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In fetal development, innate and cellular immunity start developing first with macrophages in the liver and blood and T-cell precursors in the liver by 5-6 weeks gestation. At 9-10 weeks, compliment synthesis begins, B precursors appear in the liver, and T precursors appear in the thymus. By 12-14 weeks, the fetus has macrophages in lymph nodes and APC MHC class II, Pre-B cells with IgD, IgG, and IgA; CD4+ and CD8+ T cells in the liver and spleen, and the start of mother's IgG transfer. By 16-17 weeks, fetus has mature macrophages in the liver and circulating neutrophils, Large numbers of B cells in the spleen, blood and bone marrow, and T cells in the blood and lymph tissues with rearrangement of receptors. At 20-30 weeks, babies B-cells secrete antibodies, there is a gradual increase of T cells secreting lymphokines, and a gradual increase of IgG transportation from the mother.

When babies are born prematurely, they lack physical barriers (skin), stomach acidity (less pepsin and trypsin), normal flora, and IgA (needed in respiratory and urinary tracts). Leukocytes are less able to concentrate, are less bactericidal, and less phagocytic. Dendritic cells have low expression of co-stimulatory molecules (eg. CD40) to activate naive T cells and also produce IL-4 and IL-10 that activate Th2 more so than IL-12 that activates Th1. Th2 cells produce IL-4, which induces apoptosis in Th1 cells. This promotes Th2 response more than Th1, leading to reduced production of pro-inflammatory cytokines. Reduced CD40 expression by B cells reduces T-dependent antibody responses, decreasing antibody production, isotope switching, and affinity maturation.
~Light Microscopy - fresh or stained specimens are examined directly to visualize bacteria, protozoa, or host cells with good specificity but low sensitivity

~Culture - recovery of live organisms requires media (host cells if viral culture), incubator, and sometimes light microscopy to identify microbes. It has high specificity and higher sensitivity than light microscopy but lower sensitivity than nucleic acid amplification tests (NAATs). Necessity of live organisms decreases risk of false positive (due to remnants of dead organisms still in system)

~Immunoassays - detect antigens or antibodies in biological specimens. Antigen indicates current infection while antibodies indicate past infection (note: not all infections cause antibody production).
ELISA (enzyme-linked immunosorbent assay) - to detect antigens, attach the Fc portion of a specific antibody to the ELISA plate so that the Fab region can bind to specific antigen in the sample if present. Then add the primary detection antibody that will bind to that antigen followed by a labeled secondary detection antibody that binds to the primary detection antibody's Fc region. To detect antibodies, attach the antigen to the plate first and then follow with the sample that may contain the antibody. Follow with a labeled antibody that binds to the Fc region of the sample antibody.
Western Blots
Rapid immunochromatographic strip tests - a liquid sample travels up through absorbent material and if the antigen is present, it will bind to a certain area containing antibodies and turn a color (eg. rapid strep)
Particle agglutination tests - to test for presence of an antigen (eg. staph aureus), add a solution with antibody that will make the antigen clump up if present.

~Nucleic acid amplification tests (NAATs) - Molecular detection assays for bacteria, viruses, and eukaryotic pathogens that target and amplify microbial DNA or RNA using PCR, rcpt., transcription mediated amplification, strand displacement amplification, etc. These are more sensitive than microscopy, culture, or antigen detection and more specific. They don't require live organisms (which can lead to misleading positive results even after all the pathogens have been killed). Increased sensitivity allows for use with non-invasive specimens (urine sample rather than endocervical/urethral swab)
~Inactivated vaccines include whole bacteria/viruses that are produced by growing large number of them and killing them with heat or chemical fixation. Inactivated bacterial vaccines provide limited, short lived protection and are not used routinely in the US. Inactivated viral vaccines also don't provide as good or long-lived protection but some are used in the US (flu, rabies, polio (Salk) vaccine.

~Attenuated, live vaccines - produced by repeated passages of the organism through cell culture or lab animals until a non-virulent organism (weakened but can still replicate) is isolated. They are effective and generate long term protection that may be lifelong (but sometimes need boosters). Live viruses can infect cells so that a good antibody response and CTL response is produced. Examples include measles (rubeola), mumps, rubella, chickenpox, rotavirus, and live (oral) influenza vaccine. Live vaccines can also be bacterial (eg. BCG for TB). Those with immune deficiencies should not get live vaccines because they can become infected (if CD4+ is above 15% of normal, then it's OK). Those seeing patients who are immunocompromised shouldn't get live vaccines because they might spread it to them.

