CHAPTER 4 Flashcards
1
Q
What are the two arms of the adaptive immune system?
A
Humoral and cellular systems
2
Q
What fundamental role does the adaptive immune system play?
A
It allows the body to attack an invading pathogen.
3
Q
What is the immunologically specific cellular component of the immune system organized around?
A
Two classes of specialized cells: T lymphocytes and B lymphocytes
4
Q
What are the functions of lymphocytes?
A
Recognize foreign antigens, directly destroy some cells, or produce antibodies as plasma cells
5
Q
What is the total immune response composed of?
A
The interaction of many different cell types and cell-mediated and antibody-mediated responses
6
Q
What recent findings have been discovered about T cells?
A
T cells are not just latecomers in inflammation but may also play a key role in the early phase of the response.
7
Q
What cell subsets, in addition to NK cells, contribute to acute and chronic inflammatory diseases?
A
T cell subsets together with classic innate immune cells
8
Q
Before 1979, how were human lymphocytes classified?
A
As T or B cells based on electron microscopy observation
9
Q
How do T lymphocytes appear under electron microscopy?
A
They have a relatively smooth surface.
10
Q
How do B lymphocytes appear under electron microscopy?
A
They have a rough surface pattern.
11
Q
What technological advancement led to the identification of surface membrane markers?
A
Monoclonal antibody (MAb) testing
12
Q
What are the practical applications of surface membrane markers?
A
Identifying and enumerating lymphocyte subsets, establishing lymphocyte maturity, classifying leukemias, and monitoring patients on immunosuppressive therapy
13
Q
What are cell surface molecules recognized by monoclonal antibodies called?
A
Antigens or markers
14
Q
Why are surface molecules called markers?
A
They identify, discriminate between, and ‘mark’ different cell populations.
15
Q
How were surface markers originally named?
A
According to the antibodies that reacted with them
16
Q
What standardized system is now used to name surface markers?
A
Cluster of Differentiation (CD) system
17
Q
What are the criteria for a surface marker to be classified under the CD system?
A
It must identify a specific lineage or differentiation stage, have a defined structure, and be detectable using a group or cluster of monoclonal antibodies (MAbs).
18
Q
What are the two major categories of CD markers?
A
Markers specific for cells of a particular lineage or maturational pathway; Markers that vary in expression based on activation or differentiation state
19
Q
What is an example of a CD antigen used to classify lymphocyte subsets?
A
CD4 and CD8
20
Q
Besides identification, what roles do CD antigens play?
A
Promotion of cell-to-cell interactions and adhesion; Transduction of signals leading to lymphocyte activation
21
Q
Where do the precursors of lymphocytes arise from in early immunologic development?
A
Progenitor cells in the yolk sac and liver
22
Q
What becomes the main source of undifferentiated progenitor cells later in development?
A
Bone marrow
23
Q
What happens to progenitor cells in the bone marrow?
A
They further develop into lymphoblasts.
24
Q
Where does continued development and proliferation of lymphoid precursors occur?
A
As the cells travel to primary and secondary
25
What are the primary (central) lymphoid organs in mammals?
Bone marrow (and/or fetal liver) and thymus
26
From which embryonic structures are the stroma and nonlymphoid epithelium of the thymus derived?
Third and fourth pharyngeal pouches
27
How does the thymus change with aging?
Aging reduces naïve T cell production, causes intrinsic defects in mature T cell function, alters naïve T cell lifespan, and changes the naïve-to-memory T cell ratio in peripheral lymphoid tissues.
28
Where is the thymus located?
In the mediastinum
29
What role does the thymus play in immune system regulation?
It controls the entire immune system and is believed to be a major site for the development of immune diversity.
30
Where can clonal expansion occur?
Anywhere in the peripheral lymphoid tissue
31
What are thymocytes?
Lymphocyte precursors that acquire surface membrane antigens under the influence of thymosin
32
What is thymosin?
A humoral factor that influences the proliferation and differentiation of progenitor cells in the thymus
33
What is the function of the thymus’ reticular structure?
It allows a large number of lymphocytes to pass through and become fully immunocompetent (thymus-derived T cells).
34
How does the thymus regulate immune function?
By secreting multiple soluble hormones
35
Why do many cells die in the thymus?
To eliminate lymphocyte clones reactive against self
36
What percentage of cortical cells die in the thymus before becoming mature T cells?
Approximately 97%
37
Where do viable T cells migrate after leaving the thymus?
To secondary lymphoid tissues
38
What happens if the thymus is absent or develops abnormally?
T lymphocyte deficiency
39
What is the first age-related change in the human immune system?
Involution of the thymus
40
When does the thymus begin losing function postnatally?
As early as 3 months of age
41
How much of its mass does the thymus lose within the first 50 years of life?
Up to 95%
42
What functional changes occur due to thymic involution?
Decreased thymic hormone synthesis, loss of ability to differentiate immature lymphocytes, increased number of immature lymphocytes in the thymus and peripheral blood
43
What immune dysfunctions are correlated with thymic involution?
T and B lymphocyte dysfunction, increased circulating immune complexes, increased autoantibodies, monoclonal gammopathies
44
What is immune senescence?
The age-related decline in immune function leading to increased susceptibility to infections, autoimmune diseases, and neoplasms
45
What is the source of progenitor cells in mammals?
Bone marrow
46
What can progenitor cells differentiate into?
Lymphocytes and other hematopoietic cells (granulocytes, erythrocytes, megakaryocytes)
47
Which lymphocytes differentiate in the bone marrow?
