Brainscape Spring Semester - Immunology Exam 1 Flashcards
(166 cards)
1
Q
What are the four classes of pathogens?
A
(1) Extracellular bacteria/fungus/parasites (2)Intracellular bacteria/parasites (3) Viruses (4) Parasitic Worms
2
Q
What is the first line of defense of the immune system?
A
Barriers: physical and chemical
3
Q
What are the three types of barriers protecting the body in the immune system?
A
(1) Mechanical (2) Chemical (3) Microbiological
4
Q
What are the regions of the body that contain barriers?
A
Skin, GI tract, Respiratory Tract, Urogenital Tract, Eyes
5
Q
What are mucosal surfaces?
A
Linings of cavities made up of mucous membranes. These mucosa cover epithelial tissues exposed to the external environment.
6
Q
What are the major routes for infection by pathogens?
A
(1) Mucosal surfaces: Airway, GI Tract, Reproductive Tract (2) External epithelia(skin): Surface, wounds/abrasions, Insect bites
7
Q
What are the major functions of the immune system?
A
(1) Recognition (2) Elimination (3) Memory
8
Q
What does the recognition process of the immune system general entail?
A
The immune system must recognize self as self, and antigens as non-self in order to target the distruction of pathogens and protect the self-cells
9
Q
What is an antigen?
A
Anything that can be recognized by the immune system.
10
Q
What is an immunogen?
A
Antigens capable of producing an immune response. NOT ALL antigens are immunogens
11
Q
What is an epitope?
A
A small 3D portion of the antigen that is ultimately recognized
12
Q
What is a multivalent antigen?
A
An antigen that has multiple epitopes to which the immune system can recognize and mount responses from
13
Q
What type of molecule is most commonly immunogenic?
A
Proteins are the most common immunogens. Large multi-subunit proteins are most effective at triggering an immune response, but complexes of smaller proteins can also trigger immune responses.
14
Q
What is an example of an immunogenic carbohydrate?
A
The ABO blood system. Blood of the wrong type will be attacked by the immune system.
15
Q
Can lipids be immunogenic?
A
Pure lipids are not immunogenic, but lipoproteins and glycolipids can be immunogenic.
16
Q
What are the two major divisions of the immune system?
A
(1) Innate immunity: inherited, early pathogen non-specific response (2) Adaptive: Specific responses to specific pathogens, driven by B and T cells
17
Q
Describe the ubiquitous responses of innate immunity.
A
An infection is recognized by preformed, nonspecific effectors, which work to remove the infectious agent. Occurs 0-4 hours from time of infection
18
Q
What are the induced responses of innate immunity?
A
Effector cells are recruited following an infection. These effector cells are activated following recognition of infection and the infectious agent is removed. Occurs 4-96 hours after infection.
19
Q
Describe the general adaptive response.
A
Following infection, antigens are transported to lymphoid organs. Naive B and T cells recognize the antigens, which leads to clonal expansion and differentiation to effector cells. The infectious agent is then removed. Takes place >96 hours after infection.
20
Q
What is protective immunity?
A
When the body is re-infected, effector T cells recognize the antigen and the infectious agent is removed.
21
Q
What is immunological memory?
A
When the body is re-infected, memory B cells and T cells recognize the antigen. Then, effector cells are rapidly produced and differentiated, leading to the removal of the infectious agent.
22
Q
Compare and contrast the primary and secondary adaptive immune responses.
A
The primary immune response occurs when a new antigen is introduced to the body for the first time. Effector T cells and antigens build up within the body, with the antibody remaining in the system longer than the T-cells. After that, the antibody will always remain in the system at low concentrations. The secondary immune response occurs when the antigen is reintroduced to the body later. The secondary response is much faster and has a higher affinity for the pathogen.
23
Q
Where do immune cells originate from?
A
The hematopoietic stem cells of the bone marrow.
24
Q
What are the four main types of immune cells?
