1
Q
Historically, the response of vertebrates to microbial invasion was divided into (2)
A
specific and nonspecific forms of defense
2
Q
Now, a vertebrate’s response to microbial invasion is composed of (2)
A
innate and adaptive immunity
3
Q
What is the key to the function of the immune system?
A
ability to distinguish self from nonself cells
4
Q
Adaptive immunity is characterized by
A
genetic rearrangements that generate a diverse set of molecules that can recognize virtually any invading pathogen
5
Q
What is the largest organ of the body?
A
skin
6
Q
What is the skin’s surface pH?
A
3 to 5, because of the oil and sweat glands
7
Q
Why is the acidic nature of skin important?
A
it’s acidic enough to inhibit the growth of many pathogenic microorganisms
8
Q
Sweat contains the enzyme
A
lysozyme, which digests bacterial cell walls
9
Q
What do epithelial cells produce as a defense?
A
produce a variety of small anti-microbial peptides
10
Q
The skin is also home to (3)
A
normal flora; nonpathogenic bacteria; fungi
11
Q
What happens to pathogenic bacteria that attempts to colonize the skin?
A
they are generally unable to compete with normal flora
12
Q
The epidermis of the skin is how many cells thick?
A
10 to 30 cells thick
13
Q
In addition to the skin, what are three other potential routes of pathogen entry?
A
digestive tract; respiratory tract; urogenital tracts
14
Q
Each tract is lined by
A
epithelial cells, which are continuously replaced like in skin
15
Q
What covers each epithelial surface?
A
a layer of mucus, secreted by cells scattered in between epithelial cells
16
Q
What purpose does the mucus lining epithelial surfaces serve?
A
traps pathogens
17
Q
What kills microbes present in food? (3)
A
saliva (which contains lysozyme); acidic stomach; digestive enzymes
18
Q
How are microorganisms in inhaled air dealt with?
A
trapped by mucus in smaller bronchi/bronchioles before reaching warm/moist lungs (where they would likely flourish)
19
Q
What happens to pathogens trapped by mucus in the bronchi/bronchioles?
A
mucus is swept up to the glottis by cilia from the epithelial cells and can be swallowed
20
Q
What effect does smoking have on respiratory tract defenses?
A
nicotine paralyzes cilia of the respiratory system which results in unclean tracts
21
Q
How does urine function as a pathogenic defense?
A
Acidic urine continually washes out pathogens from the urinary tract
22
Q
What are four additional defense mechanisms that commonly occur in people?
A
vomiting, diarrhea, coughing, sneezing
23
Q
Innate immunity involves (2)
A
soluble factors AND different types of blood cells
24
Q
What is the characteristic portion of gram-negative bacteria that make it recognizable as part of innate immunity?
A
lipopolysaccharide found in gram-negative cell walls
25
What is the characteristic portion of all bacteria that make it recognizable as part of innate immunity?
peptidoglycan found in all bacterial cell walls
26
The receptors involved in innate immunity can be found
in solution (they're soluble proteins) OR membrane proteins on the surface of blood cells
27
What is the best studied innate receptor protein?
Toll receptor in fruit flies
28
How many TLRs are there in humans? In mice?
11 TLRs in humans; 13 TLRs in mice
29
The TLRs found in humans and mice bind to
a variety of specific targets important to pathogen survival, which therefore do not vary greatly
30
Give six examples of targets of TLRs found in humans and mice.
gram-negative LPS, bacterial lipoproteins, bacterial peptidoglycan fragments, yeast cell-wall components, unmethylated CpG motifs in bacterial DNA, and viral RNA
31
How do TLRs accommodate a wide variety of shapes?
TLRs contain leucine-rich regions that fold to form binding pockets
32
What comprises the innate response to an infection? (3)
inflammatory response; production of antimicrobial peptides; production of cytokines which attract B/T/phagocytic cells
33
What was the next class of receptors to be discovered after Toll/TLR proteins?
cytoplasmic receptors
34
How do cytoplasmic receptors work?
bind to characteristic pathogen molecules and recognize invading pathogens in the cytoplasm of cells after phagocytosis
35
Cytoplasmic receptors are part of the response to
viral RNA
36
The response to viral RNA includes which receptor?
cytoplasmic receptors
37
What are soluble receptors?
receptors that circulate in serum; can respond to specific pathogen molecules
38
Give an example of a specific pathogen molecule recognized by soluble receptors.
lectin proteins
39
Lectin proteins bind to
mannose
40
Lectin proteins are important in
activating the complement system
41
Give an example of an antimicrobial peptide.
defensins
42
How do defensins work?
cysteines on defensins interact with positively charged AAs on pathogen surface; bind to outer membrane of gram-negative bacteria; can disrupt membrane and enhance phagocytosis
43
In addition to working against gram-negative bacteria, defensins can work effectively against
enveloped viruses
44
Defensins can induce what antimicrobial enzyme?
