Brainscape Spring Semester - Immuno Exam 3 Flashcards
(153 cards)
1
Q
In T cell development, when RAG-1/2 turns off following the DN stage, will it stay off forever?
A
No. RAG-1/2 is on during the DN stage while the beta chain is rearranging. It then turns off and the beta chain will never be rearranged again in that cell. RAG-1/2 turns back on during the DP stage for alpha chain rearrangement, after which RAG-1/2 is permanently turned off in that SP T cell
2
Q
During the DN stage of T cell development, which TCR genes are expressed?
A
TCR gamma, delta and beta are all expressed. There is a race between beta and gamma/delta to rearrange first. TCR alpha is not expressed until the DP stage
3
Q
What role do histone modifications play in T cell development?
A
Histones are methlyated in order to make enhancers less accessible. They can be acetylated in order to activate the enhancer by increasing accessibility due to looser winding
4
Q
Which type of T cell is more frequently formed: alpha/beta or gamma/delta?
A
The alpha/beta T cells form more frequently because only the beta chain needs to properly rearrange, wheras the other route requires two rearrangements.
5
Q
How does signaling occur in pre-T cells?
A
The pT-alpha chain and beta chain can interact with CD3 and the zeta chain in order to signal across the membrane
6
Q
Which stage comes first: Pro B-cells or Pre B-cells?
A
Pro B-cells come first, developing from Late Pro-cells into Large Pre B-cells
7
Q
How does the location of B cell development differ from that of T cell development?
A
Unlike T-cells, B cell development continues within the bone marrow and does not leave until the transition from small pre B cell to an immature B cell
8
Q
What is the goal of positive selection?
A
To verify that the BCR can recognize self-MHC
9
Q
What is the goal of negative selection?
A
To make sure that the strength of the BCR-MHC is not too strong or too weak.
10
Q
What mechanism allows for the activation and clonal expansion of B cells?
A
When B cells encounter pathogen-derived antigens, they are activated. They can then travel to the secondary lymph tissue and undergo somatic hypermutation.
11
Q
What structural component distinguishes different stages of B cell development?
A
Surface receptors present determine which stage of development the B cell is in.
12
Q
What surface receptor(s) are present on pluripotent hematopoietic stem cells?
A
CD34
13
Q
What surface receptor(s) are present on common lymphoid progenitor cells?
A
CD7, CD10, CD34, CD45RA
14
Q
What surface receptor(s) are present on B-cell precursor cells?
A
CD10 and IL-7Rα
15
Q
What surface receptor(s) are present on pro-B cells?
A
None
16
Q
Describe the rearrangement within the heavy and light chains during B cell development.
A
The heavy chain rearranges first, with D-J rearrangement during Early pro-B cell stage, and V-DJ rearrangement during late pro-B cell stage. The light chains then undergo V-J rearrangement during the small pre-B cell stage
17
Q
At what stage is IgM first detectable on the surface of developing B cells?
A
During the immature B cell stage, *but the pre-Bcell expresses IgM with VpreB and Lambda5 while the light chain is rearranged.
18
Q
Describe the adhesion molecules present during early pro-B cell stage.
A
Stromal cell factor of the stromal cell binds to Kit of the pro B cell to generate a proliferative signal. VLA-4, an integrin binds VCAM-1 also.
19
Q
During late pro-B cell stage, what cytokine serves as a proliferative signal?
A
IL-7, produced by the bone marrow stromal cell binds to IL-7 receptors on the pro-B cell surface
20
Q
What is the purpose of allelic exclusion?
A
This process makes sure that only one type of Ig is expressed on each B cell. Successful heavy chain gene rearrangement of the genetic material from one chromosome results in the shutting down of rearrangement of genetic material from the second chromosome
21
Q
Describe the B-cell rearrangement during the pro-B cell stage.
A
Heavy chain D-J rearrangements occur on both homologs (6 rearrangements per homolog). Following a productive D-J rearrangement, V-DJ rearrangement will occur on one homolog. If this results in nonproductive rearrangement, then the other homolog will attempt V-DJ rearrangement. Successful rearrangement on either homolog will allow the cells to progress to pre-B cells. Unsuccessful rearrangemen ton both homologs will signal cells to die by apoptosis.
22
Q
What are the components of the surrogate light chain in pre-B cell receptors?
