Exam #2 Flashcards
1
Q
In somatic hypermutation, a B cell that has been activated to proliferate what chemically changes DNA bases to another base, resulting in a new codon?
A
Enzyme: activation induced cytidine deaminase
2
Q
What helps this occur and where does somatic hypermutation occur?
A
T cell help, germinal centers
3
Q
Define affinity maturation and what happens if this isn’t met.
A
This is when somotic hypermutation provides better binding of the antibody pocket to the antigen. These B cells are selected for. If this doesnt occur and binding ability is decreased, these B cells die via apoptosis.
4
Q
The enzyme in somatic hypermutation converts cytidine residues to what?
Deaminates cytosines and what in what two regions of an antibody gene?
A
Uridine, which is recognized as a thymidine.
adenosines, VDJ and VJ
5
Q
Affinity maturation only occurs if ????
A
as a response to antigen stimulation. Multiple rounds of mutation/apoptosis can occur.
6
Q
On the other hand, the affinity maturation can occur via a different process called what??
This occurs in what species?
A
Gene conversion
Pigs, cattle, rabbits, horses and chickens. (humans and mice are hypermutation exclusive)
7
Q
Chickens/birds use gene conversion when? But hypermutation when? Where does gene conversion occur in birds? Ruminants?
A
During B cell differentiation. During an immune response. Bursa. Ileal Peyer’s patches
8
Q
In species with gene conversion, there is very little diversity within what? Therefore, what happens in gene conversion? Does T cell stimulation cause this?
A
V, D, and J gene segments. Short sequences within the exon are replaced by V gene segments from pseudogenes. No!! Unlike somatic hypermutation, this does NOT NEED T cell stimulation.
9
Q
When a mature B cell traffics to peripheral tissues (including 2ndary lymphoid organs), encounter with its antigen and T cell help (cytokines), the B cell converts to a?
A
Plasma cell
10
Q
After encountering antigen and converting to plasma cells, B cells will also go through somatic hypermutation, affinity maturation and isotype switching. After these occur, the B cells that survive will differentiate into 1 of 2 things. Name the 2.
A
Memory B cells and plasma cells
11
Q
Remember that somatic hypermutation and gene conversion just changes the what inside of antigen binding pockets?
A
Amino acids
12
Q
In comparison to somatic hypermutation, isotype switching causes a change to what in the antibody. Does this change it’s antigen specificity?
A
The heavy chain region. NO
13
Q
After stimulation by cytokines, isotype switching occurs how? How is switch back prevented? Does specificity change? Are light chains changed?
A
The somatic DNA is rearranged ONLY IN THE HEAVY CHAIN REGION. No switch back because the DNA loops out and is lost. Specificity is NOT changed. Light chains are NOT changed.
14
Q
IgM is the first antibody produced during a primary response. Can be bound on surface or secreted as a pentamer. Plasma cells in what 3 tissues secrete IgM. What function is IgM good at?
A
Spleen, bone marrow, lymph nodes. Activating complement, (neutralization and opsonization less.)
15
Q
Isotypes switch to which antibodies?
A
IgG, IgE, IgA
16
Q
IgG is secreted by plasma cells in which 3 tissues. What 4 functions are IgG very good at? IgG is often transported across what 2 things?
A
spleen, lymph nodes, bone marrow. Neutralization, opsonization, sensitization for killing by NK cells and activating complement cascade. Transport across placenta and into extravascular sites.
17
Q
IgE Fc portion binds to receptors on what 2 cells? Main function?
A
Mast and basophils. Sensitization of mast cells
18
Q
IgA is secreted by plasma cells where? Main function? Good at transport across 2 things.
A
Tissues near body surfaces. Neutralization (a little opsonization). Transport across epithelium and into extravascular sites.
19
Q
Some immune cells express receptors that recognize the Fc region of an antibody. Interaction between them cause activation of that cell. Which antibodies have receptors and what cells do those antibodies activate?
A
IgG=phagocytes like macrophages, neutrophils, eosinophils, Nk cells, mast cells. IgE=mast cells and eosinophils IgA (a little)
20
Q
After the first encounter with an antigen, there is a gradual rise in antibody after a lag phase of how many days? THe second encounter is much stronger due to blank blank. Isotype switches from what to what?
