Ch. 12 Congenital and Acquired Immunodeficiencies

Practice flashcards covering congenital (primary) and acquired (secondary) immunodeficiencies, including specific genetic defects, cellular disorders, and HIV/AIDS pathogenesis.

Immunodeficiency

A condition where the immune system fails to protect the host from disease-causing agents or from malignancy.

Primary Immunodeficiency

A defect in the immune system resulting from a genetic or developmental defect, present at birth.

Secondary Immunodeficiency

An acquired immune defect resulting from other diseases or environmental factors like starvation or drugs.

Lymphoid Cell Disorders

Immunodeficiencies affecting T cells, B cells, or both (combined immunodeficiencies).

Myeloid Cell Disorders

Immunodeficiencies that specifically affect phagocytic function.

Reticular Dysgenesis

A stem cell defect that affects the maturation of all leukocytes, leading to general immunity failure.

Chronic Granulomatous Disease (CGD)

A defect caused by mutations in genes encoding the subunits of phagocyte NADPH oxidase, preventing the production of microbicidal reactive oxygen species.

Leukocyte Adhesion Deficiency (LAD)

Caused by mutations in genes encoding $CD18$ (an integrin chain), preventing blood leukocytes from binding to vascular endothelium.

Chediak-Higashi Syndrome

A disorder due to mutations in a protein involved in intracellular trafficking, characterized by giant granules in phagocytes and defective lysosomal transport.

C3 Deficiency

A complement deficiency involving a component of all three pathways, resulting in severe infections that may be fatal.

Hereditary Angioedema (HAE)

A condition resulting from a deficiency in the complement regulatory protein $C1-INH$.

Severe Combined Immunodeficiency (SCID)

Genetic abnormalities causing blocks in the maturation of both B and T lymphocytes.

Common $\gamma$ chain ($\gamma_c$)

A signaling subunit of the receptor for several cytokines ($IL-2$, $IL-4$, $IL-7$, $IL-9$, $IL-15$, and $IL-21$) often mutated in X-linked SCID.

Adenosine Deaminase (ADA) Deficiency

An autosomal recessive SCID caused by an enzyme defect that leads to the accumulation of toxic purine metabolites in proliferating lymphocytes.

RAG1 and RAG2

Recombination-activating genes that encode recombinase required for $BCR$ and $TCR$ gene recombination.

ARTEMIS

An endonuclease involved in VDJ recombination; defects lead to failure of B and T cell development.

Bruton Tyrosine Kinase (BTK)

A kinase that delivers signals from the pre-$BCR$ and $BCR$; its mutation causes X-linked agammaglobulinemia (XLA).

ZAP70

A kinase involved in $TCR$ signaling; defects in this protein disrupt signaling from the T cell receptor.

Bare Lymphocyte Syndrome

An autosomal recessive disorder caused by mutations in transcription factors for Class II $MHC$ genes, resulting in a profound decrease in $CD4^+$ T cells.

X-Linked Hyper-IgM Syndrome

A disease caused by mutations in the gene encoding $CD40L$ ($CD154$), leading to defective B cell heavy-chain isotype switching.

Activation Induced Cytidine Deaminase (AID)

An enzyme essential for somatic hypermutation and class switching in B cells; mutations lead to autosomal Hyper-IgM syndrome.

Common Variable Immunodeficiency (CVID)

A heterogeneous group of disorders characterized by poor antibody responses and reduced serum levels of $IgG$, $IgA$, and sometimes $IgM$.

Hemophagocytic Lymphohistiocytosis (HLH)

Syndromes where $CTLs$ and $NK$ cells cannot kill infected cells due to perforin or granule exocytosis mutations, resulting in excessive macrophage activation.

Wiskott-Aldrich Syndrome

A rare X-linked disorder characterized by eczema, thrombocytopenia (small platelets), and defects in a protein that binds cytoskeletal components.

Ataxia-Telangiectasis

An inherited disease affecting the nervous and immune systems, characterized by gait abnormalities and vascular malformations due to defective DNA repair.

Human Immunodeficiency Virus (HIV)

A retrovirus that infects the immune system, mainly $CD4^+$ T lymphocytes, using gp120 to bind to $CD4$ and chemokine receptors ($CXCR4$ or $CCR5$).

Reverse Transcriptase

An HIV enzyme that reverse transcribes the viral RNA genome into double-stranded cDNA.

Integrase

An HIV enzyme responsible for integrating the viral cDNA into the host genome to form a pro-virus.

Clinical Latency Period

A second phase of HIV infection where the virus replicates in lymph nodes and spleen while peripheral T cell levels remain relatively stable.

Seroconversion

The event when an HIV-infected person first exhibits detectable levels of anti-HIV antibodies in the blood, usually around 12 weeks.

Antiretroviral Therapy (ART)

A triple-drug therapy that blocks the activity of HIV reverse transcriptase, protease, and integrase enzymes.