11-11-2011

1) "pure" defect in T cells
2) defect in gene that affects T and B cells
3) major problem with innate immunity (macrophages)

antibody deficiency

1) Hemophagocytic Syndrome
2) Mendelian Susceptibility to Mycobacterial Disease (MSMD)
3) Toll-like receptor defects

Defect in interferon gamma and IL-12

Mendelian Susceptibility to Mycobacterial Disease.

Toll-like receptor defect.

Macrophage Activation Syndrome (A CID, Hemophagocytic syndrome) where they don't produce granules to destroy cells.

With deep seated tissue infections with bacteria and fungi, anywhere in skin, soft tissue, bone, lungs.

Terminal pathway defect in complement system

Viral. They have maternal antibodies but they have not T cells to fight intracellular infections.

Opportunistic infections, chronic thrush, rashes, diarrhea, scarce lymphoid tissue.

1) low serum Ab levels
2) no antibody response to immunizations
3) no mitogen
4) important: low/absent T cells, often also low/absent B cells.

1) DiGeroge/Velocardiofacial syndrome
2) T cell receptor deficiencies
3) Zap 70 deficiency

1) Cardiac malformation
2) Hypoparathyroidism (so low serum Ca)
3) Thymic hypoplasia

malformed ears
fish shaped mouth
down lanting eyes
and of course other typical defects- heart, thymus, parathyroid

1) interrupted aortic arch
2) Truncus arteriosus
3) Tetrology of Fallot

You see a lot of lesions, often from disseminated mycobacterial infections. Can also get salmonella and different viral infections.

pneumococcus infections are common.

(these are all part of NF-kB signaling pathway):
IRAK-4
MYd88
NEMO
IkBa

1) Bruton's Aggamaglobulinema (bruton's tyrosine kinase deficiency)
2) Hyper IgM syndrome
3) B cell receptor and signaling deficiency
4) Common variable immunodeficiency (CVID)
5) Selective IgA deficiency
6) IgG subclass deficiency

Probably Bruton's tyrosine kinase deficiency

Autosomal Recessive Hyper-IgM syndrome

1) patients present later in life
2) doesn't look like anything is wrong
3) T cells can't activate B cells to make Ab, so lymphocytes build up and you get - lympadenopathy and splenomegaly
4) chronic infections - esp Giardia

Multifocal osteomyelitis - infections of the bone

1) Leukocyte adhesion deficiency (LADI) - leukocytes can't get firm adhesion to endothelium
2) Chediak-Higashi syndrome --> defect in granules
3) chronic neutropenia - neutrophils can't make elastase, can't mature
4) interferon/IL-12 pathway defects - mycobacterial infections
5) TLR defects - already mentioned

Inability of phagocytes to make hydrogen peroxidase due to defect in NADPH oxidase.

Staph. aureus, serratia marcescens, aspergillus, and mycobacteria. Particularly organism that have catalase to destroy the little H202 left in patients

Nitroblue tetrozolium or flow cytometry

autoimmune disease due to inability to clear Ab-Ag complexes

Infections in infants 6-18 months, when they run out of maternal antibodies. This is often seen with IgG deficiency.

Sickle cell occluding vessels causing ischemia of spleen.

Asplenia, Sickle Cell, COPD in lungs, CSF leaks, thoracic duct damage, protein loss in gut, kidney problems, burns.

Malnutrition

Encapsulated organisms - streptococcus pneumoniae, haemophilus influenza, Neisseria meningitidis.

Howell-Jolly bodies in the blood --> basophillic nuclear remnants in RBC's

Autosomal recessive with:
Spleen --> hypoplasia or aplasi
Complex heart formation
Malposition of Gi
Neurological abnormalities

Intestinal Lymphangiectasia --> messed up lymph drainage in GI that leads to loss of IgG

1) Malabsorption, loss of antibodies, intestinal lymphocytes, and overall blood protein
2) leg edema
3) lymphopenia
4) skin anergy - delayed reaction in skin test, proof of decreased T cell function

B2 transferrin in the nasal drainage.

