Module 2: Normal Leukocytes Flashcards
(137 cards)
1
Q
Define leukopoiesis
A
Production of leukocytes
2
Q
Where are leukocytes produced?
A
Bone marrow (neutrophils, monocytes, eosinophils, basophils, and a few lymphocytes) Lymphatic tissue (lymphocytes and plasma cells)
3
Q
How is leukocyte production similar to erythrocyte production?
A
Mitosis and differentiation of a stem cell
Immature cell replicates itself and then transforms into a more mature form by undergoing physical and chemical changes induced by leukopoietins
4
Q
What are leukopoietins?
A
Hormones and cytokinds that alone or in synergy induce growth and/or differentiation in leukocyte stem or blast cells
5
Q
Name 4 leukopoietins
A
IL-1 to IL-19
GM-CSF
G-CSF
M-CSF
6
Q
What is the major function of leukocytes?
A
Protection against foreign and malignant cells and molecules
7
Q
How do leukocytes remove foreign bodies?
A
- Phagocytosis of foreign antigen that is labelled by antibodies
- Lysis of foreign and infected cells by direct killing mechanisms
8
Q
What are the 6 main functions of the immune system?
A
- Encounters
- Recognition
- Activation
- Deployment
- Discrimination
- Regulation
9
Q
What occurs in the encounter stage of the immune system?
A
Foreign bodies are encountered by recognition cells (lymphocytes and macrophages) by
- Lymphatic circulation bringing antigens and cells through the lymph nodes where lymphocytes and macrophages are
- Patrolling lymphocytes and macrophages in the blood, lymph, and extracellular fluid
10
Q
What happens in the recognition stage of the immune system?
A
There are antigen specific receptors on the surface of lymphocytes that recognize the antigen and produce specific antibodies
11
Q
What happens in the activation stage of the immune system?
A
After an antigen is recognized as foreign the lymphocytes are activated and produce antibodies or chemical mediators to direct activities of other cells
12
Q
What happens in the deployment stage of the immune system?
A
Activated lymphocytes amplify and distribute defense products and collaborate with phagocytes and complement to destroy the antigen
13
Q
What happens in the discrimination stage of the immune system?
A
Discrimination between self and non-self avoids autoimmune tissue damage
14
Q
What happens in the regulation stage of the immune system?
A
Regulation of the response intensity ensures an appropriate size reaction takes place and shuts off when the antigen is eliminated
15
Q
What do lymphocytes do?
A
Responsible for detection and recognition of foreign and abnormal self-antigens and initiating specific responses
Cytolytic killing, production of antibodies and lymphokines, and facilitating phagocytes
16
Q
What are the 3 types of lymphocytes?
A
B lymphocyte
T lymphocyte
Null cells
17
Q
What do B lymphocytes do?
A
Humoral immune responses by transformation into plasma cells
18
Q
What do T lymphocytes do?
A
Cellular immune response, involved in regulation of antibody reactions by helping or suppressing B lymphocyte activation
19
Q
What are the 2 types of Null cells? What does each one do?
A
Killer cells - antibody dependent cell-mediated lysis
Natural killer cells - direct cytotoxic activity
20
Q
What are 4 things that make lymphocytes different from other leukocytes?
A
- Resting cells, get stimulated to undergo mitosis and produce memory and effector cells
- Circulate from blood to tissues and back
- B and T cells rearrange antigen receptor gene segments to produce a variety of antibodies and surface receptors
- T and null cells develop and mature outside the bone marrow
21
Q
Where do lymphocytes mature in utero and after birth?
A
In the embryonic stage they develop from the pluripotent cells of the yolk sac and liver
Fetuses and adults have stem cells that differentiate to CFU-L stem cells in the bone marrow which are stimulated and then mature in the lymphatic tissue
22
Q
What are primary and secondary lymphoid tissues?
