1. Immunodeficiency: Primary immune deficiency:
-Caused by intrinsic or congenital defects.
-Over 100 diseases of this type are known in humans, and
for many of these diseases, the specific defective genes
have been identified.
-Types:
1-Defects in stem cells.
2-Defects in T lymphocytes.
3-Defects in B lymphocytes.
4-Defects in phagocytes and NK cells.
5-Defects in complement system.

2. Defects in stem cells: 1-Severe combined immune deficiency (SCID):
Genetics:
Mode of Inheritance: Autosomal recessive (chrom. 11).
X-linked recessive.
Defective genes: RAG 1,2 gene.
IL2RG gene.
Function: Rearrangement of DNA to form variable
regions of Immunoglobulin and TCR.
Production of γ chain (common cytokine receptor)
: IL-2R, IL-4R, IL-9R, IL-15R, INF γR.

3. 2-Ataxia telangiectasia: Genetics: AR
Effect: Defect in B and T lymphocytes maturation.
Features: Lethal susceptibility to both viral and bacterial
infections due to deficiency of both humoral and
cellular immunity.
2-Ataxia telangiectasia:
Genetics: AR
-Rearrangement of gene at chromosome 7, 14.
-Gene: T cell receptor genes.
-Function: T lymphocyte clonal selection.

4. -Oculocutaneous telangiectasia (dilated blood
Feature:
-Oculocutaneous telangiectasia (dilated blood
vessels in the conjunctivae, ears, and face).
- Low serum IgA, and IgG.
-Thymus hypoplasia.
- Recurrent infection: Sinusitis, and pneumonia.
- Increased risk of Leukemia and Lymphoma.

5. 3-Wiskott-Aldrich syndrome: Genetics: - XR gene mutation.
- Etiology: defect in lymphocyte cytoskeleton.
Feature:
Boys have eczema, diarrhoea and recurrent infections, thrombocytopenia, low IgM level, and Tc -Th function.

6. Defect in T Lymphocytes:
1-bare Lymphocyte syndrome:
Genetics: AR gene on Chromosome 1 or 16.
Etiology:
Type 1: Mutation in the TAP gene prevent export of
Class I MHC to the cell surface.
Type 2 : Defects in MHC II specific transcription
factor, cause defect in T-helper function.
Features:
-Increased susceptibility to infection.
-CD4 and CD8 cells numbers decreased.
- Intracellular infection could cause lethal effect.

7. AD gene deletion in chromosome 22 q 11. Etiology:
2- DiGeorge syndrome:
Genetics:
AD gene deletion in chromosome 22 q 11.
Etiology:
1- Complete or partial absence of thymus.
2- Defect in T-cell clonal selection and maturation.
Features:
-Increased susceptibility to viral infection.
-Reduced active T cell production.

8. Defect in B Lymphocytes:
1- Bruton’s agammaglobulinaemia:
Genetics: X-linked recessive gene (BTK).
Etiology:
Defective B-cell tyrosine kinase prevents the B cell maturation.
Features:
-Increased susceptibility to infection (capsulated bacteria).
-Very low level of Immunoglobulin or lost level.
- 5-6 months boys develop lethal multiple infections of lung.

9. 2-Immunodeficiency with Hyper-IgM:
Genetics : X-linked recessive gene (CD40L G).
Etiology:
1-Defect in expression of CD40L on B lymphocyte.
2-Inability of B lymphocyte to undergo isotype switching.
Features:
-Elevated IgM and IgD in blood stream.
-Decreased IgG, IgA, and IgE concentration.
-Increased susceptibility to pyogenic infection. N

10. 3-Selective IgA deficiency: Genetics: Multiple genes and forms.
Etiology:
-Defect in IgA production in body fluids.
Features:
-No increased susceptibility to infection.
-Low IgA level.
-Normal level of other antibodies.

11. Defect in Phagocytes and Natural Killer cell:
1-Chronic granulomatous disease (CGD):
Genetics:
-XR ;Beta-chain of cytochrome b oxidase.
-AR (chr.1,7); NADPH oxidase.
-AR (chr.16); alpha chain of cytochrome b oxidase.
Etiology:
-Inability of Phagocytes to generate superoxide metabolites.
Features:
-Granulomatous infection in skin, lymph nodes, lung, liver.

