S THT BI CA CC C CH KHNG

Trn Khim Hng

TNG QUAN:
1. Mc tiu ca cc p ng min dch:
2. p ng min dch thng qua:
- Min dch t nhin.
- Min dch c hiu:
+ Min dch dch th.
+ Min dch t bo.
3. Nu tht bi:
S TRN TRNH KHI H THNG MIN DCH CA CC TC NHN GY BNH

Hinh 1. Hnh minh ha.

SUY GIM MIN DCH DI TRUYN SUY GIM MIN DCH MC PHI
I. S TRN TRNH KHI H THNG MiN DCH CA CC TC NHN GY
BNH:
1. Khng nguyn thay i:
a. Type huyt thanh (serotype):
VD: Streptococcus pneumoniae c khong 84 serotype.
b. t bin gen (mutation):
VD: Trong trng hp cm:
Bang 1. t bin trong trng hp cm.

Trt khng nguyn (Antigenic drift) Sang s khng nguyn (Antigenic shift)

+ Ti sp xp li ARN ca virus ly bnh v

+ t bin im gen cho KN hemagglutinin. virus c sn ca k ch.
+ Xy ra thng xuyn trong qu trnh sao H5N1 (2003)H7N9
chp, xy ra chm v dn dn. + Xy ra t ngt, khng d bo trc c,
thng gy ra nhng i dch.
Hinh 2. Trt khng nguyn to ra t bin nh, sang
s khng nguyn to ra chng mi.
Hinh 3. C ch t bin ca virus cm.
c. Ti sp xp ADN ca tc nhn gy bnh:
VD: African trypanosomes. VSG (variant Specific Glucoprotein) a dng hnh thnh trong qu
trnh c ng c th k ch.

Hinh 4. Vng i rui x x, k ch trung gian gy bnh ng thip.

 - There are at least 200 active VSG alleles and more than 1000
silent alleles and pseudogenes also encoding VSG variants. Thc
t ch cn mt allele l c 1 VSG tng ng.
Commented [KD1]: C t nht 200 allele VSG hot
ng v hn 1000 allele yn lng v cc pseudogene
(tm dch: gene gi, l bn copy hng ca mt gene c
chc nng) cng m ha cc bin th VSG.

Hinh 5. Trypanosoma
brucei sp. (trng mi
khoan), k ch gy bnh
bun ng.

Hinh 6. iu ha biu hin VSG.

2. Ng, yn lng:
- Herpes simplex virus:
+ HSV biu hin LAT (latency Associated
Transcript) c tc dng duy tr s sng ca
t bo m virus ang k sinh.
+ Mt loi protein c trong t bo thn kinh,
kt hp vi DNA ca HSV c tc dng iu
ha qu trnh tim tng ca virus.

Hinh 7. HSV n np hch thn kinh sinh ba.

- Herpes zoster hay varicella zoster virus:

Hinh 8. Din tin bnh zona.

Hinh 9. Biu hin bnh zona (1).

Hinh 10. Biu hin bnh zona (2).
3. Tc nhn gy bnh tc ng ln cc t bo min dch, c th:
- HSV:
+ Ngn cn hot ng ca TAP bng ICP-47, mt cht c tit ra bi HSV
+ c ch qu trnh tng hp MHC-1
Hinh 11. C ch hot ng ca TAP (1).

Hinh 12. C ch hot ng ca TAP (2).

- Mycobacterium tuberculosis:

Hinh 13. Mycobacterium tuberculosis trong i thc bo.

- Listeria monocytogenes:
+ Haemolysin called listeriolysin O and two other enzymes: phospholipase A and phospholipase
B
Hinh 14. Immune evasion strategy used by Legionella
pneumophila to prevent being presented by MHC
class II molecules. This schematic depicts L.
pneumophila evasion at the cellular level. The word
endosome and phagosome are synonymous. Commented [KD2]: Cch Listeria monocytogenes n
trnh h min dch khng b trnh din bi phc hp
ph hp t chc chnh (MHC) loi II. Hnh bn din t
s n trnh cp t bo. 2 t endosome v
phagosome c cng ngha l th thc bo.

Hinh 15. Minh ha Listeria monocytogenes.