Both T and B lymphocytes, probably from a common lymphoid progenitor cell
48
Which other tissue may play a role in B lymphocyte differentiation?
Gut-associated lymphoid tissue (GALT)
49
Secondary Lymphoid Organs
Provide a unique microenvironment for the initiation and development of immune responses
50
Secondary Lymphoid Tissues
lymph nodes, spleen,
GALT, thoracic duct, bronchus-associated lymphoid tissue
(BALT), skin-associated lymphoid tissue, and blood
51
Cells found throughout the body in secondary lymphoid organs
Mature lymphocytes and accessory cells (e.g.
52
What does the structure of secondary lymphoid organs allow?
Migration and interactions between antigen-presenting cells
53
Cooperative activities of lymphoid cells
Increase the probability of interactions of rare B
54
Cytokines essential to the formation and maintenance of secondary organs
Tumor necrosis factor (TNF) and lymphotoxin
55
Which cells produce TNF and lymphotoxin?
B and T lymphocytes
56
What is proliferation of T and B lymphocytes dependent on?
Antigenic stimulation
57
T lymphocytes populate which regions of the lymph nodes?
Perifollicular and paracortical regions
58
T lymphocytes populate which regions of the lymph nodes?
Medullary cords
59
T lymphocytes populate which regions of the spleen?
Periarteriolar regions
60
T lymphocytes populate which structure of the circulatory system?
Thoracic duct
61
B lymphocytes multiply and populate which regions of the lymph nodes?
Follicular and medullary (germinal centers)
62
B lymphocytes multiply and populate which regions of the lymph nodes?
Medullary cords
63
B lymphocytes multiply and populate which regions of the spleen?
Primary follicles and red pulp
64
B lymphocytes multiply and populate which regions of the GALT?
Follicular regions
65
What is the role of lymph nodes?
Act as lymphoid filters in the lymphatic system
66
Lymph nodes respond to
Antigens introduced distally and routed to them by afferent lymphatics
67
When does generalized lymph node reactivity occur?
After systemic antigen challenge (e.g.
68
What is the function of the spleen?
Acts as a lymphatic filter within the blood vascular tree
69
When is the spleen an important site of antibody production?
In response to IV particulate antigens (e.g.
70
The spleen is a major organ for the
Clearance of particles
71
What does GALT include?
Lymphoid tissue in the intestines (Peyer’s patches) and the liver
72
GALT features
Immunoglobulin A (IgA) production and involves a unique pattern of lymphocyte recirculation
73
What do pre-B cells do in Peyer's patches?
Develop
74
GALT is important for the
Development of tolerance to ingested antigens
75
Thoracic duct lymph is a rich source of
Mature T cells
76
Chronic thoracic duct drainage can cause
T cell depletion and has been used as a method of immunosuppression
77
BALT includes
Lymphoid tissue in the lower respiratory tract and hilar lymph nodes
78
BALT is mainly associated with
IgA production in response to inhaled antigens
79
Antigens introduced through the skin are presented by
Epidermal Langerhans cells
80
Epidermal cells then interact with
Lymphocytes in the skin and in draining lymph nodes
81
The blood is an important
Lymphoid organ and immunologic effector tissue
82
Circulating blood has enough mature T cells to
Produce a graft-versus-host reaction
83
Blood transfusions have been responsible for
Inducing acquired immunologic tolerance in kidney allograft patients
84
Blood is the most
Frequently sampled lymphoid organ
85
What is assumed about blood samples?
What is found in blood samples represents what is present in other lymphoid tissues
86
Percentage of T Lymphocytes in the Thymus
100
87
Percentage of B Lymphocytes in the Thymus
0
88
Percentage of T Lymphocytes in the Blood
80
89
Percentage of B Lymphocytes in the Blood
20
90
Percentage of T Lymphocytes in the Lymph Nodes
60
91
Percentage of B Lymphocytes in the Lymph Nodes
40
92
Percentage of T Lymphocytes in the Spleen
45
93
Percentage of B Lymphocytes in the Spleen
55
94
Percentage of T Lymphocytes in the Bone Marrow
10
95
Percentage of B Lymphocytes in the Bone Marrow
90
96
Average lifespan of mature T lymphocytes
Several months or years
97
Average lifespan of B lymphocytes
A few days
98
Lymphocyte recirculation
Lymphocytes move freely between the blood and lymphoid tissues
99
Purpose of lymphocyte recirculation
Enables lymphocytes to come into contact with processed foreign antigens and disseminate antigen-sensitized memory cells throughout the lymphoid system
100
What occurs regionally?
Clonal expansion
101
What happens after clonal expansion in lymph nodes draining a contact allergic reaction?
The whole body becomes susceptible to rechallenge because T cells recirculate
102
Do T cells return to the thymus?
Generally excluded from returning to the thymus
103
How is a pool of T cell clonal elements developed?
By a combination of positive selection of clones able to recognize and react to foreign antigens
104
How do lymphocytes recirculate back to the blood?
Through the major lymphatic ducts
105
How do lymphocytes enter the lymph node from the blood circulation?
Via arterioles and capillaries to reach the specialized postcapillary venules
106
What happens to lymphocytes after entering the venule?
They enter the node and remain in the node or pass through the node and return to the circulating blood
107
Virgin or naïve lymphocytes
Cells that have not encountered their specific antigen
108
What do virgin lymphocytes express?
High-molecular-weight variants of leukocyte common antigen
109
Memory cells
Populations of long-lived T or B cells that have been stimulated by antigen
110
What is a characteristic of memory cells?