A
3-7 days. Immunological memory. IgM to IgG.
21
Q
Does memory involved B or T cells specific for an antigen?
A
BOTH
22
Q
Where are memory cells stored? B cells have much larger response in 2nd responses.
A
Secondary lymphoid tissues. B cells primarily in bone marrow.
23
Q
Is somatic hypermutation higher at the first or 2nd response?
A
2nd!!
24
Q
What are the 3 P’s of MHC and define each.
A
Polygenic-several genes exist for a given MHC class. Polymorphic-a large umber of alleles exist for a given gene. Promiscuous-will bind a range of similar epitopes.
25
What is special about the peptide binding cleft of the MHC that makes it able to present almost every possible antigen?
HIGH rate of mutation (many alleles)
26
Define MHC restriction
T cells will not recognize a MHC allele or an epitope that it is not educated in. Change the MHC allele or epitope and no recognition will occur.
27
Epitopes are also known as blank blank
antigenic determinant
28
What are the 3 APCs. What degrades endogenous antigens? Exogenous?
Dendritic cells, macrophages, B cells. Endogenous=proteosomes. Exo=phagolysosomes
29
Cytosolic pathogens degraded in the cytosol will have peptides bound to what MHC class? Presented to what? Effect on presenting cell? If Exogenous antigen is presented by a dendritic cell in the cytosol, MHC class? Presented to? What happens?
1, Effector CD8 T cells, Cell death.
1, Naive CD8 T cells, dendritic cell ACTIVATES the CD8 T cell.
30
On the other hand, intravesicular pathogens in an endocytic vesicle in WHAT CELL binds to MHC class what? Presented to? Effect? Extracellular pathogens and toxins in endocytic vesicles IN WHAT CELL bind to MHC class? Presented to? Effect?
macrophages. MHC Class 2, Effector CD4 T cells, Activation to kill intravesicular bacteria and parasites. B Cells, MHC 2, Effector CD4 T cells, activation of B cells to secrete Ig to eliminate extacellular bacteria and toxins.
31
In the MHC class 1 pathway, endogenous proteins are broken down into peptides via what (2 types)? Name the transporter that allows peptides into the ER. If the peptides find an MHC class 1-calnexin that fits, what happens?
proteosomes (20s and immunoproteosome), TAP protein transporter. It blebs outs of the ER, moves to the golgi and finally to the cell surface=presentation.
32
The MHC Class 1 is bound to 2 things in the ER. Name them. What happens to these when the peptide binds?
Calnexin protein and beta2 microglobulin. Calnexin is released and the MHC changes conformation before being exported.
33
Exogenous antigen presentation is blank and blank dependent. Uses what 3 proff APC phagocytes? Connect innate to humoral immunity. This uses the MHC class 2 pathway
time and energy. b cells, dendritic cells, macrophages.
34
In the MHC Class 2 pathway (exogenous), the antigen binds (non specific receptor mediated) and is brought in by 3 ways. An endosome (or phagosome is formed). What happens to activate proteases? This fuses with blank which contains 2 things. Thus, MHC class 2 now associates with the process antigen. This phagolysosome fuses with the PM and interacts with what kind of T cell?
endocytosis, pinocytosis, phagocytosis, pH decreases to activate the proteases. Lysosome containing more proteolytic enzymes and the MHC class 2 molecules. CD4+ T cells.
35
Many phagocytes have receptors. Many recognize opsonins like 3!! Without receptors, can still phag. just not as efficient.
Antibodies, complement and acute phase proteins.
36
How are T cells activated and where does this occur?
by complexing with MHC and occurs in secondary lymphoid organs
37
Macrophages (myeloid progenitor) are highly phagocytic, highly secretory- can regulate immunocytes, mediate killing of pathogens and stimulate tissure repair. highly activational-respond to changes quickly, like BLANK on bacteria. And highly polymorphic-what does this mean?
LPS, different in different tissues (monocytes, microglia, kupffer, mesangial, langerhans, etc.)