A
Primary - bone marrow and thymus
Secondary - lymph nodes, spleen, tonsils, Peyer’s patches, etc
23
Q
How do lymphocytes develop in primary tissue?
A
Lymphocytes are produced and differentiated without antigenic stimulation
Thymus cells become T lymphocytes, bone marrow cells become B lymphocytes
24
Q
How do lymphocytes develop in secondary tissue?
A
Depends on antigenic stimulation
Secondary lymphoid tissue acts as a storage area for already differentiated lymphocytes
25
What cytokines stimulate lymphocytic differentiation from stem cells?
IL-1 and IL-6
26
Describe the morphology of a lymphoblast
15-20um
4:1 N/C ratio
Round/oval finely clumpped nucleus with 1-2 nucleoli
Small medium blue cytoplasm with no granules, possibly dark border
27
Describe the morphology of a prolymphocyte
15-18um
4:1 to 3:1 N/C ratio
Oval/slightly indented slightly clumped nucleus with 0-1 nucleoli
Small medium blue cytoplasm, possible azuorphilic granules, dark rim
28
Describe the morphology of a lymphocyte
6-9um (small) 17-20um (large)
4:1-3:1 N/C ratio (small) 2:1 N/C ratio (large)
Round/oval/indented dense nucleus with no nucleoli
Scant light blue cytoplasm with possible azuorphilic granules
29
What is the common CD marker that a lymphoblast would have?
CD34
| TdT
30
What are common CD markers that B lymphocytes would have?
```
CD10 - precursors
CD19 - precursor and mature
CD20 - activation
CD22 - activation (cytoplasmic)
CD38 & CD138 - plasma cells
```
31
What are common CD markers that T lymphocytes would have?
```
CD2 - early
CD3 - Pan-T cell
CD4 - T cell subset
CD5
CD7 - early
CD8
CD56 - T cell subset
```
32
What percentage of lymphocytes are found in the peripheral blood?
20-40% in adults (60-80% T, 20-35% B)
| Higher in children up to age 4
33
How can small and large lymphocytes be distinguished morphologically?
Small - darker and denser nucleus usually no nucleoli, scant to moderate usually darker cytoplasm rarely have granules
Large - lighter less clumped nucleus may be stretched and contain nucleoli, more abundant lighter cytoplasm may contain azurophilic granules
34
What is a variant lymphocyte?
A stimulated lymphocyte, increased DNA and RNA activity
| Normal, immune system function
35
What do variant lymphocytes look like?
Larger
Possible folded/indented/lobulated nucleus with varying chromatin clumping, often 1-3 nucleoli
Cytoplasm may be gray to deep blue, foamy/vacuolated, usually abundant with uneven staining, may have granules
36
How many variant lymphocytes in the peripheral blood are normal?
5-6% of lymphocytes
| Increased in viral disorders (mono, etc)
37
How many neutrophils are usually present in the blood?
50-70%
| Most numerous in blood and bone marrow
38
How long does a neutrophil live in different areas of the body?
Blast > Promyelocte > Myleocyte - 1 day
Metamyelocyte > Band > Neutrophil - 6-10 days
In the blood - 10 hours
In the tissue - 3-5 days
39
Describe the morphology of a myeloblast
15-20um
7:1-5:1 N/C ratio
Round/oval, central/eccentric fine nucleus, 1-3 nucleoli
Scant basophilic cytoplasm, no granules
40
Describe the morphology of a promyelocyte
12-24um
5:1-3:1 N/C ratio
Round/oval, central/eccentric slightly clumped nucleus, 1-2 nucleoli
Basophilic cytoplasm, azurophilic and non-specific granules
41
Describe the morphology of a myelocyte
10-18um
2:1-1:1 N/C ratio
Oval/round/slightly indented eccentric slightly more clumped nucleus, 0-2 nucleoli
Bluish-pink moderate cytoplasm, azurophilic and specific granules
42
Describe the morphology of a metamyelocyte
10-18um
1:1 N/C ratio
Indented kidney shaped central/eccentric clumped nucleus, 0 nucleoli
Clear pink moderate cytoplasm, specific granules
43
Describe the morphology of a band
10-16um
1:1-1:2 N/C ratio
Elongated horseshoe central/eccentric clumped nucleus, 0 nucleoli
Pink abundant cytoplasm, fine violet-pink granules
44
Describe the morphology of a neutrophil
10-16um
1:3 N/C ratio
2-5 clumped lobes, 0 nucleoli
Pink abundant cytoplasm, violet-pink granules
45
What is present in primary and secondary granules?
