Biology and Human Welfare

Dysgerminomas, the most frequent germ cell malignancy, are principally solid. Such tumors are most frequent in women with dysgenetic gonads. Pure ovarian dysgerminomas cause an elevated LDH with normal hCG and a-fetoprotein levels.

Endometrial cancer begins in the layer of cells that form the lining (endometrium) of the uterus. The causes of endometrial cancer are still unknown.

Mutations in the BRCA 1 gene (located on chromosome 17) cause most of the ovarian epithelial cancers seen on a hereditary basis.

CA 125 is a mucin-type glycoprotein which is usually not expresses by mucinous tumors. The antigen (CA 25) is expressed by fetal amniotic and coelomic epithelium.

It is correct. 80% cases of lung cancer are due to smoking.Cigarette smoking is the most important cause of lung cancer. Cigarette smoke contains more than 5,000 chemicals, many of which are cancer causing.

There is a failure to make reactive oxygen intermediates and to raise the pH in the phagocytic vacuole which facilitates microbicidal action.

The c-myc gene (chromosome 8q24) involved in the entry of cells from resting G0 into the cell cycle is translocated to the mu heavy chain gene (chromosome 14q32) in most cases of Burkitt's lymphoma studied.

The HIV envelope protein gp120 binds to CD4. This targets the virus to this T-cell subset.

Strongly immunogenic tumors appears in immunosuppressed patients. For example, certain types of skin cancer and lymphoma seen in transplant patients receiving immunosuppression.

CXCR4 is a chemokine receptor which HIV utilizes as a coreceptor for entry into naive CD4+ T-cells and mature dendritic cells. Another chemokine receptor, CCR5, is used particularly for entry of HIV into immature dendritic cells, macrophages and activated effector or memory CD4+ T-cells.

The common gamma chain is encoded by the gene IL-2 receptor gamma, or IL-2Rγ, which is located on the X-chromosome. For this reason, immunodeficiency caused by mutations in IL-2Rγ is known as X-linked severe combined immunodeficiency. The condition is inherited in an X-linked recessive pattern.

gp120 is an envelope protein which binds to CD4 on the T-cell. Antibodies to the V3 loop of gp120 arise during the disease and are particularly effective as neutralising agents in vitro, although less so in vivo. Generally, neutralising antibodies are more effective against HIV-2 than against HIV-1.

CD8 numbers are largely unaffected. It is the ratio of CD4:CD8 that falls dramatically.

CLL is uncommon in people under 50 years of age.

There is no evidence that a high fat diet can lead to secondary immunodeficiency.

Epstein-Barr virus, human papilloma virus, hepatitis B virus, and human herpes virus-8 are the four DNA viruses that are capable of causing the development of human cancers. Epstein-Barr virus is associated with Burkitt's lymphoma and with naso-pharyngeal carcinoma.

Tum – cell lines are those which have mutated such that they cannot be grown in syngeneic animals with a normal immune system.

Point mutation leads to a single amino acid substitution at either position 12, 13 or 61. These mutations are found in over 90% of patients with pancreatic carcinomas, in 40% of patients with colorectal cancers and their preneoplastic lesions, in acute myeloid leukemia (AML) and in preleukemic syndromes.

Production of cytokines and of cytotoxic T-cells are important in the protective response.

In case of HIV infection this test finds either the RNA of the HIV virus or the HIV DNA in white blood cells infected with the virus. The PCR test is very useful to find a very recent infection.

Lack of CD154 (CD40L) prevents signalling to the B-cell CD40 to bring about Ig class-switching away from IgM.

Individuals with HLA-DR2 are more at risk of developing multiple sclerosis than those with other HLA-DR specificities. Thus a higher frequency of HLA-DR2 is found in MS patients versus the normal population.

Failure of regulatory T-cells would release the T-helper for direct stimulation by antigen. This statement is therefore incorrect, since this would not be a bypass of the T-helpers.

The mutation of the antibody variable region genes in B-cells in the germinal center produces a range of antibody affinities, and those B-cells bearing higher affinity antibody will be favourably selected for further stimulation by antigen.

The drug is called cyclophosphamide. It can be taken orally . Since it is a prodrug, it is not toxic to the gut wall when taken orally.

Integrins are a family of transmembrane glycoprotein receptors that mediate cell-matrix. They are involved in the anchoring of cells to an extracellular matrix. They affect tumour progression has made them an appealing target for cancer therapy.

