Foundations 2 - Week 2
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What are the effects of IL-1?
Interleukin-1 causes fever and production of IL-6.
What are the effects of IL-6?
Interleukin-6 causes fever and acute phase protein production by hepatocytes.
What are the effects of TNFα?
- Increased permeability
- Mobilization of metabolites
What are the effects of IL-8?
Interleukin 8, aka CXCL8 is a chemokine that recruits neutrophils, basophils, and T cells.
What are the effects of IL-12
Interleukin-12 activates NK cells and converts CD4 T cells to TH1 cells.
What are the effects of CD40L?
The binding of CD40L (aka CD154) to CD40 on TH cells is required for TH activation. It activates antigen presenting cells and induces a variety of downstream effects.
What is perforin?
A protein released by cytotoxic CD8 T cells to make a hole in the membrane wall of other cells.
What is granzyme?
A protease released by cytotoxic CD8 T cells that enters the perforin pores and causes apoptosis.
What is TCR?
T Cell Receptor
What do you call it when cells are transplanted from one individual to another?
An Allogeneic transplant. Without therapeutic intervention, most allogeneic transplants will be rejected. Genetically identical individuals are an exception.
What is the term for cells that are transplanted from one’s self.
An autologous transplant.
What is the term for antibody mediated immunity?
What is the structure of an MHC class I molecule?
- MHC class I molecules consist of two polypeptide chains, α and β2-microglobulin.
- The α chains include HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, and HLA-G. (HLA-D turned out to be a pseudogene.)
- A, B, and C are highly polymorphic and are responsible for presenting antigens to T cells. Their heavy chains bind with a monomorphic ß2 microglobulin to form HLA class I molecules. Each one has a single unique chain and then the ß2 microglobulin.
What is the structure of MHC class II molecules?
- MHC class II molecules have an α and a ß chain.
- Isotypes include HLA-DM, HLA-DO, HLA-DP, HLA-DQ, and HLA-DR.
- DP, DQ, and DR are highly polymorphic and responsible for presenting antigens to T cells.
- (Mnemonic: Dairy Queen, Please, Dr.)
What is serotyping?
- Serotyping is an outdated technique used to determine what variations of each polymorphic MHC gene a person had. (HLA-A,B,C,DQ,DP,DR)
- Since each person has a copy from their father and a copy from their mother, we all have two copies of each type, and it is usually written as follows: HLA-B7,B27 (version 7 and 27 of HLA-B).
- We later learned that there is additional variation in these serotypes, displayed as HLA-A0102 or HLA-A-0109.
What is HLA restriction?
HLA restriction (aka MHC restriction) is when some T cells will only bind to specific HLA proteins, even if they have affinity for the antigen.
Describe the differences between the MHC molecule and the TCR, and how they interact.
The TCR (T cell receptor) receives antigens from the MHC molecule. The MHC molecule receives free antigens from within (type 1) and from without (type II)
What happens if a person's thymus is deficient or absent?
- The patient becomes immunocompromised.
- This is called DiGeorge’s syndrome.
What are the primary lymphoid organs?
- Bone and the thymus.
- These are the organs where progenitor cells become other cell types.
What is Thymic education?
The generation of a diverse repertoire of T cells that distinguish between self and non-self. AKA, T-cell development.
What are the main NSAIDs?
- COX-1 and COX-2 Inhibitors
- Ibuprofin (Motrin, Advil)
- Indomethacin (Indocin)
- Naproxen (Aleve)
- COX-2 Inhibitos
- Celecoxib (Celebrex)
What inhibits the COX-2 pathway?
- COX-2 Inhibitors
What is the result of the COX-1 pathway?
- Increased gastroprotection, platelet aggregation, and renal function.
- Inhibition of COX-1 promotes stomach problems and bleeding.
What does COX-1 produce?
What does COX-2 produce?
What condition can NSAIDS treat in newborns?
- Patent ductus arteriosus (PDA)
- Prostaglandin E1 is responsible for keeping the ductus patent (open), so COX inhibitors can cause the ductus to close.
- Indomethacin (ie, Indocin) and special forms of Ibuprofen are used.
What are some of the adverse effects of NSAIDS?
Headaches, tinnitus (ear ringing), fluid retention, hypertension, nausia, vomiting, asthma, abnormal liver function, rashes.
How does aspirin work?
- Aspirin (acetylsalicylic acid, a weak acid) is hydrolyzed to acetic acid and salicylate.
- Salicylate binds to albumin and travels through the plasma.
- Aspirin then irreversibly acetylates (inhibits) COX-1 and modifies COX-2 activity.
- Aspirin also irreversibly inhibits Thromboxane A2 (TXA2) in platelets, preventing platelet aggregation.
When should aspirin be given to children?
- Only to treat Kawasaki Disease (an autoimmune disease that attacks medium-sized blood vessels).
- Otherwise, it may cause Reye's Syndrome (rash, vomiting, liver damage - potentially fatal).
How do you treat an aspirin overdose?
- You give the patient bicarbonate to increase the rate of secretion of salicylate.
- This is also known as alkalinization of the urine.
What are some of the advantages and disadvantages of COX-2 inhibitors? (eg Meloxicam, Celecoxib, aka Celebrex).
- They have 50% less GI problems/fewer uclers
- Celcoxib is a sulfanimide, which can cause rashes
- It does not have the same cardioprotective features of normal NSAIDS, so it increases the risk of MI, stroke, and fatal cardiovascular thrombic events.
What are the uses of acetaminophen?
- Acetaminophen (tylenol) reversibly inhibits COX-1 and COX-2, but does not provide inflammatory relief. (only works on the CNS, does not work peripherally).
- It is preferred over aspirin for children with viral infections.
- Caution, it is fatally toxic above 15 g. Doses greater than 4-6 grams is not recommended! It causes centrilobular necrosis of the liver!
How do you treat an acetaminophen overdose?
Provide the antidote, N-Acetylcystein.
What are the benefits and disadvantages of glucorticoids?
- Glucocorticoids (cortisone, hydrocortisone, prednisone, etc) are among the most powerful anti-inflammatory and immunosuppressant drugs.
- They are great for treating asthma, Addison's disease, inflammation, and suppressing the immune system.
- They are also highly toxic, causing Cushing's Syndrome (buffalo humps, muscle wasting, etc), diabetes, and much more.
What are DMARDs?
- Disease-modifying antirheumatic drugs.
- Methotrexate (MTX) is the first choice for treating rheumatoid arthritis. MTX is a folic acid that interferes with the production of tetrahydrofolate.
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