen carrying molecule of the red cell.
- RBCs live about 120 days
- Because they lack mitochondria, they don’t use any of the oxygen they carry
12
Q
Hemoglobin
A
Each red cell contains approximately 280 million hemoglobin molecules.
- Hemoglobin is the oxygen and CO2 carrying molecule in the body. Hgb transports O2 to the cells and CO2 from the cells.
- A Hgb molecule consists of: 4 heme molecules (ringed molecue with Iron atom at the center; each heme carries one oxygen molecule) and 4 globin chains (polypeptides: 2 alpha and 2 beta)
- Each Fe2 can pick up one oxygen molecule at the lungs, because the Iron atom is the binding site for oxygen.
13
Q
Erythropoiesis
A
Is part of hematopoiesis, specifically relating to the production and maturation of red blood cells.
- Red cells are produced continuously (approximately 2 million per second) to keep up with red cell production.
- The average person has 4.00-6.00 x 10^6 RBCs/mm^3
14
Q
Hypoxemia
A
If the number of red cells lost exceeds the number made, hypoxemia (too little oxygen in the blood) will result.
- Stimulates the kidneys to release the hormone erythropoietin
15
Q
Erythropoietin (EPO)
A
Hypoxemia (decreased amount of oxygen) detected in the kidneys stimulates the release of Erythropoietin, a hormone which increases the rate of Erythropoiesis.
- Measured by a reticulocyte (retic) count
- A reticulocyte is a new, not yet fully mature red cell
16
Q
Red Blood Cell Maturation
A
#1. Large cell with nucleus & very little cytoplasm - lack hemoglobin #2. Nucleus is lost, gains its bioconcave shape. Not mature yet, still contains some mitochondria, ribosomes, & endoplasmic reticulum. This almost-mature cell is called a reticulocyte. #3. Hemoglobin increases #4. Decreased cellular size
17
Q
Hematocrit (Hct)
A
Percentage of the whole blood that is occupied by red blood cells. Average is 45%, but women tend to be a little lower.
18
Q
What are the 2 types of Erythropoiesis Imbalances?
A
#1. Polycythemia #2. Anemia
19
Q
Polycythemia
A
Excess number of red blood cells. Increases the blood viscosity.
- Primary polycythemia (polycythemia vera): may cause an increase in all formed elements
- Secondary polycythemia: is an increase in red blood cells due to another condition.
#1. Hypoxia, smoking,sleep apnea, or any other
because of hypoxemia
#2. Dehydration
20
Q
Anemia
A
Is a decrease in the normal number of red blood cells. Insufficient RBCs or hemoglobin. Classified based on:
- Size: macrocytic, normocytic, and microcytic
- Hemoglobin Content: hypochromic & normochromic
- Etiology: Iron deficiency, red cell destruction, autoimmune disease, hemorrhage, lack of production in the bone marrow.
21
Q
What are 5 examples of Anemia?
A
- Hemorrhagic anemia: Normocytic, Normochromic, and caused by bleedin
- Iron deficiency anemia: Microcytic, Hypochromic, and caused by lack of iron
- Pernicious anemia: Macrocytic, Normochromic, and caused by Vitamin B12 deficiency
- Hemolytic anemia: Normocytic, Normochromic, and caused by destruction of RBCs
- Aplastic anemia: Normocytic, Normochromic, and caused by bone marrow failure
22
Q
Leukocytes
A
Are white blood cells. They are larger than RBCs, they have nuclei, they don’t have hemoglobin, and there are fewer white than red. There are 2 groups of WBCs:
- Granulocytes (granular leukocytes)
- Agranulocytes (agranular leukocytes)
23
Q
Granulocytes
A
The granulocytic group includes three specific WBCs, named from staining characteristics:
- Neutrophils: Stain somewhere in between red and purple
- Eosinophils: Stain red
- Basophils: Stain purple
24
Q
Agranular Leukocytes
A
Contain some cytoplasmic granules but they are much less prominent and they don’t stain as well as their granulocytic counterparts.
- Monocytes: macrophages in tissues
- Lymphocytes: T lymphocytes, B lymphocytes, Natural Killer (NK) cells.
25
What are the terms for white blood cell increases and decreases?
- Leukocytosis
| - Leukopenia
26
Leukocytosis
Is an increase in the number of white blood cells. It is a normal physiological response, up to a certain point. WBCs increase as a response to disease or conditions, and any disruption of homeostasis. Common causes would be bacterial infections, viruses, parasites, stress, temperature extremes, etc.
