Blood and Immune System Flashcards
1
Q
Functions of blood
A
- Transport nutrients, hormones, and metabolic wastes
- Regulates composition of interstitial fluid(pH, ions
- Restrict fluid loss via blood clotting
- Defends against toxins and pathogens
- Regulates body temperature by absorbing and redistributing heat
2
Q
Hematocrit
A
- % of total blood volume occupied by packed red blood cells
- Normal hematocrit: 40-54% in males, 37-47% in females
3
Q
Functions of plasma proteins
A
- Generate colloid osmotic pressure
- buffer pH
- Albumins: Maintains blood pressure, carries substances throughout body
- Globulins a, b, y: Clotting factors, enzymes, carriers, antibodies
- Fibrinogen: Cleaved to form fibrin in blood clotting
- Transferrin: Iron transport
4
Q
Formed elements
A
- Erythrocytes: Red blood cells
- Leukocytes: White blood cells
- Thrombocytes: Platelets
- Lymphocytes
- Phagocytes: Monocytes and Neutrophils
- Granulocytes: Eosinophils, Basophils
5
Q
Where do the cells come from
A
- In embryo: yolk sac, liver, spleen, and bone marrow
- After birth: bone marrow
- Adults: Pelvis, spine, ribs, cranium, proximal end long bones
6
Q
Hematopoiesis
A
- Process of producing blood cells
- Pluripotent hematopoietic stem cells -> uncommitted stem cells -> committed progenitor cells -> erythroblast, megakaryocyte, leukocytes -> erythrocyte, platelets, neutrophils, monocytes, basophils, eosinophils, lymphocytes
- In bone marrow: 25% are developing erythrocytes, 75% are developing leukocytes
7
Q
Cytokines regulate hematopoiesis
A
- Erythropoietin in kidney cells influences growth/differentiation of red blood cells
- Thrombopoietin in liver influences megakaryocytes
- Interleukins, stem cell factors in endothelium/fibroblasts of bone marrow and leukocytes influence all types of blood cells and mobilizes hematopoietic stem cells
- Effect: survival, proliferation, and differentiation of different cell types
8
Q
Red blood cells
A
- Bags filled with hemoglobin and enzymes
- Needed for oxygen and CO2 transport
9
Q
Erythropoiesis
A
- RBC production
- Erythropoietin: cytokine made in kidney
- Promote erythropoiesis
- Produced in response to low O2 levels, which stabilize transcription factor: hypoxia-inducible factor(HIFa) -> activate transcription of erythropoietin gene
- Requires iron, vitamin B12, and folate
10
Q
RBC removal
A
- RBC formation in bone marrow -> 120 day life span of RBC -> macrophage breakdown into Heme and iron -> iron transported into circulation by transferrin or stored in liver in ferritin -> Heme turned into bilirubin -> transport to liver or kidneys -> and elimimated in feces or urine
11
Q
Jaundice
A
- High turnover of RBC
- Bile duct obstruction
- Too much bilirubin
12
Q
Anemia
A
- Reduced ability to carry oxygen
- Caused by low number of RBCs
- Symptoms: Tired, weak, pale skin, headaches, dizzy
- Low production: caused by stem cell destruction, inadequate nutrients, low erythropoietin
- High removal: Hemolytic: caused by genetic defects in RBC proteins, drugs, autoimmune reactions. Hemorrhagic: Excessive blood loss
13
Q
Polycythemia
A
- Hematocrit too high(> 54%)
- Caused by abnormal erythrocyte precursors, low oxygen delivery to tissues
- Too many RBCs
14
Q
Function of immune system
A
- Destroys pathogens
- Detects and kills abnormal cells
- Remove cell debris from body
15
Q
Basic steps in immune response
A
- Detect and identify pathogen
- Communicate with other immune cells
- Recruit and coordinate response all participants
- Destroy and suppress pathogen
16
Q
Types of immune responses
A
- Innate immunity: rapid, non-specific
- Adaptive immunity: slower, specific
17
Q
Components of immune system
A
Primary lymphoid tissue:
- Thymus: produces T lymphocytes
- Bone marrow: produces most blood cells
- Lymphatic vessels
Secondary lymphoid tissue:
- Tonsils: diffuse lymphoid tissue
- Lymph nodes and Spleen: Encapsulated lymphoid tissues
- Mucose-associated lymphoid tissue(MALT) and skin: diffuse lymphoid tissue
18
Q
Lymphatics
A
- Return excess tissue fluid to blood
- Transport pathogens/dendritic cells to lymph nodes
- Transport fat from digestive system to blood
19
Q
Specialized lymphoid organs
A
- Lymph nodes: monitor lymph
- Spleen: monitors blood
- Both contain mature immune cells that interact with pathogens and initiate an immune response