A
(1) Granulocytic cells (2)Agranulocytic cells (3)Lymphocytes (4)Dendritic cells
25
List the immune cell types in order of prevalence in a healthy person.
Neutrophils, Lymphocytes, Monocytes, Eosinophils, Basophils ("Never Let Monkeys Eat Bananas")
26
What is the typical ratio of WBC to RBC?
1WBC:1,000 RBC
27
What are the antigen presenting cells?
Multiple types of dendritic cells, Monocytes, Macrophages. Lymphocytes can also phagocytose antigens.
28
What are granulocytes?
Immune cells including neutrophils, eosinophils, and basophils. They are named granulocytes because of their staining pattern. They are all derived from a myeloid progenitor cells and have multilobed nuclei.
29
What are lymphocytes?
The T and B cells,responsible for specific interactions with antigens. Also includes NK cells involved in innate response.
30
Which immune cells are found in the blood AND lymph?
B and T cells
31
Which immune cells are found in the blood, but not the lymph?
Neutrophils, Eosinophils, Basophils, Monocytes, Platelets
32
Describe the structure of lymphatic vessels.
They are blind-ended vessels made of permeable endothelial cells. The lymph flows one way through the lymphatic vessels. The capillaries dump into larger and larger vessels. The fluid is propelled through these vessels by nearby cellular muscle contractions.
33
What prevents backflow within the lymphatic system?
There are one-way valves throughout the vessel that prevent back flow.
34
What tissues are considered primary lymph tissue?
The thymus and the bone marrow.
35
What tissues are considered secondary lymph tissue?
Lymph nodes, appendix, spleen, and Peyer's patches
36
Describe the pattern of draining lymph from different parts of the body.
Fluid from the right arm and right side of the head drains into the right subclavian vein. The fluid from the rest of the body drains into the thoracic duct to the left subclavian vein
37
What are chemokines?
Short proteins with conserved C residues. They act as a chemoattractant to guide the migration of cells. There are two types: CCL and CXC
38
Describe the structure of a typical lymph node.
Afferent lymphatic vessels feed into lymph nodes. The nodes are made up of 3 major areas: Cortex, Paracortex, and Medulla. Spherical germinal centers, where B cell activation occurs, are found between the cortex and the paracortex.
39
What are HEV's?
High endothelial venules. They are found in all secondary lymph tissues and enable lymphocytes circulating in the blood to directly enter a lymph node.
40
What two chemicals are found in high concentrations in secondary lymph tissue?
(1) IL-7: Interleukin-7, which is critical for the survival of T cells. (2) BAFF: B-cell activator factor, a critical survival cytokine for B cells
41
What are fibroblast reticular cells?
FRCs: Cells that surround and produce extracellular matrix. They are responsible for producing the lymph conduit system used as a pathway for cellular movement. Antigens up to 70 kDa can enter lymph nodes through these conduits.
42
What is 2 photon microscopy?
A method for intravital imaging that uses 2 photons from lasers. The combined energy from the two wavelengths is sufficient to cause the tissue to fluoresce without distroying the cells of interest.
43
What is proliferation?
After a pathogen is introduced to the body, a relatively small amount of the lymphocytes recognize the antigen. The pathogen activated lymphocytes are then mass-produced into effector cells that will function to terminate the infection.
44
Describe the motion of WBCs through blood vessels.
They move in a rolling motion much slower than RBCs. They are constantly sampling the endothelia with receptors for chemokines. The WBC can then squeeze between HEV cells passing from circulation to secondary lymph nodes.
45
What are the two functions of the spleen?
RBC reclamation and blood-borne pathogen destruction
46
What are the two main areas within the spleen?
White pulp (immune function) and Red Pulp (area of RBC reclamation)
47
Where are Peyer's patches found?
Within the gut.
48
Describe the function of the M-cells of the gut.