27
Leukemia
WBC numbers above 40,000 would indicate an abnormal proliferation. Frequently this is one of the various types of leukemia.
Leukemia is a cancer of the blood-forming cells, most often white cells.
28
Leukopenia
Is a decrease in white cell numbers, and is never a normal response. There isn't a normal physiological reason for a person's white count to go down. Causes can include AIDS, chemotherapy, or bone marrow failure (aplastic anemia).
29
White Blood Cell Functions
Physician's use the percentage of white blood cells in the blood to aid in the diagnosis of specific diseases. White blood cells work together to provide a powerful immune response, but each type has a unique role:
- Increased granulocytes in bacterial infections
- Increased lymphocytes in viral infections
Doctors will order a WBC differential analysis when a patient has an increased WBC count.
30
Neutrophils
60-70% of total WBCs in blood stream. Powerful phagocytes, increased in bacterial infections and inflammation. Granular cytoplasm
31
Lymphocytes
20-25% of total WBCs in blood sream. Increased and major role in viral infections and cancer prevention. Specific cellular immunity.
32
Monocytes
3-8% of total WBCs in blood stream. Differentiate into macrophages (phagocytes), present in chronic inflammation and infections.
33
Eosinophil
2-4% of total WBCs in blood stream. Allergic reactions, parasitic infections. Large red granules.
34
Basophil
0.5-1% of total WBCs in blood stream. Function poorly understood, chronic inflammation. Large dark blue granules.
35
Thrombocytes (Platelets)
Are cytoplasmic fragments of large cells in bone marrow called megakaryocytes. Platelets have a very short life span, approximately 5-9 days.
- Megakaryocytes are too large to leave the bone marrow
- 2000-5000 platelets develop from one megakaryocyte
- They assist with clot formation limiting blood loss by forming a platelet plug.
- Release chemicals to encourage vasoconstriction and activate coagulation.
36
Thrombocytes (Platelets)
Are cytoplasmic fragments of large cells in bone marrow called megakaryocytes. Platelets have a very short life span, approximately 5-9 days.
- Megakaryocytes are too large to leave the bone marrow
- 2000-5000 platelets develop from one megakaryocyte
- They assist with clot formation limiting blood loss by forming a platelet plug.
- Release chemicals to encourage vasoconstriction and activate coagulation.
37
Hemostasis
Is the overall process by which bleeding has stopped. There are 3 mechanisms involved in the process of bleeding cessation:
- Vascular Spasm
- Platelet plug formation
- Coagulation (clotting)
38
Vascular Spasm
Is the constriction of damaged blood vessels. Smooth muscle contraction reduces blood loss. The vascular constriction is due to chemicals released from platelets, damage to the smooth muscle of the vessels, and pain receptor reflexes.
39
Coagulation
A series of complex enzymatic reactions designed to activate specific coagulation proteins; most are plasma proteins.
- Activated in a stepwise/cascading fashion - similar to knocking over dominos. Most of these factors are synthesized by the liver and are enumerated with Roman numerals.
40
Coagulation
A series of complex enzymatic reactions designed to activate specific coagulation proteins; most are plasma proteins.
41
What are the 2 pathways to activate coagulation?
```
There are 2 separate pathways to activate coagulation, and they merge to form a common pathway. The presence of 2 attempts to guarantee that bleeding stops. Each is activated in a slightly different fashion.
#1. Extrinsic Pathway
#2. Intrinsic Pathway
```
42
Extrinsic Pathway
Is activated by damage outside of the vessel, specifically tissue. The extrinsic pathway has fewer steps and occurs rapidly.
- Fast activation and fewer steps
- A tissue protein called tissue factor (TF) or tissue thromboplastin is released from damaged tissue into the blood vessels.
43
Intrinsic Pathway
Is activated by substances within or associated with the vessel. Exposed vascular collagen, damaged endothelium, or activated platelets are all potent coagulation activators.
44
Stages of Coagulation
Regardless of the pathway, the goal is to merge at a common pathway by activating an enzyme called prothrombinase.
- Merge at common pathway - Formation of prothrombinase
- Formation of thrombin from prothrombin
- Formation of fibrin from fibrinogen
- Fibrin forms the clot and strengthens the platelet plug
- Ca++ plays a role throughout almost every step of the clotting process
45
Cofactors in the clotting process
There are a number of cofactors that must be present for clotting factor synthesis and for coagulation to occur:
- Vitamin K for clotting factors II, VII, IX, and X
- Ca++ required for almost every step of the coagulation process.