20
Q
Immune cells
A
- Lymphocytes: Required for both adaptive(T/B cells) and innate immunity
- Monocytes: Migrate into tissues and become macrophages. Phagocytes and present antigens
- Neutrophils: Circulate in blood and migrate into tissues. phagocytes
- Eosinophils: Found in the digestive tract, lungs, urinary, and genital epithelia. Defend against parasites. Participates in allergic reactions
- Basophils and mast cells: Release chemicals that contribute to inflammation and innate immune response
- Dendritic cells: found in skin and other organ. Present antigens
21
Q
Elements of innate immune system
A
- Physical barriers
- Phagocytes
- NK cells
- Antimicrobial proteins
- Inflammation
- Fever
22
Q
Physical barriers
A
- Epithelium is a protective barrier of skin and mucous membrane. Body first line of defense
- Glandular secretions of mucus, antibodies, enzymes to trap and disable pathogens
- Low pH of stomach helps destroy pathogens
- Pathogens physically removed by tears, coughing, etc.
23
Q
Phagocytes
A
- Macrophages and neutrophils
- Recognize pathogens and sites of injury via PAMPs and DAMPs
- Engulf, ingest, and breakdown pathogens
- Chemotaxins: PAMPs(bacterial toxins + cell wall components) and DAMPs(eg. DNA), cytokines
- Antibody is opsonin, coating substance with an opsonin is opsonization
- Macrophage and dendritic cells display antigen fragments
24
Q
NK Cells
A
- Kill cells when infected with virus or cancerous
- Some viruses evade immune system by blocking synthesis of MHC class 1 -> with no MHC class 1, host cannot display viral antigen -> NK cells look for host cells without MHC class 1 and kill them
25
Antimicrobial proteins
- Interferon: a and B prevent viral replication in cells. y activate macrophages and other immune cells
- Complement: 25 plasma proteins, destroy target cell membranes, stimulate inflammation, attract phagocytes, enhance phagocytosis
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Inflammation
- Localized tissue response to injury producing
- Slows spread of pathogens
- Mobilization of local, regional, and systemic defenses
- Sets stage for repair
- Tissue damage -> mast cells release histamine and heparin -> dilation of blood vessels, increase blood flow and increased vessel permeability -> area becomes red and swollen -> clot formation -> attraction of phagocytes, especially neutrophils -> activation of specfici defenses and removal of debris by neutrophils and macrophage stimulation of repair -> tissue repair
- Kinin cadcade leads to formation of bradykinin(vasodilator and stimulates pain receptors)
27
Fever
- Body temperature >37.2 C
- Pyrogens change the thermoregulatory set point in hypothalamus(raises set point(feel cold), body setpoint back to normal when no pyrogens
- Speeds metabolic activity of host, inhibits some pathogens
- Pyrogens: interleukin-1 released from activated macrophages
28
Adaptive immunity
- Specificity: activated by and responds to a specific antigen(Both B and T cells have receptors that recognize specific shapes)
- Versatility: ready to confront any antigen at anytime(Different B and T cells have different receptors)
- Memory: remembers any antigen it has encountered(Some activated B and T cells are long lasting)
- Tolerance: responds to foreign substances(B and T cells with receptors that recognize self are deleted/not activated)
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Specificity
- B cell receptors bind to extracellular antigens
- T cell receptors bind to antigens displayed on surface of cells(macrophages, tissue cells, etc)
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Memory
- Clonal selection, expansion and memory: short-lived effector cells carry out immediate response, memory cells are long-lived and continue to reproduce
- First antigen exposure: antibody concentration decrease and low, second antigen exposure: antibody concentration stays high
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Tolerance
- T cells undergo positive(can see MHC molecules) and negative selection(self-antigen deleted) in thymus
- B cells undergo positive and negative selection in bone marrow
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How are B cells activated
- Antigen binds to specific B cells via B cell receptors