They can make a quick response to a previously encountered antigen
111
Memory B cells carry
Surface IgG as their antigen receptor
112
Memory T cells express
The CD45RO variant of the leukocyte common antigen and increased levels of cell-adhesion molecules (CAMs)
113
What are CAMs?
Chemical mediators involved in inflammatory processes throughout the body
114
Most lymphocytes found in the circulating blood are
T cells
115
Where do T cells derive from?
Bone marrow progenitor cells
116
Where do T cells mature?
In the thymus gland
117
What are T cells responsible for?
Cellular immune responses and are involved in the regulation of antibody reactions in conjunction with B lymphocytes
118
The average lifespan of mature T lymphocytes
Several months or years
119
The average lifespan of B lymphocytes
A few days
120
Lymphocytes move freely between the blood and lymphoid tissues
Lymphocyte recirculation
121
Enables lymphocytes to come into contact with processed foreign antigens and disseminate antigen-sensitized memory cells throughout the lymphoid system
Purpose of lymphocyte recirculation
122
A type of immune response that can occur regionally in the body
Clonal expansion
123
The result after clonal expansion in lymph nodes draining a contact allergic reaction
The whole body becomes susceptible to rechallenge because T cells recirculate
124
Whether T cells typically return to the thymus
No
125
How the T cell repertoire is developed
By a combination of positive selection of clones able to recognize and react to foreign antigens
126
How lymphocytes recirculate back to the blood
Through the major lymphatic ducts
127
How lymphocytes enter the lymph node from the blood circulation
Via arterioles and capillaries to reach the specialized postcapillary venules
128
After entering the venule
what happens to lymphocytes
129
How lymphatic fluid
lymphocytes
130
How lymphatic fluid
lymphocytes
131
Cells that have not encountered their specific antigen
Virgin or naïve lymphocytes
132
What virgin lymphocytes express on their surface
High-molecular-weight variants of leukocyte common antigen
133
Populations of long-lived T or B cells that have been stimulated by antigen
Memory cells
134
A key characteristic of memory cells
They can make a quick response to a previously encountered antigen
135
What type of antigen receptor do memory B cells carry
Surface IgG
136
What memory T cells express
The CD45RO variant of the leukocyte common antigen and increased levels of cell-adhesion molecules (CAMs)
137
Chemical mediators involved in inflammatory processes throughout the body
CAMs (cell-adhesion molecules)
138
What type of lymphocytes are most commonly found in circulating blood
T cells
139
Where T cells originate
Bone marrow progenitor cells
140
Where T cells mature
In the thymus gland
141
What T cells are responsible for in the immune system
Cellular immune responses and are involved in the regulation of antibody reactions in conjunction with B lymphocytes
142
How the expression of T lymphocyte function–associated antigens changes during cellular development
It varies
143
What happens to some T lymphocyte antigens during cellular development
They appear early and remain on mature T cells
144
What happens to other T lymphocyte antigens during cellular development
They appear at an early or intermediate stage and are lost before maturity
145
Lymphocyte differentiation begins in this organ as a thymocyte
Thymus
146
Early surface markers on thymocytes committed to becoming T cells
CD44 and CD25
147
Occurs in an orderly fashion as thymocytes develop to code for an antigen receptor
Rearrangement of the genes
148
The length of the maturation process in the thymus
3 weeks
149
The path that cells filter through during maturation
From the cortex to the medulla of the thymus
150
The types of cells that are included in thymic stromal cells
Fibroblasts
151
Early thymocytes lacking CD4 and CD8 surface membrane markers
Double-negative thymocytes
152
The cytokine under whose influence double-negative thymocytes proliferate in the outer cortex of the thymus
Interleukin-7 (IL7)
153
What is critical for the growth and differentiation of early thymocytes
IL-7
154
The genes that code for the antigen receptor
the T cell receptor (TCR)
155
The main part of the T cell antigen receptor
CD3
156
Recognize specific antigens
Variable regions of two of the eight chains of the T cell antigen receptor
157
What happens first in rearrangement
Rearrangement of the beta (β) chain
158
What happens when a functional β chain appears on the cell surface
Sends a signal to suppress any further β chain gene rearrangements
159
The combination of the β chain with the CD3
Pre–T-cell antigen receptor (TRC)
160
What signaling by the β chain promotes
The development of a CD4+ and CD8+ thymocyte
161
What thymocytes that express gamma (γ ) and delta (δ) chains do
Follow a different developmental pathway
162
What cells expressing gamma-delta (γδ) chains typically remain
Both CD4− and CD8−
163
Where double-negative cells represent most of the population of T lymphocytes
In the skin and intestinal and pulmonary epithelium
164
How circulating CD3+ double-negative lymphocytes are characterized
Phenotypically and functionally distinct from single-positive CD3+CD4+ and CD3+CD8+ lymphocytes
165
What the presence of low numbers of double-negative T cells in healthy individuals suggests
A pathogenic or immunoregulatory role for this population of T lymphocytes
166
Cells with both CD4+ and CD8+ surface markers
Double-positive thymocytes
167
What double-positive thymocytes begin to demonstrate
Rearranged genes coding for the alpha (α) chain
168
When the CD3-αβ receptor complex (TCR) is expressed on the cell surface
Positive selection
169
What positive selection permits
Only double-positive cells with functional TCR receptors to survive
170
What T cells must recognize
Foreign antigen in association with class I or II major histocompatibility complex (MHC) molecules
171
What happens to any thymocyte that is unable to recognize self-MHC
Dies without ever leaving the thymus gland
172
What functioning T lymphocytes must be able to recognize
A foreign antigen along with MHC molecules
173
What takes place among the surviving double-positive T cells
Negative selection
174
Percentage of double-positive thymocytes that survive in the cortex
1% to 3%
175
Where double-positive (DP) CD4CD8 Tαβ cells have been reported