They sample the lumen of the gut constantly through a process called macropinocytosis. The material taken up is transfered from the lumen of the gut to the Peyer's patches, which are full of dendritic cells and T cells
49
What are PRRs?
Pattern Recognition Receptors. They recognize specific molecular patterns. Can be less specific than 1 receptor for each antigen.
50
What are the functions of the innate immune response?
(1) Defend host from pathogenic challenge in first minutes/hours of infection (2) Restrict the infection (3) Direct/Modulate the adaptive immune response
51
In response to a surface wound, what do effector cells secrete and why?
Effector cells secrete cytokines, which will stimulate the production of inflammatory chemokines. This will lead to vasodilation and increased vessel permeability.
52
Why is increased vascular permeability helpful for the innate immune response?
It allows for fluid, proteins, inflammatory cells to leave the blood and enter the injured tissue.
53
What symptoms are associated with inflammation?
Redness, heat, swelling and pain
54
What are defensins?
Proteins that function to coat, and ultimately destroy the cell membrane of pathogens. They are short, amphipathic proteins rich in arginine (R) residues. They are synthesized as inactive pre-proteins.
55
What are the two major categories of bacteria?
Gram positive and Gram negative
56
What are the differences between gram positive and gram negative bacteria?
Gram positive bacteria have one plasma membrane with a thick peptidoglycan cell wall outside of that. The cell wall is coated in teichoic acid and lipoteichoic acid. The gram negative bacteria have two plasma membranes with a thinner cell wall between them. Gram negative bacteria have lipopolysacharide LPS on their surface.
57
Which type of bacteria can penecillin effectively treat?
Gram positive. It is ineffective against gram negative bacteria.
58
Describe how a defensin is able to compromise the lipid bilayer of a pathogen.
The cationic side of the defensin molecule is able to align with the polar head of the lipid bilayer via electrostatic interactions. Multiple defensin peptides form together to make a pore. This pore causes an intermixing between the cytosol and the extracellular matrix, which leads to cell lysis.
59
What class of defensins is produced in neutrophils?
alpha defensins that defend the intestinal epithelium, placenta, and cervical mucus plug
60
What class of defensins is produced in paneth cells?
Alpha defensins that defend salivary glands, GI tract, urogenital tract
61
What class of defensins is produced by epithelial cells?
Beta defensins in the GI tract, respiratory tract, urogenital tract, skin, stomach and testes
62
What are the main source of defensins in the intestines?
The paneth cells, which are found at the base of the crypts of the intestinal epithelia.
63
Why is it advantageous to have resident biota within the GI tract?
These bacteria provide constant exposure to a wide variety of bacterial antigens. Because there are a finite number of microbial building blocks, the constant exposure allows the body to recognize patterns.
64
What are toll like receptors?
TLRs: A type of PRR that recognizes structurally conserved carbohydrate molecules derived from microbes and activate immune responses.
65
What is the shape of a coccus bacteria? What is the shape of a bacillus bacteria?
Coccus bacteria are spherical. Bacillus bacteria are rod shaped.
66
What was the phenotype of homozygus recessive drosophila mutants for the TLR gene?
They were very susceptible to fungal infections leading to a furry appearance.
67
What is the structure of a toll-like receptor?
They are transmembrane proteins that dimerize. They have an extracellular N-terminal pathogen-recognition domain, and an intracellular C-terminal TIR domain. TIR=toll-interleukin receptor, the signaling end of the receptor.
68
How can TLRs be sensitive to different types of pathogens?
They are able to dimerize in different combinations leading to different functions. For example, the TLR2:TLR6 heterodimer can recognize gram positive bacteria, and the TLR4:TLR4 homodimer can recognize gram negative bacteria.
69
In endosomes, does the TIR domain of TLRs face the cytosol or the inside of the endosome?
The TIR domain is ALWAYS on the cytosolic side.
70
What does the complex between TLR4, MD2, and CD14 recognize?
bacterial lipopolysacharide of gram negative bacteria
71
What are the two major transcription factors that TLRs activate?