lysozyme
45
Gram-bacteria/enveloped viruses are targeted by
membrane attack complexes (MAC)
46
MACs come from
the complement cascade
47
Bacteria/fungi/enveloped viruses are targeted by
antimicrobial peptides
48
Antimicrobial peptides come from (2)
circulating phagocytes OR directly from epithelial cells
49
Bacteria/fungi are targeted by
circulating phagocytes
50
Circulating phagocytes come from (3)
cytokines; chemokines, complement cascade
51
Virus-infected cells are targeted by
natural killer (NK) cells
52
Natural killer cells come from
directly from virus-infected cells
53
What are the two types of interferons?
interferon type I and interferon type II
54
Type I interferons are synthesized when
a virus infects a cell
55
How do type I interferons act when a virus infects a cell?
act as messengers to protect normal, uninfected cells in the vicinity; induce degradation of RNA and block protein production in these cells; leads to cell death but stops spread of virus
56
Type II interferons are synthesized by (2)
T lymphocytes; natural killer cells
57
What is the name for type II interferons in humans?
IFN-gamma
58
IFN-gamma is secreted as part of
the immunological defense against infection and cancer
59
Cytokines are produced in response to signaling from
TLR receptors; internal receptors
60
Cytokines attract and cause (3)
attract nonspecific phagocytic cells; cause inflammation; signal to the adaptive immune system
61
What are the three basic defending leukocytes?
macrophages; neutrophils; natural killer cells
62
Phagocytic cells are associated with what type of immunity?
innate immunity
63
What are macrophages and what do they do?
large, irregularly-shaped cells that kill microorganisms by ingesting them through phagocytosis
64
Once a microorganism is inside the macrophage, what happens?
membrane-bound phagosome fuses with lysosome and lysozomal enzmes kill and digest the microoroganism
65
What other unusual molecule can be found within phagosomes?
oxygen-containing free radicals, which are reactive and degrade the pathogen
66
Oxygen-containing free radicals are found in what structure?
phagosomes in macrophages; neutrophils
67
(T/F) Macrophages exclusively digest bacteria.
False, they can digest viruses/debris/dust
68
Where are macrophages found in the body?
extracellular fluid that bathes tissues
69
What are monocytes?
undifferentiated macrophages found in the blood
70
In response to an infection, what do monocytes do? (2)
squeeze through endothelial cells and go to site of infection; there, they mature into active phagocytic macrophages
71
What is the most abundant circulating leukocyte?
neutrophils, which account for 50-70% of peripheral blood leukocytes
72
What is the first type of cell to appear at a site of damage/infection?
neutrophils
73
How do neutrophils digest pathogens?
also by phagocytosis similar to that of macrophages except that they produce even more oxygen radicals
74
In addition to oxygen radicals, what else do neutrophils produce as a defense?
defensin peptides
75
(T/F) Natural killer cells attack invading microbes.
False, they kill cells of the body that have been infected by a virus.
76
How do natural killer cells work?
kill cells of the body via apoptosis
77
On a molecular level, how do natural killer cells work? (3)
NK cells release perforins, which insert into the membrane and create pores; NK-produced granzymes enter pores and activate proteins that induce apoptosis; macrophages digest remaining cellular debris
78
NK cells attack tumor cells, often before
the tumor has a had a chance to divide sufficiently to be recognized as a tumor - this makes NK cells a very important defense against cancer
79
NK cells are said to play a role in
immune surveillance
80
(T/F) Inflammatory response involves only the immune system.
False, it involves several systems of the body.
81
The inflammatory response can be either ____ or ____
localized or systemic
82
What is an acute inflammatory response?
a response that starts rapidly but lasts for a short amount of time
83
What are some chemical alarm signals released by infected/injured cells? (3)
histamine; prostaglandins; bradykinin
84
Chemical alarm signals like histamine cause
vasodilation of local blood vessels, which increases flow of blood to site and causes the area to become red and warm; increase permeability of capillaries in area which causes edema; swelling puts pressure on nerves which causes pain
85
What is edema?
tissue swelling
86
The increased capillary permeability as part of the inflammatory response does what? (2)
initially promotes migration of phagocytic neutrophils from blood to extracellular fluid; neutrophils can digest pathogens
87
The pus associated with infections is a mixture of (3)
dead/dying pathogens; tissue cells; neutrophils
88
Neutrophils that are sent to an injury site as part of an inflammatory response do what? (2)
digest pathogens; signal other monocytes to enter and become macrophages to help digest
89
What is one manifestation of the acute inflammatory response?
fever
90
On a molecular level, what causes fever?
when a macrophage with a TLR on surface binds to pathogen, interleukin-1 is released and carried to brain, where it causes neurons in hypothalamus to raise body temp above 37 C
91
Why is an increased body temperature as a result of fever necessary?
promotes activity of phagocytic cells and impedes growth of microorganisms
92
Which cytokine is associated with fever?
interleukin-1
93
In addition to stimulating phagocytosis, how else does fever contribute to the body's defense? (2)
causes spleen and liver to store iron; this reduces blood levels of Fe which bacteria need to grow
94
Why is a very high fever dangerous?
can denature critical enzymes
95
What is considered the max temperature limit?
