Disease X-Linked Agammaglobinemia or Brutons CD40 Ligand Deficiency

Gene/Absence BTK gene Heavy Chain Formation in Pre B cell CD40L Gene

Symptoms No B cells, No tonsils, Recurrent extracellular bacterial infections Susceptible to Pyogenic & Opportunistic infections

Diagnosis Susceptible to pyogenic infections FACS for CD 19 Hyper IgM; Very low IgG and undetectable IgA No class switching or Somatic Hypermutation Hyper IgM; Very low IgG and undetectable IgA No class switching or Somatic Hypermutation Flow Cytometry CD 27 and IgD

Treatment IgG injections Antibiotics

Immunoglobulin Replacement Therapy Intravenous Immunoglobulin Therapy Intravenous Igs

AID Deficiency

AID Gene

Susceptible to Pyogenic Infections only

Common Variable Immunodeficiency

Unknown

X-linked Severe Combined Immunodeficiency (SCID)

Defect in common gamma chain of IL-2 receptor (shared by IL-4R, IL-7R, IL-9R, IL- 15R, and IL-21R) (Xq11)

Variable but mostly respiratory GI infections, No specific antibodies Low IgG, M, A Skin rash, thrush, diarrhea, pneumonia

Low Lymphocyte count, no reaction with anti-cd3, anti cd16, low igA

Adenosine Deaminase Deficiency (ADA)

Bacterial antigen bound to Red Blood cell stimulating an autoantibody reaction by IgM or IgG. RAG gene missense mutation

Low haemoglobin count. Pale palour, and persistent cough.

Agglutination of IgM at 4 degrees (blood clumping) Or IgG at 37 degrees.

Omenn Syndrome

Characteristic red rash. Opportunistic infections

Decrease of both T and B cells, eosinophilia, immunoglobulins low except for IgE

Bone marrow transplant, gene therapy, immunoglobulin replacement therapy, treatment with polyclonal mitogen Erythromycin (to treat the bacterial infection) or in extreme cases plasmaphoresis. Bone marrow transplant and immunosuppressan ts

MHC II Deficiency

C11TA

Increase susceptibility to extracellular pathogens.

Decrease CD4 count decrease Ig, CD8 count normal, neutrophilia FISH, Flow cytometry ELISA, Western Blot, PCR

DiGeorge Syndrome HIV

Thymus CD4+ T cells

Chronic infections, heart defects Chronic infections??

Graft v.s. Host Disease

CD4+ cells from donor bone marrow initiate attack against the recipient

Watery diarrhea, fever, rash on face (1st), neck, palms, soles

Diagnosed based on prior bone marrow transplant along with the symptoms that present

Bone marrow transplant and immunosuppressan ts Thymic tissue transplant HAART (combination of NRTIs, NNRTIs) Immunosuppresant s:1. Cyclophosphamide
(interferes w/ lympho proliferation by interfering with DNA synthesis), 2.

cyclosporine A/ tacrolimus (blocks

the calcineurindependant activation of NFAT required for synthesis of IL-2 so there will not be proliferation of Tcells),

3. corticosteroids
(block IL-1 from APCs thus Th cells cant be activated/ inhibit inflammation/ inhibit macrophage cytokine production)

MHC Class I Deficinecy

Non-sense mutation in TAP2 gene

Susceptible to viral infections and respiratory infections (secondary to

damages caused by viral infections)

MHC Class 1 is not expressed (only very low amount expressed)/ Low CD8+/ Normal CD4+; Flow Cytometry

Treat as each symptom appears; if severe case then a bone marrow transplant can be done

X-linked Lymphoproliferative Disease (XLP) Hemophagocytic Lymphohistiocytosis Chediak Higashi Syndrome Wiskott-Aldrich Syndrome

Lack of SAP protein

Skin hemorrhages, Enlarged lymph node Cytopenia, Hepatosplenomegaly, Coagulopathy Oculocutaneous albinism

Use of Northern Blot, Western Blot, and Flow Cytometry Flow cytometry (absence of perforin) Peripheral blood smear = giant cytoplasmic granules Western blot to detect if there is expression of WAS protein

Bone marrow transplant, Steroids Immunosuppresant s, HSCT Prophylactic antibiotics or Bone marrow transplant Bone marrow transplant, IVIG, prophylactic antibiotics, sterioids Hormonal replacement, bone marrow transplant, anti-depressants Immunosuppressio n, hematopoietic stem cell transplant No Cure Immunosuppresion Anti inflammatory steroids Splenectomy (severe cases) IV antibiotics and Ig replacement G-CSF and Ig replacement

Lack of perforin (FLH 2) Intracellular vesicle trafficking

WAS gene is mutated, absent WASp. Poor actin polymerization in T-cells.

Eczema, bloody diarrhea, thrombocytopenia with small platelets, recurrent infections

APECED

Abnormal AIRE gene, no AIRE protein. No negative selection of T-cells in thymus- affects cental tolerance Dysfunction of FoxP3 affecting the function of regulatory T-cell

Sluggish, dry skin, retarded growth, hypothyroidism

Genetic testing for AIRE gene, blood tests to evaluate Ig & lymphocytes

IPEX

Dermatitis, diarrhea, diabetes

Genetic testing for FoxP3 gene, FACS analysis of T-cells

ALPS

FAS Gene mutation.