38
B cells have what on their surface that bind epitopes of antigens. The complex is internalized and processed. Processed peptide complexes with MHC class what--> onto cell surface and interacts with what T cell.
Ig. MHC class 2, CD4+
39
Which APC stimulates naive T cells the hardest?
Dendritic cells
40
Dendritic cells are found primarily where, but in low numbers in 3 places. Called what in T cell areas and what in B cell areas. Present with MHC class what?
Lymphoid tissues, skin/spleen/blood, interdigitating cells and follicular cells. MHC class 2
41
After taking up antigen, dendritic cells become more or less phagocytic as they migrate to what organs? Movement of the dendritic cells is regulated by what?
less towards lymph nodes. Chemokines
42
Dendritic cells take up immune complexes and shed them in exosomes AKA what? to be taken up and processed by what cells?
iccosomes. B cells.
43
Even though dendritic cells usually have MHC Class 2 molecules, can use the process of blank blank to present MHC class 1 even with originally exogenous antigens. Same antigens, both pathways!!
cross-presentation
44
When APCs activate T cells, binding isnt enough. Must 2 other things
cytokines and ligand-receptor engagments
45
Undifferentiated T helper cells differentiate into different types depending on the BLANK encountered. Name the 4 we must know the the cytokines encountered
cytokine TGF-beta=T reg, IL-12, IFN-gamma=Th1, IL4=TH2, IL-23, TGF-beta, IL6=Th17
46
What cells does each Thelper cell activate?
Treg (immune suppression=monocytes and T cells), Th1 (systemic immunity)=macrophages, Th2 (barrier immunity)=B cells, Th17 (acute inflamm)=neutrophils
47
Some of the cytokines from Thelper cells will actually have negative feedback on other T helper cell types in order to increase the pathway towards one kind of T helper. One ex?
IL4 on Th 17
48
Name the 2 forms of T cell mediated immunity in the cell mediated arm and 2 in the humoral immunity arm. Name what the action of these T cells are.
Cell Mediated/Innate- 1.) cytotoxic T cells due to Class 1 on infected cells. This causes cytolysis. 2.) T helper 1 due to class 2 on infected cells. Causes macrophage activation due to release of things like IFN-gamma. Humoral-Th2 due to class 2 on B cells. B cell activation--> antibodies. 2.) Th17 activated neutrophils for phagocytosis.
49
T Cell receptors are associated with either blank or blank type of cell. Not both
Cd4, cd8
50
T cell receptor diversity via what process? Heterodimer receptor is one of 2 types of chains? The TCR complex is associated with what=multi subunit complex that is not variable or antigen specific, but ysed for signal transduction.
somatic recombination of germline DNA, alpha/beta or gamma/delta, CD3
51
T cell receptor looks a lot like antibody Fab region. Has 3 regions to it
Variable, constant and hinge.
52
T cell receptor diversity is achieved by a lot of the same steps as antibody diversity. V,D,J regions as well as allelic exclusion, splice sites, insert bases, etc. All of these things things occur where?
Thymus
53
What has more variable regions to choose from? The alpha or beta chains of the TCR?
Alpha
54
Of the TCR, which segment is made of V, D, J and which only VJ. Rearrangement can occur multiple times if results are nonfunctional.
beta, alpha
55
In comparison to antibodies, TCRs do not go through 2 more processes to increase variability.
Somatic hypermutation and isotype switching.
56
TCR rearranges, self reactive T cells are removed and Ts become Cd4 or Cd8 where? In the presence of?
Thymus, antigen. NOT antigen specific.
57
T cells are double positive at first in the thymus. What does this mean and what happens?
Both Cd4 and cd8. Which one matures depends on if antigens presented are class 1 or 2.
58
Immature double negative thymocytes get into thymus via? and start where in the thymus? Move to where as they become double positive and finally to the where when they are mature whats? Enter the bloodstream via what vessels?
HEVs. Subcapsular region of the cortex, deeper in the cortex, medulla as single positives. High endothelial venules or lymph
59
Define positive selection of thymocytes and negative selection. CD3 is just another protein associated with TCR.