40.6 C, anything above this can be fatal
96
During an acute inflammatory response, how does the liver aid in phagocytosis? (2)
liver releases acute-phase proteins at levels 1000x above serum concentration; these proteins bind to pathogens and promote their phagocytic ingestion
97
What are the two phagocytic cells associated with the inflammatory response?
neutrophils and macrophages
98
What is the complement system?
the chemical defense of a vertebrate body that consists of a battery of proteins that become activated by the walls of bacteria/fungi
99
Approximately how many different proteins are associated with the complement system, and where are they found?
30 different proteins that circulate freely blood plasma
100
How are complement proteins activated?
mannose-binding lectin protein OR reactions involving charged species on surface of pathogens
101
When the complement system is activated, what happens? (3)
complement proteins aggregate to form membrane attack complex (MAC) that inserts itself into the pathogen plasma membrane; MAC channels extracellular fluid into pathogen; pathogen swells and bursts
102
What is C3b?
a complement protein that coats the surface of invading pathogens
103
What does C3b do?
helps direct neutrophils and macrophages to the pathogen for digestion; useful for pathogens that don't have a lipid membrane that MACs can attach to
104
Mast cells and basophils
release histamine and other mediators in response to stimulation by complement cells
105
An effective chicken pox vaccine was developed in
1991
106
Which virus causes chicken pox?
varicella zoster
107
The scientific study of immunity began with
Edward Jenner in 1796
108
Smallpox is caused by what virus?
variola virus
109
What is vaccination?
injecting a harmless agent to confer resistance to a dangerous one
110
Modern resistance to malaria/herpes involve delivering antigens associated with what virus?
vaccinia virus, which is related to the cowpox virus
111
What is an antigen?
molecule that provokes a specific immune response
112
Generally speaking, what are the most effective antigens?
large, complex proteins
113
What is the relationship between foreign-ness and immune response?
the more foreign an antigen is, the greater the immune response will be
114
What is another name for epitopes?
antigenic determinants
115
All cells in blood ultimately derive from
the division/differentiation of hematopoietic stem cells
116
What is hematopoiesis?
division/differentiation of hematopoietic stem cells to produce cells in blood
117
Where are hematopoietic stem cells originally found, and where do they migrate afterwards?
originally found in yolk sac; migrate to fetal liver/spleen and then to bone marrow
118
Hematopoietic stem cells give rise to what two types of cells?
lymphoid progenitors; myeloid progenitors
119
Lymphoid progenitors give rise to (3)
B lymphocytes; T lymphocytes; natural killer cells
120
B lymphocytes come from
lymphoid progenitors
121
T lymphocytes come from
lymphoid progenitors
122
Natural killer cells come from
lymphoid progenitors
123
Myeloid progenitors give rise to
erythrocytes; platelets; all other cells of the immune system
124
Which general blood cell is responsible for adaptive immunity?
lymphocytes
125
Monocytes give rise to
macrophages
126
Eosinophils are important in
the elimination of helminths (flatworms)
127
How do eosinophils eliminate helminths? (2)
secretion of digestive enzymes through perforin pores inserted into helminth plasma membrane; phagocytosis
128
In addition to the elimination of helminths, what else do eosinophils do?
play a role in exacerbating chronic inflammatory diseases like asthma or inflammatory bowel disease
129
(T/F) Basophils are phagocytic.
False, they are not phagocytic.
130
(T/F) Mast cells are not phagocytic.
True, they are not phagocytic.
131
Which cell is particularly important in the allergenic response?
mast cells
132
Dendritic cells are important in
the activation of T cells
133
Which cells form a link between innate and adaptive immunity?
dendritic cells
134
What is the function of helper T cells? (2)
recognizes foreign peptides on antigen-presenting cells; induces release of cytokines that activate B cells or macrophages
135
What is the function of cytotoxic T cells?
recognizes and kills "altered-self" cells like virally infected or tumor cells
136
What is the function of B cells? (3)
binds specific, soluble antigens with membrane-bound antibody; serves as antigen-presenting cell to helper T cells; when activated, it differentiates into plasma cells and memory B cells
137
What is the function of plasma cells? (2)
derived from activated B cells; is a biochemical factory devoted to secretion of antibodies against antigens
138
What is the function of natural killer cells?
rapidly recognizes, kills virally infected cells
139
What is the function of monocytes? (2)
precursor of macrophages; located in blood
140
What is the function of macrophages? (2)
phagocytic tissue cell that is a component of the body's first cellular line of defense; serves as antigen-presenting cell to helper T cells
141
What is the function of neutrophils? (2)
phagocytic tissue cell that is a component of the body's first cellular line of defense; found in blood in large numbers until attracted to sites of inflammation
142
Which cells serve as antigen-presenting cells to helper T cells? (3)
B cells; macrophages; dendritic cells
143
What is the function of eosinophils?
