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120 Cards in this Set
- Front
- Back
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What are the characteristics of cytokines? (4)
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1. Messenger molecules
2. Small proteins 3. Short lived 4. Play a role in inflammatory and immune responses |
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What types of cells release cytokines? (5)
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1. Leukocytes
2. Endothelial cells 3. Epithelial cells 4. Connective tissue cells (Mast cells, macrophages) 5. Other cells that release them under pathological processes |
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What is the difference between interleukins and cytokines? How were they historically named?
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Interleukins are cytokines who are molecularly defined. They were first discovered to communicate messages between leukocytes (inter-leukin), but have since been discovered to do much more.
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What cells produce lymphokine cytokines?
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Lymphocytes
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What cells produce Monokine cytokines?
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Monocytes and macrophages. (Mono-)
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Are cytokines autocrine, paracrine, or endocrine acting?
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They are all of them!
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What happens minutes after a cut happens?
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Arterioles dilate and there is increased permeability.
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Which WBC is first to come to the site of an infection a few hours after the cut?
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Neutrophils
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What cells do the neutrophils call over within 1-2 days?
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Monocytes, which become macrophages after they extravasate in.
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What happens in a couple weeks?
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The neutrophils die off and the macrophages will call over lymphocytes if they are needed.
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What do the lymphocytes call over and when?
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They call over the fibrocytes when the battle is over and before they disappear.
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Why are neutrophils the first to go to a battle site?
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1. They are the greatest in number
2. They are most mobile 3. The cytokine signals call for them first |
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What two classic cytokines do macrophages secrete?
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IL-1 and TNF
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What does IL-1 and TNF do to endothelial cells?
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They will activate endothelial cells to shrink and induce them to express hooks (selectins) to snag leukocytes.
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How does this immediately help fight the pathogen?
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It lets complement proteins and antibodies in immediately and will induce WBCs to come in.
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When are the hooks on the leukocytes activated in relation to the endothelial cells? Why?
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Later on. Because they need a higher concentration of IL-1 and TNF in order to start expressing their hooks.
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What do endothelial cells produce large amounts of when they are "activated?"
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PGI2 (prostacyclins)
(The prostaglandin with one ketone group cyclized to make another cycle ring) |
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What does PGI2 do?
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They act to dilate the local precapillary arteriole sphincters to increase blood flow.
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Do endothelial cells become more or less thrombogenic when activated?
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Less thrombogenic.
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How is this advantageous to inflammation?
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Less blockage for the circulation and migration of inflammatory cells and proteins to fight the infection.
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Do endothelial cells become more or less thrombogenic when injured?
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More thrombogenic
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What cytokines do activated endothelial cells produce early on?
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IL-8 and IL-1. The IL-1 signal is upregulated this way.
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What cytokines do activated endothelial cells produce later on?
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Platelet derived growth factor
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What happens when IL-1 and TNF are around for a long time? (a significant, prolonged destruction)
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They activate fibrocyte activation into fibroblasts to produce collagen.
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What symptoms do you get from a very severe inflammatory process that goes to the brain? Why?
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1. Fever
2. Anorexia 3. Sleep disturbances 4. Malaise This is because the cytokines become so great in number that they are concentrated enough to act on distant tissues. |
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What are these distant tissues?
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1. Brain
2. Liver 3. Bone Marrow |
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What part of the brain do TNF and IL-1 act on? Why?
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They alter the functions of the hypothalamus because the blood brain barrier doesn't exist in parts of the hypothalamus.
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How do TNF and IL-1 raise the body temperature for a fever?
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They induce the hypothalamus to raise it's set point by having it secrete PGE2 to act on itself.
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How does the hypothalamus cause the body temperature to go up?
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It will activate motor neurons to the muscle to start shivering and producing heat.
It will constrict blood vessels of the skin to reduce heat loss. |
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What are the outward sx of the hypothalmus trying to raise body temperature?
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Shivering and being very pale.
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How do antifever drugs work?
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They disable cyclooxygenase (COX) so arachadonic acid stop being synthesized into PGE2. The PGE2 will naturally degrade on their own and remove their effects.
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How does the hypothalamus know what temperature it is?
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It has thermoreceptors.
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How does the hypothalamus reduce body temperature?
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Sweating and dilation of skin blood vessels.
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What is malaise?
Is it a symptom or a sign? |
Feeling of being unwell. It is a symptom.
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How do cytokines produce the feeling of malaise?
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Cytokines go and mess with the mood centers in the hypothalamus and make you feel bad.
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What is the difference between fatigue and malaise?
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Fatigue is feeling tired. You can get this from just exercising. Malaise is fatigue without any activity.
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What is anorexia?
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When you don't eat enough and you still have no appetite.
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How is anorexia related to will to smoke in smokers?