A
VpreB and λ5 genes complex to form a surrogate light chain that interacts with the μ heavy chain
23
Q
What molecules give B cell receptors signalling capacity?
A
Igβ and Igα provide the B cell receptors with signaling capacity
24
Q
What is avidity?
A
The combined strength of multiple bonds between antibodies and the antigen. The individual bonds are not particularly strong, but the combined effect allows the antigen to be secured preventing it from diffusing away
25
What are the three signals for allelic exclusion?
1) Inhibit RAG-1/2 2)Degrade existing RAG-1/2 3)Alter chromatin structure
26
Describe avidity with and without the process of allelic exclusion.
Allelic exclusion allows for high avidity binding due to homogenous B cell receptors. Without allelic exclusion, heterogenous B cell receptors will develop on a cell's surface, leading to decreased avidity.
27
Is light chain rearrangement able to occur after the first VJ recombination?
Yes. Successive rearrangements are possible, allowing for the phenomenon of B cell receptor editing.
28
Describe the allelic exclusion process in the light chain locus.
Rearrangement occurs at one locus at a time. First, the κ locus on one chromosome, then the κ locus on the other. If neither are successful then rearrangement will occur at the λ locus. Without any successful recombination, the cell will undergo apoptosis.
29
Is it possible to have an IgM with one κ light chain and one λ light chain?
No. IgM's will always have 2 of the same light chain attached.
30
How do the first and second checkpoints in B cell development differ?
The first checkpoint selects for functional heavy chains in pre-B-cell receptors. The second checkpoint selects for functional light chains in Immature B cells
31
What happens to cells that fail to pass either checkpoint during B cell development?
They undergo apoptosis
32
What are the major growth factor receptors involved with B cell development, and when are they expressed?
Kit expression begins during the stem cell phase and continues through the early pro=B cell stage, ending during the late pro-B cell stage. IL-7 receptor expression begins during the stem cell phase and continues through until the end of the Large pre-B cell stage
33
Describe the expression pattern of RAG-1 and RAG-2 during B cell development.
It alternates on and off. It is first on from the early pro-B cell stage until the large pre-B cell stage. It is then off until the small pre-B cell stage, and remains on until the mature B cell is formed
34
What role does Pax-5 play in B cell development?
Pax-5 is a transcription factor that keeps cells in the B cell state. It binds to enhancer sequences in the early pro-B cell stage, loosening chromatin and allowing for increased transcription rate
35
What happens in patients with Burkitt Lymphoma?
A translocation occurs between the MYC gene on chromosome 8 and an Ig gene on chromosomes 14, 2, or 22. This mutation will prevent MYC from properly controlling cell divisions, leading to cancer
36
What surface molecule is characteristic of B-1 cells?
CD5
37
What is required for B cells to leave the bone marrow and proceed into the bloodstream?
B cells must have NO reactivity against self antigen in order to leave the bloodstream. When this occurs, the ratio of IgM:IgD will decrease as more IgD appear on the surface
38
Do B cells in the bone marrow that recognize self antigen undergo apoptosis?
No. They can first attempt to edit themselves to change their specificity by further rearrangements of the light-chain genes. This process increases the efficiency of B cell development. If the rearrangement fails, then the cell will eventually undergo apoptosis.
39
What guides B cell migration from the HEV into lymph tissue?
The chemokine gradients of CCL21 and CCL19 attract B cells into the lymph node. Once in the lymph node, chemokine CXCL13 attracts B cells into the primary follicle
40
What interactions drive the maturation of immature B cells within lymph tissue?
Interactions with follicular dendritic cells via LT from B cell and LT receptor on DC. BAFF from DC can then bind to BAFF receptor on the B cell to trigger B cell maturation
41
Where does differentiation into plasma cells occur?
Within the germinal centers of secondary lymph tissue
42
How can Southern blots of serum samples demonstrate the effectiveness of chemotherapy?
In a cancer in which rearrangement occurs in the J chain, you can visualize non-Germ line bands along with the normal Germ line band on a southern blot. Following effective chemotherapy treatment, we would expect the size of these non-Germ line bands to decrease due to suppression of the rearrangement occuring in cancerous cells
43
What was Jenner's observation in 1796?
Jenner realized that cowpox and smallpox virus share some of the same surface antigens, so immunizing humans with cowpox virus induces antibody production in humans that are capable of neutralizing the smallpox virus without major risk of infection
44
What are the features of effective vaccines?