Primary - lysozyme, myleoperoxidase, acid phosphatase, elastase
Secondary - lysozyme, NADPH oxidase, cytochrome b, lactoferrin
46
What are tertiary granules (seen through electron microscopy)
Plasminogen activator, alkaline phosphatase, and gelatinase
47
What receptors do neutrophils have on their membranes?
Fc portion of IgG
C3b and C5a complement components
Insulin and histamine (not important in immune system)
48
What is present on the outside of a neutrophil and what does it do?
Glycoprotein coating to allow adherance
| Actin, myosin, and tubulin to allow migration and phagocytosis
49
What is the function of a neutrophil?
Locate and destroy foreign antigens through phagocytosis
50
What is the neutrophil migration sequence?
How neutrophils migrate from the blood to the site of an infection
Includes: margination, adherence, anchoring, diapedesis and migration
51
What is margination?
50% of neutrophils roll along the inside of blood vessels instead of circulating
52
What is adherence?
Neutrophils flatten against the endothelium of the vessel
| Endothelial cells become more adherent near inflammation due to chemical mediators
53
What is anchoring?
Permanent adherence of neutrophils to the endothelial cells due to large amounts of chemical mediators
54
What is diapedesis?
Neutrophils moving through junctions between endothelial cells to reach the infection
Aided by vasodilators from the infected site and proteases secreted by the neutrophil to digest the basement membrane
55
What is migration?
Neutrophils in the tissue moving toward the infection, following chemotaxins
56
What are chemotaxins?
Substances produced by the bodys activated coagulation, kinin, and complement systems
OR
released from injured/infected tissues, lymphocytes, or other leukocytes
57
Name some chemoattractants and what releases them
```
N-formyl oligopeptides - bacteria
C5a, C3b, and C3bi factors - complement
Interleukin-8 - monocytes
Leukotrine B - membrane phospholipid
Platelet-activating factor - endothelium
```
58
What is the most chemotactic chemotaxin?
Leukotrine B
59
What happens to the neutrophil as it moves towards the chemotaxins?
Chemotaxins bind to receptors and a pseudopod extend
The neutrophil crawls through the tissue towards the infection with the pseudopod leading (move via microtubules and movement of pseudopodia by contractile proteins actin and myosin)
60
What happens inside the neutrophil when it is stimulated by chemotaxins?
```
Changes in membrane electrical charge
Calcium ion movement
Phospholipid synthesis
cAMP concentreation
Generation of leukotrienes and prostaglandins by arachidonic acid oxidation
```
61
What is the killing cascade?
When the neutrophil gets to the infection and begins phagocytosis
62
What are the steps of the killing cascade?
1. Immune adherence (recognition)
2. Endocytosis (engulfment)
3. Lysosome function
4. Killing and digestion
5. Exocytosis
63
What happens during immune adherence?
The neutrophil recognizes the antigen by binding to it (must be opsonized by antibodies or complement)
Endocytosis is stimulated
64
What happens during endocytosis?
Actin-rich pseudopods extend and surround the bacterium forming a phagocytic vacuole (phagosome)
65
What happens during lysosome fusion?
Activated azurophilic and neutrophilic granules (lysosomes) attach to the phagosome and then empty their contents (lysozymes, myeloperoxidases, etc) into it
66
What bacterias don't activating the granules in a neutrophil? What happens to the bacteria?
