1. Primary Immunodeficiency Disorders
Inherited or congenital and are generally rare

2. Defects causing primary immune deficiencies may occur in :
the combined lymphoid cell lineage,
T- or 8-cell lineages separately,
Lineages producing phagocytic cells and natural killer (NK) cells, and even
Cells producing complement components
Autosomal gene defects affect both sexes equally. However, defective X-linked genes affect males far more frequently than females.

4. Pleuripotent stem cells that generate granulocytic, erythrocytic, monocytic, thrombocytic, and lymphocytic lineages of the hematopoietic system are initially found in the aorta-gonad­ mesonephros of the developing embryo.
2 migrations : fetal liver and bone marrow
Lymphoid system cells generate B cells (B-1 and B-2) and T cells .
Defects in stem cells
B2 cell lineage remains within the bone marrow for development
B1 lineage relocates to and self replicatesin the peritoneal/pleural tissues, and the T-cell lineage migrates to the thymus.

5. Defects in lymphoid stem cells give rise to both the T and B cell lineages result in defective function of both cell types
Individual defects may result in abnormal T and B cell numbers or functions or both.
Cell mediated responses are usually reduced as in immunoglobulin production.

6. Stem cell defects Adenosine deaminase (ADA) deficiency
Immunodeficiency with ataxia telangiectasia
Purine nucleoside phosphorylase deficiency
Severe combined immune deficiency (SCID)
Wiskott-Aldrich syndrome
Stem cell defects

7. Defects in the combined lymphocytic lineage (loss of B and T cell systems)
A group of diseases caused by different defects in individual genes that have similar functional consequences.
SCID

10. Defects in T cells Abnormal T-cell numbers and/or functions
Delayed type hypersensitivity response is largely responsible for clearance of fungi, frequent or recurrent fungal infections are suggestive of defects in T-cell function
Secondary category of T-cell defects comprises those in which the responsible mutation are not limited to T cells but may occur in cells that are critical to the developent or activation of T cell
Some T cell defects arise from mutations in other cells that influence the developent or activation of T cells.
Defects in T cells
T cell help is critical to the activation of naïve and memory B cells.

11. T cell defects CD3 deficiency DiGeorge syndrome
MHC class II deficiencies (bare lymphocyte syndrome)
Purine nucleoside phosphorylase deficiency
Transporter associated with antigen presentation (TAP)- 1 or -2 deficiency
ZAP-70 deficiency
T cell defects
DiGeorge syndrome or congenital thymic aplasia is a t-cell deficiency that is due to the failure of the thymus to develop normally during embryogenesis. Cell mediated immune responses are undetectable.

13. Defects in B cells Autosomal recessive agammaglobulinemia
X-linked (Bruton) agammaglobulinemia (XLA)
Common variable immunoodeficiency (CVI or CVID)
Immunodeficiency with hyper-IgM ( X-linked hyper- IgM / XHIM)
Ig heavy chain gene deletions
Kappa chain deficiency
Selective IgA deficiency
Defects in B cells
XLA is due to mutations in the Bruton tyrosine kinase gene which is important for B cell receptor signalling. They lack mature B cells, plasma cells and all 5 classes of AB
XHIM is characterised by high levels of serum IgM and very low levels of serum IgG,A and E. B cells function normally. T helper cells lack a ligand important for signalling to the B cells to undergo isotype switching and generate memory B cells. CD 4o ligand is important for T cell interaction with dendritic cells and macrophages.
Selective IgA deficiency is the most common primary immunodeficiency disorder characterised by a reduced level of IgA in the presence of normal levels of the other Ab isotypes.

15. Defects in phagocytes and natural killer cells
Defects in nonlymphocytic cells such as phagocytes, neutrophils and NK cells.
Defects in phagocytic cells are significant because of their key roles in both innate and adaptive immune responses
Affects
Ability to kill microbes
Interactions with other cell types
Defects in phagocytes and natural killer cells

16. Defects in phagocytes and NK cells
Chronic granulomatous disease (CGD)
Chédiak_Higashi syndrome
IFN- gamma receptor deficiency
Leukocyte adhesion defect 1 (LAD-1)
Leukocyte adhesion defect 2 (LAD-2)
Defects in phagocytes and NK cells
CGD involved the inheritance of defects in nicotinamide adenine dinucleotide phosphate oxidase which is esential for the production of the reactive oxygen species during respiratory burst that accompanies phagocyte activation.
LAD is a group of rare inherited disorders that is due to the defect in adhesion molecules of neutrophils and often other leukocytes that are necessary for leukocytes to enter the tissue from the blood.

18. Defects in complement system
Affect innate and adaptive immune responses
C1q, C1r deficiency
C2/3/4/5/6/7/8/9 deficiency
Factor H/P deficiency
Hereditary angioedema
Paroxysmal nocturnal hemoglobinuria
Defects in complement system
Complement component c3 is common to all pathways of complement activation and as such, deficiencies in c3 have the most dramatic effect.
Patients lacking in c6-c9 components are unable to form Membrane attack complex. However they are competent for opsonic function, immune clearance and initiating inflammation via complement cascase.