Dr. Ziyad 4-11-2018
Immunodeficiency syndromeQuantitative or qualitative defect of immune system
Either congenital (primary) or acquired (secondary).
Affect T-cell (cell-mediate), B-cell (Ab mediate), complement or phagocytosis
Associated with an increased risk of infections & lymphoproliferative diseases.
Primary Immunodeficiency: -
Early onset, usually between 6 months & 2 years of age
Recurrent infections
Classification
B-cell deficiencies: -
1-X-linked agammaglobulinemia of Bruton
2-Common variable immunodeficiency
3-Isolated IGA deficiency
T-cell deficiencies: -
1-Hyper IGM syndrome
2-DiGeorge syndrome
Severe combined immunodeficiency
X-linked agammaglobulinemia of Bruton:
Is an X-linked disorder that presents in male infants but is usually not manifest clinically until after 6 months of age because of the persistence of maternal antibodies.
Immune system defects:
Failure of Ab synthesis caused by a block in maturation of pre B cells to B cells due to a mutation in the tyrosine kinase gene, cell mediated immunity is unaffected.
Absence of plasma cells in tissue, resulting in absence of serum Igs.
Absence or poorly defined germinal centers in lymphoid tissue.
Effects:
Propensity to recurrent bacterial infections with organisms such as pneumococci, streptococci, staphylococci, and Haemophilus influenza; does not affect resistance to viral and fungal infections or phagocytosis and killing bacteria by neutrophils.Isolated IgA immunodeficiency:
Most common inherited B cell defect, occurring in 1/600 persons.
Either familial or acquired (in association with toxoplasmosis & measles).
Many of these men & women are asymptomatic.
Increase incidence of infection especially those involving mucosal surfaces (respiratory, GIT & urogenital tract ).
Increase incidence of autoimmune diseases esp. SLE & rheumatoid arthritis.
Anaphylactic reaction to transfused blood.
Results from the inability of IgA B cells to mature to plasma cells. Other Igs are normal
DiGeorge syndrome (Thymic hypoplasia)
Is a congenital T-cell deficiency due to the failure of the 3rd and 4th pharyngeal pouches to develop, with resultant hypoplasia of the thymus and parathyroid glands as well as abnormalities of the mandible, ear and aortic arch.
Is characterized by failure of T cell maturation, leading to lymphopenia, B cells remain unimpaired.
Is manifest clinically by recurrent viral and fungal infections and tetany from hypoparathyroidism with hypocalcemia.
Can be summarized by CATCH 22 syndrome which denotes Cardiac defect, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia, and microdeletion of chromosome 22.
Severe combined immunodeficiency syndrome
Is characterized by marked deficiency of both B and T cells manifest as profound lymphopenia and severe defect in both humoral and cell mediated immunity.
Occur in both autosomal recessive and X-linked forms.
Clinical manifestations:
Severe infections (bacterial, viral, and fungal)High incidence of malignancy.
Failure to thrive.
Graft-versus-host disease as a result of blood transfusions.
Phagocytic cell defect
Chronic granulomatous disease in which the monocytes and neutrophils fail to generate the bactericidal oxygen species resulting in recurrent and chronic infections.Chediak Higashi syndrome in which the neutrophils have large but functionless lysosome.
Secondary Immune Deficiencies
much more common than the primary (inherited) disorders.may be encountered in patients with malnutrition, infection, cancer, renal disease, or therapy-induced immune suppression.
Acquired immunodeficiency syndrome
AIDS is a retroviral (RNA virus) disease characterized by: -1-Profound immunosuppression that leads to opportunistic infections
2- Secondary neoplasms
3- Neurologic manifestations
Epidemiology
First described in United States.