important in the elimination of parasites; involved in chronic inflammatory diseases
144
What is the function of basophils?
circulating cell that releases mediators like histamine, prostaglandins for inflammation
145
Where are mast cells located?
under mucosal surfaces
146
What is the function of mast cells? (2)
releases mediators like histamine, prostaglandins; triggered by inflammatory and allergenic responses
147
What is the function of dendritic cells?
antigen-presenting cells to naive helper T cells; helps activate naive cytotoxic T cells
148
The adaptive immune system is characterized by what four traits?
specificity of antigen recognition; wide diversity of antigens that can be recognized; memory, where the immune system responds faster to an antigen the second time; ability to distinguish self-antigens from nonself
149
What are lymphocytes?
type of white blood cell involved in immune response
150
What are the two principal classes of lymphocytes?
B cells and T cells
151
What kinds of proteins do lymphocytes have on their surfaces?
have receptor proteins on the surfaces that recognize epitopes
152
Which system dominates in the early part of pathogen response, and which system dominates later?
innate system dominates first, and then adaptive system dominates
153
Which cells bind antigens/have the receptors necessary to bind antigens?
B cells and T cells
154
Describe B cell receptors. (2)
immunoglobulin (Ig) molecules with a Y-shaped structure; each B cell has a single Ig that binds to a single antigenic determinant
155
Describe T cell receptors. (2)
simpler than Ig molecules; can only bind to antigens bound to another cell
156
(T/F) Lymphocytes tend to have similar specificities.
False, they tend to be unique.
157
What is a naive lymphocyte?
lymphocyte that hasn't encountered an antigen before
158
What is clonal selection?
amplification of a clone of an immune cell stimulated by antigen recognition
159
What happens to the cells produced by clonal selection?
some respond to the antigen, others become memory cells
160
What is humoral immunity?
part of adaptive immune system involving B cells that produce soluble antibodies specific for foreign antigens
161
(T/F) T cells secrete antibodies.
False, T cells do NOT secrete antibodies
162
What is cell-mediated immunity?
part of adaptive immune system mediated by T cells
163
What are the two types of T cells?
cytotoxic T cells; helper T cells
164
What are the two ways someone can acquire immunity?
infection/immunization; getting antibodies from another human (like a mother)
165
What is active immunity?
activation of specific lymphocytes and generation of memory cells
166
What is passive immunity?
obtainment of antibodies from another human (like your mother), without generating memory cells
167
(T/F) Antibodies are immortal.
False, they degrade with time.
168
T cells are produced in
the thymus
169
What are the two sets of organs in the immune system?
primary lymphoid organs; secondary lymphoid organs
170
What organs are part of the primary lymphoid organs? (2)
bone marrow; thymus
171
What organs are party of the secondary lymphoid organs? (3)
lymph nodes; spleen; mucosa-associated lymphoid tissue (MALT)
172
Where do B cells mature?
bone marrow
173
What is the name for immature B cells?
progenitor B cells
174
Which process gives rise to B cells?
hematopoiesis
175
Where does DNA rearrangement of immunoglobulin genes occur?
in the bone marrow when B cells are maturing
176
How many Ig molecules does a B cell contain on its surface?
10^5
177
What happens to lymphocytes that bind to self-antigens?
are killed via apoptosis
178
Where is MALT located?
small intestine
179
Where do progenitor T cells get produced?
bone marrow
180
Where do progenitor T cells go from the bone marrow?
thymus
181
What receptor is located on T cells?
T-cell receptor (TCR)
182
TCR is produced by
gene rearrangements as T cells mature in thymus
183
How many TCRs can be found on one T cell?
10^5
184
B cells recognize what kinds of epitopes?
epitope of an intact antigen that may or may not be a protein
185
T cells recognize what kinds of epitopes?
only recognize the peptide fragment of a protein antigen, and peptide fragment must be bound to series of self-proteins
186
What is the major histocompatability complex? (2)
set of protein cell-surface markers anchored in plasma membrane which helps immune system identify "self"; all cells of a given individual have the MHC protein
187
What percent of B cells are ultimately released from the bone marrow?
10%
188
What percent of T cells pass the two-step screening?