Positive is when the double positive thymocyte recognizes either MHC1 or 2 and receives maturation and survival signals to become Cd8 or 4. Negative is when the thymocytes bind both or none--> apoptosis.
60
Rearrangement of TCR in thymus is complicated. Do most do it successfully?
No. many die within thymus
61
After leaving the thymus, T cells end up where? If that t cell encounters their antigen, cytokines and ligand receptor interactions, what happens!
2ndary lymphoid tissues. Activated. Start replicating itself and mature into effector cells as Th or Tc cells.
62
If a T cell does not encounter antigen OR activated/proliferated T cells go where after lymphoid tissues?
Leave via lymphatics and circulate to other lymphoid organs.
63
Many activated T cells go where in the end to be apoptosed?
LIver
64
Remember: which Th activated phags/innate. B cells/humoral. and Neutrophils
1, 2, 17
65
Even though co stimulation must occur for a T cell to be activated, how do T helper cells help in this process? Once activated, T helpers make many copies of themselves, is there somatic hypermutation? Do they diff into memory cells?
Secrete factors to upregulate the costim molecules. NO, all are copies with same specificity. Yes, SOME become memory cells.
66
Remember, are Th cells naive or mature when leaving thymus?
Naive. Differentiate in lymph nodes in presence to Ag and its costims.
67
So, remember!! IL-12 and IFN gamma favor what t helper diff? IL-4?
Th1, th2
68
The primary function of the TH1 cell is what? Name some factors released by them
Macrophage activation. IL-3, IFN gamma, TNF alpha, GM-CSF, TNF beta
69
We know IFN gamma activates macrophages. What are the primary effects of GM-CSF, TNF alpha/beta and CCL2.
GM-CSF induces macrophage diff in the bone marrow. The TNFs activate macrophage diapedesis. CCL2 causes chemtaxis of the macrophages to the site of infection.
70
Primary function of Th2 cells? IL4 and IL5 are secreted, which regulate blank switching.
Activate and diff B cells. Isotype (to IgE)
71
Both Th 1 and 2 secrete cytokines that inhibit what?
The other Th cell diff.
72
The pathway of Thelper differentiation is determined by what? Some pathogens can release different cytokines depending on form/location.
Cytokines encountered at very first activation.
73
Th17 protect against extracell microbes by promoting what? Release what pro-inflamm cytokine?
Neutrophil, IL-17
74
Cytotoxic t cells extra imp with viruses and intracell bact. What are the 3 main granules released from these T cells and their functions?
Perforin-polymerize on surface and form pore. Granzymes-serine proteases which cleave proteins on a target cell membrane. Lympho-toxin alpha-incudes apoptosis
75
CTL cells kill specific target cells and doesnt hurt cells around it. Is CTL itself injured? Th release what cytokine to increase Tc? Tc release what cytokine to block virus rep?
No! Il 2, IFN alpha
76
Does apoptosis due to CTL cause inflammation? Why? Granzymes activate what molecules in the target cell to start the cascade?
NO. all the granules are released in a very POLAR FASHION which causes only targeted cell to be affected.There is actually a cytoskeletal change in the T cell to help with this focused release of granules... caspases
77
After an immune response, memory T cells are formed. Is this for CD4 or CD8? What is special about these cells? Chemokines that they release tell you if they will be in certain tissues. What does CCR7 mean?
Both, live a very long time, respond very quickly. Remains in lymphoid tissue/homes in on lymph node very quickly
78
Other than homing to lymph nodes, what are other functions that the released cytokines do in memory T cells?
Modulated t cell receptor signaling and make the cells live longer!!
79
In order for memory Tc cells to be made and activated, what cells are required to help?
Thelper
80
Define tolerance. Why must this be maintained?
The absence of an immune response to antigens. To keep from a response against self=decrease autoimmunity.
81
Define central tolerance
Deletion of T and B cell clones that might recognize self antigens during lymphopoiesis, never reach periphery.
82
What happens in central tolerance B cells to a multivalent self molecule? Soluble self molecule? Low affinity non-cross linmking self molecule?