NF-κB, an inflammatory cytokine and IRF-3, interferon regulatory factor, which is important for response to viral infections
72
What is MyD88? What does it do?
Myeloid primary differentiation primary resposne gene 88. It is an adaptor protein that binds to the activated TIR domain of a TLR and connects it to the protein kinase IRAK4. This leads to the activation of a kinase cascade that activates IκB Kinase (IKK)
73
How does IKK cause the release of inflammatory cytokines?
It phosphorylates IκB, which induces the release of NFκB from the complex. NFκB enters the nucleus and activates genes that cause the transcription of inflammatory cytokines.
74
What are the NOD proteins?
Nucleotide-binding oligomerization domain-containing proteins that recognize bacterial infections and stimulate an immune response. NOD1 detects gram negative infection, and NOD2 detects gram positive infection
75
What are examples of local effects of pro-inflammatory cytokines?
Activation of vascular endothelium, increased vascular permeability, increased entry of complement and cells to tissues, increased lymph drainage, recruitment of immune cells, activation of NK cells
76
What are examples of systematic effects of pro-inflammatory cytokines?
Fever, acute-phase protein production by liver hepatocytes, mobilization of metabolites, shock
77
What pathologies are associated with defects in NOD1?
LOF mutations can cause asthma, and sarcoidosis
78
What pathologies are associated with defects in NOD2?
GOF mutations can cause Blau Syndrome, early-onset sarcoidosis. LOF mutations can cause Crohn's disease, Graft vs. Host Disease (GVHD)
79
Describe the process of killing bacteria that occurs within neutrophils.
The bacteria is phagocytosed by the neutrophil to form a phagosome. The phagosome fuses with granules that cause the pH to rise. The increased pH kills the bacteria. Then, the phagosome fuses with lysosomes, which causes complete degradation of the bacteria by hydrolases. The neutrophil eventually dies via apoptosis, and is phagocytosed by a macrophage.
80
What is the universal post-phagocytosis response of cells?
(1) Oxidative (respiratory) burst (2) Acidification (3)Toxic nitrogen (4) Antimicrobial peptides (5) Enzymes (6) Competitors
81
What are the three functions of inflammation?
(1) Deliver more effector cells and molecules to the site of infection (2) Induce local blood clotting (3) Promote tissue repair
82
What is the complement system?
A system made of \>30 proteins that interact to help/"complement" the functions of the immune system. Complement is activated by injury or infection and is associated with inflammation. It involves proteases that cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages.
83
What are the major effector functions of the complement system?
(1) Opsonization (2) Recruitment of effector cells (3) Lysis of pathogen by Big MAC
84
What are the three pathways leading to complement activation?
Alternative pathway, Lectin pathway and Classical pathway
85
What enzyme is associated with complement activation?
C3 Convertase
86
What is Big MAC?
MAC=membrane attack complex. It is associated with the alternative and classical pathways. MACs form transmembrane channels that disrupt the phospholipid bilayer of target cells, leading to cell lysis and death
87
Describe the molecular process that initiates the alternative pathway of complement activation.
The thioester bond of C3 hydrolyzes, forming iC3 (activated C3). Factor B then binds iC3. B is cleaved by factor D into Bb and Ba, which produces a soluble C3 convertase called iC3Bb. iC3Bb can activate C3 molecules by cleaving them into C3a and C3b fragments. C3b fragments become covalently bound to the surface. (Figure 2.6)
88
Once C3Bb is covalently bound to the pathogen surface, how does the alternative pathway proceed?
Membrane bound C3b can bind factor B, which is cleaved by factor D to form C3bBb. This complex can interact with free C3 molecules and attach them to the adjacent membrane surface. This process rapidly radiates until the pathogen is coated in C3b.
89
What is the function of Properdin?