Brucella, Legionella, and Mycobacterium
| They are phagocytosed only
67
What is the respiratory burst?
The most potent killing mechanism in the neutrophil
68
How does the respiratory burst work?
Increased glycolysis in the emdben-meyerhof pathway and hexose monophosphate shunt produce energy and reduced co-enzymes
NADPH is activated and reduced oxygen to superoxide
Superoxide combines with hydrogen to form H2O2
Myeloperoxidase uses H2O2 and halides to generate oxidizing radicals that kill bacteria by peroxidation
HOCl reacts with amines to form chloroamines that destroy bacteria, viruses, mycoplasms, fungi, and tumors
Excess H2O2 is reduced by catalase or reduced glutathione
69
What other killing mechanisms does the neutrophil have?
Generation of oxygen singlets
Acid pH (5.7) in phagosome to kill pneumococcus
Microbicidal enzymes: lysozyme-arginase, primary glucoxidase, lactoferrin
H+ ions kill E. coli
lysozyme hydrolyzes mucopolysaccharide walls of some bacteria
70
What happens after the neutrophil kills an organism?
Hydrolytic enzymes from lysosomes digest it and the cytoplasm absorbs useful components
Waste is ejected by exocytosis
71
When do neutrophils die?
When they have used up their lysosomes and are full of vacuoles
They lyse and turn into pus (pus cells!)
72
What happens when neutrophils lyse?
The inflammation response increases
Hydrolases injure and lyse tissue, endogenous pyrogens increase local fever, tissue thromboplastin causes coagulation, cations vasodilate
73
How are neutrophil losses offset?
Release of reserve neutrophils and bands from the bones marrow
Stimulation of stem cells and myelocytes by IL-3 and CSF-GM to proliferate and differentiate
74
What happens to the neutrophil count in a pyogenic infection?
Neutophilia from 15-30x10^9/L
75
Describe the morphology of a monoblast
Round/oval/slightly folded nucleus with fine chromatin, up to 5 nucleoli
Moderately basophilic/grayish cytoplasm, no granules
76
Describe the morphology of a promonocyte
Folded/convoluted nucleus with chromatin creases, 0-5 nucleoli
Abundant blue-gray cytoplasm often with pseudopods and vacuoles
77
Describe the morphology of a monocyte
Large variability!!!
Indented/curved nucleus with lacy chromatin
Abundant cytoplasm, fine granules giving ground glass appearance, vacuoles are common
78
How many monocytes is normal in the peripheral blood?
2-9%
| Higher in newborns and young infants
79
How long do monocytes live in the blood?
36 hours, then move into the tissue
80
Why do monocytes move out of the blood and into the tissues?
As a response to chemotactic stimuli or in a random fashion
81
What happens to monocytes once they get into the tissue?
In the blood they are immature and mostly inactive
Once in the tissue they rapidly transform into a macrophage with a higher energy level and metabolic rate
They produce hydrolases in their endoplasmic reticulum and pack them into lysozymes in the golgi apparatus until the cytoplasm is full of azurophilic granules
They can be up to 50 um in diameter to accommodate the granules
82
Define reticuloendothelial system of cells
Whole diffuse system of monocytes and motile and fixed macrophages
Also called mononuclear phagocytes system or macrophages
83
What are the 4 functions of macrophages?
1. Phagocytic response to foreign antigens
2. Immune recognition
3. Secretory epithelial cells
4. Iron metabolism / preservation of a youthful and healthy population of red cells
84
What do macrophages do in acute and chronic infections?
Acute - clean up dead neutrophils and body tissues of the aftermath
Chronic - predominate because neutrophils are ineffective, they arrive slowly but survive unlike neutrophils
85
How are macrophages stimulated?
Cytokines from CD4 T cells (interferron gamma)
86
What do monocytes do once they are activated?
