Immunodeficiencies Flashcards
Associated infections with T cell deficiencies
Viral Fungal yeast Atypical microorganisms Cancer
Associated infections with B cell and phagocyte deficiencies
Microorganisms requiring opsonization
associated infections with complement deficiencies
Resemble b cell deficiencies: Microorganisms requiring opsonization.
Two categories of immunodeficiencies
Primary (congenital)
Genetic anomaly- inherited or mutation (sporadic)
Generally more severe
Secondary (acquired)
Caused by another illness
More common
5 groups of Primary ID
B lymphocyte def (50%) T lymphocyte def (30%) Phagocyte def Complement def Combined B and T cell def
What kind of defect is a primary ID
Usually single gene. Mostly sporadic (75%) Family history (25%)
manifest early in life- first 2 years.
two B lymphocyte deficiencies
Hypogammaglobulinemia (low Ab) or agammaglobulinemia (no Ab)
Hypogammaglobulinemia
Type of B lymph Deficiency. Low Ab production
agammaglobulinemia
Type of B lymph Deficiency. No Ab production
What are the two causes of B lymphocyte deficiencies?
Receptor defects: Ineffective intracellular signaling. BCR and cytokine receptors. Wont get full activation.
Ab class switch defect: Altered ability to change Ab class. due to co-stimulatory signal defect.
(B cell needs CD4, cytokine, and costimulatory signal to fully activate and class switch)
3 types of B lymphocyte deficiencies
Brutons (X-linked) Agammaglobulinemia
Common Variable Immunodeficiency (CVID)
Selective IgA deficiency
Brutons (X-linked) Agammaglobulinemia
Most severe B lymphocyte deficiency.
Receptor defect.
no mature B cells.
Recurrent bacterial infections.
Common Variable Immunodeficiency (CVID)
Most common primary immune deficiency (1 case in 25,000)
Class switch defect. Lacking IgG, M, and A.
Onset of symptoms delayed until late 20s.
Results in recurrent bacterial respiratory infection and increased cancer risk.
Most common primary immune deficiency (1 case in 25,000)
Common Variable Immunodeficiency (CVID)
Selective IgA deficiency
Unable to produce IgA Abs. Causes compromised secretory immune system.
Severe allergies and recurrent sinus/lung/Gi infection.
Severe mucopurulent conj.
Primary T cell immunodeficiencies
DiGeorge Syndrome/22q11.2 Deletion Syndrome Severe combined immunodeficiency (SCID) Reticular Dysgenesis (type of SCID)
DiGeorge Syndrome/22q11.2 Deletion Syndrome
- What causes it?
- What systems are affected?
- What infections are common?
- Incidence?
- how many cases are sporadic?
Partial or complete absence of T cell immunity (CD4 and CD8)
Due to thymus aplasia or hypoplasia (prevents development of thymus)
Causes endocrine (bc parathyroid also not developed right), vascular, and facial abnormalities (cleft pallet)
Higher viral and fungal infections (due to CD8 loss) and bacterial infections (due to CD4 loss)
Higher incidence of autoimmune diseases.
90% of cases are sporadic. People who have this disease are unlikely to pass down- don’t live long.
Severe combined immunodeficiency (SCID)
- What kind of deficiency?
- Possible causes
Combined T and B cell deficiency
Possible causes:
1. Toxic metabolic byproducts of bone marrow.
2. Cytokine receptor defects
3. VDJ recombination defects in clonal diversity
4. TCR doesn’t have proper proteins. Could be bare Class I: no Tc or CD8. or Could be bare on Class II: No CD4 or Th (most severe. Without, can’t activate humoral or cytotoxic)
Reticular Dysgenesis (type of SCID)
Most severe form of SCID
Absent/defective stem cells results in no circulating lymphocytes or granulocytes (neutrophils, basophils, eosinophils)
Usually fatal before or after birth.
Bubble boy?
Complement deficiencies
- What do they resemble?
- What infections result
- 2 kinds of complement deficiencies
Resemble B lymphocyte deficiencies
Results in bacterial infections
- C3 deficiency. Bad bc focal part of complement activation.
