Normal: ~1.25 mg/mL

Immunodeficiency or monoclonal gammopathy of Ig A or IgG: <~0.4 mg/mL

Infection, polycythemia vera, heroin addiction/infection, Waldenstrom's macroglobulinemia, etc: >~3mg/mL

Myeloma, Monoclonal gammopathy: >~10 mg/mL

IgA nephropathy --> high circulating levels of IgA complexes deposit in mesangial region of kidney, activate complement.  Eventually leads to renal failure. (50% of transplant pts)

Normal: ~2.1 mg/mL

Immunodeficiency or monoclonal gammopathy of Ig G or IgM: <~0.4 mg/ml

Infection, Liver dz, IgA neuropathy or Berger's dz, etc: >~4.5 mg/mL

Myeloma, Monoclonal gammopathy: >~10 mg/mL

Normal - 0.0003 mg/mL

Decreased - immunodeficiency, hypo/agammaglobulinemia

Increased - allergic disorders, hypersensitivity disorders, parasitic infections, immunologic disorders, infectious mononucleosis, IgE myeloma

Normal: ~12 mg/mL

Immunodeficiency or monoclonal gammopathy of Ig A or IgM: <~0.6

Infection, Liver dz, autoimmune dz, cystic fibrosis, etc: ~17

Myeloma, Monoclonal gammopathy: >~50

Chlamydia - myocarditis (cardiac muscle)

Hepatitis B - Multiple Sclerosis (myelin)

Herpesvirus - Myasthenia gravis (nAChR)

highly-aggressive B-cell lymphoma

Cause: tranlocatons of Chr. 8 (protooncogene myc)

to Chr. 14, 2 or 22 (where H, kappa and lambda chains are)

Multiple myeloma is a plasma cell malignancy, which produces too much monoclonal antibodies.

Primary amyloidosis

Multiple myeloma causes extra light chains in the blood and ECM which forms amyloid plaques. These plaques build up in extracellular spaces in systemic tissues and lead to multiple organ failure.

Chronic inflammatory conditions (i.e. TB)

or familial Mediterranean fever (hereditary)

plasma cells and lymphocytes secrete too much IgM.

Causes primary amyloidosis, visual impairment, neurologic problems, bleeding, hyperviscosity

Alzheimer's (amyloid plaques in brain)

type II DM (amyloid in pancreatic islets_

Within Tissues:

- Abscesses: focal areas of suppuration

- Phlegmons (cellulitis): spreading abscess

On surfaces:

- Ulcers: focal necrosis and inflammation

- Pseudomembranes: diffuse ulceration, spreading ulcers

IL-1, TNF, CSF, GSF

Differential Dx: Immature Band Cells = leukocytosis (inflammation)

1) Non-necrotizing

- Sarcoid

- Foreign Bodies

2) Necrotizing

- TB (caseating)

- Rheumatoid arthritis

3) Suppurative

- chalazion

- cat-scratch dz

1) Nodular scarring

2) Calcification (if necrosis)

3) Cavity formation

Too much:

- Strictures

- keloid (tumor-like)

- Exuberant granulation tissue

Too little:

- Fistulas

- Sinus tracts

- Dehiscence (wound pulls apart, 4 days after MI)

Fluorescence-Activated Cell Sorting

- Uses flow cytometry identify cell with cell markers

- provides relative and absolute counts of cell types in blood

Dx: infections, neutropenia, leukopenia, or other immunodeficiencies

1) Gamma-globulins

2) Bone marrow transplantation

3) Supportive antibiotics

4) Cytokines

5) Gene Therapy

Most effective: supportive antibiotics

- Failure to thrive

- Oral/cutaneous candidiasis

- chronic diarrhea

- opportunistic infections

1) X-linked recessive

2) Adenosine deaminase (ADA) or purine nucleoside phosphorylase (PNP) deficiency

3) RAG mutation

In X-linked recessive SCID, what deficiency of what cytokine is responsible for the majority of cases?

Why is this cytokine deficient?

IL-2

X-linked SCID has mutations encoding the common gamma-chain shared between IL-2, -4, -7, -9, and -15

T cell - low to none

B cell - normal

Humoral immunity - deficient

- severe hypogammaglobulinemia because B cell are not stimulated by T cells to form antibodies.

T cell - low

B cell - low

NK cells - low

Humoral immunity - severe hypogammaglobulinemia

RAG mutations = no TCR or Ig gene rearrangement --> no diversity on T and B cells

T cell: low

B cell: Low

NK cell: normal

1) MHC II deficiency

- APCs have little MHC II

- decreased CD4 cells (no positive selection)

- deficient DTH responses

- deficient antibody response to T-dependent antigents

2) MHC I deficiency or deficiency of TAP

- decreased CD8 T cells

- more respiratory and bacterial infections

What disease causes increased mycobacterial, viral and fungal infections?

Associated symptoms include with abnormal calcium homeostasis, muscle twitching, cardiovascular anomalies and abnomral faces?

Deletion on Chr. 22

Absence of thymus 3rd and 4th pharyngeal pouches fail to develop

Bruton's agammaglobulinemia (XLA)

X-linked

Pre-B cells: present

Mature B cells: absent

Ig: absent (all classes)

Cause: defect in CD40L

B-cell levels are normal, but no memory cells.

IgM dominates, all other Igs deficient.  Also autoantibodies present to neutrophils, platelets, and RBCs.

IgA is most common

IgM is most severe (but rare).

IgG can be treated by gamma globulin therapy

B cells: can be normal

T cells: normal

Igs: none or little, because B cells fail to mature into antibody-secreting cells

What disease is caused by a defect in a protein that's importnat for signal transduction and regulation of the cytoskeleton in lymphocytes?

What are some characteristics associated with this disease?

Wiskott-Aldrich Syndrome (WAS)

Also associated with

- eczema

- thrombocytopenia

- bacterial infections

- low IgM

What disease is characterized gamma/delta T cells representing 50% of the peripheral lymphocytes?

What are some other characteristics associated with this disease?

Ataxia telangiectasia

Also associated with:

- cerebellar ataxia

- oculocutaneous telangiectasias (broken caps in eye)

- radiation sensitivity

- Immune defects (thymic hypoplasia, IgA/IgG2 deficiency)

Defects to ATM or ATR genes

Normally involved in cell cycle regulation and DNA repair

defect in CD43 (sialophorin)

Required for actin assembly --> without it cannot activate B cells

Chronic granulomatous disease (CGD) - inability to form superoxide anions and hydrogen peroxide.

Associated characteristics:

- decreased antigen-presenting ability

- excessive inflammatory reactions

- gingivitis

- swollen lymph nodes

- granulomas

- bacterial & fungal infections

Leukocyte adhesion deficiencies

1) LAD-1 - problem with Beta-2 integrin

- also CTLs and NK cannot adhere to these target cells

2) LAD-2 - cannot convert GDP-mannose to fucose --> cannot bind to P- and E-selectins

Chediak-Higashi Syndrome

LYST: regulation of intracellular trafficking --> canot secrete lysosomes to kill bacteria.

Also - lack of skin & eye pigment

- protein-calorie malnutrition

- irradiation and chemo for cancer

- cancer metastases to bone

- immunosuppressive drugs

- removal of spleen

- HIV

- related to TLRs

- deficiency will resude production of IFN and TNF-alpha

- system autoimmunity developed in 1st year of life

- elevated IgE

- associated with T-regs