Splenomegaly Lymphodenopathy Increased WBC/Immunoglobulins

Lymph node biopsy Blood work Flow Cytometry

Hyper IgE Syndrome WHIM Syndrome

Missense mutation of STAT3 (defect in JAK signalling path) Mutation of gene coding CXCR4 (defective cell homing)

No inflammatory response since TH17/IL-17 fucked up Warts, Hypogammaglobinemia, Infections, Myelokathexis

Serum IgE, Flow Cytometry of IL-17 CXCR4 gene sequencing on Chr 2

Severe Congenital Neutropenia

Mutation of ELA2 gene (codes for neutrophil elastase)

Persistent bacterial/fungal infections

ANC, Bone marrow aspirate

Rheumatoid Arthritis

Constant B cell activation, IgM antibodies against IgG and IgA, Excess pro inflammatory cytokine production by macrophages Type I Interferons secretion in response to TLR , Type I interferons activates T cell which activates B cell (class switching & Ab production),

Morning sickness, Arthritis in hand joints, swelling in wrist, MCP joints & Interphalangeal joints

Antibodies against Rheumatoid factor and citrullinated peptides, immune complexs deposited in joint tissues NO rheumatoid factor, Antibody against self ds- DNA, Anti-Smith (for ribonucleoprotein) Coombs test, Increase IgG, Excess immune complexes present EMSAf, Flow Cytometry of B-cells or CD23 and CD54 with anti-40 Antibodies Ultrasound and CT scan Blood test Lymph node biopsy Acid-fast stain for mycobacteria Genetic testing for IFNGR1 gene mutation

Systemic Lupus Erythematosus

Butterfly facial rash, myalgia, fever, enlarged lymph nodes behind ear, weight loss, Raynauds phenomenon (fingers and toe discolouration in cold temp)

therapy Give rhG-CSF to stimulate proliferation and maturation of neutrophils (note: AML as side effect) Anti-inflammatory drugs, Intravenous infusion of monocolonal Ab against TNF-alpha NSAIS for inflammation, Corticosteroid creams For rash

X-linked Hypohidrotic Ectodermal Dysplasia and Immunodeficiency Interferon-gamma Receptor Deficiency

NFkB Signaling Pathway Lack of Ab Response to Polysaccharides

Mutation of interferon-gamma receptor 1 (FNGR1) gene

Ectodermal Dysplasia Bacterial infections Diffuse granulomatous Inflammation Skin rashes Recurrent mycobacterial infections Poor appetite; diarrhea; weight loss Enlarged lymph nodes and spleen Lung infiltrates Sepsis

Immunoglobulin replacement therapy Anti-mycobacterial antibiotics Antibiotics IFN-gamma administration Bone marrow transplant

Chronic Granulomatous Disease

Killing (NADPH Oxidase)

Recurrent infections Abscesses of the skin Elevated serum IgG, IgM, and IgA Cotton Ball densities in lungs

NBT dye to test for reduction in neutrohils DHR reduction by neutrophils tested will FACS

Injections of interferon- Prophylactic Ab. Bone Marrow transplant Bone marrow transplantation Some gene therapy IV erythromycin Rhogam, blood transfusion Epinephrine, Antihistamines (benedryl), and avoidance of allergens Benadryl, naproxen, prednisone Corticosteroid and avoidance

Leukocyte Adhesion Deficiency

CD18 Beta 2 integrin

Autoimmune Hemolytic Anemia Hemolytic Disease of the Newborn Acute Systemic Anaphylaxis

Hypersensitivity Type 2 Hypersensitivity Type 2 Hypersensitivity Type 1 (IGE and Mast cells)

Omphalitis , Systematic infections, poor wound healing, unimpeded spread of infection, and injury to important tissue. Persistent cough, pale hands, rhonci sounds in lungs Anemic fetus Vasodilation, bronchoconstriction

WBC differential Neutrophil count Monoclonal-Ab testing for CR3 Blood work Coombs Test (direct or indirect) Symptomatically, confirmed by Allergen Scratch Test

Drug-Induced Serum Sickness Contact Sensitivity to Poison Ivy

Hypersensitivity Type 3 (due to penicillin administration) Hypersenstivity Type 4

Rashes, splenomegaly, swelling in joints/mouth, enlarged lymph nodes Rash and blisters

Blood smear

Rash and blisters without any other symptoms such as fever

Note: The last 5 diseases are more general on the table, because they are specific examples of each type of hypersensitivity. You may need to look at their presentation for more details on the topic. Note 2: I did not get DiGeorge, HIV, Autoimmune Hemolytic Anemia, Hemolytic Disease of the Newborn, nor Drug-Induced Serum Sickness from the groups, so please do verify if the content on the table is accurate. I just put on the table, whatever I could find on their presentation.