46
Plasma vs. Serum
Plasma and serum are almost the same liquid - side by side, one can't tell the difference:
- The liquid portion of clotted blood is serum. If the blood forms a clot by activating the soluble clotting factors, the liquid is called serum.
- The liquid portion of unclotted is plasma. If the clotting process is inhibited an the clotting factors remain inactive and soluble, the liquid is called plasma.
47
What are the 3 kinds of clots?
- Thrombus: Stationary Blood Clot
- Embolus: A circulating particle, often a clot that may obstruct a blood vessel. Can be fat, air, cholesterol plaque, blood, clump of platelets, etc.
- Thromboembolus: A stationary clot that dislodged from its primary site and traveled to another location.
48
Fibrinolytic System
Coagulation is not infrequent. The body has a mechanism to dissolve clots so they are not allowed to persist and accumulate called the Fibrinolytic System.
- As coagulation occurs, substances from tissue and blood activate the enzyme plaminogen to become plasmin.
- Plasmin is a potent proteolytic enzyme. It dissolves the clot by digesting fibrin and interferes with new clot formation by inactivating fibrinogen, prothrombin, and other clotting factors.
49
Anticoagulants
No, they are not blood thinners. Anticoagulants interfere with the coagulation process. Some examples of anticoagulants include:
- Heparin
- Coumadin (warfarin)
- EDTA
- Sodium Citrate
- Aspirin
50
Heparin
An Anticoagulant
Administered intravenously to a stroke or heart attach victim, also used in surgery and dialysis
51
Coumadin (warfarin)
An Anticcoagulant
Oral medication used to inhibit clotting in high-risk patients
52
EDTA
An Anticoagulant
Present in the blood-draw tubes used for blood counts
53
Sodium Citrate
An Anticoagulant
Present in blood collection bags for blood donations
54
Aspirin
An Anticoagulant
Inhibits platelet aggregation
55
Thrombolytics
Are chemicals used in medicine that break down clots that have already formed.
- Used after strokes, myocardial infarction, emboli, and thrombi
- Tissue-plasminogen activator (TPA)
56
ABO Blood Group Types
ABO blood types are determined by the presence or absence of A and B antigens (markers) on the surface of red cells. The A and B antigens on the individual red cells are genetically determined.
- the A gene codes for the development of the A antigen
- the B gene codes for the development of the B antigen
- the O gene results in lack of either A or B
57
Blood Group Genetics
For the ABO group, an individual inherits two genes, one from their mother and one from their father.
- If a person inherits at least one A gene, they will make A antigen
- If a person inherits at least one B gene, they will make B antigen
- If they inherit both A and B, they will express both antigens on their red cells
- An individual that doesn't inherit an A or a B will lack the antigens, and they have the O blood type
58
Blood Group Antibodies
A person develops antibodies in their plasma for the A and B antigens they lack on their red cells.
- A antigens on the red cells, B antibodies in the plasma
- B antigens on the red cells, A antibodies in the plasma
- A and B antigens on the red cells, no A and B antibodies in the plasma.
- No A or B antigens on the red cells, A and B antibodies in the plasma
Antigens are present at birth, but the antibodies are not.
59
Rh Factor
The Rh blood type identifies whether a person has the Rh antigen or not
- If they have it, they are Rh+, if they don't they are Rh-
- 85% of the population has the Rh antigen (Rh+)
- People do not normally have antibodies to the Rh antigen in their plasma
- Rh- people can develop an anti-Rh antibody if they are ever exposed to Rh+ blood. This is because they don't have the antigen, and it is foreign to them.
60
Blood Transfusions
It is important to understand that it is very rare for a person to receive a whole-blood transfusion. Only red cells are transfused.
- Blood-type O is the universal donor because there are no A or B antigens on the red cells. There aren't any A or B antigens to react with.
- AB is the universal recipient because these individuals don't have any A or B antibodies in their plasma.
61
Blood Type Compatibilities
```
Blood Type
A: A or O Compatible
B: B or O Compatible
AB: A, B, AB, or O
O: Only O
```
62
Transfusion Reactions
In a blood transfusion, if a patient receives the wrong blood type, their antibodies to the corresponding antigens will cause the incorrect RBCs to be destroyed by the immune system.