They get big, sticky, hypermobile, aggressively phagocytic and secrete chemicals (oxidizing halides and halo amines) called monokines
Also undergo long metabolic oxidative respiratory burst
87
What is the best known monokine? What does it do?
Interleukin-1
activates CD4 T cells, stimulates hepatocytes to secrete acute phase proteins, stimulates CSF-GM production by other macrophages, and acts as an endogenous pyrogen
88
How do macrophaes kill organisms?
Engulf them in a phagosome and release lysosomal ingredients into it
If they live they are isolated in Langhans giant cell granulomas made of many fused macrophages to wall it off
89
How are macrophages suppressed? How do some organisms take advantage of this?
T4 cells and macrophages themself secrete prostaglandin E2 which suppresses them.
Organisms like HIV stimulate PGE2 secretion and then live in the deactivated macrophages
90
How do macrophages work in immune recognition?
Act as antigen presenting cells for lymphocytes
Engulf, digest, and modify the antigen and present it in association with HLA-D antigens on its membrane to T4 and B lymphocytes
Also secrete IL-1 which activates T4 cells
91
How do macrophages work as secretory effector cells?
Secretions:
- remove old RBCs
- stimulate self defense against tumors
- modulate immune function
- regulate hematopoiesis
- stimulate inflammatory reactions
- remove infectious organisms by phagocytosis
92
How to macrophages work in regards to iron metabolism?
In the spleen and liver they detect and removed old defective RBCs and tissue cells by phagocytosis, and retain useful components (like iron)
93
What else do macrophages do to keep the blood youthful and healthy?
Remove defective coagulation factors and antigen-antibody complexes
Convert protoporphyrin from RBCs to biliverdin and excrete it
Remove toxic substances from the blood
94
Where are eosinophils and basophil present in high numbers?
Places with epithelial interface with the environment
| Respiratory, GI, and genitourinary tracts
95
How long do eosinophils and basophils live in tissues?
Can live for several weeks
96
How many eosinophils are normal in the blood?
| Basophils?
2-4%
| 0-2%
97
What are specific eosinophilic granules made of?
Major basic proteins
| Eosinophil peroxidase, arylsulfatase B, histaminase, catalase, lipidoxidase, lectin, and phospholipase D
98
What kind of receptors do eosinophils have?
H1 and H2 histamine receptors
| IgE receptors
99
How do H1 and H2 histamine receptors work?
Histamine attaches to both
H1 receptors produce active allergic reaction symptoms
H2 receptors are negative feedback and turn off allergic reaction symptoms
100
What is the function of eosinophils?
Release their secondary/specific granules to kill parasites and function in hypersensitivity reactions
101
What do basophils turn into in tissues?
Mast cells
102
What do mast cell granules contain?
Sulphated gylcosaminoglycans (chondroitin sulphates and heparins)
Histamine ** almost all histamine in the body is synthesized and stored in mast cells
Some enzymes like trypsin and chymotrypsin
Eosinophilic chemotactic factor (ECF-A) to attract eosinophils
103
What receptors are on mast cell membranes?
IgE-Fc receptors (the side that DOESN'T attach to the antigen)
104
What is the function of basophils?
```
Not understood
Ingest foreign particles
Produce heparin and histamine (induce inflammation)
Associated with asthma and allergies
Provide mediators for immune response
```
105
How do allergies work?
Allergens stimulate IgE production by plasma cells
| Mast cells produce immediate hypersensitivity reaction of anaphylaxis and eosinophils suppress everything
106
How do eosinophils and basophils fight parasite infections?
Parasites excrete/secrete allergens and sensitize IgE coated mast cells, histamine, heparin, and ECF-A are released by them
Eosinophils are attracted and if the parasite is coated in IgE and/or complement they will bind to them and release cytotoxic substances from their granules onto the parasite
(H2O2, superoxide, oxygen singlets, hydroxyl radicals, eosinophil cationic particle, eosinophil peroxidase, phospholipase D, major basic protein)
107
Which activities of the stem cell and blast cells are supported by the hematopoietic inductive microenvironment of the bone marrow?
