Download Immunology

Immunology
1- decrease numbers of helper T
( CD4 positive ) lymphocytes
( leading to a decreased T- helper / T-suppressor ratio & to an
absolute lymphppenia.
2- hypergammaglobulinaemia ( polyclonal rise in IgG
3- Impaired response to recall antigens on skin testing ( i.e. impaired
delayed type hypersensitivity “ DTH “
T-helper test
Mixed lymphocyte reaction
T4
Response to soluble antigen
Lymphokine production
T8
..
…
T4
..
Specific cytotoxicity
..
NK
NK activity
..
B
Polyclonal activity
Specific Ig production
M
Parasite killing
chemotaxis
T4 receptor
RNA
Reverse
transcriptase
DNA
RNA
RNA
Diagrammatic representation of retrovirus replication.
Schematic representation of genome of HIV
5’
tat
Trs/art
////
////
gag
ior
sor
env
pol
(P55)
p17
p24
(P66)
p15
o
p51
o
3’
(gp 160)
gp 120
gp41
gp 120 ( major envelope glycoprotein
gp 41 ( transmembrane glycoprotein)
RNA
P24 ( major core protein )
Two clinical findings of HIV infection , plus two
laboratory abnormalities suggestive of it
Clinical findings:
- Fatigue
- Night sweats
- Lymphadinopathy
> 3 months
- Weight loss
10% total body w. loss
- Fever > 3 months
- Diarrhea
Lab. abnormalities
- Decrease T helper cell
count
- Increase serum
globulins
- Anergy
- Anemia
Persistent generalized lymphadinopathy ( PGA )
1- lymphadinopathy of at least three months
duration involving two or extra inguinal sites
2- absence of any current illness or drug use
known to cause lymphadenopathy
3- presence of reactive hyperplasia in a lymph if
biopsy is performed
CDC classification of HIV
disease
Group I
Acute infection
Group II
Asymptomatic infection
Group III
progressive generalized lymphadenopathy
Group IV
Other diseases :
a- Constitutional disease
b- Neurological disease
c- Secondary infectious disease
i- Specified secondary infectious
diseases listed in the CDC Surveillance
definition for AIDS
ii- Other specified secondary
infectious disease.
d- Secondary cancers
e- Other conditions
Stage
HIV
Chronic
Ab/Ag
Lymph- TIsolation adenop helper
athy
Cell/mm
DTH
Thrush
O.I
WR0
_
_
>400
Normal
_
_
WR1
+
_
>400
Normal
_
_
WR2
+
+/-
>400
Normal
_
_
WR3
+
+/-
<400
Normal
_
_
WR4
+
+/-
<400
partial
_
_
WR5
+
+/-
<400
Anergy/+
+
_
WR6
+
+/-
<400
Anergy/partial
+/-
+
Oral cavity problems in HIV disease
Oral Thrush
Hairy leukoplakia
Kaposi’s sarcoma
Gingivitis
Aphthous ulceration
Dental abscess
Intra oral warts
Skin disease
1234567-
Seborrheic dermatitis
Papuloprritic eruptions/ folliculitis
Shingles
Herpes simplex
Xeroderma ( dry skin )
Molluscum contagiosum
Tineas (fungal skin and nail eruptions)
ENT problems
1.
2.
3.
4.
5.
6.
Catarrh/postnasal drip
Sinusitis
Otitis media
Serous otitis media
Otitis external
Nerve deafness
Gastrointestinal disease
1) Diarrhea
1.
cryptosporidium
2. Cytomegalovirus
3. A typical mycobacteria
4. Giardiasis
5. Salmonella
6. Campylobacter
2) Oesophagitis
3) Anal herpes
4) Kaposi’s sarcoma of the gastrointestinal
tract
Paediatric HIV disease
HIV infection for infants & children
under 15 months
1- Virus in blood or tissue
2- HIV antibody plus evidence of both
cellular & humeral immune deficiency plus
one or more categories in class P2
3- Symptoms & sign meeting the CDC case
definition for AIDS
Precautions in the dental surgery
- Gloves should always be used when touching blood , saliva ,
mucous membranes. They should be changed between
patients & hands should be washed.
