Transcript 1-Defensive breakdownx

Dr. Ebtihal Chiad Abass
Ph.D. Immunology
Department of Pathology
- Immunodeficiency
•Congenital – rare
•Acquired – more than just AIDS
– Iatrogenic immunodeficiency
•Chemotherapy
•Splenectomy
•Immunosuppress
– Opportunistic infections related to
immunodeficiency
Congenital Immunodeficiency
• B Cell
-X-Linked Agammaglobulinemia
Failure of pre-B cell to differentiate into B-cell; these
result absence of gamma globuline in the blood.
- hypogammaglobulinaemia
Recessive, early presentation, very low levels of all
immunoglobulins ( IgA, IgG, IgM, IgD and IgE).
Congenital Immunodeficiency
• T cell
– Di George syndrome
results from defect in thymic development with deficient
T-cell maturation.
• Severe combined immunodeficiency (SCID)
low B and T cells, treated by bone marrow transplant
• Ataxia telangiectasia – Recessive, thymic hypoplasia,
low B cells treated by BMT.
• complement deficiencies ( hereditary angioedema) an
uncommon autosomal dominant disease caused by a
deficiency of C1 inhbitor.
Chronic granulomatous disease (CGD)
X-linked , defective bacterial killing by phagocytic
cell , in which certain cells of the immune system have
difficulty forming the reactive oxygen compounds
(most importantly, the superoxide radical ) these lead
to persistent infections of skin, respiratory and GI
tract
- treated by BMT
Acquired Immunodeficiency
• B cell
– Hypogammaglobulinaemia :chronic
lymphatic leukaemia and other
lymphoproliferative disorders, myeloma,
nephrotic syndrome
• T cell
– HIV, chemotherapy, Hodgkin’s disease,
immunosuppression e.g. transplantation
• B and T cells
– Radiotherapy
– chronic lymphocytic leukaemia
– Malnutrition
• Neutrophils deficiencies
– Neutropenia
– Myelodysplasia
• Complement deficiencies
liver failure e.g. hepatitis B and C can reduce
the synthesis of complement.
Acquired immunodeficiency syndrome (AIDS)
• Human Immunodeficciency Virus infection
• Transmission of HIV by sexual contact ,
parenteral inoculation and passage the virus from
infected mother to their newborns.
• Virus infects via CD4 molecule on T helper cells
• Lymphopenia and alterations in T cell subsets
common
• immunosuppretion lead to opportunistic
infections
Infections associated with HIV
People with advanced HIV infection are susceptible to
infections and malignancies that are called 'opportunistic
infections' because they take advantage of the opportunity
offered by a weakened immune system.
These infections includes
- Fungal infections
– Pneumocystis jiroveci (carinii) cause pneumonia
– Candida albicans , GIT (thrush)
– Aspergillus fumigatus , pneumonia
– Histoplasma capsulatum , disseminated
– Cryptococcus neoformans ,
meningoencephalitis, pneumonia
Cryptococcus neoformans
-Most infections with C. neoformans occur in the lung.
However, fungal meningitis and encephalitis , especially
as a secondary infection for AIDS.
-It is a facultative intracellular pathogen.
- In human infection, C. neoformans is spread by
inhalation of aerosolized spores and can disseminate to
the central nervous system, where it can cause
meningoencephalitis .
- In the lungs, C. neoformans cells are phagocytosed by
alveolar macrophages.
Cryptococcus neoformans
stained with silver stain
Cryptococcus neoformans infection of the
lung. There are numerous organisms that have
a large mucoid capsule, giving the appearance
of a clear zone around a faint round nucleus.
Pneumocystis jiroveci
- Pneumocystis organisms are commonly found in the
lungs of healthy individuals
-Causative agent of Pneumocystis pneumonia
particularly among immunocompromised hosts such as
AIDS
- Disease occurs when immunity is defective. Once
inhaled, the trophic form of Pneumocystis organisms
attach to the alveoli. Multiple host immune defects allow
for uncontrolled replication of Pneumocystis organisms
and development of illness. Activated alveolar
macrophages without CD4+ cells are unable to
eradicate Pneumocystis organisms.