- Antigen is internalized, digested, and combined with MHC, and then transported to cell surface
- Specific helper T cells recognize antigen and MHC class 2become activated and secrete cytokines
- Activated B cell divides. Some daughter cells become plasma cells and secrete antibodies, others become memory B cells
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Antibody functions
- Antigen clumping(creates structure to be engulfed by phagocyte)
- Inactivation of bacterial toxins
- Act as opsonins to tag antigens for phagocytosis(encapsulated bacteria coated w/ antibody, antibodies bind to phagocyte receptors to trigger phagocytosis)
- Trigger degranulation
- Activate complement
- Activate B lymphocytes
34
Classes of antibodies
- IgG: most common, transferred across the placenta from mother to baby
- IgM: first type of antibody to be secreted in response to new antigen, good at causing antigen clumping and activating complement
- IgA: Crosses epithelial cells. Protects epithelial surfaces and present in breast milk
- IgE: fights parasites. Eosinophils have receptors for IgE. Release histamine and associated with allergic reactions
- IgD: B cell receptors on surface of B cels
35
Types of adaptive immunity
- Active: naturally acquired, artificially acquired(vaccination with antigen)
- Passive: naturally acquired by breast milk, artificially acquired(vaccination with antibodies)
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Response to extracellular bacteria
- Bacteria invasion activates complement protein(makes membrane attack complex, activates mast cells to secrete chemotaxins(attract leukocytes) and histamine. acts as opsonin to coat bacteria -> activate B lymphocytes to become plasma cells to secrete antibodies
37
T cell activation
- Cell with MHC-antigen complex binds to T lymphocyte
- Signal transduction activates T lymphocyte
38
Types and functions of T cells
- Helper T cells bind to MHC-2 antigen-presenting cells to release cytokines
- Cytotoxic T cells kill MHC class 1 target cells by using perforin and granzymes or by activating death receptor(Fas)
39
MHC Class 2
- Located on dendritic cells, macrophages and B cells
- Present exogenous antigen(antigen endocytosed onto cell)
- Activate helper T cells
40
Activation of helper T cells
- Cytokines stimulate helper T cells, cytotoxic T cells, and B cells
- Helper cells can be identified by CD4
- Antigen presenting cells(APCs) costimulate inactive CD4 T cells -> activate and cell division of active Th cells
41
MHC Class 1
- Located on all nucleated cells
- Present endogenous antigen
- Activate cytotoxic T cells
- Class 1 MHC incorporate abnormal peptides -> Class 1 MHC proteins transported to cell membranes -> abnormal peptides displayed by MHC Class 1 proteins on cell membrane
42
Activation of cytotoxic T cells
- Infected cell with viral antigen stimulate CD8 T cells -> activate cytotoxic T cells -> bind to infected cell -> release cytokines and perforin, activate Fas domain -> stimulate apoptosis and destruction of target cell
43
Immune response to a virus
- Antibodies act as opsonins to coat viral particles to make them better targets for macrophages
- Macrophages insert viral antigen to MHC-2 molecules and also secrete cytokines
- Helper T cells bind to viral antigen on macrophages -> activate helper T cells and stimulate B lymphocytes and cytotoxic cells
- Activated memory B lymphocytes become plasma cell for antibody production
- Activated cytotoxic T cells attack and destroy infected cells
44
Effect of response to antigens
- Infectious agent: immune response cause protective immunity and deficient response cause recurrent infection
- Innocuous substance: immune response cause allergy
- Grafted organ/unmatched blood: immune response cause rejection
- Self organ: immune response cause autoimmunity
- Tumor: Immune response cause tumor immunity
45
Allergy
- Immune response to nonpathogenic antigen
- Intermediate hypersensitivity and Delayed hypersensitivity
46
Intermediate hypersensitivity
- Allergen ingested by APC -> activates helper T cells -> activates B lymphocyte -> become plasma and memory cells
- Reexposure cause IgE mediated degranulation of mast cells -> vasodilation -> inflammation
- Can result in local rashes or most severely anaphylaxis
47
Blood types
- Type A: Surface antigen A, anti-B antibodies
