Immunology Chapter 13 – Failures of the body defences
3 types of immune failures:
1. Inherited or primary immunodeficiencies: induced by genetic defects –
dominant, recessive or X-linked
SCID (severe combined immune deficiency): develops when there are
inherited defects in T cell function
No cellular and high affinity humoral responses
Susceptibility to broad range of persistent or recurrent infections
X-linked SCID: caused by a mutation in a signalling component of
multiple cytokine receptors (the common gamma chain) – no signalling
occurs and T and B cells cannot become functional
LAD (leukocyte adhesion deficiency): neutrophil and
monocyte migration into tissue comes into danger
No beta2 integrin:
o Non-functional LFA-1 --> no migration
o Non-functional MAC --> no phagocytosis – no
bacterial infections can be cleared and they persist
Treatment: bone marrow transplantation using hematopoietic stem
cells
2. Acquires or secondary immune deficiencies
AIDS: caused by an infection with HIV (human immunodeficienty virus)
It causes a massive reduction in CD4+ T cells. After infection there can
be a seroconversion where number of CD4+ T cells remain low. When
the level drops below a certain count the immune deficiency state
occurs --> pneumocystis, Kaposi’s sarcomas and co-infections that lead
to dead
HIV is a retrovirus which infects macrophages, DCs and CD4+ T cells.
This take place upon blood infection or by sexual transmission.
The HIV is transported to lymph node by DCs
How can HIV specifically target CD4+ T cells? It uses the spike
proteins in the membrane gp120 attached to gp41 to enter the
cell.
The gp120 binds to CD4 receptor and the CCR5/CXCR4 co-
receptor infect CD4+ T cells --> viral envelope fuse with cell
membrane and genome enters the cell --> reverse
transcriptase of RNA into DNA --> DNA enters the nucleus and
integrates into host DNA (pro-virus) --> pro-virus uses NFkB
transcription of the host cell to make new RNA --> RNA transcripts are
spliced to allow synthesis of proteins --> The proteins are assembled
with viral RNA into virions which bud from the cell
The CD4 T cell produces massive number of virions. They kill the CD4
T cell leading to reduced number. So this lead to induced apoptosis and
CTL attack
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