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It decreases desire to smoke as well because this craving is also regulated by the hypothalamus.
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Where are the hunger centers in your brain compared to the satiety center?
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They are more lateral.
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What do people at a party wanting to grab for food represent?
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That the hunger center is more out there (lateral).
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What do angry hungry people represent?
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The anger center is at the lateral side along with the hunger center.
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What do happy, full people with their arms crossed represent?
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That the satiety and happiness centers are next to each other in the medial hypothalamus.
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What do IL-1 and TNF do to the centers in the hypothalamus?
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They shut off the hunger centers
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What is cachexia?
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When you have profound weightloss with reduced appetite
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Why do people with tumors and severe, prolonged infections get cachexia?
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They have prolonged shut off of the hunger centers and also disable hormone sensitive lipase.
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Which cytokine affects the liver?
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IL-1 and TNF
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What does the liver do in response?
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It secretes acute phase proteins.
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What laboratory finding is relevant to liver mobilization of acute phase proteins?
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Erythrocyte sedimentation rate (ESR)
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How do you do the ESR test?
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You put the blood in an anticoagulant filled vertical tube and see how far down the RBC's have sank each hour.
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What does a high ESR mean?
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The erythrocytes are sinking quickly because there are a lot of acute phase proteins stuck to them.
It is a nonspecific finding in inflammation. |
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When is a high ESR normal?
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During pregnancy.
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Is ESR in sync with the current inflammatory response? How are they related?
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No. It is slightly delayed.
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What is a more accurate depiction of current inflammation in the body?
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C Reactive Protein (CRP)
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What can CRP help you manage?
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Therapy for inflammatory diseases. You can tell if the inflammation is coming back up and if you need to increase the dose.
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What will IL-1 and TNF do in the bone marrow in an acute inflammatory reaction.
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They will take neutrophils out of the stores and stimulate more production of neutrophils.
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How do IL-1 and TNF work at low concentrations?
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They work locally as pro inflammatory factors.
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How do IL-1 and TNF work at moderate concentrations?
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They act to initiate inflammation on the systemic level especially in the brain, liver, and bone marrow.
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What generalized processes do IL-1 and TNF initiate at high concentrations?
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Shock sytemically and ARDS in the pulmonary circulation
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What tissues do IL-1 and TNF act on at high concentrations and what is their effect?
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1. They lead to depression of myocardial contractility
2. They cause all the endothelial cells to release NO and become sticky to WBC's and platelets |
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What is disseminated intravascular coagulopathy?
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When there is a depletion of coagulation factors in the blood and you start bleeding everywhere. They are depleteled because there is so much endothelial damage from high cytokine levels.
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What does platelet derived growth factor do?
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It helps fibroblasts proliferate to help tissue repair.
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What does platelet activating factor (PAF) do?
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It does the same thing as histamine, except it is 100-1000x stronger and it also causes platelets to clump.
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What hormone does IL-1 and TNF promote the secretion of? (hint: it is in the hypothalamus)
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ACTH
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What enzyme creates PAF?
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Phospholipase A2
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How are chemokines molecularly defined? How are the three classes different from one another?
What is the mnemonic? |
There is conservation of their first 4 cysteine residues, but the different classes of them have some of the residues shifted around or deleted.
Cysteine for Chemokine. (C-C) |
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What do chemokines do?
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They are CHEMOotaxic cytoKINES
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What is a CxC or alpha chemokine?
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A class of chemokine where the second cysteine residue is replaced with something else.
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What are CxC chemokines powerfully chemotaxic for?
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Neutrophils
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How can you remember this mnemonically?
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Neutrophils are multilobated and have 3 lobes. You can write C-x-C into them.
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What is a classic CxC chemokine?
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IL-8 (V8)
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What is a CC or beta chemokine? What cells do they attract?
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Leukocytes with one or two lobed nucei. (basically all of them except for neutrophils)
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What is eotaxin?
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The chemokine that attracts eosinophils.
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What are the major chemokines that attract all the white cells except neutriohils called?
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Monocyte Chemo Attractant Protein 1 (MCAP1)
RANTES |
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What is a C or gamma chemokine? How is it molecularly defined?
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They lack the first and third cysteine residues.
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What is the most important chemokine in the C or gamma chemokine group?
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Lymphotactin
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How can you think of how the alpha, beta, and gamma chemokines are ordered?
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They are ordered by the order in which the leukocytes would migrate to the site of an infection.
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What is the classic example of CX3C chemokines?
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Fractalkine
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What does fractalkine attract?
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It attracts large mononuclear cells like lymphocytes and monocytes.
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Since chemokine receptors look for the motifs and are so conserved, what is the danger?
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Certain viruses like HIV can bind with these receptors and infect the leukocytes.
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What other process do chemokines help out in besides immune response?
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Organogenesis during early embryo development to tell the different germ layers where to go.