United States has the majority of the reported cases
Infection in Asia & Africa now is large & expanding
Adults at risk for developing AIDS are: -
1-Homosexual men constitute by far the largest group
2-Intravenous drug abusers compose the next largest group
3-Hemophiliacs esp.. before 1985, make up 0.8 % of all cases
4-Recipients of blood & blood components who are not hemophiliac
5-Heterosexual contacts
6-Approximately 10 % of cases, the risk factors can’t be determined
7- Newborn of infected mothers
Close to 2 % of all AIDS cases occur in pediatric population, more than 90 % result from transmission of virus from infected mother to her baby. The remaining 10 % are hemophiliacs or received blood & blood products before 1985
Etiology: -
HIV is human retrovirus belonging to the lentivirus family
2 genetically different but related forms of HIV called HIV-1 & HIV-2
HIV-1 is most common type associated with AIDS in U.S, Europe & central Africa
P24 (major capsid protein) is the most readily detected viral Ag & target for Ab that is used for the diagnosis of AIDS
gp120 & gp41 are viral envelope which are critical for infection
HIV-1 subdivided into; M & T
M form is most common form worldwide
Pathogenesis:
Two major targets of HIV: -Immune system and -CNS
Immunopathogensis of HIV disease:
Profound immunosuppression primary affecting cell-mediate immunity
Severe loss of CD4 T-cells& impairment in the function of surviving helper T cell
Macrophage & dendritic cells are also target of HIV infection
For infection, binding of the virus to CD4 is not sufficient, therefore HIV gp120 must also bind to co-receptor (CCR5 & CXCR4) for entry into the cells
HIV strains can be classified into 2 groups on the basis of their ability to infect macrophage & CD4 T-cell
1- M-tropic which can infect both monocytes / macrophages & freshly isolated peripheral T-cell
2- T-tropic which infect only T-cell
* M-tropic strain use CCR5 receptor whereas T-tropic strain bind to the CXCR4 receptor which only present in T-cell
B) Pathogenesis of CNS involvement: -
Nervous system is a major target of HIV infection
Macrophages & microglia cells are the predominant cell type infected with HIV
Infection transmitted to CNS through monocytes & are almost exclusively of M-tropic type
HIV does not infect Neurons
Injury to the nervous system occurs indirectly by viral products & soluble factors produced by macrophage / microglial cells e.g., IL1, TNF & IL6
Natural history of HIV infection:
3 phases can be recognized
-Early acute phase
-Middle chronic phase
-Final crisis phase
1-Early acute phase: -
Represent the initial response of immunocompetent adult to HIV
Clinically is associated with self limited acute illness that develop in 50-70 % of HIV infected patients such as rash, cervical adenopathy, diarrhea & vomiting which persist for 3-6 weeks
2-Middle chronic phase: -
There is continue HIV replication predominantly in lymphoid tissue
Patient are either asymptomatic or develop persistent generalized lymphadenopathy
Many patients have minor opportunistic infection such as thrush or herpes zoster
3-Final crisis phase: -
Characterized by break down of host defense
Dramatic increase in plasma virus & clinical disease
Patients present with a long standing fever (> 1 month), fatigue, weight loss & diarrhea
CD4 cell count is reduced below 500 cell / ml
Serious opportunistic infection, secondary neoplasm or clinical neurological diseases, these called AIDS defining conditions
Opportunistic infections: -
1) Pneumonia caused by pneumocystis carinii, about 50 % of AIDS patients develop this infection
2) Candida albicans infections of mouth, esophagus, vagina & lungs
3) cytomegalovirus enteritis & pneumonia & retinitis
4) Atypical mycobacterial infection (esp. M. avium-intracellulare) of G.I.T
5) Herpes simplex infection of mucocutanous areas
Most Common Neoplasms associated with AIDS
1)Kaposi Sarcoma: -
* Vascular tumor
* Most common tumor in AIDS patients
2)Non-Hodgkin lymphoma: -
* 120 times more risk in AIDS patients than in general population
3)Carcinoma of uterine cervix
4)Squamous cell carcinoma of the skin