Properdin stabilizs C3 convertase C3bBb on the pathogen surface, making it more difficult to break up and form C5, which would cause excessive degradation.
90
How can C3b on the pathogen surface be inactivated?
Factor H binds to C3b and changes its conformational change to one that is susceptible to cleavage by factor I. This results in C3b being cleaved into iC3b, which remains bound to the pathogen surface, but cannot interact with C3 to form more C3b.
91
How is C3b prevented from being active on the surface of human cells?
DAF and MCP disrupt C3bBb on the surface of human cells, ensuring that much complement is fixed to pathogen surfaces and little is fixed to human cells. DAF displaces Bb from the C3b. MCP forms the inactive iC3b protein without the action of factor H.
92
What is the function of mannose-binding lectin (MBL)?
MBL activates the lectin pathway for complement activation by binding to sugars on the surface of bacterial cells.
93
What is the function of C1?
C1 activates the classical pathway of complement fixation by binding to C-reactive proteins on the pathogen surface.
94
What is the classical pathway analog to the C3bBb C3 convertase of the alternative pathway?
C4bC2a is the C3 convertase found in the classical pathway.
95
How is C4bC2a formed on the pathogen surface in the classical pathway?
Activated MASP-2 cleaves C4 into C4a and membrane-bound C4b. MASP-2 also cleaves C2 to C2a and C2b. C2a can interact with C4b to form the C4bC2a. This complex can then interact with C3 to form membrane bound C3b.
96
How is the Big MAC complex formed on the surface of the pathogen?
C5 is activated to C5b, which then forms a complex with C6 and C7. This C5bC6C7 complex attaches to the membrane surface. C8 then binds to the complex, which allows several C9 molecules to form a large pore through the membrane.
97
What is the general purpose of adaptive immunity?
Adaptive immunity allows for specific responses against pathogens. It is driven by lymphocytes which are able to detect pathogens and mount specific responses after antigen presentation.
98
What role do naive lymphocytes play in adaptive immunity?
They are specific to epitopes of antigens, but they do not directly partake in the immune response. They play more of a surveillance role for recognizing infection.
99
What are the four types of adhesion molecules?
(1)Addressins (2)Selectins (3)Integrins (4)Ig Superfamily
100
What type of adhesion molecule recognizes and interacts with addressins?
Selectins recognize addressins and bind weakly to them.
101
Describe the rolling adhesion of a neutrophil within a blood vessel.
Selectins weakly interact with the lectin on the neutrophil surface as the cell rolls along the endothelial surface. Chemokine signalling alters the affinity between LFA (an integrin) and ICAM (an Ig) which leads to tight binding. The neutrophil can then slide through the tight junction and migrate through the ECM to the site of infection.
102
What is diapedesis?
The process of neutrophils migrating through the endothelial cells from the blood vessel into the ECM
103
What are lymphocytes derived from?
They are derived from common lymphoid progenitor cells in the bone marrow. Each lymphocyte has a different form of a cell-surface receptor.
104
Describe the proliferation process of lymphocytes.
Lymphocytes that react with pathogens are triggered to divide and multiply within the lymph nodes. They then differentiate into effector B and T cells that eliminate the pathogen.
105
Describe the structure of a B-cell receptor.
2 heavy chains are connected via a disulfide bond. Each heavy chain is connected via a disulfide chain to a light chain. Each light chain has an antigen binding site at the end. The heavy chain contains a transmembrane region which attaches the receptor to the membrane.
106
What is the difference between a B-cell receptor and an antibody?
They are identicle in structure except antibodies do not have the transmembrane domain.
107
Describe the structure of a T-cell receptor.
T-cell receptors are heterodimers, usually between alpha and beta chains. Each chain has a transmembrane region and an antigen binding site.
108
How are the variable domains of B and T cell receptors produced?
They are produced via nonhomologous irreversible rearrangements which lead to massive diversity of recepter specificities. Somatic recombination rearranges the gene through a process of programmed mutagenesis.