- Giving the wrong blood type can cause the patient to develop a fever, go into shock, result in acute renal failure.
63
Expectant Mother Blood Compatibility
Normally, a baby's blood never mixes with a mother's. With a miscarriage, trauma, but especially childbirth, it is very common for a few of the baby's red cells to get into the mom's bloodstream.
- If there are any antigens the mother doesn't recognize as hers, she can make an antibody against it.
- Throughout pregnancy, a mother is transferring antibody to the fetus to protect against disease.
- As long as these antibodies are not targeting baby's cells, this relationship works great
64
Hemolytic Disease of the Newborn (HDN)
Is caused by a blood incompatibility beween a fetus and an expectant mother.
- The most serious cause of HDN is an Rh incompatibility
- This problem arises if: Dad is Rh-positive, Mom is Rh Negative, Baby is Rh-positive, due to genetics inherited from the father.
65
Avoiding Rh Incompatibility
To help with this incompatibility, mothers who are Rh- are given an injection of Rhogam.
- Rhogam is commercially produced anti-Rh
- The administered Rhogam flags any Rh-positive cells in the mother, from the baby, to be destroyed before the mother's immune system can produce it's own anti-Rh. The Rhogam antibodies will disappear in a few weeks. If the mother makes her own anti-Rh, she can make it for the rest of her life.
66
The Lymphatic System
System consisting of lymyphatic vessels through which a clear fluid (lymph) passes. Functions include:
- Draining interstitial fluid
- Transporting dietary lipids absorbed by the gastrointestinal tract to the blood
- Facilitating immune responses
67
Lymphatic Vessels
Lymphatic vessels are a little different from blood vessels. Blood vessels contain blood that circulates to and from the heart. Lymphatic vessels carry lymphatic fluid (lymph) one way, from the tissue, back into the blood stream.
-Lymph vessels begin as small lymphatic capillaries that are located throughout the body in the interstitial spaces.
68
Lymph Nodes
Are present at intervals along the lymphatic vessels. The lymph nodes provide an opportunity for the lymphatic fluid to come into contact with the immune system. The immune system gets a continuous flow of information about what is taking place in the body.
69
Parts of the Lymphatic System
- Lymphatic capillaries
- Lymphatic vessels
- Lymph nodes
- Lymphatic trunks
- Lymphatic ducts
- Primary lymphatic organs
- Secondary lymphatic organs and tissues
70
Extracellular Fluids of the Lymphatic System
Plasma:
- Liquid component of blood
- Filtered through capillary walls to form interstitial fluid
- Large proteins don't pass through the capillaries
Interstitial Fluid:
- Clear fluid
- Less protein than plasma
- Most is reabsorbed back into the blood
Lymphatic Fluid:
- Unaltered interstitial fluid in the lymphatic vessels
- Absorbed dietary lipids
71
Flow of Lymphatic Fluid
Two mechanisms assist with lymph flow. In both scenarios, the valves present in the lymphatic vessels restrict back-flow of lymph.
- Skeletal Muscle Contraction "milks" the lymphatic vessels and encourages lymph movement
- Respiratory movements encourage lymph flow by increasing and decreasing thoracic and abdominal pressures.
72
Flow of Fluids Steps
```
1- Plasma in the blood vessels
2- Interstitial fluid
3- Lymphatic capillaries
4- Lymphatic vessels
5- Lymphatic ducts
6- Back into the blood stream
```
73
Assisting with Lymph Flow
Lymphatic fluid is moved by:
- Pressure in the interstitial space
- The milking action of skeletal muscle contraction
- Changes in thoracic and abdominal pressures - Respiratory movements and abdominal muscle contraction.
74
Primary Lymphatic Organs/Tissues
The primary lymphatic organs are the bone marrow and the thymus gland.
- Locations where stem cells divide to produce immune cells. In bone marrow, divide to produce both B lymphocytes and T lymphocytes.
75
Secondary Lymphatic Organs/Tissues
The secondary lymphatic organs are lymph nodes, lymphoid tissue (tonsils, malt) and the spleen.
- Locations of cell maturation and immune responses.