1.) deletion or editing 2.) migrates to periphery, but is anergic/asleep 3.) migrates to periphery but is clonally ignorant-doesnt crosslink/cause reaction
83
Where does central tolerance for T cells occur? What is the goldilocks hypothesis?
Thymus. Too little binding to self antigen or too much=apoptosis. Must be the right amount of positive and negative selection.
84
Any given APC can have self antigens as well as foreign normally due to protein turnover. Should T cells react to this?
NO. Mature T cells should only react to the foreign antigens here
85
What is the main goal of peripheral tolerance?
Inactivating (primarily by anergy or apoptosis) of B and T cell clones in the peripheral tissues that might react to self.
86
For self reactive T cells in the periphery, what is anergy?
TCR finds the MHC recept, but NO COSTIM. THis causes anergy=lack of responsiveness that is long lasting
87
Anergy can occur in peripheral B cells too! How?
If they do not receive enough positive help (like T cell help)
88
Immune complexes can block activation how>
Binding to inhib receptors. Like Fc recep on B cells. Fc receps are great at phag, but doesnt guarantee B/T cell immune response.
89
Define immune privilege. Name 5 sites
Certain tissues are capable of restricting the extent of an immune response or the activation of immune cells. Brain, eye, testis, uterus/fetus, hamster cheek pouch
90
What is the difference between immune privileged sites and tissues?
Sites=foreign tissues grafts survive here for long periods of time ex: skin from one animal onto brain of another. Tissues=Organs that live for extended periods of times in a conventional site ex. cornea from one animal to skin of another.
91
4 main steps are taken to allow for immune privilage to occur. Please list them.
1.) expression of ligands on target cells that BLOCK access/effector function of Tc cells 2.) induce apoptosis of T cells via Fas-FasL 3.) Reduced MHC class 1 molecules 4.) Expression of anti-inflamm cytokines and immuno suppressive factors in those tissues.
92
Not only are self reactive T cells deleted in the central tolerance branch, T regs are also made. Explain how these are made.
TSLP (thymic stromal lymphopoietin) derived dendritic cells in the thymus from near hassall's corpuscles interact with self reactive T cells and "save them" by making them into T regs. These are capable of muting responses to self antigens in the periphery. These dendritic cells do not release cytokines that usually push T cells to be one thing or another.
93
Name the 4 functions of T regs in the periphery
1.) inhibit APC activation 2.) secrete cytokines that suppress T cell function 3.) binding cytokines needed by T cells to survive and 4.) POSSIBLY kill autoreactive T cells directly
94
In the absence of infection, dendritic cells release more of what cytokine which causes more of what type of T cell? Infection causes dendritic cell to release more of what cytokine--> what T cell?
Treg like cells in gut are called what?
TGF-beta--> T reg IL-6--> Th17 Th3
95
Induced tolerance also has a few more mechanisms: explain immunological immaturity and clonal exhaustion.
Neonate immune system still has a bit of plasticity. Immune system develops tolerance to antigens exposed at these times. Clonal exhaustion is induced by high doses of antigens causing overstimulation=wearing out.
96
Define oral tolerance and how we become tolerant to fetuses
Feeding antigens=tolerance. Hide the placenta, block maternal abs, presence of t regs. Deplete tryptophan to starve autoreactive t cells. Fetuses also release a complement inhib.
97
T cell receptors are not always alpha/beta. They can also be what? These are more common where? Associated with APCs?
Gamma/delta. Skin and intestinal epi (microbial invaders). NO.
98
What is the complement system made of? Made where? Attack what kind of pathogens? And attack via 3 main functions.
20 heat labile plasma proteins. Synth in the liver. Extracel pathogens. Lysing bacteria, opsonization, recruiting inflamm cells.
99
Name the 3 complement pathways and what activates them.
Classical-activated by IgG or IgM Abs binding to surface.
Alternate-spontaneous activation in blood/bacterial surfaces
Lectin-activated by opsonins binding to bacterial cell surfaces
100
In the classical cascade, each factor is called what? What about in the alternative pathway
All the factors are just C1-9. Alternative is the same thing plus anything not included in the classical is a letter. When wither is cleaved, they become little a and b next to their name.
