Chapter 19 – Immunodeficiency Diseases

What is a primary immunodeficiency?

A genetic defect that impairs immune system development or function.

Which cell deficiency is most damaging and why?

T cells—because they regulate and activate multiple immune responses.

What happens with B cell defects?

↓ antibodies → recurrent bacterial infections.

What happens with T cell defects?

Broad immune failure → ↑ viral, fungal, protozoal infections.

What is SCID?

Severe immunodeficiency with little/no functional T cells.

What are the main causes of SCID?

Cytokine signaling defects, purine metabolism defects, V(D)J recombination defects, signaling defects.

What is the effect of SCID?

Severe infections (viral/fungal) + shortened lifespan.

How is SCID detected in newborns?

PCR for T cell receptor excision circles (TRECs).

What is the cause of DiGeorge Syndrome?

Thymus developmental defect (chromosome 22 deletion).

What is the cause of Wiskott-Aldrich Syndrome?

Cytoskeleton protein defect (WASP gene).

What is the cause of Hyper IgM Syndrome?

CD40L deficiency → impaired class switching → ↑ IgM.

What is the cause of Hyper IgE Syndrome?

STAT3 mutation → ↓ Th17 cells.

What is the cause of X-linked agammaglobulinemia?

Btk defect → no mature B cells → ↓ antibodies.

What is the effect of Selective IgA deficiency?

Normal other antibodies but ↑ respiratory/GI infections.

What is an example of a phagocyte defect?

Chronic granulomatous disease (NADPH oxidase defect).

What happens in leukocyte adhesion deficiency?

WBCs can't migrate to infection sites.

What causes IPEX syndrome?

FoxP3 mutation → no Treg cells → autoimmunity.

What are the main treatment strategies for immunodeficiencies?

Replace protein (Ig, cytokines), replace cells (bone marrow transplant), replace gene (gene therapy).

What are nude mice?

No T cells → study cancer/transplantation.

What are SCID mice?

No T or B cells → humanized models.

What are RAG knockout mice?

No V(D)J recombination → no T/B cells.

What are RAG + γc knockout mice?

No T, B, or NK cells → best humanized model.

What is a secondary immunodeficiency?

Immune loss due to external factors.

What is the most common cause of secondary immunodeficiency?

Severe malnutrition.

What are other causes of secondary immunodeficiency?

Drugs, disease, age, infections (HIV).

What type of virus is HIV?

Retrovirus.

What are the key components of HIV?

2 RNA genomes, reverse transcriptase, gp120 + gp41 envelope proteins.

What receptors does HIV bind?

CD4 + CCR5 or CXCR4.

What is unique about HIV replication?

Reverse transcription (RNA → DNA → integrates into host genome).

What is a provirus?

Viral DNA integrated into host DNA.

Why is HIV hard to eliminate?

Latency (hidden reservoirs).

What occurs in Stage 1 (Acute) of HIV infection?

High viral load → initial immune response.

What occurs in Stage 2 (Asymptomatic) of HIV infection?

Long period, gradual CD4 decline.

What occurs in Stage 3 (AIDS) of HIV infection?

Low CD4 (<200) + opportunistic infections.

What are the 4 criteria for AIDS?

HIV infection, CD4 <200, impaired DTH, opportunistic infections.

What are the most common transmission routes for HIV?

Sexual contact, needle sharing, blood products, breast milk.

What are LTNPs?

HIV+ individuals with high CD4 for years.

Why are LTNPs important?

Help develop therapies/vaccines.

What is HAART?

Combination of 3+ antiretroviral drugs.

Why use multiple drugs in HIV treatment?

Prevent resistance.

Is HAART a cure for HIV?

No—latent virus remains.

What steps can drugs target in HIV treatment?

Entry (CCR5 blockers), fusion inhibitors, reverse transcriptase, integrase, protease.

How is mother-to-child transmission of HIV prevented?

Antiretroviral therapy during pregnancy and after birth.

What is the effectiveness of preventing mother-to-child transmission in developed countries?

↓ transmission >90%.

Why is HIV hard to vaccinate against?

High mutation rate, glycan shielding, many viral variants.

What are broadly neutralizing antibodies?

Antibodies that target conserved viral regions.

What are the key features of broadly neutralizing antibodies?

Long CDR3 regions, high somatic hypermutation.