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Which helper T cells are responsible for humoral vs cell mediated immunity?
Mnemonic? |
Th1 - cell mediated immunity
Th2 - humoral immunity That is too (2) humoral! |
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What is the difference between IL-2 and IL-4 function in terms of what they act on?
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IL-2 is mainly for T helper cell proliferation (both cytotoxic and humoral)
IL-4 is mainly for B cell proliferation |
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What on a helper T cell will recognize a MHC II receptor?
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CD4
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What on a helper T cell will recognize the antigen on the MHC II?
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TCR
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What on a helper T cell will bind to the B7 receptor on an APC as another necessary costimulatory signal?
Mnemonic? |
CD28
28 divided by 7 is CD4 |
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What is the primary stimulation T helper cells?
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Binding of CD4 and TCR with MHC II and antigen respectively
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What is the co stimulatory signal for Th2 differentiation?
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IL-1
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What will the Th2 cell start making and secreting when it is stimulated?
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It will create IL-4, IL-3, IL-2 and the receptor for IL-2.
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How will IL-2 act?
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This will give autocrine stimulation for the differentiated T helper cells (both Th1 and Th2) to proliferate.
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What is BCR?
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B cell antigen receptor
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What happens when B memory cell binds with an antigen?
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It starts expressing receptors for IL-4.
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How will the IL-4 from T helper cells affect B memory cells? (3 things)
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1. It will activate it to undergo proliferation
2. Antigen switching. 3. Increased expression of MHC II |
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What antibody do naive B cells produce by default?
Mnemonic? |
IgM and IgD
Dougie Houser MD was naive. Also, Mace and Daggers. |
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How can plasma cells switch to produce IgE?
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High levels of IL-4
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What happens if you produce a lot of IgE?
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You are prone to allergic reactions
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What cytokine will the newly proliferated T helper2 cells secrete?
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IL-5
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What will the newly proliferated B memory cells express?
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IL-5 receptors
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What will IL-5 do for the new memory cells? What alternate name does this function give IL-5?
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Helps them differentiate into plasma cells.
B cell differentiation factor |
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What type of antibody class switching does IL-5 promote?
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Switch to IgA
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What granulocyte does IL-5 work on and what does it do?
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It will help the proliferation of Eosinophils.
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What do macrophages secrete when they bind with T helper cells?
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IL-6 and IL-3
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What does IL-6 do? (3 functions)
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1. Helps plasma cell differentiation
2. Helps liver cells produce CRP and acute phase proteins 3. Creates fever in the hypothalamus |
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What tissue will IL-3 act on?
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Bone Marrow
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What will it do there?
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Activate the proliferation of all sorts of hematopoeic cells.
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What stimulatory and co stimulatory signals do T helper cells need to differentiate into Th1 cells?
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The same ones as Th2, but in addition they need the costimulatory effect of IL-12.
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What cytokines will the Th1 cells produce?
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1. IL-2 with receptors for self proliferation
2. interferon-y |
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Why do they not produce IL-6 and IL-3?
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Because those will stimulate B cells and Th1 cells are not concerned with humoral immunity involving antibodies.
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What is the effect of INF-y on macrophages?
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They will become superactivated and increase their capacity for:
1. phagocytosis 2. expression of MHC I and II 3. cytokine secretion |
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What is the effect of high levels of INF-y on macrophages?
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Macrophages turn into epitheloid cells?
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What is the effect of VERY high levels of INF-y on macrophages?
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Macrophages turn into giant cells.
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What cytokines do both macrophages and Th2 cells secrete when they bind together?
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IL-3 and IL-6
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What is the mnemonic for IL-7?
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baby IL-7's from high heavens for high heavens (bone marrow and thymus)
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What cells in the bone marrow and thymus produce IL-7?
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stromal cells
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What is a microphage?
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A neutrophil
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How does the Th2 pathway inhibit the Th1 pathway?
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It produces IL-10 to stop the differentiation.
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What are the two functions of TGF-b?
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1. Downregulation of inflammation
2. Upregulation of fibrotic cells. |
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What is the TCR complex composed of?
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TCR and CD3
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How do CD8+ cells kill? 2 ways. Think about the enzymes involved.
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They secrete granzymes through perforins put into the target cell. This induces apoptosis by activating caspases.
They will secrete FasL ligand to bind to Fas receptors to induce apoptosis. |
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How can naive B cells be activated without a helper T cell?
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An antigen can bind directly to their existing IgM or IgD and automatically induce proliferation.
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How are naive B cells activated with a helper T cell?
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They ingest an antigen and present it to Th2 cells. They will also bind their CD40L receptor to the Th2's CD40 for a second activation signal.
This induces the Th2 cells to secrete IL-4 and IL-5 to help the B cell mature and proliferate. |