No bc with Ab deficiency you will see sinusitis AND respiratory infection.

1) aspiration pneumonia
2) neonatal lung diseases
3) heart problems
4) immunodeficieinc y
5) asthma (severe)
foreign body
6) cystic fibrosis
7) ciliary dyskinesis

lower respiratory infections, bronchiectasis, asthma, and pseudomonas infections

Kartagener Syndrome

In addition to the peripheral neuropathy in feet, yo uget defecting chemotaxis and phagocytosis due to chronic acidosis

Rhinocerebral mucormycosis, which are molds (Mucro and Rhizopus), which have more iron avaiable to them due to low pH

Chronic Lymphocytis Leukemia - here you get normal b cells replaced with malignant ones, and you get hypogammaglobulinemia

Systemic Lupus erythematosus

Vasculitits of small blod vessel due to high levels of circulating immune complexes. Treat with steroids to decrease immune response.

A drug that targets CD on B cell and eliminates B cells. Good treatment for rheumatologic conditions

a monoclonal antibody taht wipes out a lot of leukocytes. Used in cancer chemo.

Type I (IgE mediated)

Type I - IgE mediated
Type II - Fc receptors/complement
Type III - immune complex mediated
Type IV - delayed type hypersensitivity, cellular

Allergic rhinoconjunctivits (hay fever) - 20% of people affected

Atopic dermatitis - chronic inflammatory skin problem. Sometimes caused by leaky epithelium tight junctions

1) Alpha chain that binds IgE with HIGH affinity
2) gamma chain with signaling ITAM domian

Antibodies to IgE or IgE receptor.

Eicosanoids - leukotrienes and prostaglandins
Cytokines - TNF-a, IL-4,5,6

Tryptase (mostly alpha isotype)

1) pruritus (itching)
2) increase vascular permeability/vasodilation
3) smooth muscle contraction - lungs/bronchii especially
4) gastric acid secretion

1) local arteriolar dilation and redness (erythema)
2) widespread flare from realease of substance P
3) Wheal produced by vascular permeability

a prolonged, mostly cellular response caused by cytokines and leukotrienes that continue to increase mucous secretion and inflammatory process. TNF-a is big and important here

The idea is that a high dose will convert the IgE response to an IgG response, so that IgG will bind antigen before it even gets to IgE

a monoclonal anti-IgE antibody used to treat Type I hypersensitivity

Type II occurs on surface (i guess of pathogen)
Type III occurs with immune complexes.
BOTH involve IgG

Type II

Type II

1) first pregnancy, mother who is Rh- has an Rh+ baby, and some of his RBC's leak into her, so she makes Ab to it.
2) subsequent pregancy, with Rh positive fetus, can cause hemolytic anemia

drugs absorb to surface of RBC's, and usually IgM or IgG3 will bind to them and lyse RBCs. It's a type II hypersensitivity.

in situ activation of complement, anaphylatoxin (activation of mast cells/phagocytes), complex mediated phagocytosis and release of granules

1) arthus reactions
2) hypersensitivity pneumonitis
3) Immune complex-mediated glomerulonephritis
4) serum sickness

A type III hypersensitivity reaction that occurs after introduction of antigen into individual with LOTs of antibody to it, so you get a lot response within 3-6 hours

different "workers lungs" b/c people make IgG to proteins they are inhaling repeatedly, leads to an "arthus reaction" in the lungs essentially

allogeneic serum, antivenom from other animals, infections, drugs, autoimmune disorders. It's a type III hypersensitivity event, lead to a lot of immune complexes in the blood

In areas of tortuosity - blood vessels of kidney, choroid plexus, brain, ciliary bodies in eye) and can cause glomerulonephritis

Type IV - Cellular hypersensitivities

Type Iv hypersenstivity - b/c antigen persist (TB) and T cells are constantly activaetd

1) Contact dermatitis - poison IV
2) Foreign body reaction - implant
3) Infecction related (TB, fungal)
4) Chronic graft

Type IV.....?