They must be safe, protective, give sustained protection, induce neutralizing antibodies, and induce protective T cells. They also ideally will have a low cost and be easy to administer with few side-effects
45
What is a toxoid?
An inactivated toxin that can elicit an immune response against the components of the toxin without actually producing the illness associated with the toxin
46
What are attenuated viruses?
They are live viruses, but weakened by reducing the ability to replicate in human cells. These are not dangerous in healthy people, but can cause problems in individuals that are immunocomprimised.
47
Describe the process of producing an attenuated virus.
First the pathogenic virus is isolated from a patient and grown in human cultured cells. Then the culture is used to infect and animal, like a monkey. The virus adapts and mutates to grow well in the monkey cells. After several mutations, the virus will no longer be able to grow well in human cells, so it can be used as a vaccine.
48
What are the three components of the DTaP vaccine?
Diptheria, Tetanus, and Pertusis
49
What do bacteria involved with the DTaP vaccine all have in common?
They all produce secreted exotoxins
50
What are A-B toxins?
A common group of bacteral toxins that have multiple subunits. The A component possesses the catalytic activity. The B component binds to receptors of the host cell
51
Describe the interaction between diptheria toxin and the human host.
It affects host eEF-2, which is important for the translocation of ribosomes between adjacent codons during translation. The cells form a pseudomembrane in the throat following infection of airborne pathogen. Bleeding of underlying tissue often occurs.
52
Describe the interaction between tetanus toxin and the human host.
Tetanus toxin affects neurons resulting in spastic paralysis. These toxins are obligate anaerobes found in the soil, introduced into the human body via puncture wounds.
53
Describe the interaction between pertussis toxin and the human host.
Pertusis toxin inhibits the enzyme adenylate cyclase, leading to intracellular accumulation of cAMP. The clinical symptoms of "whooping cough" are due to the release of toxin from the site of colonization.
54
Why is it advantageous for vaccines to contain whole bacterial extracts rather than toxoids?
Toxoids rely on recognition by B cells. Whole bacterial extracts contain multiple epitopes and non-protein components like cabohydrates and lipids. These components can be recognized by CD1 (carbs) or TLR's (lipids) in order to illicit strong immune responses.
55
Describe the structure of the influenza virus.
Influenza is an RNA virus made of 8 strands of -RNA (7 -RNA in type B). This RNA is enclosed in a capsid covered with hemagglutinin and neuraminidase. +RNA is produced from the template -RNA by viral RNA-dependent RNA polymerase
56
What are the three types of influenza virus?
A: responsible for global pandemics, very fatal. B:causes local outbreaks. C:Mild pediatric cases
57
Which types of influenza exhibit antigenic drift?
Type A and Type B are highly mutagenic. They change the types of hemagglutinin and neuraminidase on the surface
58
How are strains of influenza named?
Based on the two antigens found on the viral surface: hemagglutinin (H) and neuraminidase (N). The antigen subtypes are numbered, giving rise to influenza strains like H1N1 and H5N1
59
What are the two different types of administration possible for the influenza vaccine?
(1)A trivalent vaccine (TIV) composed of components of killed viruses made of 3 strains of influenza (2)Live attenuated vaccine (LAIV) made of 2 strains of influenza
60
Explain why the LAIV method for vaccination is advantageous compared to the TIV method.
During a real influenza infection, a CD8 response will occur via presentation by MHC class I. The TIV will trigger an IgG response, following phagocytosis and presentation through MHC class II. The LAIV administered nasally will trigger a more realistic response.
61
Which influenza proteins could potentially be vaccinated against that would only require one vaccination in a lifetime?
The internal proteins that are not as mutagenic. These proteins will constantly mount vigorous CD8 responses in healthy individuals
62
How is the influenza vaccine developed?
The virus strains are grown in fertilized chick eggs. The viruses are then killed to make TIV, or weakened to make the LAIV
63
What is an ISCOM?
Immune stimulatory complex, which is basically a lipid micelle capable of delivering peptides into the cytosol of a cell. The peptides are packaged in the hydrophobic core of the ISCOM until the ISCOM fuses with the cytosol. This is followed by presentation via MHC class I to CD8 T cells
64
What is an adjuvant?