~Purified antigen/subunit vaccines - Toxoids are inactivated usually via chemical modification and are very effective immunogens (diphtheria, tetanus).
Purified polysaccharide antigens - not efficient at inducing longer protection because T independent, but they are more effective when coupled to proteins (adjuvant) to create conjugate vaccines. Purified antigen and subunit vaccines are very safe but have a short shelf-life, are hard to produce, and con't stimulate CTL response because they are recognized as exogenous antigens.

~Synthetic/recombinant antigen vaccines - the active part is a synthesized protein or amino acids that mimic antigenic epitopes on a particular virus or bacteria. An example is Hep B vaccine. These are safe but have a short half life, are hard to make, and don't stimulate a significant CTL response.

~Polyvalent/combination vaccines - these reduce the number of injections but not all can be combined because immune response to one component may hinder the response generated to another. There is a combination vaccine with antigens for diphtheria, tetanus, pertussis (acellular vaccine), hep B (recombinant protein), and Haemophilus influenza b (Hib)
When HIV first invades the host through epithelial mucosa, it reaches regional lymph nodes within a few days and then enters the blood stream to travel to many organs. At first it is not detectible because it has entered cells, but products of replication make HIV detectible. p24 can be detected after 1-2 weeks (recombinant peptide ELISA) and antibodies can be detected after 3 (viral lysate ELISA). Its p24 antigen (capsid protein) is detectible but then decreases with seroconversion (when antibodies created targeting it). Antibodies are created to respond to it and other envelope and core antigens, but they are quickly obsolete because of HIV's quick mutation rate. CD8+ T cells are activated and can be detected throughout infection and CD4+ T helper cells stimulate cytokines like IL-2, IFN-gamma, TNF to evoke a multi-cellular cell mediated immunity response. The highest viral load is often 2-3 weeks into infection (and you are most infectious) as immune response tries to catch up.

Acute HIV infection causes decimation of T cells so that MALT is wiped out within the first few weeks from the huge viral load. After this, you may never regain your full T cell levels. While CD4+ levels plummet, HIV antibody and CD8+ cells rise and remain elevated throughout long-term infection. CD4+ levels rise somewhat at the end of acute infection (weeks) as viral load drops with immune system activation. During the asymptomatic period, people reach a viral load set point where viral replication is balanced by the immune response. If untreated, T cell levels fall and viral load increases in an asymptomatic state until the person develops AIDS. AIDS or death is reached in 2-20 years (10year average). (Some are elite non-responders with undetectable viral load even without antivirals. HIV with deleted nef gene leads to low viral load and slow CD4 loss in some). AIDS is the result of HIV-induced loss of pathogen-specific immunity.
Fungal infections are common in AIDS (CD4 < 200), including cryptococcus (causes meningitis and disseminated infection), candida (esophagitis), and Pneumocystis jiroveci pneumonia (PCP - the most common opportunistic infection causing pneumonia). PCP causes shortness of breath, non-productive cough, sometimes fever, hypoxemia (O2 desaturation), and elevated lactate dehydrogenase. On X-ray, the heart often has a wispy rather than crisp border. Bacteria or Septra are used prophylactically in those with CD4 < 200.

Viral infections common with AIDS include Cytomegalovirus (CMV) that causes retinitis, esophagitis, colitis, and affects the CNS. CMV is an enveloped dsDNA virus that most people have been infected with but that becomes reactivated in 80-100% of those with HIV when they have a very low CD4 count (<50). DNA viruses can establish latency and become oncogenic - HHV-8, EBV, HPV, HBV/HCV.

Human herpes virus (HHV)-8 is also common and causes Kaposi's sarcoma and primary effusion lymphomas. Kaposi's sarcoma can present in those with a CD4>200 and includes lymphadenopathy and edema and can involve the lungs and GI tract. Cutaneous forms may resolve with immune recovery.

Protozoa that cause infections in AIDS patients include Toxoplasma gondii and Cryptosporidia in the GI tract (causes diarrhea).