5%
189
Under what conditions are T cells eliminated in the thymus during the selection process?
if the T cells' TCRs bind to strongly or don't bind at all to MHC proteins
190
What explains swollen glands during an infection?
lymphocytes responding to antigens pass out of capillaries and back into lymph nodes
191
The immune response to neisseria meningitidis occurs in
the spleen
192
Which blood vessel carries blood to the spleen?
splenic artery
193
What is the white pulp?
regions of the spleen immediately surrounding arterioles
194
Where are antigens released in the spleen?
ground tissue
195
How do antibodies and active lymphocytes exit the spleen?
splenic vein
196
The mucosa-associated lymphoid tissue (MALT) includes (3)
tonsils; appendix; follicles located under mucosal surfaces
197
The MALT follicles are composed of (2)
lymphocytes (mostly B cells but some T cells); macrophages
198
How does the MALT tissue serve as a line of defense?
any antigens that pass through mucosa are stopped by lymphocytes in the follicles
199
Adaptive immunity first arose in
cartilaginous fish
200
Which immune organs do sharks and rays have? (3)
thymus; spleen; MALT
201
Bone marrow with hematopoiesis first originated in
amphibians
202
Lymph nodes first appeared in
birds
203
Describe the second form of adaptive immunity found in jawless fish. (3)
don't have B/T cells, but instead lymphocytes have receptor proteins with repeats of leucine; similar diversity; different structure
204
Cytotoxic T cells have what protein on their surface?
CD8 protein (CD8+ cells)
205
Helper T cells have what protein on their surface?
CD4 protein (CD4+ cells)
206
CD8 proteins are found on
cytotoxic T cells
207
CD4 proteins are found on
helper T cells
208
How are CD4/CD8 cells activated?
these cells must recognize peptide fragments bound to MHC proteins
209
How are CD4/CD8 cells distinguished? (2)
they recognize different classes of MHC proteins; they differ in roles after being activated
210
What is the name for proteins encoded by the MHC complex in humans?
human leukocyte antigens (HLAs)
211
The genes encoding MHC proteins are
highly polymorphic (in some cases, over 500 alleles), so HLAs are different for each individual, like a fingerprint
212
What are the two classes of MHC proteins?
MHC class I proteins; MHC class II proteins
213
Where are MHC class I proteins found?
present on every nucleated cell of the body
214
Where are MHC class II proteins found?
found only on antigen-presenting cells (macrophages, B cells, dendritic cells)
215
Cytotoxic T cells respond to which class of MHC proteins?
cytotoxic T cells respond to peptides bound to MHC class I proteins
216
Helper T cells respond to which class of MHC proteins?
Helper T cells respond to peptides bound to MHC class II proteins
217
(T/F) B cells recognize MHC proteins.
False, they don't recognize MHC proteins - only Tc and Th cells do.
218
Where are T cells normally activated, and why?
normally activated outside of primary lymphoid organs (in secondary lymphoid organs) so that they don't target self cells, and instead target foreign antigens
219
The TCRs of Tc cells recognize
peptides of endogenous antigens bound to MHC class I proteins
220
What are endogenous antigens?
self-protein or viral protein produced by an infected cell -- produced by self cells
221
Which cell in particular presents antigens that activate Tc cells?
dendritic cells
222
What is cross-presentation?
process in dendritic cells in which virus/tumor cells are ingested and then viral/tumor peptides are placed on MHC Class I proteins
223
What happens when a Tc cell binds to a dendritic cell undergoing cross-presentation? (4)
binding to dendritic cells occurs at CD8 site; activated Tc cells are generated; memory Tc cells are generated; activated Tc cells circulate through body to bind to similar dendritic cells with the same foreign peptide
224
How do Tc cells induce apoptosis? (3)
Tc cell secretes perforin monomers to create pores in target membrane; granzymes enter and activate caspases; caspases cause apoptosis
225
What do Th cells secrete?
low-MW proteins called cytokines
226
What is the purpose of cytokines in the context of Th cells?
they initiate signaling cascades in immune system cells that promote activation or differentiation
227
(T/F) Cytokines promote activation/differentiation of immune system cells only.
False, they can initiate cascades in other cells, too.
228
Cytokines are secreted at what concentration?
cytokines are secreted at low concentrations because they are very potent and so that they only bind to nearby cells
229
What is an exception to the norm that cytokines only bind to nearby cells?
IL-1, which travels to the hypothalamus to induce fever
230
What is another name for humoral immunity?
antibody-mediated immunity
231
What are the two types of immune responses?
humoral or cell-mediated
232
How do B cells acquire foreign antigens?
receptor-mediated endocytosis
233
How are foreign antigens made presentable to Th cells? (4)
once inside macrophages/dendritic cells/B cells, they are degraded in acidic endosomes or lysozymes; bind to MHC class II peptides and are displayed on surface; Th cells recognize and bind to this complex
234
The CD4 protein of Th cells bind to what part of MHC class II proteins?
CD4 protein binds to conserved regions of MHC class II protein
235
Naive Th cells express
a protein called CD28
236
What must CD28 do?
must bind to protein B7 if the T cell is to be activated
237
Where is B7 found? (2)
only on antigen-presenting cells; highest levels on dendritic cells
238
Why is B7 important?
form of regulation necessary due to the potency of cytokines
239
Activated Th cells give rise to
both effector Th and memory Th cells, just like Tc cells
240
Which cells mediate transplant rejection?
T cells
241
What happens when T cells encounter non-self MHC-peptide complexes on transplanted tissues?