- Surgical masks & protective eyewear should be worn if blood or
saliva could be spattered .
- Instruments which come into contact with oral tissue should be
sterilized after use . Debris should be removed by scrubbing
with soap & water before sterilized . Instruments should be
sterilized by autoclaving for three minutes at 134C minimum.
Dry takes longer ( two hours at 150 C – 160 C . Heat
sensitive instruments may sterilized using glutaraldehyde
- Disposable gowns or washable work overalls or shirts should be
worn . Gowns & work clothing should be changed daily or if
they soiled with blood
- Surface should be decontaminated by wiping down with sodium
hypochlorite or an iodophor. Surface difficult to disinfect
should be isolated with an impervious cover as plastic .
- Droplet & aerosol production should be avoided where posible
by use of rubber dams and high speed evacuation
- Great care should be taken with hypodermic needles & sharps
containers are available for use with dental syringes which
enable the needle to be unscrewed from the syringe without
resheathing
Full definition of AIDS
A case of AIDS is defined As:
An illness characterized by
one ore more of the following ‘
indicator ‘ diseases, depending
on the status of laboratory
evidence for HIV infection
-
-
-
Without laboratory evidence regarding HIV infection:
Pneumocystis carinii pneumonia
Toxoplasmosis of the brain in patient > month of age
Cryptosporidiosis with diarrhoea persisting for>
1month
Extrapulmonary creptococcosis
Mycobacterium avium complex or M. kansasii disease
at a site other than lungs or lymph nodes
Cytomegalovirus infection of an internal organ other
than liver in a patient > 1 month of age
-
-
-
-
Herpes simplex virus infection causing a
mucocutanneous ulcer that persist for more
than 1 month , or bronchitis , pneumonitis, or
oesophagitis for any duration in a patient > 1
month of age
Progressive multifocal leucoencephalopathy
Primary lymphoma of the brain in patient < 60
years of age
Kaposi’s sarcoma in a patient < 60 years of age
PLH/ LIP complex ( pulmonary lymphoid
hyperplasia & /or lymphoid interstitial
pneumonia ) in a child < 13 years of age
With laboratory evidence for HIV
infection
Disease diagnosed definitively
- Isosporriasis with diarrhea persisting > 1 month
- Extrapulmonary or disseminated histoplasmosis
- Extrapulmonary or disseminated
coccidioidomycosis
- Extrapulmonary or disseminated tuberculosis
- Any noncutaneous extrapulmonary or
disseminated mycobacterial infection other than
TB or leprosy
- Recurrent non typhoid Salmonella septicaemia
- kaposi’s sacroma at any age
- Primary lymphoma of the brain at any age
- Other non-Hodgkin’s lymphoma of B- cell
immunologic phenotype
- HIV encephalopathy ( AIDS demential complex
- HIV wasting syndrome
Diseases diagnosed presumptively
-
-
Pneumocystis carinii pneumonia
Toxoplasmosis of the brain in patient > 1 month
of age
Oesophageal candidiasis
Extrapulmonary or disseminated mycobacterial
infection
Kaposi’s sacroma
Lymphoid interstatial pneumonitis( LIP/PLH
complex ) in a child < 13 years of age
With evidence against HIV infection
Pneumocystis carinii pneumonia diagnosed
by a definitive
Any other disease indicative of AIDS listed
above
T- helper T4 lymphocyte count <400 /mm
None of the other causes of
immunodeficiency listed above.
Antigen / Antibody response to HIV
Antigen
Antigen
Ab ( gp 41 )
Ab (p 24 )
Months
Years
Cumulative of number of HIV/AIDS
by mode of transmission in Palestine
2003
Sexually
Blood
Transmission
Hetro Bisex Homo
30
2
1
Hemophilia Others
4
6
Drug
Vertical
Unknown Total
Addicts Transmission
3
1
8
55
Maternal Factors
1.
2.
3.
4.
Advanced immunosuppressant
Advanced clinical disease
High viral load
Recently acquired HIV infection & placental
barrier distribution ( through chronic
amnionitis, placental malaria , smoking )
Delivery factors
- Vaginal delivery or caesarian section
- Invasive procedures
- Prolonged rupture of membrane
Factors after delivery
-
Breast-feeding
Cracked nipple
Oral lesion in the infant
Diagnosis
1)
Elisa
2) Western Blot ( W.B )
3) P.C.R.