+ Listeriosis is characterized by its ability to
cause septicemia, meningitis, or spontaneous
abortion in infected individuals, especially
those who are immunocompromised (people
with cancer or AIDS). Commented [KD3]: Listeriosis c trng bi kh nng
gy nhim trng huyt, vim mng no, h thai
ngi b nhim, nht l nhng ngi b suy gim min
dch (nhng ngi mc K hoc AIDS).
- HIV:
Commented [KD4]: The Herpesviridae
Cancer and viruses are similar in that they both
"pirate" normal cells. Compromised cells try to
signal the need to be killed, preferably by the
"shrinky-dink" method of apoptosis, so the viral
particles don't burst out ilke a piata full of
candy.
In the top right of this cartoon, the virally
infected cell uses the MHC-1 as a flagpole to
signal its need to be killed to the Cytolytic (aka
killer or CD8) T cells.
In the the bottom right, the virus tries to hide
by removing the flagpoles. Natural Killers are
activated by an alternative signal and would
usually be inhibited by MHC-1 on the surface.
The Herpesviridae family of viruses are a
lifelong challege for most of us. They cannot be
cured, only controlled. Much of our T-cell
resources are used and used up to keep them in
check. If your T-cells are old or dysfunctional, or
if you're system is supressed by stress,
chemotherapy, or overwhelming infection - the
following conditions appear:

Hinh 16. HIV chn s chuyn phn t MHC loi I n b mt t bo. Commented [KD5]: Nn google khi nim original
antigenic sin v cytokine storm. i loi l khng
4. Gy ng p lng ng: nguyn u tin s to np sau ny h min dch s
bt cc khng nguyn sau theo cch tng t nh
thng u, nn ch cn mt s thay i nh thi cng
s lt c khi s truy bt ca h min dch. Cn
cytokine storm c th hiu nm na l phn ng qu
mn cng c (nh comment pha di).
Commented [KD6]: S hot ha qu mc h thng b
th theo con ng khng c in cng c th dn
n phn ng qu mn gy ra cc tn thng t chc
nh ng mu ni mch ri rc. Mt v d c th minh
ha r rng cho c ch ny l phn ng Schwarzmann
c thc hin trn th bng cch a ni t vo tnh
mch ca th. Ni c t hot ha b th theo con
ng khng c in ri sau n gn vi mnh
C3b v nh vo tiu cu nh kt dnh min dch; phc
hp C5, 6, 7 c to ra s gy tn thng tiu cu v
gii phng ra cc yu t ng mu. Mc d ngi
C3b c xu hng kt dnh ln hng cu v bch cu
mnh hn tiu cu, nhng trong trng hp nhim
- St xut huyt: trng huyt gram m v st xut huyt c sc c
ch ny ng vai tr quan trng trong vic gy
Hinh 17. Vn cha hiu sao hnh ny li c trong slide :v tiu th b th mnh.
II. Suy gim min dch:
1. Lm sao bit c bnh nhn b suy gim min dch bm sinh hay mc phi ch bng pp
vn chn?
2. Tng t, lm sao bit c bnh nhn b suy gim min dch t bo hay dch th?
Bang 2. Phn bit suy gim min dch bm sinh v suy gim min dch mc phi.
Bm sinh (< 10%) Mc phi (90%)
Lin quan cc yu t bn trong (intrinsic Lin quan mt bnh l c trc (Underlying
factors): disease):
- Thiu enzyme cn thit. - Bnh l lympho c tnh.
- Thiu t bo cn. - Nhim HIV.
- T bo khng thc hin c chc nng. - Suy dinh dng.
- Thuc c ch min dch.
Do khim khuyt gene. Mc phi.
Biu hin lm sng vo giai on sm. Biu hin tt c cc giai on.
III. Suy gim min dch bm sinh: + Nhim trng nng vi loi vi khun c v
1. Gim lng khng th trong mu: bao polysaccharide.
+ Hch ngoi bin t i.
+ T bo min dch gim.
+ VD: bnh XLA (X-linked
agammaglobulinemia) do khim khuyt gen
XLA trn NST X cn cho vic tng hp
Brutons protein kinase.

Hinh 18. Mc khng th thay i theo tui.