- Terminal component deficiency. Never form MAC. Causes 8000x risk of neisseria infection.
Phagocytic deficiencies
- Resemble what?
- What types of infections?
- 4 types of phagocytic deficiencies
- What is chronic granulomatous disease
Often resemble B lymphocyte deficiencies
Bacterial infection
Types:
- Neutrophil maturation defect.
- Adhesion molecule defect. Neutrophils can’t adhere to endothelial vessels, making it hard for them to extravasate.
- Opsonin receptor defect. Neutrophils can’t find pathogens.
- Pathogen killing defect. Can engulf, but not kill pathogen- lack ROS in phagolysosome.
Chronic granulomatous disease:
Pathogen killing defect. Absent ROS in phagolysosome. Causes recurrent granuloma in points of exposure- lungs, GI, skin.
Chronic granulomatous disease
Phagocytic deficiency.
Pathogen killing defect. Absent ROS in phagolysosome. Causes recurrent granuloma in points of exposure- lungs, GI, skin, lymph nodes, stomach.
causes of secondary deficiencies
#1 cause: Protein malnutrition. Pregnancy, aging that deplete immune system Stress Metabolic or genetic. Ex: Diabetes Malignancies could cause direct effects (due to tumor) or indirect (due to suppressed immune system, other infections can easily occur that could cause death) Trauma Surgery, steroids Infections
What kind of virus is HIV and what does it infect
RNA retrovirus. RNA in the virus capsule, DNA once it is in our cells and then incorporates into our DNA.
Infects CD4 Th1 cells mostly, but can also target neurons, Gi epithelial cells, and macrophages.
Who is most likely to contract HIV
Males having sex with males
AA > latino > white
3 phases of HIV
Acute phase: mono like symptoms 3-6 weeks after contracting.
Clinic latency phase: Asymptomatic period 2-10 years after infection without treatment. 500+ CD4 cells per mm^3 of blood.
AIDS: CD4 cell count less than 200 mm^3 in blood or aids defining condition (rare infections you don’t get unless your immune system is wiped out)
Normal Cd4 cell count
500-1500 cells per mm^3 of blood
HIV related abnormalities(4)
Lymphopenia: Low Cd4 count. Less than 200
Cutanous anergy: Defect in cell mediated immunity. Inappropriate skin response. Ex: inoculated with something. Should have skin reaction, but don’t.
Hypergammaglobulinemia: If pt has had epstein-Barr virus in the past, it may re-emerge since immune system is wiped out. Will cause B cells to produce Abs with no regulation.
CD4: CD8 ratio usually between 1-4. If less than 1, indicative of Aids.
Lymphopenia:
Low Cd4 count. Less than 200
Cutanous anergy:
Defect in cell mediated immunity. Inappropriate skin response. Ex: inoculated with something. Should have skin reaction, but don’t.
Hypergammaglobulinemia:
If pt has had epstein-Barr virus in the past, it may re-emerge since immune system is wiped out. Will cause B cells to produce Abs with no regulation.
Normal CD4:CD8 ratio
Between 1-4. If AIDS, will be less than 1.
Most common aids defining infection
Pneumocystis jiroveci pneumonia and systemic candidiasis (yeast infection)
CBC with differential
Complete blood count (WBC, RBC, platelets) with differential (WBC subtypes: Neutrophils, monocytes, MO)
Ways to evaluate immunity
- CBC with differential
- Classes and conc of Ig in the blood
- Assay for complement proteins
- Skin tests. Ex: cutaneous anergy
4 ways to treat immunodeficiencies
- Gamma globulin therapy.
- Effective for B cell deficiencies.
- Transient. Must have injections often.
- Low risk - Transplantation or transfusion
- Bone marrow or umbilical cord stem cells
- Effective for some primary combined deficiencies
- High risk of GVHD - Treatment with soluble immune mediators. Injections for complement deficiencies.
- Gene therapy
GVHD
Before graft, person’s immune system will be wiped out. When they put in graft, the graft might attack the HOSt. bad.