- Symptoms
-Progressive exertional dyspnea (95%)
-Fever (>80%)
-Nonproductive cough (95%)
-Chest discomfort
-Weight loss
-Chills
-Hemoptysis (rare)
Diagnosis
-Direct microscopy of bronchoalveolar lavage. is the most common
invasive procedure used to diagnose P jiroveci
- Lung biopsy : is the most invasive procedure and yields 100%
sensitivity and specificity because it provides the greatest amount of
tissue for diagnosis.
– Treatment : cotrimoxazole
Cluster of P. jirovecii stained
with immunofluorescing
antibody, the best microscopic
method for diagnosis
At higher magnification, the granular pink exudate
of Pneumocystis jirovecii, pneumonia is seen. The
exudate consists of edema fluid,
protein, Pneumocystis organisms, and dead
macrophages. One can see why gas exchange is
severely compromised.
Candida albicans
- Is a diploid fungus that grows both as yeast and
filamentous cells
-Candida yeasts normally live on the skin and mucous
membranes without causing infection; however,
overgrowth of these organisms can cause symptoms to
develop.
- In immunosuppressed it may disseminated to many
organs , Candida esophagitis, often accompanied by
involvement of stomach and small intestine , is seen in
patients with leukemia and lymphoma.
- Candidiasis
is often observed in immunocompromised
individuals such as HIV-infected patients.
– Diagnosed clinically
– white plaques
– Treatment – fluconazole or related drugs
Oral thrush is an infection that is cause by a fungus, Candida albicans.
The yeast fungus thrives in the lining of the mouth thus resulting to
oral thrush.
• Bacterial infection
- Mycobacterium Tuberculosis
- Mycobacterium avium intracellular
• Other bacteria
– Haemophilus influenzae
– Streptococcus pneumoniae
• Parasites
– Cryptosporidia – GIT
– Isospora – colon (Cystoisospora belli)
– Toxoplasma gondii – CNS, eyes, lymph nodes
• Mycobacterium tuberculosis – Common in HIV
patients but all immunocompromised patients at risk
• Mycobacterium avium intracellulare
– May cause systemic infection, GI disturbance etc.
– Large numbers of organisms usually present
Mycobacterium avium
intracellulare
Under the microscope
multinucleate giant cells and
granulomatosis are seen
• Viral infection
– Cytomegalovirus (CMV) – GIT, CNS etc.
– Herpes zoster – shingles
– Herpes simplex – muco-cutaneous
Cytomegalovirus
– Usually reactivation of old infection
– Subclinical CMV common in normal
people
– Pneumonitis, oesophagitis, colitis,
hepatitis
– Treatment - acyclovir/gancyclovir
Owl's eye appearance of inclusion bodies, which is highly specific
for cytomegalovirus infection
• Herpes simplex
– Skin lesions ( recurrent herpes labialis)
keratoconjunctivitis , encephalitis, systemic
- The virus replicates in the skin or mucous membrane at
the initial site of infection, then migrates up the neuron
by retrograde axonal flow and becomes latent in the
sensory ganglion cells (trigeminal ganglia)
- Treatment acyclovir/gancyclovir
• Herpes zoster – Shingles
– reactivation
viral disease characterized by apainful skin rash
with blisters in a limited area on one side of the body
(left or right), often in a stripe
– May be extensive and severe
– May involve conjunctivae
• Epstein Barr virus (EBV)
– Reactivation of infection common
• Post-transplant lymphoproliferative disorder
– B cell proliferation driven by EBV
- May progress to lymphoma
– Responds to reduced immunosuppression
• JC virus or John Cunningham virus (JCV) is a type
of human polyomavirus
The virus causes progressive multifocal
leukoencephalopathy and other diseases only in cases
of immunodeficiency
• BK (polyoma)virus
The BK virus is a member of the polyomavirus family.
Past infection with the BK virus is widespread, but
significant consequences of infection are uncommon,
with the exception of the immunocompromised and
the immunosuppressed.