Which two additional activities require induction by a poietin hormone?
Mitosis and renewal of resident stem and blast cells
Increased mitosis and differentiation from blast to mature forms
108
List the names and abbreviations for each of the various hematopoietic stem cells and blast cells and the name(s) of the cell(s) that each produces by differentiation.
[eg: Colony forming unit - granulocyte, monocyte (CFU-GM) produces the myeloblast]
CFU-S --> CFU-L and CFU-GEMM (colony forming unit-stem --> colony forming unit lymphoid and colony forming unit granulocyte, erythroid, monocyte, megakaryocyte)
CFU-L --> T lymphoblast and B lymphoblast
CFU-GEMM --> CFU-GM, CFU-MEG, BFU-E (colony forming unit - granulocyte, monocyte; colony forming unit erythroid; colony forming unit megakaryocyte)
BFU-E --> CFU-E (colony forming unit-erythroid)
CFU-GM --> myeloblast/monoblast
CFU-MEG --> megakaryoblast
CFU-E rubriblast (pronormoblast)
109
In proliferating cells, what is the difference between the mitotic pool and the post-mitotic pool?
Mitotic pool - cells that are actively dividing (myeloblasts, promyelocytes, myelocytes)
Post-mitotic pool - cells that are no longer dividing but still differentiation (metamyelocytes, bands, neutrophils)
110
Define leukopoietin
A growth hormone, usually secreted close by by lymphocytes, macrophages, endothelial cells, fibroblasts, etc
Induces mitosis and/or differentiation of a cell or cell line, alone or in synergy with other leukopoietins
111
Give at least one important action and at least one major producing cell for IL-1
Produced by monocytes/macrophages
With TNF activates and stimulates cytokine production by T lymphocytes and bone marrow stromal cells
112
The blast cells of the monocytes and neutrophils appear morphologically to be the same
a. true
b. false
a. true
113
A CD4 T cell may induce macrophage proliferation by secreting INF-B
a. true
b. false
b. false
CD4 T cells secrete INF-G (gamma)
114
The storage pool and the post-mitotic pool are the same thing
a. true
b. false
b. false
They are not the same
Post mitotic storage pool includes metamyelocytes, bands and neutrophils
Storage pool includes myeloblasts, promyelocytes, and myelocytes
115
The mitotic pool of neutrophil progenitors includes two kinds of cells
a. true
b. false
b. false
There are 3 cells: myeloblast, promyelocyte, and myelocyte
116
The storage pool is released only when neutrophil production fails
a. true
b. false
b. false
It is released anytime there is a marked increase in demand for neutrophils like bacterial infections
117
Neutrophils spend a longer time developing in the marrow, but a shorter time circulating before moving into the tissues than macrophages
a. true
b. false
a. true
118
Differentiate primary from secondary lymphocyte production
Primary - production in the marrow and thymus; goes on without contact with foreign antigens, designed to populate the peripheral lymphoid tissues with B cells, T cells, and null cells
Secondary - production in lymph nodes, spleen, and other peripheral lymphoid tissue; dependent on contact with foreign antigens; accounts for most lymphocyte production in adults
119
Describe primary lymphocyte (T and B) production by giving the location of primary production, types of mature cells produced, and the distinguishing surface markers
T cells - located in the thymus, produce CD4 and CD8 T cells, CD4 = CD2, 3, 4, 5 CD8= CD2, 3, 5, 8
B cells - located in bone marrow, produce B cells, CDs = Slg, HLA-DR(la), CD19, 20, 21, 22
120
What are monoclonal antibodies? What are they used for? How are they produced?
Reagent antibodies produced by hybridoma techniques that will bind with and identify a particular antigen epitome
121
What are clusters of differentiation? (ie what does it mean when you refer to CD3?)
CDs are groups of monoclonal antibodies that all bind with and identify a particular cell surface marker (antigen).