Bacterial infections include mycobacterium avium complex. Mycobacterium avium complex involves diffuse infection of multiple organs (GI, spleen, liver, marrow) in those with CD4<100. Symptoms include fevers, night sweats, diarrhea, weight loss, high alkaline phosphatase, and anemia. Diagnosis is done with lysis centrifugation culture. In those with CD4<50 Azithromycin is taken prophylactically.
Diagnostic testing - testing someone based on clinical signs

Targeted testing - testing subpopulations at higher risk

screening - testing all persons in a population. All age 13-64 and those at high risk should be screened.

Opt-out screening - today you must tell patients that you are testing them for HIV and they must decline in writing if they don't want it done.

In the past, western blots and ELISA were used to test for HIV antibody, and HIV culture and HIV DNA/RNA PCR were used to test for the virus. Today, 4th generation HIV immunoassays (Abbott Architect HIV Ag/Ab Combo Assay) are performed that detect antibody and antigen (using p24) with 99.8% specificity and 100% sensitivity in established infection. If the result is positive, you do a differentiation immunoassay (Bio-Rad Multispot HIV-1/HIV-2 Rapid Test) using a rapid enzyme immunoassay that detects/differentiates HIV-1 and HIV-2 antibodies using recombinant and synthetic peptide sequences representing envelope proteins.

Other tests include rapid tests like OraQuick Rapid HIV Ab Test, which can be used at home (has less sensitivity) and get results in 20-40min.

To diagnose HIV in infants, use Qualitative RNA PCR. At 1-2 days old, detects 30-40% of cases, at 2-3 weeks detects >90%, and detects 100% after 4 months of age. HIV ELISA or western blood can also be used after age 18 months. Can't use 4th generation screening tests with <18mo infants with HIV+ mothers because they will have received mom's antibodies and those test don't differentiate between HIV Ab and Ag.
Chronic Granulomatous Disease - causes recurrent bacterial infection with catalase positive organisms (Staph, Serrate, Aspergillus) and granulomas of the skin, liver, lungs, and lymph nodes. Phagocytic cells ingest but can't kill bacteria because they can't form oxygen radicals. An X-linked or AR gene defect prevents electron transfer by phagocyte NADPH Oxidase (PHOX) needed to produce the superoxide (O2+). CGD is diagnosed using nitroblue tetrazolium dye test, superoxide radical formation (chemiluminescence) test, or flow cytometry (dihydrorhodamine 123 assay).

Leukocyte Adhesion Deficiency - caused by an absent beta subunit (CD18) of 3 cell surface glycoproteins (beta2 integrins). Neutrophils can't migrate to inflammatory stimuli or adhere to the vascular endothelium. It's diagnosed using recurrent soft tissue infections, delayed umbilical cord separation, severe periodontal disease and no pus formation despite high white blood cell counts.

HyperIgE syndrome (Job syndrome) - causes recurrent staph abscesses, sinopulmonary infections, and severe eczema; regained primary teeth; recurrent Candida; and recurrent bone fractures. IgE levels are very high, usually >2000, and they have peripheral eosinophilia. The underlying defect affects CD17 and neutrophil migration.

Compliment disorders - deficiencies in the classical pathway (C1, C4, C2) can cause autoimmunity. For example, defects in C1 esterase inhibitor lead to Hereditary Angioedema that causes massive swelling without itching or hives. Deficiencies in C3 can lead to problems with encapsulated bacteria and autoimmune disease. Deficiencies in late compliment (C5b-C9) lead to susceptibility to neisserial infections.

Defects in innate immunity are diagnosed using CBC with differential, neutrophil function tests (oxidative burst, chemotaxis assays, and presence of CD18beta), and assays for compliment.
HIV/AIDS, malnutrition, immunosuppressive therapy, malignancy, autoimmune disease

Disorders of biochemical homeostasis leading to chronic imbalance of hormones, nutrients, and toxic metabolic waste products like diabetes, dialysis/uremia, cirrhosis. Diabetes is associated with decreased neutrophil function that correlates with the level of hyperglycemia, poor peripheral circulation that increases the risk of skin ulceration, and candidiasis and other fungal infections. Hemodialysis reduces T cell, neutrophil, and dendritic function and decreases Ig production. Chronic peritoneal dialysis removes immunoglobulin and complement with the dialysate, compromising peritoneal neutrophil function. Cirrhosis increases risk of bacterial sepsis and peritonitis and leads to higher endogenous glucocorticoids and low complement levels.