76
Lymph Node Function
Lymph nodes serve as filters for lymph fluid, foreign objects are trapped and destroyed
- The 4 important groups/locations of lymph nodes are:
1- Submandibular
2- Cervical
3- Axillary
4- Inguinal
- Lymph fluid enters through the afferent vessels. It flows through the cortex, where it comes into contact with large populations of B lymphocytes, dendritic cells, and macrophages. Lymph continues to flow through the node to the medulla and is exposed to more B lymphocytes, plasma cells and macrophages. It then exits through the efferent vessels.
77
Lymph Node Anatomy
Are bean-shaped lymphatic organs and are anywhere from 1 to 25 mm in length. There are approximately 600 lymph nodes in the body.
- A lymph node is surrounded by a connective tissue capsule. Extensions of the capsule (trabeculae) divide the node into compartments.
- There are 2 regions of a lymph node: the cortex and the medulla. Both regions contain large numbers of white blood cells and macrophages.
78
Innate Immunity
```
Consists of a number of different cellular and chemical barriers which non-specifically protect the body and respond to pathogenic organisms.
- Non-specific
- Non-adaptive
- Barriers:
1- Skin and mucous membranes
2- Endogenous antimicrobials
3- Inflammation, Phagocytosis
4- Fever
```
79
Adaptive Immunity
```
In contrast with innate immunity, the adaptive immune response is specific, adaptive, and generates memory.
- Barriers:
1- T Lymphocytes
2- B Lymphocytes
3- Plasma cells
4- Antibodies
5- Enzymes
-The ability to respond against specific invaders is the main function of adaptive immunity.
```
80
What are the 2 lines of defense associated with Innate Immunity?
1- First Line of Defense
2- Second line of Defense
If the first barrier is compromised, the second takes over, and to guarantee a response, the adaptive immunity takes over.
81
Innate Immunity: First Line of Defense
- Skin
- Mucous Membranes
- Lacrimation
- Salivation
- Flow of Urine
- Vaginal secretions
- Defecation
- Vomiting
82
Innate Immunity: Second Line of Defense
Internal defenses:
- Endogenous antimicrobials
- Complement system
- Iron-binding proteins
- Interferon
- Phagocytes: Wandering and fixed macrophages
- Natural killer (NK) cells: actually a type of Lymphocyte
83
Phagocytosis
There are 2 groups of phyagocytes in the second line of defense (Innate Immunity):
- Neutrophils: are released in large numbers, very quickly, but their lifespan is relatively short.
- Macrophages: bone marrow releases monocytes that enlarge and develop into macrophages as they migrate to sites of infection.
84
Fever
Is part of our non-specific internal defenses. It's an abnormally high body temperature due to resetting of the hypothalamic thermostat. It's a non-specific response.
- Speeds up body reactions
- Increases the effects of endogenous antimicrobials
- Sequesters nutrients from microbes
85
Inflammation
Is a non-specific, non-adaptive, innate response. The stimulus for inflammation could be a burn, chemical exposure, heat, cold, or trauma. Local signs and symptoms include:
- Redness
- Pain
- Heat
- Swelling
- Possible loss of function
86
What are the 3 stages of Inflammation?
The local signs and symptoms relate to the stages of inflammation
1- Vasodilation and increased permeability
2- Emigration of phagocytes from the blood into the interstitial space
3- Tissue Repair
- Redness and heat are due to the increased blood flow
- Swelling is because of the increased vascular permeability
- Cytokines and pro-inflammatory chemicals are released as part of inflammation and target free-nerve endings that result in perception of pain.
87
Adaptive Immunity and Response to Antigens
A substance recognized as foreign is an antigen. An adaptive response provides a specific, adaptive response that also generates memory. A substance is an antigen if it is:
- Foreign: most important
- Organic
- Structurally complex
- Large enough
88
Antigens
One antigen can have multiple sites that will induce an immune response.
- If a molecule fits all criteria, except for size, it is referred to as a hapten. A hapten doesn't trigger an immune response unless it binds to another molecule to make it big enough.
89
What are the 2 main players in Adaptive Immunity?
1- T Lymphocytes
| 2- B Lymphocytes
90
T Lymphocytes
Originate from stem cells in the bone marrow, leave as pre-T cells, and mature in the thymus gland. There are 4 subtypes of these lymphocytes:
- T-Helper Cells
- T-Cytotoxic Cells
- T- Regulator Cells
- Memory T-Cytotoxic & Memory T-Helper Cells
91
T-Helper Cells
A subtype of T Lymphocytes
The middle-man or main "helper" of the immune response. The T-helper cells will receive information from non-specific phagocytic cells and pass that information on to generate a specific response to a particular antigen,
- These are also called CD4 T-Cells, due to the presence of the CD4 marker.