TCRs on these T cells bind weakly to the MHC complex because the structure of the non-self MHC-peptide complex resembles the structure of a self MHC-foreign peptide complex
242
What is cyclosporin?
drug that blocks activation of lymphocytes to suppress immune system rejection of a transplant
243
(T/F) Cytokines are released exclusively by Th cells.
False, many other cells do, as well.
244
What is IL-12? (2)
a cytokine released when PAMP molecules bind to TLRs; IL-12 binds to Th cells to increase their level of activation
245
What does tumor necrosis factor-alpha do?
bind to blood vessels to induce local/systemic increase in vascular permeability
246
Plasma B cells produce
soluble antibodies of the same specificity as the same antibodies produced by the parent B cell
247
Draw the structure of an immunoglobulin molecule.
pg. 1070
248
What region of the immunoglobulin is responsible for its specificity?
the specificity resides in the amino-terminal half of each Fab region
249
What is the variable region of the immunoglobulin?
the amino-terminal half of the Fab region
250
Which chains of the immunoglobulin have variable regions?
both the light chain and heavy chain have a variable region
251
Which chains of the immunoglobulin have constant regions?
both the light chain and heavy chain have a constant region
252
In mammals, the light-chain constant regions consist of (2)
a kappa sequence and a lambda sequence, which have equivalent functions
253
In mammals, the heavy-chain constant regions consist of (5)
gamma, alpha, mu, epsilon, delta sequences (basis for IgG, IgA, IgM, IgE, IgD)
254
Which characteristics of the immunoglobulin determine the specificity for antigen epitopes? (3)
size, shape, and AA sequence in the antigen-binding site
255
How many epitopes can bind to an immunoglobulin?
2 epitopes
256
The function of immunoglobulins depends on
its class
257
The class of immunoglobulins depends on
the Fc portion of the heavy-chain constant region
258
How does the Fc region help in the elimination of antigens? (2)
Most cells have Fc receptors, so when an antigen binds to an antibody, a phagocyte can bind to the Fc region and make it easier to eliminate the antigen; specific immunoglobulins can interactions between non-specific cells and antigens
259
(T/F) Antibodies kill pathogens directly.
False, they target pathogens and let phagocytes destroy them.
260
Describe the function of IgG. (3)
major antibody secreted during secondary response; neutralizes antigens by promoting phagocytosis; activates complement
261
Describe the function of IgA. (2)
most abundant form of antibody in body secretions; high density of IgA-secreting cells in MALT
262
Describe the function of IgM. (3)
first antibody to be secreted during primary immune response; promotes clumping and precipitation; activates complement
263
Describe the function of IgE. (2)
Fc binds to mast cells + basophils; allergen binding to V regions promotes release of mediators which triggers allergic reaction
264
Describe the function of IgD. (2)
present only on surfaces of B cells; serves as antigen receptor
265
What is the shape of IgM? (2)
monomeric in the membrane of a B cell; secreted as a pentamer
266
What is the shape of IgD?
monomer
267
What is the shape of IgG?
monomer
268
What is the shape of IgA?
dimer
269
What is the shape of IgE?
monomer
270
Which immunoglobulins are monomers? (3)
IgG, IgE, IgD
271
Which immunoglobulins are found on mature, naive B cells?
IgM, IgD
272
How are B cells activated by IgD?
B cells can be activated by the cross-linking of two IgD molecules
273
Once a B cell is activated, what happens to IgD?
IgD is no longer displayed on the cell surface?
274
Which immunoglobulin(s) are normally not secreted by B cells?
IgD
275
Which immunoglobulin is the major antibody in blood plasma/tissues?
IgG - makes up 75% of plasma antibodies
276
Which antibodies involved in providing passive immunity to a fetus?
IgG (through placenta), IgA (through breastmilk)
277
Which immunoglobulin is the major antibody in external secretions?
IgA
278
Which antibody has a low concentration in plasma?
IgE
279
On secretion, most IgE becomes
bound to mast cells and basophils that recognize the Fc portion of IgE
280
Which antibody provides a defense against helminth worms, and how?
IgE, through perforin pores
281
How many different antigen binding sites can a human B cell generate?
10^10
282
How is the variable region assembled, and why is this important?
assembled by joining 2-3 DNA segments together; provides genetic diversity needed to recognize many epitopes
283
What is the name for the process that generates variable regions?
DNA rearrangement
284
How is DNA rearrangement different from crossing over in meoisis? (2)
DNA rearrangement occurs between loci on the same chromosome; DNA rearrangement is site-specific
285
When does DNA rearrangement occur?
as a progenitor B cell matures in the bone marrow
286
What happens after DNA rearrangement occurs in the bone marrow?
mRNA is produced that can be translated as either a heavy or light chain
287
What is allelic exclusion?
DNA rearrangement occurs for the heavy chain and light chain loci on only one homologue, which makes the B cells of only one specificity
288
What are V/D/J segments?