Large adenomas in vital hormone producing organs raise the hormones the organ produces leading to serious complications called paraneoplastic syndromes.

Metastasis refers to the spread of a cancer to different parts of the body and the appearance of secondary tumours.

Angiogenesis is the term used to indicate the growth of new blood vessels.It is a normal and vital process in growth and development, as well as in wound healing.

Adenoma is a type of non-cancerous tumor or benign that may affect various organs. It is derived from the word “adeno” meaning 'pertaining to a gland'.Every cell in the body has a tightly regulated system that dictates when it needs to grow, mature and eventually die off. Tumors and cancers occur when cells lose this control and divide and proliferate indiscriminately.

Depsipeptide is derived from a bacterial strain and is reduced to an active compound that promotes apoptosis and inhibits cell proliferation and angiogenesis.

ADEPT stands for antibody-directed enzyme prodrug therapy entangling the association of an enzyme to an antibody. It is the use of monoclonal antibodies (or mAb) to specifically bind to target cells or proteins.

Neuroendocrine tumors (NETs) are a diverse group of benign and malignant tumors that arise from the body's neuroendocrine cells, which are responsible for integrating the nervous and endocrine systems.

For the HIV infection to occur the cell fusion is essential. This is done by the transmembrane glycoprotein gp 41. HIV-1 utilizes two major co-receptors along with CD4 to bind to, fuse with, and enter target cells.

LMP1 is the best-documented oncoprotein of the Epstein-Barr virus (EBV), latent gene products.

The gag gene is encoded as a large gag-pol protein with another gene then cleaved to the precursor protein assemblin, which is then cleaved to Gag. It is involved in virion assembly and produces some of the capsid and nucleocapsid proteins. It does not encodes for the lipid bilayer of the virus.

MASA syndrome, is a rare X-linked recessive neurological disorder. It is caused by mutations in the L1CAM gene.

HHV-8 infects lymphocytes and epithelial / endothelial cells and is the causative agent of Kaposi's sarcoma. It has also been associated with hematologic malignancies, including primary effusion lymphoma, multicentric Castleman's, MCD-related immunoblastic / plasmablastic lymphoma.

This is the major structural protein and covers the RNA genome. It protects the genome from nucleases and holds it in a conformation that allows transcription.

Although an X-linked disease, this is still the SCID with the highest incidence

LMP-2A is a transmembrane protein that act to block tyrosine kinase signaling. It inhibits activation of the viral lytic cycle.

Organ-specific autoimmune diseases, are defined as disorders in which the body’s immune response attacks healthy cells in a specific organ.Individuals with selective IgA deficiency have a higher risk of developing an organ specific autoimmune disease or allergies than the general population.

Candida dubliniensis has recently been recognised from the oral cavity of HIV-infected patients and are most frequently implicated in cases of recurrent infection following antifungal drug treatment.

Pneumocystis pneumonia is a disease caused by the fungus Pneumocystis jirovecii. It is one of the most frequent and severe opportunistic infections in people with weakened immune systems, particularly people with HIV/AIDS.

Rous sarcoma virus is a retrovirus and is the first oncovirus to have been described. It causes sarcoma in chickens.

It is a rare cause of subcutaneous, sinusitis, endocarditis, peritonitis and disseminated infection in immunosuppressed patients.

Vif stands for viral infectivity factor. It is a protein found in HIV and other retroviruses. Its role is to disrupt the antiviral activity of the human enzyme APOBEC by targeting it for ubiquitination and cellular degradation.

Unusual in HIV (except at a late stage when any infection is possible); more often associated with complement deficiencies

HIV is transmitted through certain body fluids that are capable of containing high concentrations of HIV antibodies, such as blood and semen.

This has been proven not to transmit HIV but is not recommended on general health grounds!.

64% of ALL are the pre-B cell type. The commonest ALL in children is the pre-B cell ALL.

Almost all infants with SCID have reduced lymphocyte counts. Remember that infants have a higher lymphocyte count range than adults by 3.5-fold.

There is no known problem with the class switch mechanisms for IgG in most IgA deficient patients (as yet) but a small proportion, usually those who present with infections, have poor responses to either carbohydrate or protein antigens +/- low IgG subclass levels. There is linkage with MHC class II and class III genes but almost certainly this is not the whole story; the precise mechanisms are not known.

After the diagnosis of AIDS is made, the average survival time has been estimated to be 2-3 years.

