12- Congenital And Acquired Immunodeficiencies Flashcards
What are the traits of primary immunodeficiency?
- 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
What are the traits of secondary immunodeficiency?
- acquired: external force acting (disease, drugs, etc)
- IS damage due to infection, drug exposure, radiation, dietary deficiencies
Clinical manifestations of immunodeficiency commonly include:
- recurrent and overwhelming infections in very young children
- allergy
- abnormal proliferation of lymphocytes
- autoimmunity
- cancer
Three specific types of immunodeficiencies?
B cell
T cell
Innate immune
What do people’s signs depend on?
Signs that present depend on what is deficient
Fun facts about primary immunodeficiencies
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
How are immunodeficiencies classified?
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
What is the fundamental difference between primary and secondary immunodeficiency?
Primary: inherited/genetic basis
Secondary: acquired–> external force acting (disease/drugs,etc)
Match the deficiency with outcome for the following maturation deficiencies:
No RAG1/2:
No TAP:
No CD3:
No RAG1/2: no B/T cells, no adaptive
No TAP: no MHC 1= no CD8
No CD3: no T cell
SCID
Severe combined immunodeficiency
No adaptive response (no b or T cells)
X-linked agammaglobulinemia
“Without (A) antibodies (gammaglobulin)”
Innate deficiencies Mutation in compliment genes: E&P selectin mutation: Integrin mutation: Phagocyte oxidase enzyme mutation:
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)
Two innate deficiencies
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
Immunodeficiencies in activation: CD40 ligand defect: No IL4: IL17 defect: IL12 defect:
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
Immunodeficiency therapies, what do we do?
What are the replacement therapy examples?
Try to replace the deficiency, but replacing is not easy (Replacement Therapy)
- cytokines
- delivery of enzyme
- Pooled human gammaglobulins (IVIG)
Three types of immunodeficiency therapies
1) gene therapy
2) transplantation
3) replacement therapy
What do we do in gene therapy for immunodeficiency therapies?
Restore or complement the deficient gene (ex: ADA)
Not easy: viral based–> give a copy of intact gene
Transplantation as an immunodeficiency therapy, what do we do?
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
Secondary immunodeficiencies
Something else acting in it:
- Cancer radiation treatments or chemotherapy
- Viral infection (HIV)
- Immunosuppression for graft rejection
- Bone marrow cancers
- Malnutrition
- Spleen removal
What does HIV target and kill?
CD4s
Describe the clinical course of HIV
-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
Summary of primary and secondary immunodeficiencies
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