109
How many types of antigens can a single lymphocyte bind?
Every single receptor on a given lymphocyte is specific to the same antigen. So, 1 lymphocyte can only bind one specific antigen.
110
What are the two major processes that antibodies function in?
Neutralization and opsonization
111
Describe the process of neutralization in terms of antibody function.
When toxins are released, the antibodies function to bind up all of the toxin before it has the opportunity to bind to its receptor and cause damage.
112
Describe the process of opsonization in terms of antibody function.
Bacteria becomes coated in antibodies, which then allows for complement proteins to further opsonize the bacteria. This leads to phagocytosis and destruction of the pathogen.
113
What is the difference in affinity constants of antigens between the primary and secondary response.
The primary response has an affinity constant of between 104 and 105 M-1. The secondary response is much stronger, with an affinity constant of 109 M-1.
114
Explain how B cells can act as antigen presenting cells.
Immunoglobins on the surface of B cells bind bacteria leading to phagocytosis. The bacteria is then degraded into protein fragments, which are bound to class II MHC in vesicles. The MHCs are then exported to the cell surface and presented to Helper T cells (CD4+) which activates the B cell.
115
What is the major difference between class I and class II MHCs?
Class I MHCs recognize intracellular pathogens such as viruses and signal for the distruction of the infected cells. Class II MHCs recognize extracellular pathogens and present them to helper T cells, which in turn activate the presenting cell.
116
Class I MHCs are associated with which type of CD: CD4 or CD8?
CD8
117
What is the difference between how B-cell receptors recognize antigens and how MHCs recognize antigens?
B-cell receptors recognize 3D protein surfaces (epitopes) while MHCs only bind to short peptide fragments that may be folded into non-native conformations.
118
What is the first type of antibody made against an infecting pathogen?
IgM, a pentameric antibody with 10 antigen binding sites. The interaction between IgM and the antigen is a weak one.
119
How are antibodies with higher affinities than IgM produced?
Somatic hypermutation selects for antibodies that bind more tightly to the pathogen than IgM. This process produces antibody isotypes like IgGs which allows for the delivery of the pathogen to phagocytes.
120
What happens to the lymphocytes that do not become terminally differentiated effector cells?
They become long-lived memory cells that allow for rapid response to subsequent infections by the same pathogen.
121
What happens in autoimmune diseases?
The immune system has lymphocytes which recognize self as antigen, and immune responses are produced against one's own tissues and cells.
122
What is meant by immunological tolerance?
the immune system recognizing but not attacking healthy tissues of self. Also involves not mounting responses against beneficial foreign items such as food and the biota of the GI tract
123
Describe positive and negative selection in the thymus.
Positive selection is the promotion of growth of cells that recognize MHC of self. Negative selection is the removal of cells that bind self-MHC with too high of an affinity. Less than 1% of T cells survive positive and negative selection in the thymus.
124
Describe the human MHC gene locus
The MHC genes are autosomal, with the Human Leukocyte Antigen (HLA) cluster found on chromosome 6. It contains approximately 4 million base pairs. The MHC-I alpha chains are encoded by HLA-A,B and C. The MHC-II alpha chains are encoded within the HLA-D region
125
Are the β2m and Ii genes linked with the HLA gene cluster?
No. The β2-m gene is found on chromosome 15 and the Ii gene is found on chromosome 2. Both are unlinked with the HLA cluster.
126
Which genes within the MHC class II cluster present external peptides?
DP, DQ and DR present external peptides
127
What proteins are encoded from the MHC class III gene locus?
Complement proteins C4 and Factor B are encoded from the MHC III cluster.
128
What is the recombination rate within the MHC gene cluster?
The recombination rate is relatively low, only about 2%
129
Which MHC class I isotypes are most polymorphic?
The antigen presenting cytoplasmic HLA isotypes A, B and C show the most polymorphisms, with hundreds of different alleles.
