Page 68 - Color Atlas Of Pathophysiology (S Silbernagl Et Al, Thieme 2000)

Immune Defects
Immune defects express themselves through cell and T-cell disorder (severe combined im-
frequent, prolonged, and often life-threatening munodeficiency disease [SCID], e.g., due to a de-
infections (also caused by otherwise harmless ficiency of adenosine deaminase or purine nu-
infectious agents) and through certain tumors. cleoside phosphorylase).
Among defects of nonspecific defense are AIDS (acquired immunodeficiency syn-
those of the complement system (infection drome) is caused by HIV-1 or HIV-2 (HIV = hu-
with extracellular pathogens, e.g., the Neis- man immunodeficiency virus) (→ A). The ge-
seria), of the NK cells (infection with intra- nome of these retroviruses is coded in two al-
cellular pathogens, e.g., listeria or herpes vi- most identical molecules of a single-strand
rus) as well as of mannose-binding proteins RNA (ssRNA). Built into the virion (complete
([MBP] → p. 44). Disorders of phagocytosis can virus particle) cover is the gp120-protein
concern the cell number (e.g., leukopenia due (→ A1) that docks simultaneously on CD4 and
to G-CSF deficiency; agranulocytosis due to on a chemokine receptor (= CCR5 at the begin-
radiotherapy or chemotherapeutic agents), or ning of an infection; = CXCR4 at the final stage)
may be functional. In leukocyte adhesion defect of the host cell membrane, thus eliciting mem-
(LAD), a defect of the integrin subunit (CD18) brane fusion and virion endocytosis (→ A2).
prevents margination; in lazy leukocyte syn- (People with a CCR5 defect are largely protect-
drome, migration is slowed down; in chronic ed against an HIV infection). In addition to CD8
Blood (or septic) granulomatosis oxidants are not cells, it is mainly the CD4-T H cells that are af-
fected. In the latter, ssRNA is transcribed to
formed; and in Chediak–Higashi syndrome the
3 fusion of phagosomes with lysosomes is ab- cDNA by a virion-endogenous reverse tran-
normal. scriptase, finally being incorporated as a dou-
Humoral immune defects can be caused by ble-strand dsDNA (provirus) into the host
disorders of maturation, function, or activation cell’s genome (latent stage). Activation of the
of B cells. Without antibodies the organism is CD4 cells (at the onset of infection and the
powerless, especially against pus-forming late stage) triggers expression of the provirus.
pathogens, because their polysaccharide mem- The proteins that result from this, tat and rev
brane cannot be phagocytized without opson- as well as NFκb from the host cell, take part in
ification. Examples are 1) selective IgA defi- the formation of new virions that are exocy-
ciency (very common, with an incidence of 1 tozed (viremia; → A3,4). The CD4 cell may be
in 700), in which a lack of mucosal protection destroyed during these stages (see photo-
frequently leads to respiratory and gastro- graph), particularly as it is attacked by its own
intestinal infections and to an increased inci- immune defenses (anti-gp120-IgG + comple-
dence of susceptibility to allergies; 2) congeni- ment; viral peptide recognition by cytotoxic T
tal agammaglobulinemia, in which a (X-linked) cells). Noninfected CD4 cells may also die
defect of Bruton-type tyrosine kinase hinders (HLA-independent apoptosis) so that in the
the maturation of B cells; 3) hyper-IgM syn- late stage a serious CD4 cell deficiency develops
drome, in which IgM concentration is greatly (→ A4). The changes in cytokine concentration
increased, but that of IgG and IgA is reduced (→ A5) decimate T H1 cells and cytotoxic T cells.
(no class jump due to defect of CD40 ligands; The body is now ever more helplessly exposed
→ p. 47, B4); and 4) so-called variable immune to other, normally harmless, pathogens (e.g.,
defect (deficient stimulation of B cells by CD4- fungi) and certain tumor cells (Kaposi’s sarco-
T cells). ma, lymphoma) (< 500 CD4 cells/µL blood:
Disturbances of cellular immune defense ARC [= AIDS-related complex]; < 200: full-
occur in thymus aplasia (DiGeorge’s syndrome) blown AIDS). Many years can pass from the
and in combination with humoral immune de- initial viremia (high p24-antigen level with
fects. They extend from abnormal stem cell IgM formation) and the ARC with renewed vi-
differentiation (reticular dysgenesis) via defec- remia (no more IgM) (→ A4), during which the
58 tive HLA formation (naked lymphocytes syn- proviruses survive in relatively few (10 ), inac-
6
drome) to the life-threatening combined B- tive CD4 cells (mostly in lymph nodes).
Silbernagl/Lang, Color Atlas of Pathophysiology © 2000 Thieme
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