Facts on File Encyclopedia of Health and Medicine

PROSTAGLANDINS, and other biochemical messengers
determine histamine release and what histamine
binding will occur. Each histamine receptor regu-
lates a different response:

• H1 receptors are on cell membrane surfaces of
  arteriole and capillary cells. H1 binding causes
  the arterioles to dilate (open) and the capillar-
  ies to increase the permeability of their walls.
  The effect of these actions is to allow additional
  fluid to seep from these blood vessels into the
  interstitial spaces (spaces between cells). The
  fluid floods the cells with INFECTION-fighting
  molecules, notably antibodies and cytokines.
  IMMUNOGLOBULIN E (IgE) binds with antigens
  and allergens, triggering H1 release. H1 is pri-
  marily responsible for type I hypersensitivity
  reactions such as ALLERGIC RHINITISand ALLERGIC
  ASTHMA. Common antihistamine medications
  that block H1 receptor binding include diphen-
  hydramine, chlorpheniramine, and hydrox-
  yzine.


• H2 receptors are in parietal cells of the
  STOMACH. H2 binding acts to increase the flow of
  gastric acid in the stomach. Excessive secretion
  of histamine binding with H2 receptors is pri-
  marily responsible for GASTROESOPHAGEAL REFLUX
  DISORDER(GERD). Medications to limit histamine
  secretion and H2 receptor binding include H2
  ANTAGONIST(BLOCKER) MEDICATIONSsuch as cime-
  tidine and ranitidine.


• H3 receptors are neuroreceptors in the CENTRAL
  NERVOUS SYSTEMwith high concentration in the
  areas of the HYPOTHALAMUSthat regulate alert-
  ness. H3 binding decreases NEURON(NERVEcell)
  secretion of histamine, serotonin, acetylcholine,
  EPINEPHRINE, and NOREPINEPHRINE. The effect is to
  reduce alertness, which takes place as a natural
  aspect of the circadian cycle (body’s rhythm of
  sleep and wakefulness). These neurotransmit-
  ters also affect the NAUSEAcenter. The antihista-
  mine medications doxylamine and hydroxyzine
  are highly effective H3 receptor blockers.

Doctors typically consider only H1 receptor
binding in the context of the immune response
and focus primarily on whether its actions to initi-
ate INFLAMMATIONare helpful or counterproductive.

See also ALLERGEN; ANTIBODY; ANTIGEN; LEUKOCYTE;

LEUKOTRIENES; MAST CELL; NEURORECEPTOR; NEURO-

TRANSMITTER; PROTON PUMP INHIBITOR(PPI) MEDICA-

TIONS.

human leukocyte antigens (HLAs) Unique pro-

teins (antigens) present on every nucleated cell

(cell that has a nucleus) in the body. Also called

histocompatibility locus antigens, HLAs allow the

IMMUNE SYSTEMto identify cells as self (belonging to

the body). Genes on CHROMOSOME6, in a region

called the MAJOR HISTOCOMPATIBILITY COMPLEX(MHC),

regulate HLAs. Each person has unique HLAs. The

nomenclature (naming convention) for HLAs

identifies the ALLELEand GENElocus (position on

the chromosome), designating the former with a

letter and the latter with a number.

HLAs have various immune roles, including

identification of self and nonself cells. This func-

tion makes HLAs of crucial importance in ORGAN

TRANSPLANTATION. Incompatibility in HLAs can

result in GRAFT VS. HOST DISEASEand rejection of the

transplanted organ. IMMUNOSUPPRESSIVE THERAPYto

subdue the IMMUNE RESPONSEin people who have

organ transplants in part targets HLAs. Some

research suggests that HLAs also may play crucial

roles in the development of AUTOIMMUNE DISORDERS

such as SYSTEMIC LUPUS ERYTHEMATOSUS(SLE), MULTI-

PLE SCLEROSIS, and SJÖGREN’S SYNDROME.

Though there are nearly endless configurations

of HLAs, there are three broad groups of HLAs:

HLA-A, HLA-B, and HLA-DR. Each set of three is

called a haplotype. Every person has two specific

HLAs from each of the three groups, for a total of

two haplotypes (six HLAs). Each parent passes one

haplotype to each child. Tissue matching for organ

transplantation compares the donor’s six HLAs

with the recipient’s six HLAs. The more that

match, the more likely the organ transplant will

be successful. The fewer that match, the greater

the risk that the recipient’s immune system will

attack the donor organ.

The other key factor in HLA matching is

immune reactivity (ANTIBODYreaction). It is possi-

ble to develop antibodies to HLAs that, even with

a match, make it almost certain that the recipient

will reject the organ. The most common cause for

HLA antibodies is exposure to nonself HLA as a

result of BLOOD TRANSFUSION. HLA matching is not a

human leukocyte antigens (HLAs) 267