101
The early cleavage events provide what for the next step? All of the pathways make a blank convertase which does what?
protease enzyme. c3/c5, this cleaves and activates the c3 and c5 and after this convertase is formed, the pathways overlap and use the same proteins.
102
In the classical pathway how many IgM or IgGs bind to the surface? What binds to it?
1 igM is required, at least 2 igg are bound. C1 binds to them.
103
C1 cleaves, and what does it cleave? That sticks to the surface next to C1. C1 cleaves what next? This makes the complex WHAT which is the c3/c5 convertase!!! So this complex cleaves many what. So? What about the C3a that floats away?
C4, C2, C4bC2a, C3 so MANY C3b molecules bind to the surface (opsonins)! promotes inflamm.
104
The lectin pathway uses one of 2 proteins to start that are VERY much alike to C1. Name them and describe. The rest is the same as classical.
Mannose binding lectin (MBL)-binds to mannose and other sugars on pathogens. Also made by liver (increased with acute phase proteins). and Ficolins-binds carbs on bact and fungus. Higher in serum (more import than MBLs
105
In the alternate pathway, how is the first step activated and what is the first protein? What are the next steps and what is the C3/C5 convertase???
C3 is spontaneously activated by bacterial cell surfaces or in plasma (forms C3h20) to form C3b which binds factor B. Factor D cleaves this complex to form C3bBb which is the convertase!! Cleaves many C3 molecules.
106
Next, in all pathways, c5 must bind to the c3b component. What cleaves C5 in the classical/lectin and what does in the alternate? C5 binds to C4b2a3B in classical/lectin and C3bBb3b in alternate
C2b in classical/lectine. Bb in alternate
107
C5b does what?
Initiates MAC
108
What is properdin?
This is a component of the alternative pathway that stabilizes the C3bBb convertase on bacterial cells.
109
C5a floats off and does what? explain the MAC starting with C5b
C5a is inflammatory. C5b binds c6, c7 (releases c3b), bind c8, and a ton of c9 to form a pore. Cell is lysed.
110
What is THE most important complement action? Why? How does this work?
Opsonization. Many pathogens can prevent MAC. Enhances uptake by phagocyte via complement receptors
111
Which complement receptors are most important and what cell types are they with?
CR1-macrophages, B cells, but primarily CR3- macrophages, monocytes and neutrophils
112
The 3rd function of the complement cascade is that many of the fragments (ESPECIALLY which one?) are what? Which promote inflamm locally by doing 3 things.
C5a, anaphylatoxins
1.) increase vascular permeability 2.) trigger mast cell release (leaky vasculature) and 3.) increase phag adherence to BV endothelial.
113
What are the 4 results of the anaphylatoxins?
leakage of Abs and other factors like complement into the site of immune challenge, migration of cells of the innate immune system into inflamm lesions, smooth muscle contractions, and activation of phags entering the lesion
114
Why must complement be regulated? What are the 2 main regulatory factors and what do they do?
To make sure that complement doesnt occur to our own cells. Decay accelerating factor (DAF)-displaces Bb or C2b (dissociation of convertase). and CD59-prevents MAC. BUT ALL OF THE STEPS can be affected by different factors.
115
Complement deficiencies have been noted in animals and humans. Name a couple ex. What does this cause?
C3 def in Brittany spaniels, C3 receptor def in bovines=BLAD bovine leukocyte adhesion def. Causes high occurence of bacterial infections
116
Name some benefits of inflammation
Dilution, destroy damaged tissue/invading microorganisms, isolate, initiate repair.
117
What are some pathological effects?
Wide spread inflamm (sepsis), re occuring inflamm (allergies), chronic inflamm (autoimmunity)
118
Tissue damage and infection are cardinal signs of early inflamm. This leads to vasoactive factors that cause what clinical signs?
Redness, heat, pain, swelling
119
Some systemic effects of inflamm?
fever, weight loss, systemic lymph node enlargements, hematological changes, acute phase proteins.
120
What are the 3 main vascular effects of inflammation?