Elisa Test
Negative
Negative
Repeat
Negative
Positive
Repeat
Positive
W.B
Indeterminate
Repeat
Indeterminate
P.C.R
Positive
Causes of false- Negative ELISA
reactions to HIV:1.
2.
3.
4.
5.
6.
7.
Incubation period or acute disease before
seroconversion (widow-period)
Malignancy
Intensive or long-term immunosuppressive
therapy
Replacement transfusion
Bone-marrow transplantation
Kits that detect antibody to p24 primarily
B-cell dysfunction
Cause of false positive ELISA
Reactions to HIV:Antibody against smooth muscle ,parietal cell,
mitochondria, nuclear , leukocyte, and T-cell
antigen ; anti-HAV-IgM and anti HBc- IgM
Antibodies against class II leukocyte antigen( HLADR4,-DQw3) present on H-9 cell (more
frequently observed in multiply transfused
patients)
Several alcoholic liver disease , primary biliary
cirrhosis, sclerosing cholangitis






Heat inactivation or RPR positively of serum
tested ( abott EIA only )
Hematologic malignangies, lymphoma
Acute DNA viral infections, HIV-2 infection
Renal transplants, chronic renal failure
Stevens-johnson syndrom
Passively acquired HIV-1 antibody (
hepatitis B immunoglobulin)
Causes of false-positive W.B.
reactions to HIV-1 antigen ( gag,
env, and pol proteins ):Cross reactions with
Normal human ribonucleoproteins
Other human retroviruses
Antibody to mitochondrial, nuclear ,T-cell , and
leukocyte antigen
Antibodies to HLA antigens (classes I and II)
Globulins produced during polyclonal gammopathy
Recommendations for when to
initiate treatment
Symptomatic HIV disease*
Therapy recommended for all patients
* Include symptoms as recurrent mucosal
candidacies , oral hairy leukoplakia,
chronic or other wise unexplained fatigue,
night sweats or weight loss
Asymptomatic
CD4 cell count <500/uL :therapy recommended+
CD4 cell count <500/uL : therapy recommended for
patients with > 30,000-50,000 HIV RNA copies/ mL or
rapidly declining CD4 cell counts consider therapy for
patients > 5000- 10000 HIV RNA copies.
+ some would defer therapy in subset of patients with
stable CD4 cell count between 350-500/uL
And plasma HIV RNA consistently below 5000-10000
copies/ mL
LTR : long terminal report .promoter/enhancer for
the HIV genes ( it interacts with the cell proteins
that undulate viral replication)
Pole gene: codes for construction of reverse
transcriptase ,protease & integrase enzyme
nef gene : contributions to the virulence of HIV
rev. gene : the rev protein swiches the replication
cycle to the production of whole virus particles
tat gene : accelerate viral replication.
vif gene : determines the infectivity of cell –free
virus
vpr gene : facilitate the transport of HIV DNA into
the cell nucleus & regulates the cell cycle itself
Transcriptase
enzyme
Entry to the cell & HIV replication:
1.
HIV bind to the CD4 protein on the cell membrane
2.
After binding , the looped segment V3 of the gp 120
molecule interacts with chemokine receptor CKR5,
CKR3, CKR2b, CXCR4 , to allow fusion of the cell &
viral membrane
3.
After penetration , the virus loses its envelope
4.
The reverse transcriptase enzyme of DNA copies of
viral RNA
5.
Viral RNA is conveyed to the nucleus & inserted into
cellular DNA . This integrated DNA copy of the HIV
genome is called provirus
6- The HIV DNA provirus is transcribed into RNA
copies, which are either incorporated into new
virus particles as the genome or function as
messenger RNA and are translated into core,
envelope or accessory proteins.
7- The core proteins and genomic RNA are
assembled into viral cores in the cytoplasm
beneath patches of the cell membrane
containing the envelope proteins.
8- The virus particle buds out through the altered
cell membrane into infect other cells.