L21: Immune Deficiencies Flashcards
1
Q
Primary deficiencies include:
A
- SCID
- lymphoid deficiencies
- myeloid deficiencies
- Thymic deficiencies
2
Q
Secondary deficiencies include:
A
HIV and AIDS
3
Q
Severe Combined Immunodeficiency Disorder (SCID)
A
- A bucket term that encompasses a variety of defects that have multiple effects
- Caused by mutations near the beginning of the developmental branch points or to some proteins that affects overall function.
- Ex- Reticular Dysgenesis
4
Q
Reticular Dysgenesis
A
- Caused by mutation of adenylate kinase 2, a mitochondrial protein central toenergy metabolism.
- Red cell and megakaryocyte production is relatively normal
- Myeloid and lymphoid cells are largely absent
- Individuals lack both innate and adaptive functions, and die of septicemiawithin days.
5
Q
Lymphoid deficiencies
A
- Many of these are also classified as SCID, because a failure of adaptive signalingcauses malfunction in innate responses as well
- Most of the defective genes are recessive, although several are X-linked
- The defect tends to involve T cells (If TH cells ain’t happy, ain’t nobody happy.)
- Example- Bubble boy disease
6
Q
Bubble Boy disease
A
- results from a mutation in gene for the γ-chain of the IL-2 receptor. Recall that IL-2 signaling is central to all adaptive responses.
- Gene coded on the X chromosome
- Lack T and NK cells, tonsils nor lymph nodes, and only vestigial thymusesd. B cells present, but are ineffective at producing antibody
- David, its most famous victim (see Newsweek article).
7
Q
Thymic deficiencies:
A
DiGeorge (in humans)
Nude (in mice)
8
Q
DiGeorge/Nude
A
- Errors in function of neural crest cells lead to no or vestigial thymus, whichleads to no T cells (except NK) and sometimes no B cells (lack of signaling).
- Other structures produced by the neural crest cells may also be abnormal: thyroid, parathyroid, major heart vessels, head and neck structures, and hair follicles in mice.
- Disease is dominant in humans, resulting from the deletion of a region of chromosome 22 coding for a T-box transcription factor. It’s autosomal
recessive in mice.
- Particularly susceptible to intracellular infections: virus, intracellular bacteria,and fungi. Attenuated vaccines can kill them (TH1 signaling defect).
- Less susceptible to extracellular bacteria, which are targeted by complement,neutrophils, and B cells producing antigen to thymus-independent antibodies.No T17 signaling, however
9
Q
Nude mice can accept ____ from mice from other strains; they need not have the same MHC types.
A
skin grafts and other tissue transplants
10
Q
Myeloid defects
A
- low neutrophil counts (produced by a variety of defects) Can be caused by failureto produce granulocytic colony-stimulating factor (G-CSF), or acquired by radiation, chemotherapy or other drug treatments.
- Chronic granulatomous disease (CGD) - defect in the cytotoxic hydrogenperoxide pathway that kill phagocytized cells (affects neutrophils andmacrophages, interfering with antigen presentation to T cells).
- LAD – Leukocyte Adhesion Deficiency – defective CD18, which is part of threedifferent adhesion complexes.
11
Q
HIV is classified as AIDS once:
A
- your immune system is compromised to the point where your TH (and other CD4 T cells) levels have declined to under 200 cells per mm3 (from about 1000)and you have begun to experience recurrent opportunistic infections.
12
Q
HIV is a ____
A
- retrovirus-genetic information stored in RNA, in two single strands, which have the same nine genes in the same order, but which may have different alleles (the virus is essentially diploid)
13
Q
Once inside the cell, HIV RNAs are copied into DNA by an enzyme, reverse transcriptase, into DNA and then integrated into the genome of the cell as a provirus. The enzymes that carry out these processes are ___?
A
64 reverse transcriptase
p32 integrase
p10 protease
all are included in the internal capsid with the RNA
14
Q
A
15
Q
The packaing and delivery system of HIV includes:
A
- an outer membrane derived the plasma membrane of the cell it infectedpreviously studded with protein projections made of up gp20 and gp41 andother protein components derived from the cell membrane including class I MHC
- a round capsid made up of p17 internal to the membrane
- bullet-shaped capsid at the core, made up of p24, surrounds the two RNAmolecules and infection enzymes
- A protein that attaches the ssRNA to the inner core
21
Q
HIV infection is classified into 3 clinical stages:
A
- Acute phase
- Chronic phase
- AIDS
