Immune disorders

IgE sits on mast cells and basophils through their Fc receptor proteins. When an antigen cross-links two IgE molecules, the mast cell releases histamine.

• IgG:
• Correct: IgE:
• IgM:

Distributive shock is widespread vasodilation, so total peripheral resistance falls, and blood pools in widened vessels.

• Correct: TPR:
• Heart rate:
• Blood viscosity:

Beta-2 receptor proteins raise cyclic AMP in smooth muscle, and the muscle relaxes: the small airways widen.

• Makes it contract:
• Correct: Makes it relax:
• Has no effect:

Body-wide mast cell degranulation lowers TPR and plasma volume, so venous return and MAP fall into distributive shock. The baroreceptor reflex speeds the heart, and airway smooth muscle contracts. The immune trigger reaches the circulation, the nervous system's reflexes and breathing.

• Histamine and leukotrienes in the blood: up. Venom cross-links IgE on mast cells and basophils throughout the body, and they degranulate at once.
• Total peripheral resistance (TPR): down. Histamine and leukotrienes relax the smooth muscle of arterioles, which widen.
• Plasma volume: down. The mediators make capillaries and venules leak, and plasma moves into the tissues.
• Venous return: down. Plasma is lost from the vessels and blood pools in widened veins, so less returns to the heart.
• Mean arterial pressure: down. MAP = CO × TPR, and TPR falls while cardiac output falls with venous return.
• Heart rate: up. Lower MAP reduces baroreceptor firing, so the cardiovascular center raises sympathetic output to the SA node.
• Airway diameter: down. Mediators contract airway smooth muscle and swell the airway lining.

Helper T cells coordinate almost every adaptive response. As HIV destroys them, cytotoxic and antibody responses fail, the virus climbs again, and opportunistic infections define AIDS.

• CD4 count in the blood: down. HIV enters cells through CD4, and infected and bystander helper T cells die faster than they are replaced.
• Cytotoxic T cell response to a new virus: down. Cytotoxic T cells need helper T cell IL-2 and licensed dendritic cells to expand strongly.
• Class-switched antibody made against a new protein antigen: down. B cells need helper T cell contact and cytokines to respond to protein antigens and to switch class.
• Infections by microbes that rarely trouble healthy people: up. With both arms of adaptive immunity weakened, opportunistic fungi, viruses and bacteria can grow.
• Amount of HIV in the blood: up. As helper T cells collapse, cytotoxic T cells lose their help and no longer hold the virus down.

A rash that takes one to three days to appear, at the site of contact, in someone sensitized before, is delayed hypersensitivity. Memory Th1 cells gather at the site, release cytokines and call in macrophages, and cytotoxic T cells kill skin cells displaying the altered proteins.

• Type I, IgE on mast cells: Type I reactions begin within minutes, not days.
• Type II, antibody against skin cells: Type II needs antibody against a fixed cell-surface antigen; this rash is caused by T cells.
• Type III, immune complexes: Type III involves soluble immune complexes lodging in vessels, joints and kidneys, not a rash exactly where a plant touched.
• Correct: Type IV, delayed, T cells: Correct. The two-day delay points to T cells.

In type II hypersensitivity, IgG or IgM binds an antigen fixed on a cell. Recipient antibodies destroy donor red cells, maternal anti-D destroys fetal red cells, and antibodies against the acetylcholine receptor protein and the TSH receptor protein change how those receptor proteins work.

• Correct: An ABO-mismatched transfusion reaction: Correct. Recipient anti-A or anti-B bind the donor red cells.
• Poison ivy rash: Poison ivy rash is type IV, caused by T cells over days.
• Correct: Myasthenia gravis: Correct. Antibodies against acetylcholine receptor proteins reduce their number.
• Hay fever: Hay fever is type I, IgE on mast cells.
• Correct: Graves disease: Correct. An antibody switches on the TSH receptor protein.
• Correct: Hemolytic disease of the newborn: Correct. Maternal anti-D binds the fetus's red cells.

This is anaphylaxis with shock. Intramuscular epinephrine into the outer thigh raises TPR and cuts leak (alpha-1), supports the heart (beta-1) and widens the airways (beta-2). Fluids, oxygen and lying flat support it.

• An oral antihistamine: An antihistamine is slow, blocks only histamine and does not treat shock or airway narrowing.
• A corticosteroid tablet: Corticosteroids take hours to act and do not reverse the immediate problem.
• Correct: Intramuscular epinephrine: Correct. Epinephrine is the first-line treatment.
• A beta blocker to slow her heart: Her fast heart rate is the baroreceptor reflex holding up cardiac output. A beta blocker would worsen shock and block epinephrine's effects.

Antibodies have reduced her acetylcholine receptor proteins, so each end plate potential is smaller and the normal safety margin is gone. With repeated firing, each impulse releases a little less acetylcholine, and more and more fibers fail to reach threshold.

• Her motor neurons stop making acetylcholine after a few hours: Her motor neurons release acetylcholine normally. The fault is at the receptor proteins on the muscle side.
• Her acetylcholinesterase is missing, so acetylcholine builds up: Her acetylcholinesterase is normal. Drugs that inhibit it actually help her.
• Her muscle fibers run out of ATP faster than normal after repeated contractions: Her muscle fibers are normal when they are excited. The failure is in transmission at the end plate.
• Correct: Her end plates have fewer receptor proteins, so they fail as release declines: Correct. Fewer receptor proteins leave no safety margin as acetylcholine release falls with use.

IgG carried across from his mother protected him for the first months. It fades over weeks to months and leaves no memory. Because he has no working T cells, he cannot make his own adaptive response, so infections begin as the borrowed IgG runs out.

• Correct: His mother's borrowed IgG was being broken down: Correct. Fading maternal IgG unmasks the missing T cells.
• His thymus only began making T cells at 4 months: In healthy babies the thymus makes T cells well before birth. In SCID the T cells never develop at all.
• He had just received his first vaccines: First vaccines are given at 2 months, and a single vaccine would not explain one severe infection after another with many kinds of microbe. (A live vaccine, such as oral rotavirus vaccine, can itself make a baby with SCID ill.) The timing matches the loss of maternal antibody.
• His B cells stopped working at 4 months: His B cells were never able to make useful antibody without helper T cells; that did not change at 4 months.