• A failing of one or more of the body's defensive mechanisms resulting in morbidity or mortality 
• Any part of the immune system can be deficient cells, proteins, signaling mechanism...
• The body is susceptible to infection by organisms that meet with little or no resistance.
• Or, in certain cases, other homeostatic systems in the body will be disrupted by the defect
• Severity is variable
• Immunodeficiency may be Primary or Secondary

• born with it
• inherited (mutations in gene controlling immune cells)
• susceptible to recurrent, severe infections, starting in children.
• cannot recover without treatment
• > 150 immunodeficiency

it's aquired. 

-as a consquence of other disease or env't.

  -infection, aging starvation, medication

-Recurrent infections with:

  -Viruses

  -Fungi

  -Opportunistic organisms (PCP)

-we see a lot of: Diarrhea, wasting, growth retardation

the pathology:

• Abnormal genes producing altered cell proteins
• defective synthesis of specific protein
• Molecular lesions produce failure of cell differentiation
• Enzyme deficiency
• Anything that make you sick can happen

-HSC are multi-potent

-self renewing cells

-CD34+, c-Kit, stem cell Ag (Sca-1+) on cell surface

-Defect in HSC results in Reticular Dysgenesis

• Failure to thrive
• Usually fatal in early years
• Onset of infections in the neonatal period
• Opportunistic infections
• Chronic or recurrent thrush
• Chronic rashes
• Chornic or recurrent diarrhea
• Paucity of lymphoid tissue (small size)

- Very low number of circulation lymphocytes

- Failure to mount T cell mediated responses

- Thymus does not develop

The most common cause is a defect in the IL-2 receptor (affects many cytokine receptors)

• IL-2 is common receptor
• shared and common is same

• Most have lymphopenia, decreased IgG, IgA, and IgM.
• diagnosis made by analysis of T, B, & NK cell subsets

• isolation
• treat underlying infections
• bone marrow transplant
• past: infection can be limited by confinement to a sterile environment
• present: bone marrow transplant
• future: gene therapy to repair leukocytes

• No class II MHC molecules
• Lack of positive T-cell selection events
• impaired peripheral T-helper responses

• mutated TAP genes
• impaired positive selection of CD8+ T cells
• Heightened susceptibility to viral infections

• Deletion of regions on chromosome 22, including TBX1
• Affects development offacial features and thymus
• Lack of immune responses, but degree varies
• May be helped by thymic transplant and/or passive Ig treatments

• defect in WASP gene for a cytoskeletal protein expressed in hematopoietic cells
• Manifests with eczema and thrombocytopenia, as well as impaired humoral/cell-mediated immunity
• Higher susceptibility to bacterial infections and autoimmunity may develop
• symptomatic treatment includes transfusions and passive antibodies/antibiotics
• Long-term treatment may require hematopoietic stem cell transfer

-able to make IgM but they can't switch to isotype switching.

-Deficiency in CD40L, impairing communications between helper T cells and APC's

-impairs interactions between B & helper T cells, leading to limited production of antibodies to T-dependent Ag

-Production of Ab to T-independent Ag not affected, leading to high levels of IgM. 

• characterized by skin abscesses (Staph), recurrent pneumonia
• 3 E's: eczema, eosinophilia and high IgE levels
• May be accompained by facial abnormalities and bone fragility
• Induced by STAT3 gene mutation
• Causes dysregulation of the TH pathways
• particularly the TH 17 group

• aka: Bruton's hypogammaglobulinemia, XLA
• 1st immunodeficiency described
• Extremely low levels of IgG, absence of other isotypes
• Recurrent bacterial infections occur
• Caused by a defect in Bruton's tyrosine kinase (Btk) required for BCR signal transduction
• B cells are locked in the pro-to pre-B cell shape in the bone marrow

• Disease managed by antibiotics and passive antibodies. 

