Immunopathology: Immune Deficiency

Question 1

Immune deficiency

Answer 1

A state in which immune response is ineffective because of an intrinsic abnormality in the structure and/or operation of the immune system
Structurally, it may arise from congenital or developmental anomalies, or from acquired disorders of organs and cells involved in immune system

Question 2

Causes of acquired immune deficiency

Answer 2

Age: Relative ineffectiveness at the extremes of life

Malnutrition: Probably due to reduced protein synthesis

Lymphoreticular malignancies: Lymphomas (cancer originating in lymph nodes), multiple myeloma (cancer formed in plasma cells), chronic lymphocytic leukaemia

Infections: Immunodeficiency may be mild (malaria) or severe (AIDS)

Question 3

Immunity against malaria is based on what?

Chronic malaria results in what?

Answer 3

Immunity against malaria is based on:
Antibodies to sporozoite surface antigen
Cytotoxic T-cell-induced apoptosis in infested hepatocytes
Antibodies against modified surface antigens on parasitised erythrocytes

Chronic malaria results in:
Increased synthesis of Ig, especially IgM and IgG
Persistence of parasites at low densities, thus paradoxically preventing severe infection (premunition)

Question 3

AIDS

Answer 3

AIDS is a chronic disease first reported among homosexuals in Los Angeles, USA
In Western countries, up to 60% of sufferers are homosexual and bi-sexual males, 23% IV drug users, 2% each are heterosexual contacts of bisexual men and children born to HIV-infected mothers, 1% are haemophiliacs treated with blood products prior to 1985
In Africa, AIDS is transmitted largely through heterosexual contact. This makes prostitution, polygamy, and marital infidelity the major vehicles of transmission

Question 4

AIDS-defining opportunistic infections and neoplasms: Protozoal

Answer 4

Cryptosporidiosis
Pneumocystis carinii
Toxoplasmosis

Question 4

AIDS Pathogenesis

Answer 4

A retrovirus belonging to the Lentiviridae family. Infects primarily the CD4+ve T-helper cells; other possible targets include macrophages, monocytes, and B-cells

Caused by 2 genotypes: HIV-1 (common in North America, Europe, and East Africa) and HIV-2 (common in West Africa)
It has a lipid envelope that is studded with gp 120 and gp 41 molecules. It also has genes that code for 4 core proteins: p24, p18, genomic RNA, and reverse transcriptase

Binding: HIV-derived gp 120 molecules binds to CD4 receptor on host cell and gets internalised

DNA synthesis: Viral RNA copied into DNA using viral reverse transcriptase

Viral integration: Viral DNA is inserted into the host genome by viral integrase protein

Viral replication: Viral RNA is reproduced by transcriptional activation of the integrated HIV provirus

Viral dissemination: Nascent virus is assembled in the cytoplasm and disseminated to other target cells

Question 5

How does AIDS affect T cells, B cells, NK cells and monocytes?

Answer 5

T-cell: Inversion of CD4/CD8 ration (from 2 to 0.5); T-cell mediated cytotoxicity

B-cell: Non-specific polyclonal activation leading to polyclonal hypergammaglobulinaemia, generalised lymphadenopathy; humoural response
NK cell: ↓Activity; ↑Susceptibility to malignant tumours and viral infections
Monocyte/ macrophage: Impaired phagocytosis, ↓chemotaxis, ↓antigen presenting capacity

Question 6

AIDS-defining opportunistic infections and neoplasms: Fungal

Answer 6

Candida
Cryptococcosis
Coccidioidomycosis
Histoplasmosis

Question 7

AIDS-defining opportunistic infections and neoplasms: Bacterial

Answer 7

Atypical mycobacteria (Mycobacterium avium-intracellulare)
Mycobacterium tuberculosis
Nocardia
Salmonella

Question 8

AIDS-defining opportunistic infections and neoplasms: Neoplasms

Answer 8

Kaposi’s sarcoma
Non-Hodgkin’s lymphoma
Primary CNS lymphoma
Invasive carcinoma of cervix

Question 8

AIDS-defining opportunistic infections and neoplasms: Viral

Answer 8

CMV (Cytomegalovirus)
HSV (Herpes simplex virus)
VZV (Varicella zoster virus)