Disorders of protein loss - nephrotic syndrome, peritoneal dialysis, protein losing enteropathies (poop it out - IBS, celiac, intestinal lymphangiectasia), and severe dermatitis can lead to hypogammaglobulinemia that often presents as low IgG and IgA with near normal IgM. Patients may not have increased susceptibility to infection and have a positive but low titer. To determine that it's protein loss causing decreased Ig, give them an IVIG and see how rapidly the levels drop. In nephrotic syndrome (kidney disease with protein loss), patient have very low Igs and depressed cellular immunity from vitamin D and other serum factor loss. Patient are treated with immunosuppressive drugs like glucocorticoids that further increase the risk of infection, leading to recurrent respiratory tract infections, urinary tract infections, Varicella, peritonitis, and sepsis, especially with encapsulated bacteria like strep pneumonia. In those with recurrent infection and low IgG, IGIV may be helpful.

Trauma/burns - cellular necrosis from trauma causes widespread activation of monocytes and macrophages that release inflammatory cytokines (IL-1, TNF). Burn trauma causes more severe immune suppression than mechanical trauma because they disrupt a large area of skin that provides nonspecific defense (increased loss of fluids and proteins also increases infection risk).

Environmental exposures - ionizing radiation from X-rays and gamma rays damages DNA, impairing cell division and immune function; may induce apoptosis; cause DNA damage leading to malignancy; damage local barriers in areas with high rates of cell division (gut>skin), and decrease B and T cells (bigger impact on B cells and T cells recover faster), diminishes primary antibody response, and affects lymph tissues. The functioning of macrophages is unaffected. UVB radiation from the sun is the major risk factor for skin cancer and can diminish function of all skin immune cells. Toxic chemicals also impact immune system.

Splenectopy/hyposplenism - atrophy can be caused by sickle cell disease, autoimmune disease, severe celiac, IBS, chronic graft-vs-host disease, and untreated HIV infection. There is a greater risk of sepsis from encapsulated organisms. Immune suppression is managed with immunization and sometimes antibiotic prophylaxis.

Life events - cellular immunity is depressed during pregnancy to prevent rejection of the fetus, but this increases risk of infections controlled by cellular immunity (Hep A and B, influenza, herpes, chlamydia, listeria, TB, and fungal, protozoan, and helminthic infections). Stress diminishes cellular immune function, NK cell activity, and lymphocyte mitogen responses.

Infections (other than HIV) -
Measles suppresses the immune system, leading to superinfection, most often pneumonia, gastroenteritis, otitis media, gingivostomatitis, and other upper respiratory infections (staph aureus and strep pneumonia). Measles virus infects T cells and dendritic cells so that T-dependent areas of lymph nodes and spleen are depleted leading to T cell lymphopenia, T cells do not respond as well to mitogens, antibody production is diminished.
Herpesviruses - can cause transient depression of cell-mediated immunity, especially CMV.
Parasites - immune suppression from protozoa infection is greater than any other microbe (but HIV). Decreased cell-mediated immunity in malaria leads to increased susceptibility to infection, delayed graft rejection, and higher rate of malignancies.
Superantigens (from staph and strep) significantly stimulate the immune system but ultimately lead to a decrease in T cell number and activity and a decrease in neutrophil function.
Serum sickness - immune response to a large amount of injected antigen (like serum of other people or animals or penicillin), causing a variety of symptoms including fever, hives (C3a releases histamine from mast cells), joint pain, spelnomegaly, asthma, and disorientation (from compromised O2 delivery to brain b/c of vasculitis in small blood vessels). When there is antigen excess and a rapid IgG response, small immune complexes are formed and taken up by endothelial cells in various body parts and become deposited in those tissues, activating complement there and leading to inflammation (this is in contrast to instances when there is a large amount antibody relative to antigen and large immune complexes form and are taken up (cleared) by phagocytic cells). Very rarely, this can happen in response to chimeric mAb treatment and cause purpuric rash with neutrophil-rich vasculitis with presence of immune complexes in the vessel walls, hematuria, and proteinuria. You can see if the immune complexes are developing around mouse protein of the chimeric mAb by labeling antibody that is specific to the mouse protein with phosphorescence.