A chemical preparation that enhances immune response. Not typically used on human vaccinations, but common in animal studies. Ex: Freunds incomplete adjuvant is an oil-in-water emulsion that delays antigen release and enhances uptake by macrophages.
65
Why is the measles vaccine not useful for treating measles in many parts of the world?
It requires refridgeration, which is not available in many of the countries in need of vaccinations
66
Explain the two different outcomes of infection with Hepatitis C.
70% of those infected will develop chronic infection of hepatocytes that can cause liver damage, and in some cases liver cancer. The other 30% will develop immunity against the infection.
67
How are recombinant vaccines able to decrease the risk of viral infection following vaccination?
With a thorough understanding of a particular virus, the virulence genes can be identified and removed via deletion. The resulting virus is viable and immunogenic, but avirulent.
68
What are the two major vaccines used to protect against human rotaviruses?
Rotarix, an attenuated human virus, and RotaTeq, a group of recombinant bovine viruses expressing human VP4 and VP7 glycoprotein antigens
69
Describe the strucutre and prevalence of mucus in humans.
Mucus is made up of mucin glycoproteins that form into an integrated gel matrix. This matrix coats mucosal surfaces and moves to clear trapped material. The human body produces 4L of mucus a day.
70
What is immune privilege?
Parts of the body that possess no lymphocytes. Ex: Conjunctiva of the eye, Brain, Testicles
71
Describe the gut microbiota.
3 of the 8 bacterial divisions are found in the body, with ~500-1000 diffferent species. Most of these microbial cells are found in the colon
72
What are the advantages for having microbiota in the gut?
(1)Metabolic advantages: require fewer calories (2)Development: epithelial growth and mucosal immune system (3)Protection due to competition from antibacterial secretions from microbiota
73
What are non-pathogenic antigens?
Commensal microorganisms that the body is regularly exposed to such as food proteins and environmental antigens
74
Describe the balance that exists between Tolerance and Immunity.
The body must be able to tolerate necessary substances such as food and endogenous biota, but develop immunity to pathogenic microorganisms. Imbalance between these two processes can lead to diseases like inflammatory bowel disease, Crohns disease, Celiac disease ... etc.
75
What is the likely fate of a lymphocyte that is specific for a required food protein?
The cell will become anergic and be deleted in order to maintain tolerance for that substance
76
What are the two types of mucosal surfaces?
Type I surfaces are simple epithelial surfaces with MALT and IgA. Type II surfaces are stratified epithelial surfaces with no MALT and with IgG
77
Which type of mucosal surface is found in the mouth?
The mouth is lined with Type II mucosa
78
What is the difference between Peyer's patches and secondary lymph tissue?
Antigens do not enter Peyer's patches via afferent vessels, but rather via direct uptake from the intestinal lumen by DCs or M cells
79
How are M cells able to uptake antigen from the intestinal lumen?
M cells endocytose antigens from the lumen, and transcytose the contents to the submucosa. In the submucosa, the antigens can be presented to dendritic cells which will then activate T cells
80
Are M cells required for DCs in the gut to be presented with luminal antigen?
No. Some DCs have processes that extend across the epithelial layer and can capture antigen directly from the lumen of the gut
81
Are naive immune cells present in the intestinal epithelium and lamina propria?
No. Effector cells are present due to constant stimulation due to regular exposure to antigens in the gut.
82
What are IELs?
Intraepithelial lymphocytes. These cells are located about 1 in every 7-8 epithelial cells in the gut. Type a IELs contain TCR-alpha/beta and recognize MHC presented antigen. Type b (unconventional) IELs possess TCR gamma/delta and alpha/beta or alpha/alpha, with multiple TCR specificities
83
How do the distributions of Type a and Type b IELs differ in mice and humans?
They are similar, making mice good models to study these functions. In the small intestine, a=b. In the colon a\>b, and in the vaginal mucosa a\
84
Describe the path that a lymphocyte activated in a Peyer's patch will follow.
The activated lymphocytes will travel to mesenteric lymph nodes and re-enter circulation. They will return to the lamina propria of the site where they were activated in order to produce their effector functions.
85
What adhesion molecules are involved with Gut-homing effector T cells?