- Type B: Surface antigen B, anti-A antibodies
- Type AB: Surface antigens A and B, neither anti-A or anti-B antibodies
- Type O: neither A nor B surface antigens, anti-A and anti-B antibodies
- Cross reactions occur during blood transfusion if antigens on donor RBC meet antibodies in recipient plasma
48
Type B blood donor to Type A recipient
- Type B antigens on donor RBC attacked by anti-B antibodies in recipient -> agglutination
49
Donor/Recipient Combinations
- : no agglutination
+ : agglutination
- Recipient: O, Donor: O(-), A(+), B(+), AB(+)
- Recipient A, Donor:
O(-), A(-), B(+), AB(+)
- Recipient: B, Donor:
O(-), A(+), B(-), AB(+)
- Recipient: AB, Donor:
O(-), A(-), B(-), AB(-)
50
Rh antigen
- Rh - individuals do not normally have anti-D antibodies
- Can develop by transfusion of Rh- individual with Rh+(D antigen) blood
- Pregnancy Rh- mother and Rh+ baby
- Mother Rh- and fetal Rh+ blood mix -> maternal antibody production(anti-Rh) -> destruction of Rh+ RBCs in second pregnancy -> hemolytic disease of newborn(anemia, jaundice, severe edema)
51
Prevention of hemolytic disease
- Inject anti-D antigen antibodies into Rh- mother during/following pregnancy
- Antibodies bind and remove fetal RBCs in mothers bloodstream before they trigger a immune response in mother
- B cells are not activated in mother, and no immunological memory of D antigen acquired
- In subsequent pregnancy, mother does not produce anti-D antigen antibodies
52
Platelets needed for blood clotting
- Megakaryocytes break off to form platelets
- Thrombopoietin increases platelet numbers
53
Three phases of hemostasis
- Vascular phase
- Platelet phase
- Coagulation phase
54
Vascular phase
- Blood vessel injury -> vascular spasm(tightening of artery to reduce blood flow)
- Neurogenic and myogenic control
- Vasoconstriction prolonged by serotonin, endothelin-1, thromboxane A2
- Reduces blood loss
55
Platelet phase
- Exposed collagen(binds and activates platelets) via von Willebrand factor(binds to both collagen and platelets)
- Factors released from platelet(ADP, platelet activating factor, serotonin, thromboxane A2)
- Factors attract more platelets
- Platelets aggregate, form plug
- Activated platelets develop spiky outer surface and adhere to another
- Prostacyclin and nitric oxide prevent platelet adhesion and are vasodilators
56
Coagulation phase common pathway
- Phospholipids(PL) and Ca2+ activate factor X -> cleaves prothrombin to form thrombin -> Ca2+, factor V and PL cleave fibrinogen to form fibrin -> thrombin activate factor 13 -> cross links fibrin
57
Extrinsic pathway(cell injury)
- Damage exposes factor 3 -> active factor 3 and factor 7 -> activates factor 9 -> PL, Ca2+ and active factor 9 and 3 stimulate activation of factor X -> positive feedback loop
- von Willebrand factor regulates levels of VIII
- Vitamin K needed for synthesis of thrombin, 7, 9, 10
- Anticoagulant called coumadin blocks action of vitamin K
58
Intrinsic pathway(contact activation)
- collagen activate factor 12 -> activate factor 11 -> activate factor 9(uses factor 8) -> activate factor 10
- Thrombin positive feedback loop to make more factor 11
59
Problems with model
- Individuals with factor 9 or factor 8 deficiency have severe bleeding even though extrinsic/common pathways are normal(sufficient to promote clotting)
- Newer cell based theory of coagulation
60
Cell-based: Initiation phase
- Exposure of tissue factor(TF) and active factor 7 on cell membrane of smooth muscle cells produces small amount of thrombin(thrombin spark)
- activation of factor X and factor 9 -> cleavage of prothrombin to form thrombin
61
Amplification phase
- Thrombin activates factors 5, 11, and 8 on surface of platelets -> activation of platelets
62
Propagation phase
- Active factors on surface of platelets form tenase and prothrombinase results in large amount of thrombin
- Thrombin cleaves fibrinogen and factor 13 to result in fibrin formation and cross linking
63
Clot removal
- Plasminogen stimulated by tPA and thrombin to release plasmin -> break down fibrin polymer
64
Anticoagulants
- Plasminogen released from liver, activated by tPA and thrombin, breakdown fibrin
- tPA released from many tissues, activates plasminogen
- Antithrombin 3 released from liver, activated by heparin, blocks factor 9, 10, 11, 12, and thrombin