In normal individuals as well as in different pathologic conditions
176
What double-negative cells may act like
Natural killer (NK) cells
177
Why double-negative cells may act like natural killer (NK) cells
Because they are capable of binding to many natural
178
What double-negative cells are capable of recognizing
Antigens without being presented by MHC proteins
179
What NK cells may represent
An important bridge between natural and adaptive immunity
180
What happens to mature T cells when they leave the thymus
Their T cell receptors (TCRs) are CD4+ or CD8+
181
Where survivors of selection migrate
To the medulla
182
How survivors of selection exhibit markers
Exhibit only one type of marker
183
What cells gain with their entry into the peripheral blood circulation
Functional maturity
184
What mature T cells develop into
A variety of clones
185
What each lymphocyte displays
A single type of structurally unique receptor
186
The characteristics of the repertoire of antigen receptors in the entire population of lymphocytes
Extremely large and diverse
187
What the large and diverse repertoire of antigen receptors increases
The probability that an individual lymphocyte will encounter an antigen that binds to its receptor
188
What this process
clonal selection
189
What needs to be reinvented by every generation of cells
Antigen receptors for common pathogens
190
Why the receptor repertoire contains binding sites that can react not only with infectious microorganisms
but also with innocuous environmental antigens and self antigens
191
How the CD4+ subset was initially described
Representing the helper-inducer T cell
192
How the CD8+ subset was initially described
Representing the suppressor-cytotoxic T cell
193
How lymphocytes can be subdivided
Into several populations using various operational and phenotypic parameters
194
What lymphocytes can express
Both CD3 and CD4 (example: CD4 lymphocytes)
195
What the surface marker CD45RA subset delineates
A naïve helper T cell population
196
What the CD45RO subset delineates
A memory helper T cell population
197
What CD8+ lymphocytes express
Both CD3 and CD8 surface membrane markers
198
Another name for Helper T lymphocytes
T-helper (Th) cells
199
Which subsets can Helper T lymphocytes be assigned to
Helper T type 1 (Th1) cells
200
What Helper T type 1 (Th1) cells are responsible for
Cell-mediated effector mechanisms
201
What Helper T type 2 (Th2) cells do
Play a greater role in the regulation of antibody production
202
What Regulatory T (Treg) cells are
An immunoregulatory type of Th cells
203
What this classification is based on
The in vitro blends of cytokines that they produce
204
What Th1 and Th2 cells can promote
The development of cytotoxic cells
205
What Th1 and Th2 cells are believed to develop from
Th0 cells
206
With which cells do Th1 cells interact most effectively
Mononuclear phagocytes
207
What Th2 cells release
Cytokines that are required for B cell differentiation
208
Characterized by high interferon-gamma (IFN-γ) production
Th1 responses
209
What Th1 responses promote
The elimination of intracellular pathogens
210
Characterized by IL-4 and IL-5
Th2 responses
211
What Th2 responses promote
A different type of effector response that involves immunoglobulin E (IgE) production and eosinophils capable of eliminating larger extracellular pathogens
212
What the polarization of T cell responses serves to do in situations of repeated pathogen exposure or persistent infection
Focus the antigen-specific response on a specific effector pathway
213
Factors that can influence the terminal differentiation of lymphocytes
Type of antigen-presenting cell (APC)
214
What is determined by how these factors influence T cell differentiation
A hierarchy is apparent among these factors
215
What certain cytokines acting directly on T cells during primary activation appear to be
The most proximal or direct mediators of CD4+ T cell differentiation
216
What the presence of IL-12 during primary T cell activation leads to
Strong development of Th1 responses
217
What IL-4 promotes
Th2 development
218
What activation through the TCR is
A requirement for initiating terminal differentiation
219
What the signals from the TCR appear to be
Phenotype-neutral
220
What certain T cells carry out
Delayed hypersensitivity reactions
221
What these T cells react with
Antigen MHC class II on APCs
222
How these T cells create their effects
Mainly through cytokine production
223
What phenotype these cells generally are of
CD4+ phenotype
224
The two populations that T cells can also be differentiated into depending on
Whether they use an αβ (TCR2) or γδ (TCR1) antigen receptor
225
What the TCR consists of
A heterodimer and a number of associated polypeptides that form the CD3 complex
226
What the dimer recognizes
Processed antigen associated with an MHC molecule
227
What the CD3 complex is required for
Receptor expression and is involved in signal transduction
228
What TCR1 cells constitute
Less than 5% of total lymphocytes
229
What TCR1 cells appear to recognize
Different antigens than TCR2 cells
230
What some TCR1 cells do not require
Antigen to be processed or presented by MHC molecules
231
Immunoregulatory Th cells that control autoimmunity in the peripheral blood through dominant tolerance
Treg cells
232
Types of Treg cells
Natural CD4+ Treg cells
233
Characterized by constitutive expression of CD25
Natural Treg cells
234
Where natural Treg cells are developed
Primarily in the thymus from positively selected thymocytes with a relatively high avidity for self antigens
235
Percentage of natural Treg cells represent of the total CD4+ T cell population
Approximately 5% to 10%
236
Where the signal to develop into Treg cells is thought to come from
Interactions between the TCR and MHC class II self-peptide complex expressed on the thymic stroma
237
What natural Treg cells express in humans
CD4 and CD25
238
CD4+ and are functionally induced by IL-10
Tr1 cells
239
What Tr1 cells regulate
The immune system
240
The characterization of CD8+ Treg cells
Less well characterized
241
What CD8+ Treg cells are reportedly capable of
Suppressing CD4+ cells in vitro
242
Effector cells found in the peripheral blood that are capable of directly destroying virally infected target cells
Cytotoxic T lymphocytes
243
What most Tc cells are
CD8+
244
What Tc cells recognize on the target cell surface
Antigen associated with MHC class I molecules (e.g.