Systemic lupus erythematosus (SLE) - Characterized by defective B and T cell tolerance to self antigens. Loss of self-tolerance occurs when defects increasing apoptosis and/or reducing opsonizing factors and phagocytic activity to clear apoptotic cells leads to an increase in apoptotic cells. In the peripheral tissue, this causes inflammation and CDs in the peripheral tissue phagocytose and express auto antigens to T cells so that T cells lose tolerance. In lymph nodes, auto reactive B cells are exposed to the apoptotic nuclear particles and lose self cell tolerance. B cells produce autoantibodies that mainly target the nuclear constituents. This can cause (SOAP BRAIN MD)
Serositis,
oral ulcers,
arthritis,
photosensitivity,
blood (cytopenias),
renal (nephritis),
anti-nuclear antibody production (eg. to Smith nuclear antigen),
immunologic (pleuritic, pericarditis, cytopenia (type II hypersensitivity)),
neurologic (seizures, psychosis),
malar rash (butterfly rash that spares nasolabial folds), and
discoid rash.
It is most often diagnosed after 20 years old, is more common in blacks and asians that whites, and affects females more than males, especially when women are of childbearing age. Estrogen drugs can increase symptoms, so hormones may play a role. It has a genetic component, and compliment deficiency (C1q, C2, and C4) is the strongest genetic risk factor for developing lupus because a lack of C1q prevents you from clearing immune complexes, increasing the risk for autoimmunity. A gene on the X chromosome may be involved in lupus, and those with lupus have increased prevalence of Kleinfelter's syndrome (XXY) and decreased prevalence of Turner syndrome (XO)
Bacterial infection of the kidney tubules leads to an antibody-driven hyperinflammatory response followed by infiltration of PMN immune cells. (this is in contrast to viruses that cause type IV inflammation and involve mononuclear cells).

Severe inflammation of the glomerulus can cause crescent formation when necrosis leads to the deposition of fibrinous material, and inflammatory mediators fill the Bowman space and induce the proliferation of epithelial cells. Immunofluorescence microscopy is used to detect IgG deposition using labeled rabbit anti-human IgG. This can be caused by type II, type III or noncanonical immune injury. Type II immune injury is caused by anti-glomerular basement membrane antibody (Anti-GBM) glomerulonephritis and produces fluorescent images with clear/distinct squiggles (linear staining). Anti-GBM disease can occur in the kidney or lungs and is treated with retuximab (antibody to CD20) and plasmapheresis to remove plasma with antibody and replace it with plasma without antibody. Type III immune injury from immune complex induced inflammation is seen in Lupus glomerulonephritis produces blurred squiggles (granular staining). Non canonical injury is caused by anti-neutrophil cytoplasmic autoantibody (ANCA) glomerulonephritis (neutrophils activated by antibodies, triggering compliment cascade) and leads to little IgG antibody deposition so images are dark. ANCA is detected by adding patient serum to normal human neutrophils dried onto class slides. The bound antibodies are detected with flouresceinated anti-human IgG.
Immune complex disease and ANCA disease can affect any tissue and organ, and vessels are often targeted.
When someone is first exposed to an antigen/allergen (generally a low molecular weight protein), that allergen binds to receptors on B cells and induces them to activate TH2 cells, which release IL-4, IL-5, and IL-13 that stimulate IgE class switching in the B cells. In those who become atopic, greater levels of IgE are produced than normal. The Fc region of IgE binds to receptors on mast cells, leaving the Fab region to bind to the allergen during future exposures. Allergen binding activates mast cells and basophils to release preformed granules of histamine enzymes, proteases, and vasoactive amines that increase vascular permeability and stimulate smooth muscle cell contraction, causing immediate hypersensitivity reaction. They also release lipid mediators (PG, leukotrienes, platelet activating factor) that cause vasodilation, bronchoconstriction, mucus secretion, intestinal hypermotility, and vascular permeability. Later, mast cells and basophils produce and secrete (i.e. not preformed) cytokines (IL-4, IL-5, IL-13, TNF-alpha) that cause inflammation, IgE production, and eosinophil production/activation in the late phase reaction 2-4 hours after exposure. Eosinophils are bone marrow-deprived granulocytes that are recruited by IL-4 and activated by IL-5. They contain preformed cytoplasmic granules that cause tissue damage/remodeling and that are toxic to helminths, bacteria and host cells. Lipid mediators produced on activation prolong bronchoconstriction, mucus secretion, and vascular permeability and cytokines produced upon activation further activate eosinophils and cause chemotaxis of leukocytes.
Generative (central) tolerance develops in the thymus (T cells - deletion and regulatory T cells) and bone marrow (B cells - receptor editing, deletion, and anergy).