130
Where are Class I MHC and Class II MHCs generally found in the body?
Class I MHCs are found throughout the entire body (express "self" status), but Class II MHCs are found exclusively in antigen presenting cells (B cells, Dendritic cells, Thymus...etc).
131
Describe the process of a Class I MHC interacting with an intracellular antigen.
Proteasomes degrade intracellular antigens into short peptide fragments which can be bound to MHC class I receptors in the endoplasmic reticulum. Once the peptide is bound to the MHC, it is exported through the golgi apparatus to the cell surface.
132
Describe the process of a Class II MHC interacting with an extracellular antigen.
The extracellular antigen is phagocytosed into a vesicle that breaks the antigen down into peptide fragments. The vesicle than fuses with a vesicle containing a class II MHC from the golgi. Once the antigen is bound to the MHC, it is exported to the cell surface.
133
Can MHCs exist on the cell surface wihout bound antigen?
No. Neither class of MHC can survive on the cell surface without peptide bound.
134
What is the role of TAP?
TAP moves activated peptides fragments produced by proteosomes via active transport from the cytosol to the endoplasmic reticulum. If TAP's activity is blocked, MHCs will accumulate in the ER, and none will be exported to the surface. The lack of membrane MHC's will trigger an immune response against the cell.
135
What is calnexin?
Calnexin is a chaperone molecule found in the endoplasmic reticulum that stabilizes class I MHC molecules until β2-m binds
136
Describe the peptide loading complex of MHC class I in the ER once β2-m binds.
The complex is composed of MHC class I, β2m, calreticulin, tapasin, TAP, ERp57 and PDI. This complex prepares the MHC for antigen binding, and keeps it in a conformation that will allow the peptide to reach the peptide binding groove.
137
What happens if a peptide fragment is too long to bind to the MHC class I binding groove?
An enzyme called ER aminopeptidase (ERAP) removes N-terminal amino acids to give the peptide a length of 8-10 residues.
138
What molecule stabilizes class II MHC molecules in the ER?
The invariant chain peptide acts as a place holder, keeping the alpha and beta chains of the MHC together.
139
How is the invariant chain removed from the class II MHC to allow for peptide binding?
The invariant chain is cleaved within vesicles, leaving behind a fragment called CLIP in the binding site. When a vesicle containing antigens fuses with the MHC-CLIP vesicle, the antigens cannot bind because CLIP is occupying the binding site. HLA-DM needs to enter the vesicle and cause CLIP to leave the active site, allowing for antigen binding.
140
How do class II MHC binding peptides differ from class I MHC binding peptides?
They are longer (\>13 AA) and more variable than class I peptides. Class I bound peptides are anchored at their N and C termini to the ends of the binding cleft, but class II bound peptides are not.
141
What are the coreceptors for MHC class I and II molecules, respectively?
CD8 is the coreceptor for MHC class I. CD4 is the coreceptor for MHC class II. These coreceptors function to stabilize the MHC molecules as they bind to T-cells.
142
Describe the specificity of T cell receptors.
For successful recognition by a TCR, the antigen and the MHC must both be correct. If either is wrong, then no recognition will occur.
143
Why is it advantageous to be a heterozygote for peptide selection?
Heterozygotes will have a larger subset of antigens presentable to their MHCs because they have 2 different copies of the MHC genes. Homozygotes only have 1 set of MHC genes, giving them a low range of what they can actually present.
144
What role do epidemics play in heterozygote advantage?
Homozygotes are more susceptible to infectious diseases, so large epidemics can wipe homozygotes out of a population. This leads to a large percentage of heterozygotes in a population due to "balancing selection." This is sometimes called a bottlenecking effect.
145
What are the ways that recombnination can occur between MHC alleles?
Although rare, intraallelic conversion can occur via typical meiotic crossing over. Gene conversion can also take place within a chromosome that has repetitive gene sequences.