• several defects induce this problem-often uncharacterized
• allows recurrent infections due to immunodeficiency
• Respiratory tract infections especially prevalent
• one or more antibody levels are seriously reduced
• But B-cell numbers are usually normal

• Onset usually in 2nd or 3rd decade of life
• CVID is characterized by: hypogammaglobulienmia
• slow decline in all classes of Ig
• CVID has a tendency to autoantibody formation
• Link with Epstein-Barr infection

• CVID is a heterogenous group of disorders with intrinsic B-cell defect or a B-cell dysfunction related to abnormal T-cell B-cell interaction
• Lack of inducible co-stimulator (ICOS) expression by activated T cell which associated with lack of T cel help for B cell differentiation, class switching and memory B-cell generation.
• in 10-20% of families another member may have selective IgA def. 

• B lymphs don't differentiate into plasma cells
• Recurrent sinopulmonary infections
• defect somatic hypermutations
• increased apoptosis in B & T cells
• Low IgG, IgA, IgM
• Treatment: IVIG
• Associated with autoimmune disease, lymphoma 

• Affects 1:700 individuals
• IgA-secreting B cells are unable to differentiate to the plasma cell stage
• Genes responsible are suspected of lying outside the Ig gene complex set
• Other antibody isotype levels are normal
• May show higher susceptibility to respiratory and genitourinary tract bacterial infections
• Most individuals asymptomatic, but degree of severity varies

• caused by abnormality in the gene for the common Beta chain of LFA-1, Mac-1, and gp150/95 integrin adhesion molecules
• NO chemotaxis
• limits leukocyte recruitment to inflamed areas.
• higher susceptibility to bacterial and fungal infections
• severity of defect varies for unknown reasons
• recurrent soft tissue, skin, respiratory infections, impaired wound healing (typically no pus, minimal inflammation)
• delayed umbilical separation
• increased WBC count
• treatment: BMT

• two distinct forms linked to phagosome oxidase (Phox) proteins
• x-linked form (70%)
• Autosomal recessive form (30%)
• defect in NADPH oxidative pathway used by phagocytes to generate reactive oxygen species
• Results in more bacterial/fungal infections and higher degrees of inflammation responses that produce granulomas
• treatment relies on antifungal/antibacterial drugs
• more recently helped by addition of rIFNy; mechanism unclear

• Autosomal disorder of lysosomal storage and transport
• mapped to mutations in lysosomal trafficking regulator (LYST) gene
• Affected cells produce giant granules
• Leads to recurrent bacterial infections, defects in blood clotting, pigmentation, and neurologic function.
• requires antibacterial treatments and eventual bone marrow transfusion for survival 
• may still allow neurological complication to persist

• grouping of several possible gene defects
• usually in interferon signaling or receptor pathways
• leads to a general problem in getting rid of intracellular bacterial infections (such as those caused by mycobacteria)

• mutated and inactive FoxP3 gene preventing development and function of T(REG) cells
• Allows autoreactive T cells that escape the thymus to go unchecked
• immune destruction of bowel, pancreas, thyroid, skin can result in death before 2 years of age. 

• HIV-1 is spread by intimate contact with infected body fluids
• most common means of transmission
• vaginal/anal intercourse
• receipt of infected blood/blood products
• passage of HIV from mother to infant
• dendritic cells in virus-exposed areas may take up and harbor virus, passing it to CD4+ T cells

1. Gag -nucleocapsid proteins
2. pol-protease/integrase/reverse transcriptase
3. Env -envelope glycoproteins

1. Acute phase: spike in HIV levels in blood
• spike in HIV levels in blood
• Eventually brought mostly under control by production of anti-HIV antibody
2. Asymptomatic phase:
• lengthy, possibly years
• gradual decrease in CD4+T cells and in viral load
3. AIDS:

• Crash in CD4+ T cell numbers
• High levels of HIV in blood

• Evidence of infection with HIV-1
• <200 CD4+ T cells/μL of blood
• impaired/absent DTH reactions
• occurrence of opportunistic infections

vaccine is hard to produce for the following reasons:

• virus mutates rapidly, so the production of Ab not effective.
• Good animal models are limited and expensive 
• Dangers of testing attenuated vaccines
• Trials so far have been largerly ineffective.