245
A process demonstrated by the immune response to virus-infected cells or tumor cells
The recognition of antigen on the target cell surface
246
What happens to naïve CD8+ T cells in a primary viral infection
They are primed in secondary lymph nodes and consequently proliferate and differentiate into effector CD8+ T cells to eliminate virus-infected cells
247
What happens to most effector CD8+ T cells after clearance of the virus
They contract because of apoptosis
248
What a small number of CD8+ T cells form
A memory T cell pool
249
What human CD8+ T cells undergo a change in the expression of
Costimulatory molecules (e.g.
250
Markers for effector CD8+ T cells
Cytolytic effector molecules
251
What the actual functional molecules are for killing target cells
Cytolytic effector molecules
252
The membrane marker naïve and central memory CD8+ T cells express
CCR7
253
What CCR7 is for
Homing to secondary lymph nodes
254
What effector memory and effector CD8+ T cells express
The chemokine receptors for inflammatory cytokines
255
What expressing the chemokine receptors for inflammatory cytokines enables the cells to do
Migrate toward infected and inflamed sites
256
A unique subset of the effector CD8+ T cell population expresses
CXCR1
257
What CXCR1 CD8+ T cells possess
Chemotactic activity toward the CDCR1 ligand IL-8
258
What the CXCR1 ligand IL-8 is
A potent inflammatory cytokine produced in inflamed tissues and in tissues infected with some viruses
259
What it suggests that these CXCR1+ effector CD8+ T cells do
Immediately migrate to inflamed and infected sites to exert their effector function in the initial stage of an immune response
260
What it is possible that effector CD8+ T cell subsets are
Functionally distinct populations of T lymphocytes
261
What Tc cells are major effectors in
Allograft organ rejection
262
Tc cells express CD4 or CD8
depending on
263
Functionally defined T cells that downregulate the actions of other T and B cells
Suppressor T lymphocytes
264
Whether Ts cells have unique markers
No
265
How Ts cells may operate
Through secretion of free TCRs
266
A group of functionally defined cells capable of taking up antigens and presenting them to lymphocytes in a form that they can recognize
Antigen-presenting cells (APCs)
267
How APCs take up antigens
In various ways (e.g.
268
What happens to some APCs
They are collected in the periphery and transported to the secondary lymphoid tissues
269
What other APCs normally do
Reside in lymphoid tissues and intercept antigen as it arrives
270
How B cells recognize antigen
In a native form
271
Two major pathways of antigen processing for the APC and target cell
Endogenous and exogenous
272
What the endogenous pathway processes
Proteins that have been internalized
273
What happens to proteins in the cytoplasm in the endogenous pathway
They are cleaved into peptide fragments about 20 amino acids in length
274
What these fragments are then transported into
The lumen of the endoplasmic reticulum by the transporter associated with the antigen-processing complex
275
What T cells that express the CD8+ cell surface marker recognize
Antigens presented by MHC class I molecules
276
What CD8+ functions as in this process
A coreceptor
277
What pathogen clearance requires
That CD8+ effector cells produce inflammatory cytokines and develop cytolytic activity against infected target cells
278
What happens after pathogen clearance
A small number of memory cells survive that rapidly regain effector function in the event of rechallenge
279
What differentiates during this process
A relatively homogeneous pool of naïve CD8+ T cells differentiates into heterogeneous pools of effector and memory CD8+ T cells
280
What the exogenous pathway processes
Soluble proteins that are taken up from the extracellular environment
281
How the antigens are processed in the exogenous pathway
In a series of intracellular acidic vesicles called endosomes
282
What the endosomes intersect with
Vesicles that are transporting MHC class II molecules to the cell surface
283
What CD4+ T cells recognize
Antigens that are presented by MHC class II molecules
284
How the recognition of the antigen by the T cells is described for both systems of antigen presentation
As being MHC-restricted
285
T cells are this; so that each expresses a receptor that can interact with a given peptide
Clonally restricted
286
Each lymphocyte makes only one type of this and can recognize only a very limited number of antigens
Antigen receptor
287
The TCR of most T lymphocytes is composed of this
An alpha and beta polypeptide chain
288
Regions of the TCR located close to the cell surface
Constant regions
289
The part of the TCR that binds to the antigenic peptide of appropriate fit located away from the cell surface
Variable region
290
The difference in structure of the distal regions of the alpha and beta chains allows
The development of different clones of T cells
291
TCR reacts with antigen in the context of
MHC class I or II molecules on an APC
292
T cells recognize protein antigens in the form of
Peptide fragments presented at the cell surface by MHC I or II molecules
293
When the antigen-specific TCR on the T cell surface interacts with the appropriate peptide-MHC complex
The CD3 complex triggers phosphorylation of the intracellular domains of the CD3 zeta chains
294
Subsequently
the zeta-associated protein 70 (ZAP-70) does this
295
Simultaneous colligation of the cell marker CD4 (or CD8) with the MHC class II (or I) molecule results in
The phosphorylation of particular kinases
296
What the events stimulate
The activation of at least three intracellular signaling cascades
297
T cell activation also requires this
A second costimulatory signal
298
Interaction between marker CD28 on T cells and marker CD80 on APCs
A second costimulatory signal
299
This interaction also triggers
Several intracellular signaling pathways
300
T cell activation requires a minimum of
Two signals
301
Signal 1 is delivered by
The TCR-CD3 complex through interaction of the TCR α and β chains as they recognize peptide presented by a class I CD8+ T cell or a class II CD4+ T cell MHC molecule
302
Signal 2 is usually provided by
The engagement of CD28 on the T cell with the costimulatory molecule CD80 or CD86 on the APC
303
What the surface markers CD 137 and CD134 also provide
Costimulation to T cells
304
The optimal combination of effector function
proliferation
305
Delivery of signal 1 without costimulation leads to
Anergy and apoptosis
306
Occurs if a cell does not receive a full set of signals
It will not divide and may even become anergic
307
The state of peripheral T cells
Resting (G0 or G1)
308
T cell activation is
A complex reaction involving transmembrane signaling and intracellular enzyme activation steps
309
It is through these that T cell regulation influences the action of other T cells
accessory cells
310
When activated by the proper signals
T cells may carry out one or more of these functions
311
Some antigens
particularly polysaccharide polymers (e.g.