Patients are usually over 50 years of ageand the life expectancy is 15 years, depending on the stage of disease at presentation.

Neutrophils from patients with CGD fail to produce super-oxide that enables an influx of potassium ions to activate the intracellular enzymes that kill organisms.

Replacement immunoglobulin therapy is also used in CD40 ligand deficiency. Ig is prepared from the plasma collected from a large number of normal individuals, usually between 10,000-50,000, who have been carefully screened to make sure they are healthy and do not harbor certain infectious diseases. The plasma contains a broad range of specific antibodies to many different types of bacteria and viruses.

This is not thought to be due to an infection, but a relatively benign form of leukaemia in the elderly.

Immune suppression of other, non-paraprotein Ig isotypes is a diagnostic feature.

A form of T cell lymphoma with a characteristic dermatitis in a high proportion of patients.

There are at least 93 serotypes in the world, though 23 prevalent serotypes that cause disease in different parts of the world, but no switching of the bacterium between serotypes. Infections with these organisms are common and often infect those with antibody or innate or combined deficiencies

Dr Bence Jones originally described proteins that precipitated on heating urine and then disappeared on further heating (unlike albumin which remained in the precipitate). This property turned out to be that of free light chains. Monoclonal free light chains are only seen when there are large amounts of light chain in the urine i.e. in lymphoid (usually plasma cell) malignancy.

This is a major portal of entry, though not the only one. The chemokine receptors CXCR4 and CCR5 are also major portals of entry and reduce the CD4 positive helper T cell numbers dramatically (see Case 3.11 Acquired immune deficiency syndrome: Kaposi's sarcoma

Produce immunoglobulins of all isotypes including IgE.

But only if the T cell has the correct antigen specificity in the TCR AND the same HLA class II antigens.

Etanercept is the soluble TNF receptor. Infliximab is a monoclonal antibody - as indicated in the last part of the name InflixiMAB. TNF blockade can be achieved by either the use of a chimeric anti-TNF antibody (infliximab, adalimumab) or a soluble TNF receptor (etanercept).

Part of the pathway involved in IgE production, as well as involved in Th2 cellular responses.

This is an anti-inflammatory drug. Aspirin is part of a group of medications called non-steroidal anti-inflammatory drugs (NSAIDs) and has antipyretic, anti-inflammatory and analgesic properties but does not affect immunity. Aspirin inhibits the enzyme, cyclooxygenase.

High levels of serum IgM (a large pentameric protein) make the plasma hyperviscous and this presents with headache, visual disturbances, nose bleeds, malaise or exertional dyspnoea.

Zidovudine or azidothymidine (AZT) is a type of antiretroviral drug used for the treatment of HIV/AIDS infection.

The diagnosis of all circulating B cell tumours relies on the involvement of the bone marrow. However for solid tumours, such as Hodgkin's disease and Non-Hodgkin's lymphoma, a lymph node biopsy is the essential investigation, though bone marrow trephine is often done to assess stage

These cells are the vital part of the cellular immune response, destroying the cells which bears any foreign antigen on their surface, mainly virus-infected cells.

The BRCA2 mutation is the most likely to be associated with male breast cancer.

Glycogen synthase kinase 3 is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues.

HAART is used to suppress HIV viral replication and the progression of HIV disease. It conjoins three or more different drugs such as two nucleoside reverse transcriptase inhibitors (NRTIs) and a protease inhibitor. These HAART regimens have proven to reduce the amount of active virus and in many cases.

This enzyme is involved in the production of RNA from DNA through transcription. It adds ribonucleotides to growing RNA transcripts at the 3’ end. The pol gene does not encode for NA polymerase.

This gene from human immunodeficiency virus type 1 activates viral gene expression and is essential for HIV replication.

Vpu is specific to HIV-1. It is a class I oligomeric integral membrane phosphoprotein with numerous biological functions. Vpu is involved in CD4 degradation involving the ubiquitin proteasome pathway as well as in the successful release of virions from infected cells.

In case of HIVinfection this test finds either the RNA of the HIV virus or the HIV DNA in white blood cells infected with the virus. The PCR test is very useful to find a very recent infection.

Advanced symptoms which may include unexplained chronic diarrhea for longer than a month, severe bacterial infections including tuberculosis of the lung, and a CD4 count of less than 350/µl.