MAdCAM-1 of the vascular endothelium binds to α4:β7 integrin and L-selectin on the lymphocyte. This interaction allows the lymphocyte to enter the lamina propria, where CCR9 of the lymphocyte can interact with cytokines CCL25 expressed by the intestinal epithelium. A tight interaction then occurs between E-cadherin of the epithelium and αE:β7 of the lymphocyte
86
What are the 2 main signals involved in inducing tolerant type responses?
1) Bacterial Pathogen-associated molecular patterns (PAMPs) and 2)Inflammatory cytokines
87
What role does the polymeric immunoglobulin receptor pIgR play?
The pIgR is found on the basolateral surface of the cell. This receptor can recognize polymeric IgA and IgM. The IgA dimer or IgM pentamer can be transcytosed to the lumenal face of the cell following interaction with pIgR. This allows the IgA to neutralize antigens in the lumen, and then enter back into the lamina propria through M cells.
88
What is the predominant subclass of IgA throughout the body?
IgA1 is predominant throughout the body. IgA2 is main Ig for protection in the colon.
89
Are IgA-deficient individuals still able to have mucosal protection?
Yes due to redundance with the J chain usage, IgM can pick up a lot of the slack left by the absence of IgA. IgG and IgD also help out too.
90
How do NOD2 proteins respond to bacterial products?
The NOD2 in the cytoplasm recognize muramyl dipeptides, which are components of the bacterial cell wall. NOD2 then activates NFkB in order to promote the transcription of cytokines, chemokines and defensins (innate immune response) and also preparation for specific immune response.
91
Describe the balance between Th1 and Th2 cell development.
TH2 cell effector functions lead to epithelial cell repair, eosinophil production, IgE production and Mast cell recruitment via IL-3 and IL-9. Th1 cell effector functions lead to activation of macrophages and B cells to produce IgG2a. A spectrum exists between the protective effects of Th2 cell effector functions and the host damage of Th1 effector functions
92
What is atopy?
Genetic predisposition to elevated sIgE leading to allergic hypersensitivity
93
What are the names of allergic reactions in different body regions?
Atopic dermatitis in the skin. Allergic rhinitis in the nasal passages. Atopic asthma in the lung. Food allergies in the gut. Anaphylaxis is systemic.
94
What is the atopic triad?
Food sensitivity, atopic dermatitis, allergic rhinitis/asthma
95
What are the signs and symptoms of anaphylaxis?
Skin erythema (redness), urticaria (hives) and pruritis (itch). GI: vomitting, cramps, diarrhea. Respiratory: stridor, tightness in throat, wheezing. CV: syncope (fainting), hypotension. General: uneasiness, weakness, apprehension, incontinence
96
What are the four types of allergic responses?
Types I, II, III, and IV. They differ based on the immune cells involved and the types of antigen that trigger them.
97
Describe a type I allergic reaction.
IgE mediated response to a soluble antigen, leading to mast cell activation. This is the most common type of allergic response
98
What is the difference between a type II and a type III allergic reaction?
They are both IgG mediated responses, but type II involves cellular surface antigens and receptors, and type III involves soluble antigens.
99
What is a type IV allergic response?
Abnormal effector T cell stimulation. Th1, Th2 or CTL cells respond to antigens leadint to macrophage activation, eosinophil activation, or cytotoxicity, respectively.
100
Which types of white blood cells are involved in type I allergic reactions?
Basophils and eosinophils are involved in type I reactions. They both have receptor FcεR1, which binds to the Fc domain of the ε heavy chain of the IgE.
101
What are the contents of the granules released from basophils and eosinophils following secondary exposure to a pathogen?
The granules contain histamine and heparin for inflammatory responses. They also contain enzymes to break down the extracellular matrix material, and TNFα for proinflammatory effects.
102
Describe the role of lipid mediators in the type I response.
Lipid mediators like leukotrienes and prostaglandins are important for stimulation of smooth muscle and mucus secretion. They are 1,000x more potent than histamine
103
What are the different receptors for histamine?
H1, H2, H3 and H4. H1 receptors elicit the type I allergic responses, and are a common target for pharmaceuticals
104
What are the two things that arachidonic acid can develop into?
Prostaglandin D2 via the cyclooxygenase pathway OR Leukotriene C4 via the 5-lipoxygenase pathway
105
What pathway does aspirin target and what is its effect?
Aspirin targets the cyclooxygenase pathway in order to decrease pain and inflammation
106
What are the different routes of entry of pathogens that cause Type I allergic reactions?