92
T-Cytotoxic Cells
A subtype of T Lymphocytes
These T-cells destroy abnormal cells. Virally-infected cells and cancerous cells are their main targets.
- These are also called CD8 T-Cells
93
T-Regulator Cells
A subtype of T Lymphocytes
These T-cells keep the immune system from getting out of control. They decrease the reactivity of the other types of T-cells. This is essential for maintaining self-tolerance.
94
Memory T-Cytotoxic & Memory T-Helper Cells
A subtype of T Lymphocytes
Produced with an initial exposure to an antigen to provide memory of the event and a rapid-response if re-exposed to the antigen. Memory cells do not participate the first time around.
95
B Lymphocytes
Are produced and mature in the bone marrow. Activated to become plasma cells.
96
What are the 2 main types of Adaptive Immunity
- Cell-mediated immunity
- Antibody-mediated immunity
Both mechanisms are triggered by exposure to specific antigens.
97
Cell-mediated Immunity
In cell-mediated immunity, T-cytotoxic cells are activated directly against abnormal cells, such as cancer cells or even tissue transplants.
- Virally-infected cells, cancer cells, and cells infected by intracellular bacteria
98
Antibody-mediated Immunity
In antibody-mediated immunity, B Lymphocytes are activated to become plasma cells, which produce and secrete specific antibodies.
-Because T-helper cells are the middle-men of adaptive immunity, they are a part of both cell-mediated and antibody-mediated immunity.
99
Major Histocompatibility Complex (MHC)
A group of genes that code for a group of transmembrane proteins, also called human leukocyte antigens (HLA), on the surface of all nucleated cells. There are 2 classes:
-MHC Class-I Molecules
-MHC Class-II Molecules
Both classes are important for antigen processing and presentation.
100
MHC Class-I Molecules
Present on all body cells, except red blood cells.
101
MHC Class-II Molecules
Present on the surface of antigen-presenting cells (APCs)
- APCs have a primary responsibility to present antigen to other components of the immune system. APCs are usually phagocytes, but B cells can be APCs.
102
Antigen Processing
Required for cell-mediated and antibody-mediated immunity. General steps include:
- Phagocytosis by antigen-presenting cells
- Digestion of antigen within vesicle
- Synthesis of MHC-class molecules
- Fusion of antigen fragment with MHC-class molecule
- Insertion of antigen-MHC class complex in the plasma membrane.
103
Antigen Presentation and T-helper cell Activation
Once an antigen is pocessed, it is ready to meet the middle-man, the T-helper cell.
- The T-helper cell, through a specific T-cell receptor, will bind to the antigen fragment presented by the MHC-class molecule.
- Binding as well as cytokine stimulation results in the activation and proliferation (increase in numbers) of the T-helper cell. This process is called Clonal Selection: produces more T-helpers and T-memory cells
104
T-Cytotoxic Activation
Inactive T-Cytotoxic cells bind to abnormal cells presenting viral proteins or cancer proteins on MHC Class-I molecule.
- T-helper cells act as co-stimulators
- The T-Cytotoxic cells will also undergo clonal selection. Will produce more T-cytotoxic cells and memory T-cytotoxic cells
105
B-Cell Activation
B cells can be activated by direct recognition of antigen through B-cell receptors or through T-helper cell activation. B cells undergo clonal selection.
- Activated to become plasma cells: synthesis of antibodies.
- Produce B memory cells
106
Steps in Antigen Processing and Presentation: Exogenous Antigens
- Ingestion of the antigen
- Digestion of the antigen into fragments
- Synthesis of MHC class-II molecules
- Vesicular packaging of class-II molecules
- Fusion of fragment and class-II fvesicles
- Binding of fragments to class-II molecules
- Insertion of the antigen-MHC class-II complexes in the plasma membrane for recognition
107
Steps in Antigen Processing and Presentation: Endogenous Antigens
- Digestion of the antigen into fragments
- Synthesis of MHC class-I molecules
- Binding of fragments into class-I molecules
- Vesicular packaging of class-I molecules
- Insertion of the antigen-MHC class-I complexes in the plasma membrane for recognition.
108
Cytokines
```
Are chemical signals from one cell that influences another. These chemicals act as small protein hormones to control cellular growth and maturation.