50 V segments, 30 D segments, 6 J segments - clusters of DNA sequences found in human immunoglobulin heavy-chain gene loci
289
(T/F) V segments are similar in size to each other.
True, they are equal in size, but have different nucleotide sequences - same goes for D/J segments
290
What is the first DNA rearrangement in maturing B-cells? (2)
site-specific recombination event joining one of the D segments onto one of the J segments; intervening DNA is deleted/degraded
291
V segments stand for
variable segments
292
D segments stand for
diversity segments
293
J segments stand for
joining segments
294
An immunoglobulin (Ig) protein is encoded by
V/D/J segments + constant region
295
What is the second DNA rearrangement in maturing B-cells?
combined DJ joins to V segment
296
Light chains are encoded by
V/J segments + constant region
297
What are the two types of constant regions in DNA rearrangement, and which region do they bind to?
a mu or sigma constant region, which binds to the variable region
298
IgM has what kind of constant region?
mu constant region
299
IgD has what kind of constant region?
sigma constant region
300
How many different V/D/J combinations can be formed?
~9000
301
What additional mechanisms allow for further DNA rearrangement beyond V/D/J segments?
nucleotides are added/deleted from each segment to shift reading frame; genes show elevated mutation rate
302
What is somatic hyper-mutation?
genes that code for Ig proteins show elevated mutation rates to allow for more diversity (up to 10^10 possible variable regions)
303
Draw the structure of a TCR.
*draw* pg. 1074
304
How many chains does TCR have?
2
305
Which region of TCR binds to an MHC-peptide complex?
amino-terminal domian -- the variable region, distal to the membrane
306
Which region of TCR is constant?
membrane-proximal domain -- constant region
307
(T/F) TCRs are secreted.
FALSE, TCRs are NOT secreted.
308
Which is more effective, the primary response or secondary response to an antigen?
the secondary response is more effective
309
Which is more rapidly activated, memory cells or naive lymphocytes?
memory cells
310
The class of immunoglobulin produced is dictated by
the identity of the cytokines derived from activated Th memory cells that bind to the B cells in the 2ndary response
311
What is immunological tolerance?
process where immune system learns to not react to self-antigens
312
When does the process of immunological tolerance begin in humans?
fetal stage
313
The failure of immunological tolerance leads to
autoimmune diseases
314
Autoimmune diseases, generally, are caused by
the failure of immunological tolerance
315
What happens when autoimmune diseases are produced? (3)
autoreactive T cells become activated; autoreactive B cells produce autoantibodies; extensive organ damage occurs
316
How many known autoimmune diseases are there?
more than 40
317
What percentage of the population is affected by autoimmune diseases?
5 to 7%; 2/3 of this are women
318
What drugs are administered to suppress the immune system? (2)
corticosteriods; nonsteroidal anti-inflammatory drugs (such as aspirin)
319
What is the most common form of allergy?
immediate hypersensitivity
320
Immediate hypersensitivity is the result of
overproduction of IgE in response to allergens
321
What is the most common allergy and where does it come from?
seasonal hay fever, provoked by pollen from ragweed
322
What happens the first time someone encounters an allergen?
allergen binds to/activates B cells; activated Th cells releases IL-4 cytokine; IL-4 dictates production of IgE from B cell; IgE rapidly binds to mast cells/basophils; IgE secretes histamine/prostaglandins which produces symptoms of allergy
323
What happens the second time someone encounters an allergen?
allergen binds to IgE which rapidly binds to mast cells/basophils; IgE secretes histamine/prostaglandins which produces symptoms of allergy
324
What is systemic anaphylaxis? (3)
life-threatening because BP drops; epiglottis swells to block trachea; bronchial constriction prevents exit of air from lungs
325
What is anaphylactic shock?
combination of blocked trachea; air blocked from leaving lungs; drop in BP
326
What is local anaphylaxis? (3)
itchy welts/hives; mild asthma; diarrhea (mild reaction)
327
What are some allergy treatments?
antihistamines; drugs that block activation of mast cells/basophils; hyposensitization
328
Delayed type hypersensitivity is mediated by
Th cells and macrophages
329
Delayed-type hypersensitivity symptoms occur
about 48 hours after a second exposure to the antigen
330
Give an example of delayed-type hypersensitivity.
contact dermatitis
331
A delayed-type hypersensitivity response requires
the antigen entering the body to travel to a secondary lymphoid organ (i.e. lymph nodes), where they activate Th cells; Th cells then travel around the body and release cytokines to activate macrophages
332
What acts as the antigen on blood cell surfaces?
protein-sugar complex
333
How do the antigens on blood cell surfaces differ?
differ with regard to the sugar present (or absent, in the case of O)
334
Which class of antibodies recognize the monosaccharide differences in our red blood cells?
IgM antibodies produced in response to carbohydrates on bacteria living inside of us
335
IgM, in the context of blood groups, can
recognize the monosaccharide differences in our red blood cells (only the IgM produced in response to bacterial carbohydrates)
336
What is another important blood-borne antigen?