12. 2-Chediak- Higashi syndrome:
Genetics:
-AR (Chromosome 1) Gene (LYST). (Lysosomal trafficking regulator).
Etiology:
-Defect in fusion of lysosome to phagosomes.
-Defect of release of cytotoxic granules.
Features:
-Increased susceptibility to pyogenic bacteria.
-Reduced ability of phagocytes to kill ingested microbes.
- Decreased functions of NK cell (Cytotoxicity).
-Risk for development of Lymphoma.

13. 3- Leucocyte adhesion deficiency: Genetics: AR gene (ITGB2 or CD18)
The leukocyte surface integrin Beta chains.
Etiology:
-Defect in migration of WBCs from circulation to the site
of infection (tissue).
Features:
-Increased susceptibility to infection.
-Frequent abscesses.
-Defective chemotaxis. N

14. Defect in complement system:
1- C1,2,3,…,9 immunodeficiency:
Genetics: Autosomal recessive gene
(Chr. 1,2,5,6,9,12,19).
Etiology: C1,2,3,...,9 deficiency.
Features:
-Increased susceptibility to infection.
-associated with lupus like syndrome.
-Defect in production of MAC unit of Classical pathway.

15. 2-Hereditary angioneurotic edema:
Genetics: Autosomal dominant gene (Chr. 11).
C1 inhibitor protein.
Etiology: Defect in inhibition of Classical pathway.
Features:
- Fluids accumulation in soft tissue and airways due to
uncontrolled production of C2a.
-Swelling of tracheal and bronchial passages that can be
life-threatening.

16. Secondary (acquired) immune deficiency:
-The immunodeficiency that associated with exposure to
environmental factors.
-Not related to inheritance of genetic mutations.
-Types:
1-Therapeutic immunodeficiency.
2-Malignant tumor- associated deficiency.
3-Infectious immunodeficiency.

17. Therapeutic immunodeficiency: Examples:
-Some Anti-inflammatory drugs (corticosteroids)
; treatment of Rheumatoid arthritis :
Interfere with production of some cytokines.
-Immunosuppressive drugs (cyclosporine); used during
organ transplantation: N

18. Malignant tumor- associated deficiency: Examples: -Multiple myeloma:
Increased polyclonal B cell activation non-specifically.
- Lymphoma (HK):
Uncontrolled proliferation of B lymphocytes (E.B virus).
-Chronic lymphocytic leukemia:
Reduced production of Immunoglobulin.

19. Infectious immunodeficiency:
Examples:
-Schistosoma species:
Enzymatic degradation of immunoglobulins.
-Herpesvirus:
inhibits MHC class I maturation within E.R.
-CMV: Interferes with TAP of E.R.
Redirects MHC I into cytoplasm rather than to
cell surface.
-Chlamydia: prevents phagosomes-lysosomes fusion.

20. -Kills phagocytes by its toxins. -Protein A prevents opsonization.
-Staphylococcus:
-Kills phagocytes by its toxins.
-Protein A prevents opsonization.
-Mycobacterium:
-Kills phagocytes.
-Prevents phagosome-lysosome fusion.
-Inhibits oxidative degradation within phagosome.
-Plasmodium species:
-RBCs infection.
-Human Immunodeficiency virus (HIV):
-Kills CD4, Monocytes, and CD8 cells.
-Nef gene redirects MHC I into lysosome.

21. Human Immunodeficiency Virus (HIV):
HIV infection in humans is considered pandemic by the World Health Organization (WHO).
From its discovery in 1981 to 2006, AIDS killed more than 25 million people .
Tropism:
Some immune cells have a specific HIV susceptibility due to presence of specific receptors.
-Macrophages, and dendritic cells carry the chemokine
receptor CCR5.
-CD4 T helper cells express the chemokine receptor
CXCR4. N

22. HIV Tropism: N

23. HIV infection periods:

24. 1-Asymptomatic period: CD4:8 Ratio= 2:1 2-Latency and chronic period :
-The virus is preserved in the dendritic cells of Lymph
nodes.
-Late Latency : CD4:8 Ratio= 1:1
3-AIDS period:
-No cytotoxic Tc response.
-No Humoral immunity.
-CD4:8 Ratio= 1:2
-CD4 count less than 200 cell per μL. N