Hemostasis, vasodilation, increased vasc permeability/adhesiveness.
121
Define hemostasis
The stopping of blood leakage either by vasoconstriction or clot formation (coag and platelet aggregation)
122
Define vasodilation. What does this cause? If fluid escapes BVs during vasodilation, what is it called?
increases net blood flow. Causes heat, redness, swelling, edema. Transudate=extravasc fluid with low protein content.
123
How does vasc perm and adhesiveness increase?
Endo cells contract allowing passage of fluid. Endo cells become sticky, allowing for leukocyte attachment and migration
124
Name the 4 types of exudate contents we talked about. Used for diagnostic purposes
1.) serous-watery-no cells (blisters) 2.) purulent-thick, wbcs, bacteria, cellular debris 3.) hemorrhagic-bloody 4.) fibrinous-contains high amounts of fibrin and fibrinogen=sticky meshwork
125
inflammation mechanisms are initiated by early signals that are what? What are the 2 main initiators of inflammation and what signals do they release?
Amplified. Pathogens release PAMPs (pathogen associated molecular patterns) and damaged cells release DAMPs (damage associated molecular patterns)
126
What generally amplifies those signals released from damaged cells and pathogens?
Local resident leukocytes
127
These signals cause what 2 localized effects and name some systemic effects
Increased vasodilation/permeability, increased leukocyte recruitment/activation. Systemic-fever, higher BP, acute phase proteins, loss of app, leukocytosis
128
What are the 3 main categories of factors released by leukocytes during inflamm?
Lipid mediators, amines and peptides, cytokines
129
Normal inflamm process includes cell membrane phopholipids converting to what acid that is also converted to things like leukotrienes, PGs, thromboxanes and prostacyclins. Name the 4 lipid mediators we learned about that stops these inflames?
Arachidonic acid. 1.) Corticosteroids stop phophlipids to AA. 2.) Diet lowers AA. 3.) NSAIDs (cox 1 and cox 2 inhibs) stop COX from converting AA to PGs, thromboxanes and prostacyclins. 4.) leukotriene receptor antags and synth inhibs stop leukotrienes.
130
Amines and peptides increase what? Name the 4 we covered, what releases them and derived from?
Vasodilation and permeability. 1.) histamine-from leukocytes and platelets-from AA histidine. 2.) Serotonin-from platelets granules-from AA tryptophan 3.) NO (nitric oxide)-from endothelial cells, leukocytes, etc. Soluble gas from AA arginine and 4.) neuropeptides-from nerve cells-fxn directly and indir in inflamm like sub P
131
Neutrophils are from which progenitor
Myeloid
132
What are the 3 main steps of diapedesis. Controlled via adhesion molecules. Most common in which BVs?
Rolling, adhesion, emigration. Post cap venule
133
What is the name of the cytokine family that is involved in movement of cells/molecules? Name the 4 broad classes. What does each letter stand for? Change the Ls in every name to R for receptors.
chemokines. CL#, CCL#, CX3CL#, CXCL#. C=cysteine, L=ligand, X=any other amino acid.
134
Why are the hundreds of chemokines? Neutrophils are professional whats (Main fxn)? What are the two ways that neutrophils kill the pathogens they have phaged?
Extremely specific. Phagocytes. 1.) oxygen independent killing 2.) oxygen dependent killing using reactive oxygen species.
135
What enzyme converts o2 into ROS? Name 4 typses
NAPDH oxidase. superoxide, H2O2, hydroxyl radical, hypochlorous acid.
136
Name and explain the 3 dzs that were covered in neutrophil fxn defects.
leukocyte adhesion deficiency-1 (defects in the LFA1/MAC1 subunits), Chediak Higashi causes microtubule issues=no chemotaxis/phag. Chronic granulomatous dz=NADPH oxidase defect causes no oxygen dependent killing.
137
Excessive inflamm can causes what syndrome that can lead to sepsis/shock/death
SIRS=systemic inflammatory response syndrome
138
In acute inflamm vs. chronic- in acute what is secreted. In Chronic what forms? What cells are accumulated in each? When they are restored what happened with those areas in each case?
exudate. scarring. neutrophils vs. macrophages/lymphcytes. Regeneration/normal function vs. organization/fibrosis/loss of fxn.