Rh factor
337
The Rh protein is either
present (Rh positive) or absent (Rh negative)
338
What happens if an Rh negative person receives a transfusion of Rh positive blood?
Rh negative person will produce antibodies to foreign Rh protein on transfused cells
339
(T/F) Mother and fetus can have different Rh statuses.
True
340
Mother (Rh negative) and fetus (Rh positive) having different Rh statuses results in
hemolytic disease of newborns (HDN)
341
What are the consequences of HDN?
First child is usually not harmed, but during first birth mother can be exposed to child's blood so she produces anti-Rh antibodies; if she exposed to the second child's blood, IgG antibodies can destroy fetal blood cells
342
Blood typing is done by
taking advantage of circulating IgM antibodies which are produced against foreign antigens but not against self
343
How many blood groups have been identified?
over 20
344
What is autologous blood donation?
when people stockpile their own blood before elective surgery bc they're likely to mismatch
345
What happens in a transfusion reaction? (3)
intravascular hemolysis of transfused RBCs is detected; results from IgM binding to foreign antigens and activating complement system; RBCs are destroyed via osmotic lysis
346
What molecule is released during a transfusion reaction?
hemoglobin released from RBC is converted to bilirubin
347
Describe bilirubin.
toxic and causes severe organ damage, especially to kidneys
348
What is the major treatment to a transfusion reaction?
stop transfusion and administer large amounts of intravenous fluids to wash bilirubin out of body
349
What are polyclonal antibodies?
Antibodies secreted by B-cells with many different specificities
350
What are monoclonal antibodies?
antibodies that exhibit specificity for one epitope only
351
How are polyclonal antibodies isolated in labs? (2)
Inject antigen into vertebrate; periodic bleeding of animal allows isolation of serum antibodies
352
How are monoclonal antibodies isolated in labs?
mouse is immunized several times with antigen and killed; B lymphocytes which are now specific for antigen are harvested from mouse spleen; B cells fused with cancerous myeloma cells for immortality
353
What is a hybridoma?
outcome of B-cell/myeloma cell fusion
354
What does AIDS stand for?
acquired immunodeficiency syndrome
355
AIDS is characterized in part by
destruction of Th cells
356
How can AIDS be monitored?
by examining reactivity of patient's leukocytes with a monoclonal antibody against CD4 (Th cell marker)
357
For a pathogen to establish itself in a host, what must happen?
must evade both nonspecific and specific immune systems
358
Influenza is known because
it alters its surface antigens and avoids immune system recognition
359
What are the viral proteins expressed by the influenza virus? (2)
hemagglutinin (HA) and neuraminidase (NA)
360
What is antigen drift?
Influenza virus has an RNA genome that is replicated by a viral RNA polymerase that lacks proofreading ability, which means mutations are likely to accumulate over time
361
What is antigen shift?
sudden appearance of a new subtype of influenza in which HA and NA proteins are completely different
362
Malaria is caused by what organism?
protozoan parasite Plasmodium that is transmitted when humans are bitten by Anopheles mosquito
363
How does salmonella typhimurium commonly cause food poisoning?
can alternate between expression of two flagellar proteins so that antibodies for one protein can't recognize the other
364
How does mycobacterium tuberculosis cause illness?
once it is phagocytosed into macrophages, they inhibit the phagosome from fusing with lysozomes and successfully multiply within the macrophages
365
Give two examples of bacteria that invade mucosal surfaces.
Neisseria meningitidis; Neisseria gonorrhoeae
366
How do bacteria invade mucosal surfaces?
secrete proteins that degrade the IgA antibodies that protect the mucosal surface
367
Particularly pathogenic strains of bacteria work by
blocking the binding of phagocytosis-induced complement protein Cb3, which slows the phagocytic response
368
How does HIV work?
human immunodeficiency virus binds to CD4 proteins on Th cells and utilizes these proteins to get inside the Th cells
369
(T/F) HIV only infects Th cells.
False, HIV can infect monocytes too since monocytes also express CD4.
370
Once HIV enters and infects the Th cell, what happens?
releases replicated viruses to other Th cells such that they all become infected and die
371
When is an individual considered to have AIDS?
when the Th cell levels drop dramatically
372
How does the immune system initially respond to HIV infection?
produces anti-HIV antibodies and eliminates infected cells using Tc cells
373
How does the HIV infection progress? (2)
eventually HIV kills Th cells more rapidly than can Th cells proliferate for memory purposes; HIV causes decrease in MHC class I expression on infected cells which makes them less likely to be earmarked for destruction
374
What are the implications of HIV being a retrovirus?
HIV can integrate itself into a genome and hide in a latent form
375
AIDS was first discovered when young men died of
pneumonia or Kaposi's sarcoma
376
Pneumonia generally affects
those who are immunosuppressed
377
In 2010, how many people lived with HIV?
34 million
Biology 2312
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