312
What T-independent antigens generally are not
Strong
313
What T-independent antigens provoke mainly
IgM responses
314
What T-independent antigens induce
Minimal immunologic memory
315
What happens to a relatively homogeneous pool of naïve CD8+ T cells
Differentiates into heterogeneous pools of effector and memory CD8+ T cells
316
Functionally defined cells capable of taking up antigens and presenting them to lymphocytes in a form that they can recognize
Antigen-presenting cells (APCs)
317
How B cells recognize antigen
In a native form
318
Two major pathways of antigen processing for the APC and target cell
Endogenous and exogenous
319
The endogenous pathway processes
Proteins that have been internalized
320
T cells recognize antigens that are presented by this
MHC class II molecules
321
T cells that express the CD8+ cell surface marker recognize antigens presented by
MHC class I molecules
322
How the recognition of the antigen by the T cells is described for both systems of antigen presentation
As being MHC-restricted
323
MHC-restricted is this
A process whereby T cells recognize only antigen presented by self MHC molecules
324
Activated T cells frequently express
Activation antigens
325
Expression of this occurs within 12 hours of activation
CD69
326
Markers expressed in 1 to 3 days post-activation
CD25 (IL-2 receptor) and CD71 (transferrin receptor)
327
Some of the results of T cell activation
Cell division
328
A subpopulation of circulating lymphocytes (≈10%) that lack conventional antigen receptors of T or B cells
NK and K-type lymphocytes
329
What NK and K-type lymphocytes produce
Mediators (e.g.
330
What NK and K-type cells express
A variety of surface membrane markers
331
What most of NK and K-type cells lack
CD3
332
What NK and K-type cells express
CD2
333
Essential mediators of virus immunity
Natural killer (NK) cells
334
What the deficiency of NK cells leads to in humans
Uncontrolled viral replication and poor clinical outcome
335
What is essential to NK and T cell effector and surveillance functions
MHC class I (MCH I)
336
What percentage of NK cells have the appearance of large granular lymphocytes (LGLs)
70% to 80%
337
Up to about what percentage of LGLs function as NK cells
0.75
338
How NK cells destroy target cells
Through an extracellular nonphagocytic mechanism referred to as a cytotoxic reaction
339
MHC-unrestricted cytolysis
How NK cells destroy target cells
340
What NK cell target cells include
Tumor cells
341
Where a considerable number of NK cells may be present
In other tissues
342
Roles NK cells may play in other tissues
Important roles in inflammatory reactions and in host defense
343
What NK cells will actively kill
Virally infected target cells
344
What may be stopped if NK cell activity is completed before the virus has time to replicate
A viral infection
345
What several cytokines affect
NK cell activation and proliferation
346
Cytokines NK cells are highly responsive to
IL-2
347
What these cytokines generate
High cytokine-activated killer activity in these cells
348
What NK cells synthesize
A number of cytokines involved in the modulation of hematopoiesis and immune responses and in the regulation of their own activities
349
What molecules are mainly classified under
The family of cell adhesion molecules (CAMs)
350
The main class of effector CAMs shown to mediate NK cell functions
The leukocyte integrins—more specifically
351
What several NK cell surface molecules are involved in
Target cell recognition and binding
352
How NK cells recognize targets
Using several cell surface molecular receptors (e.g.
353
What NK cells also receive
Inhibitory signals from MHC class I on potential target cells
354
How inhibitory signals are transduced
By a killer inhibitory receptor on the NK cell
355
What CD56 may mediate
Interactions between effector and target cells
356
What NK cells are able to do
Bind and lyse antibody-coated nucleated cells through a membrane Fc receptor that can recognize part of the heavy chain of immunoglobulins
357
What enabling NK cells to do
Mediate antibody-dependent
358
What may be mediated by CD16
Some
359
What CD16 exerts
A regulatory role in their cytolytic function
360
What CD16 and CD69 exerts in NK cells
Increasing the rate of proliferation of NK cells
361
What most K-type cells are
Non-T
362
What the target cell must be coated with
Low concentrations of IgG antibody
363
The different cytotoxic mechanism
The target cell must be coated with low concentrations of IgG antibody
364
Cells which exhibit An ADCC reaction
K cells and phagocytic and nonphagocytic myelogenous-type leukocytes
365
What K cells are capable of
Lysing tumor cells
366
What the precise lineage of the K cell is
Uncertain
367
B cells represent
A small proportion of the circulating peripheral blood lymphocytes
368
What the unfavorable image of B lymphocytes in the pathogenesis of immune disease has been associated mainly with
Their capacity to produce harmful antibodies after differentiation into plasma cells
369
Other roles discovered for B lymphocytes
An antibody-independent pathogenic role of B cells (e.g.