- Cc con s bt thng:
+ Lng IgG<1000 l bt thng.
+ Lng IgM<100 l bt thng.
+ Lng IgA<10 l bt thng.
- Biu hin:
+ Vim ng h hp trn v di ti i ti
li.
Hinh 19. Bnh XLA.
2. Gim lng b th: xut hin nhiu dng lm sng:
+ Thiu ht C3 hay qu trnh hot ha C3 dn n nhim vi khun sinh m.
+ Thiu ht phc hp C5-C9 tng kh nng nhim cc loi tc nhn sng ni bo,
+ VD: Neisseria spp Nht, t l nhim 1/2.000.000. Nhng nhm khim khuyt, t l 1/200
Gim kh nng loi tr phc hp MD Bnh t min?
Hinh 20. Phc hp min dch.
3. Suy gim chc nng thc bo: Sialyl-LewisX (Bch cu)-selectin (ni m):
+ Hu qu: khng vi liu php khng sinh, nhim trng dai dng mc d h thng min
dch t bo v dch th hon ton bnh thng.
Hinh 21. Neutrophils are directed to sites of infection through interactions between adhesion molecules.
Commented [KD7]: An antigen.
Commented [KD8]: The sialyl LewisX determinant is
expressed preferentially on activated Th1 cells (T
helper) but not on Th2 cells.
Commented [KD9]: Clinical significance
Defective synthesis of the sialyl Lewis X antigen
results in immunodeficiency (leukocyte adhesion
deficiency type 2). Defective synthesis can be caused
by the loss of fucosyltransferase, impairing the
glycosylation of the glycosphingolipid.
Sialyl Lewis x is being used in studies to fight tumors
and cancer cell growth. It has been shown that there is
frequent overexpression of sialyl Lewis x on cancer
cells and is found on both N-glycan and O-glycans.
Sialyl Lewis x is being researched with CD markers to
find new ways to create biosensors for cancer cells.
Also, it is being used in new ways to target cancer cells
specifically for cancer treatment.
It is also being used to achieve greater rates of
fertilization of eggs in women by coating the eggs with
sialyl Lewis x. It plays a key role in the inflammatory
response and may be used to increase the leukocyte
response to infections.
Sialyl Lewis x is an inflammation-associated antigen on
liver cells. It becomes over expressed on diseased liver
cells and can be used as a way to detect liver disease
in a patient.
Sialyl Lewis x is also being researched for detection
and treatment of immune disorders because of its
presence on leukocytes. There is congenital disorder
where there is an inclination to recurring severe
infections. This stems from an absence of sialyl Lewis x
attached to E-selectin ligands on their neutrophils.
Commented [KD10]: Bch cu trung tnh c a
n vng b nhim nh lin kt gia cc phn t dnh
( trong hnh l protein selectin).
+ Kh nng chng vi khun ca t bo thc bo suy gim nghim trng v???

Hinh 22. Thc bo vi sinh vt.

Hinh 23. Thc bo vi khun.

4. Khim khuyt chc nng t bo T trong hi chng thiu ht min dch trm trng
(severve combined immunodeficiency): nh hng nhiu cp khc nhau:
+ Khim khuyt th th Interleukin: lin quan nhim sc th X:

Hinh 25. Nhim sc th X.

Hinh 24. Th th Interleukin.

Hinh 26. C ch hot ng th th ILR2.
+ Khim khuyt ADA (adenosine deaminase):

Hinh 27. Vai tr ca ADA.

Adenosine is a component of adenine nucleotides including ATP and RNA.