Intravenously, subcutaneously, inhaled or oral. In any route, a soluble antigen is entering the system
107
What is the general goal of the mast-cell activation and granule release?
To remove offensive materials from the affected tissue
108
What are the three major tissues that mast cells release granules into?
GI tract, respiratory tract, and blood vessels
109
What is the cause of systemic anaphylaxis?
Antigens in the bloodstream enter tissues and activate connective tissue mast cells throughout the body. These mast cells will release granules and inflammatory mediators leading to problems in the heart and vascular system, respiratory tract, and GI tract
110
What is the functional part of Penicillin?
The 4 membered β-lactam ring interacts with the gram positive bacterial cell walls containing transpeptidase
111
What effect does penicillin have on human erythrocytes?
Penicillin modifies proteins on RBCs to create foreign epitopes. This leads to activation of the alternative pathway of complement activation. The complement coated RBC are phagocytosed by macrophages. These macrophages present the penicillin-protein conjugates to CD4 T cells to become Th2 cells. B cells are then activated by the Th2 cells, which can then produce penicillin specific IgG
112
Which bloodtypes can an individual with Type B blood potentially receive an organ transplant from?
Individuals with Type B blood can potentially receive transplants from individuals with Type O or Type B because they only have Anti-A antibodies in their blood.
113
What is the characteristic behavior of antibodies and their antigens in type III allergic responses?
Cross-linking between antibodies and antigens leads to large immune complexes that fix complement and are cleared from circulation.
114
Describe the immune complexes that form in type III hypersensitivity reactions.
Immune complexes form between antibodies and antigen, leading to complement activation. C5a from complement binds to a receptor on a mast cell, which leads to the binding of the immune complex to the mast cell through the FcγRIII . This binding induces degranulation, leading to a strong inflammatory response.
115
What is a hapten?
Something that is not immunogenic on its own, but in combination with other things
116
What are the different syndromes associated with Type IV hypersensitivity?
Delayed-type hypersensitivity, contact hypersensitivity, and Gluten-sensitive enteropathy (Celiac disease)
117
What is the difference between the mechanisms seen in allergic reactions and those seen in autoimmune disorders?
They have the same mechanisms, but we do not see IgE mediated, Type I responses in autoimmune diseases
118
How does tolerance relate to autoimmune disorders?
Due to decreased (or completely absent) immunity seen in autoimmune patients, one breakdown in tolerance will lead to the release of autoreactive B cells and T cells
119
What happens in rheumatoid arthritis?
RA is a T cell mediated (Type IV) autoimmune disease in which tertiary lymph tissue builds up within the joint capsule, which leads to inflammation and joint destruction.
120
What mechanisms contribute to immunological self tolerance?
(1) Negative selection in bone marrow and thymus (2) Expression of tissue specfiic proteins in the thymus (3)Immune privilege (4)Suppression of autoimmune responses by Tregs (5)Induction of anergy in autoreactive B and T cells
121
What endocrine glands are involved with autoimmune diseases?
The thyroid gland, islets of langerhans (pancreas), and adrenal gland are all affected in various autoimmune disorders
122
True or False: Many autoimmune diseases are associated with HLA gene mutations
True. Many mutations in the HLA gene increase the risk for autoimmune disease (see fig 13.24)
123
What is an autograft?
When the donor is the same person as the recipient. For example, part of the hip bone can be removed and used to help repair another bone.
124
What is the difference between an allogeneic graft and a xenograft?
Allogeneic grafts are when the donor and recipient are unrelated humans. A xenograft is when the donor is an animal.
125
What is the general process that occurs during transplant rejection?
The recipients T cells attack the transplant leading to rejection
126
What is the general process that occurs in graft versus host disease?
When bone marrow is transplanted, the T cells in the transplant attack the recipients tissues
127
Describe the innate response against an allograft.
An ischemia-reperfusion injury often occurs when the organ is drained of blood before transplantation, and then reperfused with blood when attached to the recipients circulator system. This triggers inflammation and oxidative stress. Dendritic cells are activated within the graft involving TLR's, MyD88, and NOD/NOD-like receptors
128
Describe the adaptive response against grafts.
TCD4+ and TCD8+ cells are necessary and sufficient to induce rejection. B cells PCs and Ig are also important
129
What is the major gene involved with graft rejections?