146
Explain how organ graft rejection occurs
A T-cell specific response occurs in which cells react to the allogeneic (non-self) peptides. The transplanted cells have a different MHC from the host. The host can recognize MHC-peptide complexes on grafts as foreign and begin an attack.
147
What happens to T-cells that attack autologous MHC peptide complexes?
They are negatively selected agains in the thymus. They will undergo apoptosis.
148
What role does CD1 play in antigen presenting?
CD1 is a class I MHC-like molecule present in the ER. It regularly binds to self glycolipids in the ER and is brought to the cell surface via golgi vesicles. These receptors can be re-taken up through clathrin coated pits. Vesicles containing myobacteria can fuse with the CD1 vesicle. When this occurs, CD1 exchanges the self glycolipid for the myobacterial glycolipid. It is then brought to the cell surface to be presented to a T cell.
149
How do NK cells detect the health status of cells?
They recognize general health status based on the presence of class I MHCs on the plasma membrane.
150
What are the two classes of NK cells?
(1) Inhibitory NK cells prevent the killing activity and protect self cells. (2) Activating NK cells trigger the killing sequence targeting foreign and infected cells
151
What are the two classes of NK Receptors?
(1) KLR: Killer like receptors (2) KIR: Killer cell immunoglobulin-like receptors
152
What chromosome are the NK receptor genes found on?
Chromosome 12
153
What is MIC?
A homolog to MHCs that signals cellular stress. These bind to the activating receptor NKG2D of NK cells
154
What role does HLA-E play in signaling cellular health?
Leader peptides are removed from HLA-A, B or C in the ER and bind to HLA-E. The HLA-E moves to the surface and signals a healthy, "do not kill" signal to the NK cell
155
What did Susumu Tonegawa win the Nobel prize for?
His controversial theory that the genome reshuffled, leading to the massive diversity of host cell defense.
156
If an antibody is proteolytically cleaved, how many fragments will be detectable using standard blotting methods?
2 pools will be detected. The more abundant representing the 2 Fab domains of antibodies, and the less abundant representing the Fc domain
157
How many different antibody isotypes are there?
5: each with a different Fc region. IgG, IgD and IgA have 1 variable region and 3 constant regions. IgM and IgE have 1 variable region and 4 constant regions
158
Describe the secondary structures found within antibodies
Antibodies are made entirely of beta sheets. They contain no alpha helices.
159
What portions of the antibody secondary structures are variable?
The loops in between the beta sheets of the light chain near the N-terminus are sites for programmed mutagenesis leading to highly variable domains
160
What are CDRs?
Complementarity determining regions: These are the highly variable regions within the light chain loops that act as binding sites for antigens. There are 3 CDRs in antibody light chains
161
What is the difference between a linear epitope and a discontinuous epitope?
Linear epitopes are consecutive residues within a peptide that interact with an antibody. Discontinuous epitopes are non-consecutive residues that are close together due to 3D folding of the protein sequence.
162
What are the four subclasses of IgG and how do they differ?
IgG-1,2,3, and 4 differ based on the structure of the hinge region between the variable and constant regions. IgG1 is the most abundant and binds to protein epitopes. IgG2 binds to carbohydrate antigens. IgG3 has the longest hinge region. The role of IgG4 is unknown.
163
What is the largest of the immunoglobulins in terms of molecular weight?
IgMs are the largest IgG weighing ~970kDa
164
What is the most abundant immunoglobulin?
IgG1 are most abundant in the serum of a normal healthy adult
165
What role does the relative concentration of IgG and IgE play in allergic reactions?
People with allergies have higher level of serum IgE than normal. In order to prevent large immune responses, the concentration of IgG must increase to be greater than that of the IgE.
166
Describe the flexibility of the IgG molecule
The arms of the IgG molecule can wave, rotate, and bend allowing it to simultaneously bind pathogens and effector molecules and receptors of the immune system.
