Lecture 1_Immunodeficiency_pt1: disease & lab diagnosis

A part of the immune system is missing or dysfunctional.

Recurrent infections or some types of cancer.

It is inherited.

it is acquired

AIDS, malignancies, immunosuppressive drugs.

More than 350 different PIDs have been identified; most are rare but clinically significant.

PID results from genetic defects.

Defects in lymphoid cells, phagocytic cells, regulatory molecules, and complement proteins.

They are genetic; the child is born with a defect.

At least 58% of cases are diagnosed in children under 15 years old.

The vast majority (83%) are males with X-linked recessive, autosomal recessive, autosomal dominant, and sporadic inheritance patterns.

They are acquired and may be transient or permanent due to diseases, protein-caloric malnutrition, chemotherapy, irradiation, malignancies, or immunosuppression.

Bone marrow precursor stem cells.

Lymphocytes, neutrophils, and monocytes.

Antibody, cytokines, and complement components.

1. B-cell immunity
2. T-cell immunity
3. Phagocytosis
4. Complement system

B-cell (humoral) immunity — 50% of cases.

10%.

18%.

2%.

20%.

Very mild or subclinical to severe recurrent infections or failure to thrive.

Pyogenic bacterial infections (Staphylococcus aureus, Haemophilus influenzae, pneumococcus).

Upper and lower respiratory tract, GI tract (malabsorption), and slow growth.

Otitis media, sinusitis, and pneumonia.

Back: Recurrent infections with intracellular pathogens such as viruses, fungi (commonly Candida), and intracellular bacteria.

Back: Disseminated viral infections, especially with latent viruses such as herpes simplex, varicella zoster, and CMV.

Back: Developing certain types of cancer.

Back: They adhere to vascular endothelial lining cells, migrate through the capillary wall to a site of infection, and ingest and kill microbes.

Back: It can lead to increased susceptibility to pyogenic infections.

Back: To produce inflammatory molecules and cause lysis of organisms.

Back: Pyogenic infections.
a. Recurrent Neisseria infections
b. Rheumatic and connective tissue diseases

INNATE!!!!

ADAPTIVE!!!

Back: Disorders of humoral immunity (B-cell differentiation and antibody production).

Back: After 6 months of age; can also be present in adulthood.

Recurrent infections: sinus infections, otitis media, bronchiectasis;

Chronic gastrointestinal tract problems including malabsorption;

Autoimmunity

Back: T-cell and mixed disorders (combined B-cell and T-cell defects).

Back: Before 6 months of age.

Failure to thrive
Oral thrush
GVHD from maternal lymphocytes
Excess diarrhea

Back: Infancy or childhood.

Unusually severe infections by common pathogens

Granuloma formation

Poor wound healing

Abscesses and skin infections

Oral cavity infections

Back: At any age.

Back: Neisseria infections, including meningococcal and gonococcal infections.

Back: Predominantly Antibody Deficiencies.

Back: Bruton’s agammaglobulinemia, first described in 1952, is X-linked and affects males almost exclusively.

Back: They lack circulating mature CD19 positive B cells and have no plasma cells.

Back: By the absence of CD19 positive B cells in the peripheral blood.

Back: A deficiency or lack of all immunoglobulins of all classes.

Back: They have no plasma cells in their lymphoid tissues but do have pre-B cells in their bone marrow.

Back: Recurrent sinopulmonary infections by encapsulated organisms (Streptococcus pneumoniae, Haemophilus influenzae) and bacterial otitis media.

Back: T cells are normal in number and function.

Back: In infancy, as maternal antibody is cleared.

Back: Lack of the Btk enzyme causes failure of Vh gene rearrangement.

Back: Intramuscular (IM) or intravenous (IV) immunoglobulin (IG).

Back: 70% of patients with IgA deficiency are asymptomatic.

Sino-pulmonary infections
GI infections
Allergies
An increased tendency to autoimmune diseases (SLE, RA, immune thrombocytopenia)

Allergic disorders and malignancy are also more common among these patients

Back: Impaired differentiation of B cells to become IgA-producing plasma cells.