370
What is reorganized on recognition of a specific antigen
The B cell membrane
371
What happens to internalized antigen
It is degraded and subsequently exposed to the B cell surface in association with MHC complex molecules for presentation to T cells
372
What this surface presentation of antigen elicits
The assistance of T cells required to assist B cell maturation
373
What B cells also have the capacity to do
Expand clonally
374
What activated B cells produce
A wide range of cytokines and chemokines that modulate the maturation
375
B1 and B2 cells
B cell subsets
376
B1 cells are distinguished by
The CD5 marker
377
B1 cells appear to form
A self-renewing set
378
What B1 cells respond to
A number of common microbial antigens
379
What B1 cells occasionally generate
Autoantibodies
380
What B2 cells account for
Most of the B lymphocytes in adults
381
What B2 cells generate
A greater diversity of antigen receptors
382
What B2 cells respond effectively to
T-dependent antigen
383
B cells are derived from progenitor cells
Through an antigen-independent maturation process occurring in the bone marrow and GALT
384
How participation of B cells in the humoral immune response is accomplished
By reacting to antigenic stimuli through division and differentiation into plasma cells
385
Terminally differentiated B cells
Plasma cells or antibody-forming cells
386
What plasma cells or antibody-forming cells are devoted to
Antibody production
387
What the specific antibodies produced are able to do
Bind to infected cells
388
The condition of hyperacute rejection of transplanted organs is also mediated by
B cells
389
What B lymphocytes are best known to express
CD19 but not CD3 surface membrane markers
390
When the surface molecule CD19 appears
During B-cell differentiation in the bone marrow
391
Until when the surface molecule CD19 remains on the B cell unit
Until it differentiates into a plasma cell
392
Four proteins on the surface of mature B cells
CD19
393
What four proteins form
The CD19 complex
394
Primitive B cell precursors have this in their cytoplasm
δ chains
395
Primitive B cell precursors do not have this on their surface
Ig
396
More differentiated (but still immature) B cells have this
Intact cytoplasmic IgM and surface IgM
397
Mature B cells lose this and add this
Lose their cytoplasmic IgM and add surface IgD to the surface IgM
398
What the types of B cell surface markers are
Ig receptor
399
Best studied B cell surface marker
Ig receptor
400
When specific antigen exposure does occur
The antigen will select the B cell having an Ig receptor with the best fit
401
What B cells undergo after binding and cooperative interaction with T cells
Transformation into plasma cells
402
B lymphocytes are best known to express this surface membrane marker
CD19
403
B lymphocytes do NOT express this surface membrane marker
CD3
404
During B-cell differentiation in the bone marrow
this surface molecule appears early and remains on the B cell until it differentiates into a plasma cell
405
Four proteins on the surface of mature B cells that form the CD19 complex
CD19
406
Primitive B cell precursors have this in their cytoplasm
δ chains
407
Primitive B cell precursors lack this on their surface
Ig (immunoglobulin)
408
More differentiated (but still immature) B cells have this
Intact cytoplasmic IgM and surface IgM
409
Mature B cells lose this and add this to their surface
Lose cytoplasmic IgM and add surface IgD
410
B cell surface markers in humans
Ig receptor
411
The best-studied B cell surface marker
Ig receptor
412
This receptor is actually this type of molecule with antigenic specificity
Antibody molecule
413
According to clonal selection theory
B cells exist with these
414
After binding antigen and interacting with T cells
B cells transform into
415
The secreted antibody from the plasma cell has the same specificity as
The Ig receptor on the B cell
416
Most of the antibody produced by plasma cells is
Secreted
417
Most of the antibody produced by B cells is
Expressed as surface Ig receptors
418
Some antigens can bind to the Ig receptor and stimulate an antibody response without T cell cooperation; these are called
T-independent antigens
419
T-independent antigen responses are generally
Of low intensity and restricted to IgM production
420
Except for immature lymphocytes and plasma cells
B cells have this
421
The nature of surface immunoglobulin on B cells
Polyclonal (kappa and lambda light chains)
422
Mu and delta heavy chains are found with which light chains
Kappa or lambda
423
Gamma and alpha chains are found
Rarely on normal lymphocytes
424
An Fc receptor on B cells may function to
Aid in binding to antigen already bound to antibody
425
Receptors for fragments of cleaved complement component C3 are found on what percentage of B cells
Approximately 75%
426
This receptor binds
C3b iC3b (inactivated C3b) and C3d
427
Another type of B cell surface marker
B cell surface antigens coded by the MHC class II genes
428
B cells can be stimulated in their resting state to do what?
enlarge develop synthetic machinery divide mature and secrete antibody
429
What the proper signals for B cell activation depend on
the type of triggers which can be specific or nonspecific and polyclonal
430
Specific activation of B cells involves what?
the antigen that is complementary to the particular Ig on the surface
431
Nonspecific activation of B cells occurs with what?
B cell mitogens
432
Efficient antibody production to complex protein antigens requires what?