World AIDS Vaccine Day, also known as HIV Vaccine Awareness Day, is observed annually on May 18. HIV vaccine advocates mark the day by promoting the continued urgent need for a vaccine to prevent HIV infection and AIDS.

Telomere deficiency is often linked to aging, cancers and the conditions dyskeratosis congenita (DKC) and Cri du chat. Meanwhile, over-expression of hTERT is often associated with cancers and tumor formation.

It is not a rapid test for the diagnosis of HIV infection. Western blots are considered as the benchmark, and seropositivity is diagnosed when antibodies against both the env and the gag proteins are detected.

Cancer is regarded as a genetic disease because it is caused by mutations in the genome. However, these mutations are normally in somatic cells not germ cells and mutations contributing to cancer are rarely inherited. To form a malignant cancer a cell must acquire a small number of mutations (probably about six) each of which gives the cell a growth or survival advantage.

Cancers derived from epithelial cells. This group includes many of the most common cancers, particularly in the aged, and include nearly all those developing in the breast, prostate, lung, pancreas, and colon.

An oncogene is a mutated form of a normal cellular gene (the proto-oncogene) which codes for a protein which is either controlled abnormally so that it is expressed in abnormally large amounts or has gained activity so that it is more active than the normal protein.

Tumour suppressor genes code for proteins which normally control progression through a cell cycle checkpoint. These genes only contribute to a cancer when both copies are mutated in a way which produces an inactive protein product. A single mutation inactivating one gene only has no effect. They contribute to cancer because the absence of the protein product removes controls on cell division.

Fas forms the death-inducing signaling complex (DISC) upon ligand binding. Membrane-anchored Fas ligand trimer on the surface of an adjacent cell causes oligomerization of Fas.

The non-Hodgkin lymphomas (NHLs) are diverse group of blood cancers that include any kind of lymphoma except Hodgkin's lymphomas. Types of NHL vary significantly in their severity, from slow growing to very aggressive. Since this is a T cell malignancy T cell NHL may follow.

A benign tumor is a mass of cells (tumor) that lacks the ability to invade neighboring tissue or metastasize. These characteristics are required for a tumor to be defined as cancerous and therefore benign tumors are non-cancerous.

Hamartomas are a group of benign tumors that have relatively normal cellular differentiation but the architecture of the tissue is disorganised.

Refers to a heterogeneous group of high-grade carcinomas that feature cells lacking distinct histological or cytological evidence of any of the more specifically differentiated neoplasms. These tumors are referred to as anaplastic or undifferentiated carcinomas.

Antibody-based immune responses form a first layer of protection of the host from viral infection; however, in many cases a vigorous cellular immune response mediated by T-cells and NK-cells is required for effective viral clearance. When cellular immunity is unable to clear the virus, the infection can become chronic, and serum antibodies to the viral pathogen are used as first indicator for the diagnosis of the disease.

These have dsDNA or ssRNA genomes and their replication includes the synthesis of DNA from RNA by the enzyme reverse transcriptase; many integrate into their host genomes. The group includes the retroviruses, of which Human immunodeficiency virus (HIV), the cause of AIDS, is a member. There is a single family of plant viruses in this group and this is characterised by a single component of circular dsDNA, the replication of which is via an RNA intermediate.

EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation. Mutations in this gene are associated with lung cancer. Multiple alternatively spliced transcript variants that encode different protein isoforms have been found for this gene.

The virion RNA is infectious and serves as both the genome and the viral messenger RNA. The whole genome is translated in a polyprotein, which is processed co- and post-translationally by host and viral proteases.

Type I genomes are characterized by a small circular DNA genome (approximately 2-kb), with the Rep protein and the major open reading frame (ORF) in opposite orientations. This type is characteristic of the circoviruses, geminiviruses and nanoviruses.

Herpesvirus are much larger than the DNA viruses having a genome size of 100 to 200 kilobases. These are often co-carcinogens. They may have a hit and run mechanism of oncogenesis.

Robert Charles Gallo is an American biomedical researcher. He is best known for his role in the discovery of the human immunodeficiency virus (HIV) as the infectious agent responsible for acquired immune deficiency syndrome (AIDS) and in the development of the HIV blood test, and he has been a major contributor to subsequent HIV research.

A Neutralizing antibody is an antibody which defends a cell from an antigen or infectious body by inhibiting or neutralizing any effect it has biologically. An example of a neutralizing antibody is HIV antitoxin, which can neutralize the biological effects of HIV.