2: Allorecognition, Alloreactivity, Sexuality

Teresa Binstock binstoct at essex.UCHSC.edu
Fri Apr 25 15:40:19 EST 1997


Continuation of:
     ti: Allorecognition and alloreactivity: a primary substrate
   	 of human sexuality. 			  (part 2 of 3)
     au: Teresa C. Binstock   			       (c) 1997
     so: bionet.immunology    			  April 25 1997

SALIVA, ALLORECOGNITION & ALLOREACTIVITY: Consider exchange of
small amounts of saliva, as during prolonged kissing. Desquamated
cells are present in each person's saliva. 
A.   As the XX-person receives an XY-persons cells (airborne or
via saliva, etc), certain of her dendritic cells (eg, in upper
epithelial mucosa & lips) will receive cells or cell fragments from him.
Her cells will launch a set of reactions having similarity to
early stages of alloreactivity present in graft-rejections. Her
cells will be responding to various of his cell molecules -- eg,
his HY antigen, various of his other mHLA antigens, and to his
MHC-I and to his MHC-II molecules, especially those that differ 
from hers, and her responses will differ in accord with these relative
differences between her MHC-molecules and his (consistent with Wedekind
et al 1995).  
B.  Let's consider that at an early neo-pubertal age she
romantically kisses another female. Then there will be an
exchange of XX cells, and there will be a milder alloreactivity
reaction because there will be a lack of HY-antigen in the cells
and cell fragments received via macropinocytosis (MCP). 
C. These allorecognition and alloreactivity events will induce
sexually dimorphic cytokines patterns. 
1. If an XX-female is perceiving cells and cell-fragments from
another XX-female, there will be an XX/XX cytokines-release
pattern in immunological cells of her upper mucosal epithelia.
2. An XX-female perceiving cells and cell-fragments from an XY-
male, there will be an XX/XY pattern of cytokines release.
3. These two patterns of cytokines release will have sub-
variations dependent upon the extent of haplotype similarity (or
difference) between the perceiver's cells and the "donor's"
cells. This is well established in transplant literature.
4. Released cytokines can act via autocrine, paracrine, and
endocrine processes. The cytokines release induced by
immunologically perceiving and reacting to cells and cell
fragments will have sexually dimorphic patterns based upon the
status of the perceived individual as XX or XY. These released
cytokines will transduce the immunological responses into neural
signalling events, via paracine and endocrine effects within
nearby tissues -- eg, the vomeronasal and olfactory tissues.

COMPLEXITY & INTERACTIONS: Aside from cultural influences, the
suggestions are made (i) that gender- and sexual-orientations are
perceived and expressed in a symphony-like tapestry of sensory
perceptions and communications, and (ii) that the primary
substrate of the orientations is immunological and has two
primary dimensions: (a) the person's immunological self, and (b)
the person's immunological perceptions of and reactions to other
persons' cells, cell fragments, and immunological epitopes
therefrom. Note that this is an additional dimension to hypothesized
models wherein all MHC-variations are encoded in small molecules that
differ in their various ratios from person to person and between males and
females.

IN-UTERO DEVELOPMENT: Various times are important.
(1) Molecular and cellular sex differences exist as early as the
preimplantation human embryo, as evidenced in males by the cell-
surface presence of HY antigen and by the early expression of
SRY. 
(2) As the maternal immune system senses her conceptus and as the
conceptus becomes immunologically aware of itself, males will be
expressing HY and SRY, females will not; and these sexual
dimorphisms will shape the conceptus' immune system into an XY-
or an XX-based system. 
(3) During embryonic and early fetal development, several
immunological cell types appear to be of particular importance:
(a) certain gamma-delta T cells in the liver of 8 wk human males
express SRY; (b) the earliest CD5+ B cells originate in a region
that includes the aortic arch, gonadal ridge (another site of SRY
expression in XY males), and mesonephros; and (c) from as early
as the first several days subsequent to conception, male concepti
will express HY antigen and female concepti will not and will
instead express molecular copies of the X chromosome homologue
HX. 
(4) During this ongoing time period, the in-utero male's immune
system will be establishing its sense of self as male, just as
the in-utero female's will be establishing itself as female.

NEONATAL DEVELOPMENT: An additional encoding of CD5+ cells occurs
within the neonate's gastrointestinal tract, from which certain
T-cell subsets pass into general circulation and yet become
focused upon (travel to) preferred cites with other mucosal
epithelia -- eg, a subset specific to the tongue, uterus, and
vagina.

LAYERED IMMUNE SYSTEM: The "encodings" paragraphs contain an
important nuance. There are several "layers" of the immune
system. One layer is very focused upon self-proteins, another
layer is focused upon perceiving antigens from environmental
sources. If, as argued here, these immunological processes are
contributing to sexual- and gender-orientations, an alternative
regulation of the immune-self might shut-off a male's
immunological sense of himself as male; and a similar change
might occur regarding a female and her immunological cells' sense
of herself as female. An alternative regulation of immune
perception of other individuals might cause the XY-male to
perceive other XY-males as objects of attraction; similarly, an
alternative regulation of immune perception of other individuals
might cause the XX-female to perceive other XX-females as objects
of attraction.

HETEROSEXUAL AND ALTERNATIVE ENCODINGS: In most individuals, the
immunological sense of self and the immunological perceptions of
other individuals will function in accord with the person's
status as an XX individual or as an XY individual. The immune
system "layers" relating to self and to perceiving-others will
function with overall consistency. However, in some individuals,
either or both layers will be altered. 
1.   Since HY and SRY are a binary condition (ie, most persons
either have or do not have HY and SRY), alternative immune-system
regulations have options defined primarily by the alternate
binary condition. 
2.   Strongly altered immunological perceptions of other
individuals would manifest as mHM or as fHM.
3.   Strongly altered immunological perceptions of self would be
more deeply encoded within the immune system and would manifest
as fmTS or as mfTS.
4. Items 2 and 3 can occur separately or together.
5. These alternative immune encodings can occur independently of
primary hormonal differentiation; however, a hormonal/immune link
is set forth below.

End part 2 of 3





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