12- Congenital And Acquired Immunodeficiencies

Question 1

What are the traits of primary immunodeficiency?

Answer 1

• Inherited
• genetic basis: may be congenital or expressed later in life
• gene defects that lead to blocks in the maturation or functions of different components of the immune system

Question 2

What are the traits of secondary immunodeficiency?

Answer 2

• acquired: external force acting (disease, drugs, etc)

- IS damage due to infection, drug exposure, radiation, dietary deficiencies

Question 3

Clinical manifestations of immunodeficiency commonly include:

Answer 3

• recurrent and overwhelming infections in very young children
• allergy
• abnormal proliferation of lymphocytes
• autoimmunity
• cancer

Question 4

Three specific types of immunodeficiencies?

Answer 4

B cell

T cell

Innate immune

Question 5

What do people’s signs depend on?

Answer 5

Signs that present depend on what is deficient

Question 6

Fun facts about primary immunodeficiencies

Answer 6

More than 100 known

20 represent 90% of clinical cases

Many single gene defects: know if missing this, what is likely deficiency outcome?

80% affected persons are

Question 7

How are immunodeficiencies classified?

Answer 7

Grouped by cell type: every cell involved in the immune response can be affected

Can involve:

• decreased production
• decreased activation
• adhesion deficiencies
• internal cellular processes (lysosomes trafficking)
• effector molecule production

Usually revolves around cell missing something or missing altogether

Question 8

What is the fundamental difference between primary and secondary immunodeficiency?

Answer 8

Primary: inherited/genetic basis

Secondary: acquired–> external force acting (disease/drugs,etc)

Question 9

Match the deficiency with outcome for the following maturation deficiencies:
No RAG1/2:
No TAP:
No CD3:

Answer 9

No RAG1/2: no B/T cells, no adaptive
No TAP: no MHC 1= no CD8
No CD3: no T cell

Question 10

SCID

Answer 10

Severe combined immunodeficiency

No adaptive response (no b or T cells)

Question 11

X-linked agammaglobulinemia

Answer 11

“Without (A) antibodies (gammaglobulin)”

Question 12

Innate deficiencies
Mutation in compliment genes:
E&P selectin mutation: 
Integrin mutation:
Phagocyte oxidase enzyme mutation:

Answer 12

Mutation in compliment genes: defective complement cascade
E&P selectin mutation: WBCs cannot locate and get to tissue (LAD-1 disease)
Integrin mutation: leukocyte adhesion deficiency
Phagocyte oxidase enzyme mutation: macrophages do the reactive oxygen burst and cannot kill what they eat (chronic granulomatous)

Question 13

Two innate deficiencies

Answer 13

Chronic ganalomatous: respiratory burst (toxic oxygen), people missing enzyme and cannot do that burst and macrophages cannot kill what they eat

LAD-1: e and p selections: WBCs cannot locate and get to tissue

Question 14

Immunodeficiencies in activation:
CD40 ligand defect:
No IL4:
IL17 defect:
IL12 defect:

Answer 14

CD40 ligand defect: cannot activate B cells (looks like B cell deficiency)
No IL4: no TH2
IL17 defect: decreased TH17 response
IL12 defect: TH1 response defect

Question 15

Immunodeficiency therapies, what do we do?

What are the replacement therapy examples?

Answer 15

Try to replace the deficiency, but replacing is not easy (Replacement Therapy)

• cytokines
• delivery of enzyme
• Pooled human gammaglobulins (IVIG)

Question 16

Three types of immunodeficiency therapies

Answer 16

1) gene therapy
2) transplantation
3) replacement therapy

Question 17

What do we do in gene therapy for immunodeficiency therapies?

Answer 17

Restore or complement the deficient gene (ex: ADA)

Not easy: viral based–> give a copy of intact gene

Question 18

Transplantation as an immunodeficiency therapy, what do we do?

Answer 18

Hematopoietic stem cell (cord blood; bone marrow; fetal thymus; purified stem cells) if it’s a stem cell mutation

HLA-identical sibs: >90% successful

Parental/unrelated disorders: GVHD

In utero or neonatal transplantation facilities tolerance

Question 19

Secondary immunodeficiencies

Answer 19

Something else acting in it:

• Cancer radiation treatments or chemotherapy
• Viral infection (HIV)
• Immunosuppression for graft rejection
• Bone marrow cancers
• Malnutrition
• Spleen removal

Question 20

What does HIV target and kill?

Answer 20

CD4s

Question 21

Describe the clinical course of HIV

Answer 21

-Primary infection
-infects T cells
- at first they fight back and HIV numbers decline while T cell numbers rise
-HIV overcomes and as T cells drop to zero, HIV spikes
Death

About 8years without treatment
T cell population decreases enough that there are opportunistic infections and no T cells to fight them

Question 22

Summary of primary and secondary immunodeficiencies

Answer 22

Immunodeficiency= lack of function of a component of the immune system

Immunodeficiency can affect any portion of the IS

Defects can be:
MILD: IgA lack can be compensated for
SIGNIFICANT: SCID or HIV