T cell help which in turn develops from APCs presenting antigen to the T cell
433
Activated T cells secrete what that trigger the B cell to develop into an antibody-secreting cell?
a variety of cytokines together with the specific antigen
434
What process is also involved in B cell activation?
class switching
435
In the immune response to a foreign protein what are the first antibodies to appear?
IgM class (or isotype)
436
As the immune response proceeds what other isotypes emerge?
IgG IgA and IgE from Ig class switching
437
What has considerable clinical importance because each of the four major isotypes has specialized biologic properties?
The isotype switch
438
What is the principal class of antibody in interstitial fluids?
IgG
439
What is the protective antibody of mucosal surfaces?
IgA
440
What requires collaboration between antibody-synthesizing B cells and helper CD4+ T cells?
Isotype switching
441
What molecule does the B cell use on its surface to capture the antigen and present it to the T cell?
IgM
442
Contact between the collaborating lymphocytes is enhanced by what?
complementary pairs of CAMs
443
Contact between B and T cells induces the T cell to express what?
a ligand for the B cell surface molecule CD40
444
CD40 interacts with the newly expressed CD40 ligand on the T cell which leads to the expression of what?
another B cell surface molecule B7
445
What is the latter’s partner on the surface of the T lymphocyte?
CD28
446
These cooperative and synergistic interactions between T and B cells induce the secretion of what?
cytokines such as IL-2 and IL-4
447
Isotype switching requires what?
two signals
448
What delivers the first signal for Isotype switching?
an interleukin
449
What delivers the second signal for Isotype switching?
the binding of CD40 to its ligand on the T cell
450
In the process of switching from IgM synthesis to IgE synthesis what does IL-4 make accessible?
the IgE gene in the B cell
451
What gene moves from its position near the gene that encodes for IgM to a position near the gene that encodes for IgE?
the gene that encodes the variable region (the part of the antibody molecule that contains the antigen-binding site)
452
What is the function of plasma cells?
synthesis and excretion of immunoglobulins
453
Where are plasma cells normally found?
bone marrow in concentrations that do not normally exceed 2%
454
Plasma cells arise as what?
the end stage of B cell differentiation into a large activated plasma cell
455
The pathway from the B lymphocyte to the antibody-synthesizing plasma cell forms when what?
the B cell is antigenically stimulated and undergoes transformation because of the stimulation of various interleukins
456
The immune antibody response begins when individual B lymphocytes encounter what?
an antigen that binds to their specific Ig surface receptors
457
After receiving an appropriate second signal provided by interaction with helper T cells these antigen-binding B cells undergo transformation and proliferation to do what?
generate a clone of mature plasma cells that secretes a specific type of antibody
458
An increase in plasma cells can be seen in a variety of what?
nonmalignant disorders such as viral disease (e.g. rubella infectious mononucleosis) allergic conditions chronic infections and collagen diseases
459
In plasma cell dyscrasias the plasma cells can do what?
be greatly increased or infiltrate the bone marrow completely
460
Examples of plasma cell dyscrasias
multiple myeloma Waldenström’s macroglobulinemia
461
Antibody molecules secreted by plasma cells consist of what?
four chains—two light chains and two heavy chains based on molecular weight
462
Antibody molecules can be enzymatically cleaved into what?
Fab (antigen-binding) and Fc (crystallizable) fragments
463
What does the Fab portion bind?
antigen and contains the light chains and their antigenic markers (kappa lambda) as well as heavy chains
464
What does the Fc fragment contain?
the markers that distinguish the different classes of antibody and sites that will bind and activate complement and bind to Fc receptors on cells
465
What is constant for most of the antibody protein?
the amino acid sequence
466
What has a hypervariable region and accounts for the various antigenic specificities that the antibody is programmed to recognize?
the antigen-binding portion of the molecule
467
In alterations in lymphocyte subsets what can be reversed under certain conditions?
the normal functioning of helper cells and suppressor cells in the immune response
468
For example what is phenotypically a helper cell but functionally a suppressor cell?
the target cell for human T cell leukemia or human immunodeficiency virus (HIV )
469
Functionally what signals B cells to generate antibodies control production and switching of types of antibodies formed and activate suppressor cells?
the helper-inducer subset of cells
470
What do the suppressor-cytotoxic lymphocytes do?
control and inhibit antibody production by suppressing helper cells or by turning off B cell differentiation
471
What can be reversed under certain conditions?
the normal ratio of helper cells and suppressor cells (≈2:1)
472
Except for inconsistent values seen in extremely old adults what is relatively stable throughout adult life?
the total number of T cells in the peripheral blood
473
However what changes with aging?
there is a change in the distribution of T cell subpopulations
474
What decreases and what increases in older adults?
a decrease in the number of suppressor cells and an increase in the helper cell population
475
The effect of aging on the immune response is highly variable but what is age-related?
the ability to respond immunologically to disease
476
What may contribute to poor immunity in older adults?
Faulty immunologic reactions
477
What functional deficits have been identified with aging?
of T lymphocytes causing impairment of cell-mediated immunity
478
In addition what reveals decreases in the intensity of delayed hypersensitivity in older adults?
skin testing
479
What response of T lymphocytes is impaired with aging?
The proliferative response of T lymphocytes to mitogens or antigens such as Mycobacterium tuberculosis or varicella-zoster virus
480
What is the primary cause of the impaired humoral response in older adults?
A decrease in Th cells
481
Although the total number of B cells and total Ig concentration remain unchanged what changes?
the serum concentration of IgM is decreased and IgA and IgG concentrations are increased