2-Deoxyadenosine is a component of DNA and primarily derives from its breakdown. Commented [KD11]: Adenosine l mt thnh phn
ca cc nucleotide adenine, bao gm ATP v RNA.
2-Deoxyadenosine l mt thnh phn ca DN v ch
yu thu c t s tch DNA.
 2-Deoxyadenosine behaves as a cytotoxic metabolite and is generally considered the primary Commented [KD12]: 2-Deoxyadenosine l mt cht
c trong chuyn ha v c cho rng l nguyn
cause of lymphotoxicity in ADA-severe combined immunodeficiency (SCID; Hirschhorn and nhn chnh gy c cho lympho bo trong suy gim
Candotti, 2006) min dch kt hp khim khuyt ADA.
Tng mc (nng ) adenosine trong khim khuyt
Elevated adenosine levels, as occurring in ADA deficiency contribute to apoptosis and block in ADA ng gp o s cht t bo v ngn s bit ha
the differentiation of thymocytes, causing severe T lymphopenia in mice and humans (Apasov et thymocyte (t bo tuyn c), gy ra s thiu ht
lympho bo T chut v ngi.
al., 2001; Gaspar et al., 2009; Poliani et al., 2009)
Commented [KD13]: I.D tt tim bm sinh (c bit l
K c lympho B t chng Fallot).
+ Hi chng DiGeorge: do mt mt on nh NST 22, t bo tuyn c khng pht trin bnh II.c im khun mt c trng (tai thp, mt rng,
hm nh, c rnh hp mi trn).
thng. III.Thng nhim trng do suy gim min dch (thng
do tuyn c khng pht trin c), hoc mc bnh t
Cardiac abnormality (especially tetralogy of Fallot) min (bnh Basedow, vim khp mn tnh).
Abnormal facies IV.Tt h vm ming/hng (h hm ch).
V.Nng canxi huyt thp (gy ng kinh) do thiu
Thymic aplasia sn tuyn cn gip.
Cleft palate Commented [KD14]: 1.Classification
Hypocalcemia/Hypoparathyroidism Type 1: MHC class I
Type 2: MHC class II
2.Presentation
The bare lymphocyte syndrome, type II (BLS II) is a
rare recessive genetic condition in which a group of
genes called major histocompatibility complex class II
(MHC class II) are not expressed.
The result is that the immune system is severely
compromised and cannot effectively fight infection.
Clinically, this is similar to severe combined
immunodeficiency (SCID), in which lymphocyte
precursor cells are improperly formed. As a notable
contrast, however, bare lymphocyte syndrome does not
Hinh 29. H hm ch. result in decreased B- and T-cell counts, as the
development of these cells is not impaired.
Diarrhea can be among the associated conditions.
3.Genetics
a.BLS II
The genetic basis for BLSII is not due to defects in the
MHC II genes themselves. The genetic basis is the
result of mutations in genes that code for proteins
(transcription factors) that normally regulate the
expression (gene transcription) of the MHC II genes.
That is, one of the several proteins that are required to
switch on MHC II genes in various cells types (primarily
those in the immune system) is absent. The genes
responsible were cloned by the laboratories of Bernard
Mach in Switzerland and Jeremy Boss at Emory
University in Atlanta, Georgia.
Mutation in any one of four genes can lead to BLS II.
The genes' names are:
Hinh 28. c im khun mt c trng ca hi chng DiGeorge. class II trans-activator (CIITA)
+ Hi chng lympho trn (BLS Bare Lymphocyte Syndrome) regulatory factor of the Xbox 5 (RFX5)
RFX-associated protein (RFXAP)
Thiu phn t MHC II. RFX ankyrin repeats (RFXANK; also known as RFXB)
Thiu phn t MHC I. b.BLS I
BLS I, also called "HLA class I deficiency", which is
much more rare, is associated with TAP2, TAP1, or
TAPBP deficiencies. The TAP proteins are involved in
pumping degraded cytosolic peptides across the
endoplasmic reticulum membrane so they can bind
HLA class I. Once the peptide:HLA class I complex ...
Hinh 30. Cc hi chng suy gim min dch bm sinh.
Commented [KD15]: 1.Nhim trng tai 8 ln hoc
nhiu hn trong 1 nm.
2.Nhim trng mi hng 2 ln hoc nhiu hn trong 1
nm.
3.Dng khng sinh 2 thng hoc hn c hiu qu km.
4.Vim phi 2 ln hoc nhiu hn trong mt nm.
5.Tr s sinh khng ln cn hoc pht trin bnh
thng.
6.p-xe hoc ti pht nhiu ln hoc vng da su
hoc c quan.
7.Ta (Bnh ban trng li tr s sinh khin tr
khng b c hay b kh khn) dai dng ming
hoc ni khc trn da sau 1 tui.
8.Cn tim khng sinh tnh mch iu tr nhim
trng.
9.Nhim trng su 2 ln hoc nhiu hn.
10.Gia nh c tin s suy gim min dch bm sinh.

Hinh 31. Cc du hiu cnh bo bnh min dch bm sinh.

IV. Suy gim min dch mc phi:
- HIV/AIDS
Hinh 32. Cu to virus HIV.
Commented [KD16]: Mechanism of action
HIV enters host cells in the blood by attaching itself to
receptors on the surface of the CD4+ cell.
Viral entry to the CD4+ cell begins with attachment of
the R5 HIV-1 glycoprotein 120 (gp120) to the CD4+ T-
cell receptor, which produces a conformational change
in gp120 and allows it to bind to CCR5, thereby
triggering glycoprotein 41 (gp41) mediated fusion of the
viral envelope with the cell membrane and the
nucleocapsid enters the host cell (Figure 1).
CCR5 co-receptor antagonists prevent HIV-1 from
entering and infecting immune cells by blocking
CCR5 cell-surface receptor. Small molecule
antagonists of CCR5 bind to a hydrophobic pocket
formed by the transmembrane helices of the CCR5
receptor. They are thought to interact with the receptor
in an allosteric manner locking the receptor in a
conformation that prohibits its co-receptor function.

Hinh 33. HIV entry into CD4+ cell via CCR5 co-receptor.
 Commented [KD17]: HIV-1 enters target cells by first
binding to the CD4 receptor and a coreceptor (CCR5 or
CXCR4), this allows fusion between the cellular and
viral membranes. After entry, the viral nucleoprotein
core containing the genomic RNA is released into
cytoplasm. Reverse transcription takes place in a
nucleoprotein complex termed the RTC. The synthesis
of full-length viral DNA produces an integration-
competent nucleoprotein complex called the PIC and
this nucleoprotein complex mediates integration of viral
DNA into chromatin. Integrated viral DNA, called the
provirus, serves as a transcription template for the
synthesis of viral mRNA and genomic RNA. Following
the synthesis of viral proteins, the viral components are
assembled together to produce new virions, the virus
particles then undergo a maturation step to generate
infectious HIV-1.

Hinh 34. Schematic representation of HIV-1 replication.

+ Chn on
+ iu tr
+ Phng nga Commented [KD18]: Phn ny ni g gi???