CD3 refers to the group of monoclonal antibodies that identify the presence of mature T cell antigen (formerly called T3)
122
Why was it necessary to introduce CD terminology to replace the names of the individual monoclonal antibodies and the cell markers that they identified?
The WHO adopted a naming system created by a series of workshops on human leukocyte antigen differentiation to bring some order and standardization to the name of MoAbs being produced at a rapid rate by researchers and biotech companies around the world
123
Describe T cells in regards to:
- location in lymphatic nodes
- location in the spleen
- other locations
- % distribution in the blood
% distribution in the marrow
- motility
- life span
- types of proliferation in adults
Lymph node location: paracortical areas
Spleen location: sheath around central arterioles in white pulp
Other locations: intrafollicular region of lymphatic tissue in submucosa of gut, respiratory, and urinary systems, bone marrow, blood, and tissues
% in blood: 70% of lymphocytes
% in marrow: few
Motility: highly
Life span: Memory cells may live 15-30 years
Types of proliferation: probably all secondary
124
Describe B cells in regards to:
- location in lymphatic nodes
- location in the spleen
- other locations
- % distribution in the blood
% distribution in the marrow
- motility
- life span
- types of proliferation in adults
Lymph node location: follicles in the cortex
Spleen location: white pulp
Other locations: submucosa of gut, respiratory, and urinary tract, bone marrow, blood, tissues
% in blood: 15% of lymphocytes
% in marrow: >/=70% of lymphocytes
Motility: motile but slower than Ts
Life span: memory cells may live 10 or more years
Types of proliferation: primary and secondary
125
Compare the molecular structure of the foreign antigen receptors on T cells and on B cells
B cell recptor SIg has 4 chains (2 heavy with 5 domains each, [4 constant, 1 variable], 2 light with 2 domains each [1 constant 1 variable])
T cell Ti is the same but also has 2 other associated molecules: CD3 and CD4
Both SIg and Ti are bound into the membrane
Antigen binding sequence are found in the variable domains of Ti alpha and beta chains and in the variable domains of the heavy and light chains of SIg
126
How does a B cell recognize its corresponding foreign antigen?
A mature virgin B cell encounters a foreign antigen epitope that corresponds with the paratope of it SIg - recognition occurs when the FAg is bound by the SIg, but activation and resultant proliferation and differentiation into plasma cells or memory cells requires lymphokines mainly produces by activated CD4 T cells
127
What is/are the function(s) of the immunoglobulin produced by the B effector cells after activation, blast transformation, and proliferation?
The secreted antibody circulates the blood, lymph, and tissue fluids and binds with its target antigen (FAg). This results in sensitization or opsonization of the FAg and facilitates its identification and removal by phagocytes and antibody dependent killer lymphocytes (K cells)
128
Differentiate between the kind of protection provided by humoral and cellular immunity - what kinds of foreign antigens are destroyed?
Humoral - protection by antibodies produced by activated B cells and plasma cells vs extracellular pathogens, mainly bacteria, and some viruses, fungi, interstitial parasites, and their removal by phagocytes by complement binding and hemolysis
Cellular - lymphokines secreted by immune cells activate and mediate all parts of the immune response and direct lytic activities vs extracellular and intracellular pathogens and malignant cells and transplanted tissues - involves lymphokine secretors (CD4 T cells, macrophages, fibroblasts) and lytic cell (CD8 T cells, null cells)
129
Define associative recognition
The binding of a T cell foreign antigen receptor to a complex of foreign and self antigen
130
Describe and compare recognition of foreign antigen by CD4 T cells and CD8 T cells at the cell surface on a molecular level
For CD4 T cells an APC (either a macrophage or B cell) is required and the CD4, Ti, or CD3 complex binds to the MHC class II (HLA-DR)/foreign antigen complex on the surface of the APC
For CD8 T cells an infected cell with a surface foreign antigen complexed with a MHC class I (HLA-A, B, or C) binds to the CD8, Ti, and/or CD3 complex on the T cell
131
Outline the cellular immune response of CD4 T cells once they are activated
Activated T cells function a helper/indicator cells, they do not participate directly in removal of foreign or abnormal antigen, but rather produce a great variety of chemical mediator molecules that are required throughout the immune response.