139
For regeneration: what 2 things are required for normal fxn to return? If CT and or parenchymal cells are excessively destroyed, fibroblasts and collagen bond together. this is called: ?
1.) intact CT framework and 2.) parenchymal cells must be labile (like epi), stable (like hepatocytes), but not permanent (like cardiac muscle cells) organization.
140
What is the SIRS clinical criteria
4 things that if a patient is abnormal in 2 or more, sirs concern goes up. HR, RR, temp, WBC total/bands
141
What is the PIRO scheme?
Stratification model: Predisposing factors, infection, response and organ dysfunction
142
Define Sepsis
SIRs plus infection. Infection is the process, sepsis is the response.
143
Define severe sepsis
Sepsis with sign of organ dysfunction
144
Define septic shock
Severe sepsis complicated by persistent hypotension that is not fixed with fluid therapy.
145
Human meds are trying to standardize care of sepsis to be more successful. Name 4 recommendations that have been made for Tx
Early goal directed therapy, low dose steroids, tight glycemic control and activated Protein C.
146
Feline patients with sepsis often have abdominal pain but no abdominal dz. What recommendations were made to add to SIRS criteria for felines?
Include bradycardia and higher RR.
147
Patients with all 5 SIRs criteria still have what % chance to live?
50%.
148
How are monoclonal antibodies formed?
antibodies for a single epitope are made by combining B cells with tumor cells to form Hybridomas. These release identical antibodies for cultivation.
149
Precipitation assays: agglutination. Visualize the insolubility of what complex? Name the 3 zones of the curve in a result. So best precipitation occurs where?
Prozone=too much antibody Post zone=too little antibody Equivalence zone=best precip
150
Blood typing is what kind of test? What is targeted by antibodies?
Agglutination test. Sugars on RBC surfaces.
151
What test is used to IMHA test, how does it work?
Coombs, tests for agglutination with anti-globulin or anti-complement 3 antibodies. The antibodies on the RBC surfaces with link together.
152
How does a Immunodiffusion ring test work?
Place the patients serum in agar in a tube, place solution with antigen in it over the agar. Positive test will form a precipitan ring.
153
How does agarose gel immunodiffusion work?
Agar plate has loading slots. Antigens and antibodies placed in it, band in the gel will form between if precipitate is positive. Can determine how much antibody by the distance the band forms.
154
What is radial immunodiffusion? Is this quantitative?
impregnated wells. Precipitated ring is quantitative because amount of antibody=size of ring.
155
How does an indirect elisa work?
Protein in a plastic well, serum added, if antibody is present, will attach to the antigen. Wash. Second enzyme linked antibody added and a substrate that will become colored if it meets the enzyme.
156
What is diff about sandwich elisa
antibody is on the plate, antigen binds, another antibody binds another epitope on the other side of the antigen (enzyme linked). Substrate converts to color if it meets that enzyme.
157
Immunofluoresence microscopy is when dye is added to what? How does it work? How is it detected? How can this be INDIRECT?
Dye added to Fc region of an antibody. React with tissue or sample and if antigen is present, the antibody will stick and under a microscope, a excitation light will cause the flourescence to show. Dye can be on a second Ab that binds to the first.
158
How does immunohistochem work?
Abs are tagged with enzyme. Substrate is added, color shows.
159
Complement fixation is to test if there are antibodies in a sample. how does it work?
Antibodies are fixed with antigen, the complement proteins are added. If antibodies are there, it will deplete complement. Next, RBCs are added, if those are lysed, it is NEGATIVE because complement is still available to break down. If RBCs DONT lyse, it is a positive sample.
160
What does FACs stand for and how does it work?
Fluorescence activated cell sorting. Antibodies are labeled that recognize a certain type of cell. These are passed by a laser to count the % of labeled cells.
161
What does allergy testing look for? DTH testing?
Delayed reactive T cell causing swelling at injection site. Same- tests for delayed hypersens of reactive T cells by looking for swelling under the skin.
