Primary Immune Deficiencies Flashcards
What re the 4 categories causing secondary immunodeficiency?
M DIB
Malignancy - myeloma, leukaemia, lymphoma
Drugs - corticosteroids, immunosuppressants, cytotoxic agents
Infection - HIV, measles, MT
Biochem disorders - malnutrition, mineral deficiencies (zinc, iron), renal impairment
Clinical features of immunodeficiency
TWO major
OR
One major + recurrent minor infections in one year
Unusual organisms Unusual sites Unresponsive to treatment Chronic infections Early structural damage
What fails in reticular disgenesis?
Failure of stem cells to differentiate along myeloid/lymphoid lineages
so failure of neutrophils to differentiate
What are two specific failures of neutrophil maturation?
Kostmann syndrome: AR congenital severe neutropenia
Cyclic neutropenia: AD episodic neutropenia, occurs every 4-6 weeks
What occurs in Leukocyte adhesion Deficiency?
what is the specific CD molecule that is lacking?
Deficiency in CD18
Normally: CD18 + CD11 = LFA1»_space; LFA1 binds to ICAM1 to regulate neutrophil adhesion
Lack of CD18 means neutrophils cannot enter tissues
What do people with Leukocyte Adhesion Deficiency present with?
High neutrophil count in blood
No pus formation
What is chronic granulomatous disease?
Deficiency in NADPH oxidase components > inability to generate free radicals > impaired killing
What does chronic granulomatous disease present with?
Excessive inflammation (neutrophil, macrophage accumulation)
Granuloma formation
Lymphadenopathy
Hepatosplenomegaly
What is cytokine deficiency?
Normally IL12 - IL12 Receptor > stimulate T cells > produce INF gamma > stimulates macrophages > produce INF alpha, free radicals
Cytokine deficiency is deficiency of any of these components (IL12, IL12R, INFg, INFgR)
What immune structure is particularly vulnerable with cytokine deficiency?
Macrophages
What kind of infections are common with cytokine deficiency?
atypical mycobacterial infection
What are the two tests for chronic granulomatous disease?
- Nitroblue Tetrazolium (NBT) > changes from yellow to blue
- Dihydrorhodamide (DHR) > turns fluorescent
In summary, what are the four key types of phagocyte deficiency?
Kostmann Syndrome
Leukocyte Adhesion Deficiency
Chronic Granulomatous Disease
IL12/INFg pathway deficiency
What is the aggressive management for phagocyte deficiency?
Infection prophylaxis (antibiotics, antifungals) Oral/IV antibiotics as needed
What is definitive therapy for phagocyte deficiency?
Hfaematopoeic stem cell transplant
INF-gamma therapy for chronic granulomatous disease
What are the two key types of NK cell deficiency?
Classical NK deficiency: absence of NK cells in peripheral blood
Functional NK deficiency: NK cells present, but function abnormal
What risk do NK cell deficiencies lead to?
VIRAL INFECTION risk
e.g. HSV, EBV, CMV, HPV
What is treatment for NK cell deficiency?
Prophylactic antiviral drug e.g. acyclovir
Cytokines e.g. INFalpha to stimulate NK function
Hfaematopoeic SC transplant
How does Kostmann present on FBC?
NO neutrophils
How does Kostmann present symptomatically?
Recurrent infections
How does IFNgdeficiency present on FBC?
Normal
What infections does complement deficiency predispose to?
Bacterial infections NHS
- Neisseria meningitis
- Haemophilius influenza
- Strep pneumonia
What does classical pathway complement deficiency result in the deposition of?
Deposition of immune complexes
Causing local inflammation of skin, joints, kidneys
Why does complement deficiency cause immune complex deposition?
Because deficiency means ineffective clearance of necrotic cells, increasing self antigens
These self antigens promote autoimmunity and immune complex formation
What is the most common type of complement deficiency?
C2
What disease does C2 deficiency cause?
SLE
Is MBL deficiency associated to immunodeficiency?
No
What does C1q deficiency present as?
Inherited complement deficiency
Presents as SLE in childhood
What is CH50 like in someone with C1q deficiency?
LOW
What is CH50?
Test of the classical pathway
Tests activity of C1-C9
What does AP50 test?
Tests the alternate pathway
So activity of B, D, properdin, C3, C5-9
What are test results like in someone with C7 or C9 deficiency?
Both CH50 and AP50 will be low
Because defect is in COMMON PATHWAY
What is C4 like in acquired SLE?
LOW
How do we manage complement deficiencies?
Vaccinations
Prophylactic antibiotics
Treat infection aggressively
Screen family members
Summarise C1q deficiency
Severe childhood onset SLE with normal C3, C4 levels
Summarise C3 deficiency with nephritic factor
membranoproliferative nephritis, abnormal fat distribution (lipodystrophy)
Summarise C7 deficiency presentation
meningococcal meningitis
history of sibling dying at 67yo
MBL deficiency
Recurrent infections with neutropenia following chemo
Previously well
what deficiency causes inherited SLE in childhood?
C1q deficiency
what is the state of other complements and CH50, AP50 in C1q deficiency
C3,C4 normal
Low CH50
AP50 normal