There are 4 common groups of cytokines:
- Interferon
- Interleukins
- Erythropoietin
- Tumor-necrosis factor (TNF)
```
109
Interferon
A group of cytokines
Anti-viral properties and stimulators of the immune system
110
Interleukins
A group of cytokines
Cytokines between white blood cells
111
Erythropoietin
A group of cytokines
A cytokine from the kidneys increases the number and activity of red cell precursors in the bone marrow.
112
Tumor-necrosis factor (TNF)
A group of cytokines
Produced by macrophages to encourage inflammation.
113
Antibodies
Antibodies are produced in response to antigen through antibody-mediated immunity. Also called immunoglobulins. The general antibody consists of 4 polypeptide chains, two long (heavy chains) and two short (light chains). Disulfide bonds link the chains together in a Y-shaped arrangement.
There are two main regions of an antibody:
- Variable Region: consists of distal segments of the heavy and light chains and forms the antigen-binding site
- Constant Region: gives the antibody its specificity.
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Antibody Functions
- Neutralizing Antigen: Neutralizes toxins and binds to viruses to restrict their binding to host cells.
- Immobilizing Bacteria: Restricts the spread of motile bacteria by binding to cilia or flagella
- Agglutinating & Precipitating Antigen: Multiple antigen-binding sites can result in one antibody binding to 2 or more anigens, causing agglutination. Binding may cause soluble antigen to become insoluble.
- Activating Complement: Antigen/antibody complexes initiate the classical complement pathway
- Enhance phagocytosis: Opsonize (flag) for phagocytosis
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The Immune System and Aging
Atrophy of the thymus gland: Decreased T-helper cell population which results in diminished mediation of the specific-immune response, and decreased B-cell response.
Decreased numbers of T-cytotoxic cells causes increased incidence of cancer.
Increased numbers of autoantibodies
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Self-recognition and self-tolerance
- Self-recognition: ability to recognize one's own cellular markers
- Self-tolerance: the immune system must leave self-antigens alone.
Failure of self-recognition or self-tolerance results in autoimmune disease.
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What are the 5 classes of Antibodies?
- IgG
- IgM
- IgA
- IgE
- IgD
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IgG
Monomer, two antigen-binding sites found in blood, lymph, and intestines. 80% of the antibody in the blood, only class to cross the placenta. Provides long term immunity.
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IgM
Pentamer, 10 antigen-binding sites, first to be secreted by plasma cells. It's a great activator of complement, but is a short-lived response.
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IgA
Dimer, four antigen-binding sites. Found in sweat, tears, saliva, mucus, breast milk, and gastrointestinal secretions. Levels decrease during stress.
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IgE
Monomer, two antigen-binding sites, less than 0.1% of antibody in the blood. Located on mast cells in tissue.
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IgD
Monomer, two antigen-binding sites, 0.2% of antibody in the blood. Found as receptors for antigen on B-cells.
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Formation of Antibodies
Primary antibody-mediated response
- 1st Exposure
- 5-7 day delay
- Production of IgM followed by IgG.
Secondary antibody-mediated response
- Second and subsequent exposures
- Very little delay due to memory T-helper and B cells
- Production of IgM followed by a long-lasting population of IgG.
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Antibody Titer
A test that detects the relative amount of antibody
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Acquired Adaptive Immunity Types
- Natural Immunity: immunity not gained through modern medicine
- Artificial Immunity: immunity gained though artificial means
- Active Immunity: the body responds to a pathogen (antigen) to make antibodies (long-term immunity)
- Passive Immunity: the body simply receives antibodies with no effort of its own. (short-term immunity)
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Examples of Acquired Adaptive Immunity
- Naturally acquired active immunity: Hepatitis A stimulates the production of anti-hepatitis A antibodies.
- Naturally acquired passive immunity: baby receives antibodies from its mother through the placenta and breast milk.
- Artificially acquired active immunity: A person receives an injection of an attenuated (changed/weakened) pathogen that stimulates the body to form an antibody (vaccine)
- Artificially acquired passive immunity: Injection of a prepared antibody.
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Complement System
A very powerful group of proteins that "complement" the action of the immune system.
- Consists of 9 main proteins known as C1-C9.
- Activated by multiple pathways in a step-wise or cascading fashion.
Functions:
- Encourages vasodilation and inflammation
- Antigen opsonization (flags a microbe for phagocyte ingestion)
- Destroys antigen