The HLA gene found on chromosome 6. This region is highly polymorphic and is crucial for both cellular and humoral rejection.
130
What experimental procedure can be used to verify that a donor and recipient are compatible?
A mixed lymphocyte reaction
131
What are minor histocompatibility antigens?
Antigens that can lead to organ rejection in some, but not all transplants. Even through monozygotic twins are identical genomically, the antigens on their organs may be different.
132
Can an MLR be used to detect Minor Histocompatability Antigens?
No
133
What is the H-Y?
A minor histocompatability antigen found on Male organs. Because the female lacks these antigens, they may mount an anti-male response against the Y chromosome found in the graft.
134
What are the most common bloodtypes?
O/RhD+ and A/RhD+
135
What are the different types of rejection?
Hyperacute, acute, and chronic
136
Is acute rejection of a grafted organ manageable?
Yes. They are treated using immunosuppresants can be used to prevent the decline in function in the days following the graft.
137
How frequent is chronic rejection in kidney and heart transplants?
\>50% of the kidneys and hearts transplanted are rejected by 10 years post graft due to BV occlusion
138
What drugs are used for anti-rejection therapy?
Hydrocortisone, a hormone produced by the adrenal cortex that is antiinflammatory. Prednisone can also be used, which is a similar chemical that is a 4x stronger antiinflammatory drug than hydrocortisone.
139
Describe the mechanism of how steroid drugs are able to induce changes in gene expression.
Steroid receptors in the cytoplasm are able to bind steroids that have passed through the plasma mebrane. When the steroid binds, Hsp90 is displaced. The steroid-receptor complex can cross into the nucleus and bind to regulatory sequences in order to activate transcription.
140
What is the effect of increased IkBα activity caused by steroids?
increased IkBα leads to decreased NFkB expression
141
Corticosteroid therapy decreases IL-1, TNFalpha, GM-CSF, IL-3, IL-4, IL-5 and CXCL8. What is the effect of this?
Inflammation caused by these cytokines will decrease
142
Does corticosteroid therapy increase or decrease the number of adhesion molecules?
The number of adhesion molecules decreases with corticosteroid therapy in order to decrease the emibgration of leukocytes from the vessels.
143
What are antiproliferative drugs used for?
They are used to decrease the T cells and IL-2 in order to inhibit the proliferative phase of acute cellular rejection. These are used in chemotherapy treatments for cancer
144
What is hyperacute rejection?
When the recipient already has antibodies in their system, they have a pre-existing reactivity vs the donor antigen. Transplantation triggers a rapid memory response followed by an inflammatory response. Ex: Anti-ABO or Anti-MHC I
145
What are the two different outcomes of T and B cell activation?
Most activated cells become short-lived effector cells, but some activated cells become long lived memory cells
146
How do immunizations change the frequency of antigen-specific B cells?
The frequency increases by 2-3 orders of magnitude
147
How does the quantity of IgM present in the body of an immunized person differ from that in a non-immunized person following second infection?
Without immunization, the number of IgM increases even with the second exposure due to a slightly different antigen. Immunizations allow for mainly IgG responses during additional infections.
148
What is the receptor on naive B cells that binds the gamma IgG chain?
FcγRIIB1
149
Describe the signal given to naive B cells during a secondary response
The naive B cell binds with pathogen coated with IgG via the FcγRIIB1 receptor. This interaction triggers a negative signal to the naive B cell to prevent its activation so that a memory B cell can be activated and produce high affinity antibodies (IgG, IgA, and IgE)
150
What is the preventional treatment for Rh- mothers carrying Rh+ fetuses?
They are given anti-Rh IgG ("Rhogam"). This antibody binds to naive B cells in the mother and tricks the immune system into thinking she has been exposed already. The immune system will not mount a new response with IgM production, preventing a primary response against the fetus.
151
What are the two classes of memory T and B cells?
1) Central memory cells home to the secondary lymph tissue
2) Effector memory cells do not home to the secondary lymph tissue
152
What is the difference in surface receptors between central and effector T cells?
Effector T cells do not have CCR7. This means that they will not stop rolling along the endothelia because they don't have the proper chemokine receptor for CCL19.
153
What surface receptors are responsible for tolerance?
MHC class II and TCR provide signal 1, but no co-stimulator is present on the APC, so the T cell will become anergic and disfunctoinal.