Back: IgE antibodies to IgA in very severe IgA deficiency

Back: To prevent reactions caused by anti-IgA antibodies.

Back: IgA has a very short half-life and cannot be transported to secretory sites such as mucosal surfaces.

Back: Antibiotics and possible gene therapy.

Back: A heterogeneous group of disorders, sometimes difficult to diagnose.

Back: It is the most common PID with a severe clinical syndrome that requires medical attention.

Back: There is a slow decline in more than one class of immunoglobulins.

Back: Recurrent otitis media.

Back: They usually begin in adolescence and are bacterial in origin.

Back: Increased episodes of pneumonia and an increased risk of autoimmune diseases.

Back: Normal numbers of mature B cells.

Inability to become memory B cells (CD27+) and plasma cells

Decreased activation of B cells in germinal centers

Back: IgA; patients also show a marked decrease in IgG levels due to certain subclasses.

Back: Recurrent bacterial infections, particularly sinusitis and pneumonia.

Back: MHC.

Back: When patients with recurrent bacterial infections demonstrate a low serum immunoglobulin level.

Back: They are absent or decreased.

discrepancies in ABO typing

Back: The levels of one or more of the four IgG subclasses are lower than the reference interval (RI).

IgG1: 66%

IgG2: 23%

IgG3: 7%

IgG4: 4%

Back: In patients with recurrent infections, even if the total IgG level is normal but the clinical picture suggests immunoglobulin deficiency.

when the immune system is responding to protein antigens (i.e. RH blood group, Duffy, Lutheran, or structure on a pathogen ) these antibodies are involved

polysaccharides ???why

Back: Defects in both humoral (B cell) and cell-mediated (T cell) immunity.

Back: Mutations in any of several genes.

a. A defect that affects development of both types of lymphocytes.
b. A defective interaction between the two limbs of the immune system.

Back: Using a shorthand of T⁺/⁻ B⁺/⁻ NK⁺/⁻, with the superscript +/− showing whether each cell type is deficient.

Back: Severe Combined Immunodeficiency (SCID).

Back: A group of related diseases that all affect T- and B-cell function but have differing etiologies.

Back: X-linked SCID.

Back: Mutation in the IL2RG gene located on the X chromosome — the root cause of most SCID cases.

Back: The common gamma chain, a cytokine receptor subunit common to receptor complexes for at least six different interleukin receptors.

Back: IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors.

Back: Halting lymphocyte maturation due to defective cytokine signaling.

Back: In T cells and NK cells.

Back: It processes interleukin-binding signals from the cell membrane to the nucleus.

Back: Receptors that employ the common gamma chain (γc).

Back: An autosomal SCID (Severe Combined Immunodeficiency) with the T⁻B⁺NK⁻ phenotype.

Back: About 15–20% of SCID patients have ADA deficiency, leading to a T⁻B⁻NK⁻ phenotype.

Back: On chromosome 1, region q21.

Back: An enzyme involved in the metabolism of purines, similar to PNP deficiency.

Back: Toxic metabolites of purines accumulate in lymphoid cells, impairing proliferation of both B and T cells.

Back: There is a progressive decrease in lymphocyte numbers.

Back: Lack of T cells and B cells, but NK cells remain functioning.

Lack of both T cells and B cells but with functioning NK cells .
Profound lymphocytopenia (elimination of B and T cell precursors during development)
Decreased MHC-II molecule expression

Back: Decreased MHC-II expression (leads to immune dysfunction/ aka impaired activation of CD4+ T helper cells).

Back: It is a transmembrane phosphatase that regulates signal transduction of T- and B-cell receptors.

A: Reticular dysgenesis (Adenylate kinase 2 deficiency — no myeloid cells)

ADA deficiency (enzyme involved in purine metabolism).

A: Rag 1 and 2 deficiency/ recombination deficiency.

γc-chain deficiency (IL-2 receptor; NK low or defective)

JAK3 deficiency (interleukin-binding signal; NK near absent)

A: IL-7Rα deficiency.

A: Omenn Syndrome.