In the thymus, double positive thymocytes undergo positive selection in the cortex with the help of cortical Thymic Epithelial Cells (cTEC) such that T cells with weak recognition of Class II MHC (CD4+) or of class I MHC (CD8+) are selected for. Those that survive go to the medulla and undergo negative selection with the help of medullary epithelium (mTEC), such that those that bind strongly to class I or class II MHC are deleted (apoptosis). mTEC contain Autoimmune regulatory (AIRE) proteins that present peripheral tissue self antigens on MHC to the T cells. Those that bind to self antigen either undergo apoptosis (deletion) or become regulatory T lymphocytes (CD4+ T cells only). Natural regulatory T cells (from the thymus) enter the periphery and contain CD3, CD4, and CD25 as well as FoxP3+ (necessary transcription factor) and inhibit responses against self-antigens by inducing CTLA-4 expression in T cells, expressing IL-2 receptors to capture IL-2 (so that it can't stimulate other T cells), and by releasing anti-inflammatory cytokines IL-10 and TGF-beta. (induced regulatory T cells are created in the periphery).

In the bone marrow, B cells undergo receptor editing, deletion, and anergy. In receptor editing, B cells that are too self-reactive either re-express RAG genes to modify their Ig variable region so that it is not self-reactive or are deleted (apoptosis). B cells that don't recognize self antigen become anergic B cells.
Peripheral tolerance occurs in the spleen and lymph nodes.

T cell tolerance development involves anergy, suppression, and deletion. When T cells' TCR binds to the MHC protein on an APC without costimulation by APC's B7 (binds with T cells' CD28), the T cells become functionally unresponsive in anergy. Additionally, B7 on APCs can interact with CTLA-4 on activated T cells to down regulate T cells (anergy) and promote self-tolerance. PD-L1 on many types of cells and PD-L2 on APCs can also interact with PD-1 on activated T cells (and B cells) and induce the same effect. Peripheral T cells can also be deleted. Normally, intracellular anti-apoptotic proteins keep activated T cells alive, but if the T cell isn't co-stimulated, pro-apoptotic protein can be released from the mitochondria and induce apoptosis. Alternatively, FasL (death receptor ligand) and Fas (death receptor) can become expressed when T cells aren't co-stimulated. Two T cells expressing Fas and FasL can then interact with each other and induce apoptosis.
The binding of CD28 on T cells and B7 on APCs can also stimulate the generation of regulatory T cells. Regulatory T lymphocytes that develop in the peripheral tissues (induced rather than natural) contain CD3, CD4, and CD25 as well as FoxP3+ (necessary transcription factor) and inhibit responses against self-antigens by inducing CTLA-4 expression in T cells, expressing IL-2 receptors to capture IL-2 (so that it can't stimulate other T cells), and by releasing anti-inflammatory cytokines IL-10 and TGF-beta.

B cell tolerance involves anergy, deletion, and suppression via inhibitory receptors.
Stem cell transplant aims to eradicate a hematologic malignancy using donor-derived immune cells that target the cancer. Unlike with organ transplant, tolerance is not the goal (so not as effective to use identical twin donors). Recipients are given chemotherapy and radiotherapy to reduce the number of tumor cells as well as immunosuppression to prevent graft rejection. Donor immune stem cells are given to the recipient, and the hope is that donor WBCs will "take over" immune functioning. In the graft vs. leukemia effect (GvL), T cell donation is important as removal of donor T cells from the transfusion leads to poorer outcomes and T cell donations can increase the probability of remission. Using strong myeloablative drugs with the SCT does not increase survival compared with using nonmyeloablative drugs with SCT, which demonstrates that it's the stem cell graft that is treating the cancer (not drugs wiping out the recipeint's immune system).

Donors and recipients ideally have a "12/12 HLA match" - have the same DNA sequence for HLA-A, -B, -C, -DR, -DQ, and -DP genes. Some ethnic groups have many different HLA types while others have few. US blacks and native americans are underrepresented on the donor registry. SCT is performed across APO incompatibilities because hematopoiesis will be performed by donor's stem cells. You can remove anti-A or anti-B antibodies and red blood cells from the donor plasma. Blood products given to leukemia and SCT patients should be leukocyte reduced to minimize the risk of CMV transmission (CMV reduces survival by 7%) and also irradiated to destroy alloreactive T cells that can cause graft-vs-host disease. Males are preferred as donors because they would not have alloreactivity from pregnancy or Y-antigen mediated reactivity.