The initial self activation circuit of the CD4 T cells involves:
- expression of surface receptors for IL-2
- synthesis and secretion of IL-2
- binding of IL-2
Subsequently the CD4 T cells produce a variety of lymphokines that mediate the immune response in many ways (Th1 cells produce IL-2, TNF-B, and INF-G to support cell mediated immunity response by CD8 T cells and natural killer cells; Th2 cells produce IL-4 and IL-10 that support B cells growth and antibody production
132
How is the CD8 T cell immune response (after activation) different from the CD4 T cells response?
CD8 T cells secrete some cytokines, their main functions are in the detection (by associative recognition) and direct cytolytic killing of body cells invaded by foreign antigens and malignant cells (by release of membrane perfoorating molecules like perforins, and others - collectively called lymphotoxin),
CD8 T cells also secrete suppressor factors to decrease the CD4, B cell, and NK cells responses after FAg has been eliminated
133
Name two types of large granular lymphocytes and describe the immune function of each
NK cells show a natural cytotoxicity towards cancer cells that are not sensitized by antibodies, at least in part due to their recognition of the absence of MHC type 1 molecules on the surface of the malignant cells
ADCC - K cells (antibody dependent cell-mediated cytotoxicity killer cells) recognize cells sensitized by antibodies using Fc receptors like the phagocytes; however, they then contact kill their identified victims like CD8 T cells
134
Outline the way neutrophils detect and then destroy foreign antigen. Trace their journey from the blood vessels to the source of infection in the tissue. Use and describe the terms: margination, adherence, anchoring, diapedess, migration, chemotaxis, immune adherence, endocytosis, lysosome fusion, killing, digestion, the respiratory burst, and exocytosis.
```
The migration sequence:
Margination - 50% of the neutrophils are rolling along the endothelial lining of the blood vessels at any given time
Adherence
Anchoring
Diapedesis
Migration - including chemotaxis
```
Killing cascade:
Recognition (binding or immune adherence)
Engulfment or endocytosis (phagocytosis) - phagosome formation
Lysosome fusion
Killing and digestion - including the respiratory burst
Exocytosis
135
List the 2 kinds of granules found in neutrophils and the substances that they contain
Azurophilic granules (primary lysosomes) - formed beginning at the promyelocyte stage and contain acid hydrolases, neutral serine proteases, bactericidal cationic proteins, muramidase (lysozyme), myeloperoxidase, and defensins (antimicrobial peptides)
Neutrophilic granules (secondary lysozymes) - formed beginning at the myelocyte stge and contain lactoferrin, specific collagenase, vitamin B12 binding protein, cytochrome b, histaminase (antihistamine), monocyte/macrophage chemoattractact, plasminogen activator, protein C inhibitor, fMLP receptor, and muramidase
136
Give some examples of substances that are chemotactic for neutrophils
```
C5a
Oligopeptides from bacterial proteins (fMLP - formly-methionyl-leucyl-phenylalanine)
PF4
Platelet growth factor
LTB4
```
137
Outline the important functions of the monocytes/macrophages
```
Phagocytosis of foreign antigen
Alteration of foreign antigen and presentation on its surface in association with class II MHC molecules for recognition by CD4 T cells
Secretion of a large variety of monokines including IL-1
Fusion into giant cell granulomas to isolate organisms that they cannot kill
Daily detection and removal of dead, defective, and aged blood cells and other materials from the blood
Partial metabolism (catabolism) of waste substances from phagocytosed cells (eg Hb --> heme --> protoporphyrin --> biliverdin)
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