primary and secondary immune deficiencies

1. Immunodeficienc
y
Fawzia aboali
P of internal mdicine & clinical immunology
rof
Ain shams faculty of medicine

2. Objectives:
 immune system
 Immune deficiency,classifications.
 Immune defect & organisms
 Primary immune deficiency
 Secondary immune deficiency:types
 Diagnosis of immune defects
 Management

5. The 4 Arms of Immune System & Their
command

6. Immunodeficiency
Definition
Immunodeficiency (or immune deficiency) is a
state in which the immune system 's ability to
fight infectious disease is compromised or
entirely absent. Immunodeficiency may also
decrease cancer immunosurveillance.

8. Primary Immunodeficiencies
Stem Cell
Myeloid Lymphoid
Progenitor Progenitor
Severe combined
Congenital Immunodeficiency
Agranulocytosis SCID
Monocyte Pre-B Pre-T
Neutrophil
x-linked
aγglobulinemia
xLA Mature B Thymus
DiGeorge
Syndrome d
Mature
Plasma T
Cell Memory B
Common Variable Hypoγglobulinemia
Selective Ig deficiency

9. IMMUNE DEFICIENCY
 OPPORTUNISTIC INFECTIONS:
Opportunistic infections are mild to severe
infectious diseases in a compromised host. The
infections are caused by microorganisms that
normally do not cause serious disease in healthy
people.
Viral, Bacterial, Fungal, Protozoan,
Helminthic
 Opportunistic Malignancies: Kaposi's
Sarcoma and Lymphomas

10. T h e 1 0 w a r n i n g s i g n s o f
i m m u n e d e f i c i e n c y

12. Common variable Immunodeficiency (CVI).
Heterogynous group that cause late - onset
hypogammaglobulinaemia.
Recurrent infections between 15 - 35 yrs.
Features:
1.Low IgG & IgA .
2.Impaired antibody responses.
3.Associated autoimmune diseases
•Recurring infections involving the ears, eyes,
sinuses, nose, bronchi, lungs, etc.
•The organisms commonly found in these infections
are bacteria that often cause pneumonia
(Haemophilus influenzae, pneumococci, and
staphylococci).

13. IgA deficiency (1:700)
 Most are asymptomatic. ( but have
increased rate of (R.T.I.)
 Some have recurrent R.T.I and G.I.T.
symptoms
 Increased incidence of allergic manifestations.
 anti- convlusant drugs (phenytoin) may cause
deficiency .

14. Common Variable Immunodeficiency (Late-
Onset Hypogammaglobulinemia)
 Onset usually in 2nd to 4th decade of life
 Slow decline in all classes of immunoglobulin
 Recurrent sinopulmonary infections (usually
bacterial in origin)
 Gastrointestinal, endocrine, hematologic and
autoimmune disorders can be associated
 May follow Epstein-Barr infection
 Increased incidence of lymphoreticular
malignancies

16. David Phillip Vetter (September 21,
1971 – February 22, 1984)

17. SECONDARY IMMUNE
DEFICIENCY
1. Acquired Immune Deficiency Syndrome
(AIDS)
2. Cancer / Chemotherapy:
3. Immunosuppression In Diabetes
4. Immunosuppression In Transplant Pts
5. Autoimmune disease
6. Immunosuppression Related to Steroid Use
7. Immunosuppression In Asplenic Pts
8. Effect of Aging On Immune Competence
9. pregnancy

18. 1. Acquired Immune Deficiency Syndrome (AIDS)
a) Etiology& presentation
b) Defect: Inversion of T helper/inducer cells
(OKT4) to cytotoxic/suppressor cell (OKT8) ratio
Normal T4/T8 = 2/1
In AIDS it is 0.5.

20. CD4 Count
 Greater than 500 / ul - Almost normal
defense mechanisms
 Less than 200 / ul - Opportunistic AIDS
related infections
 Less than 100 / ul - Life threatening
complications

21. Opportunistic Infections in AIDS Patients

22. 2. Cancer / Chemotherapy:
Unfortunately in cancer, both the disease
and the treatment can cause
immunosuppression :
 Neutropenia
 Cell Mediated Immunity
 Humoral factors

23. Neutropenia
 Occurs approximately two weeks after the last
dose of chemotherapy
 an absolute neutrophil count of less than 1,000
cells/mm3 on the way down are at increased risk
for a serious bacterial infection.
Management strategy:
1. All patients with anticipated severe neutropenia
(ANC < 0.5 x 109/l), should receive prophylaxis
against bacteria, fungi,viruses&G-CSF
2. Neutropenic patients who present with fever
require a prompt switch to an appropriate treatment
regime

24. Cyclic neutropenia
 is a form of neutropenia that tends to occur
every three weeks and lasting three to six
days at a time due to changing rates of cell
production by the bone marrow.
 It is often present among several members of
the same family. Treatment includes G-CSF
and usually improves after puberty.

25. 3. Immunosuppression In Diabetes
 Humoral Immunity:
normal Ab levels & vaccination responses.
 Impaired Cellular Immunity:
 Impaired Innate Cellular Defenses:
o PMN abnormalities - adherence, chemotaxis,
o Phagocytosis.
Infections In Diabetics
 rhinocerebral mucormycosis
 oral &esophageal candidiasis
 surgical / wound infection
 T.B

26. GSACEP © 2005

27. 4. Immunosuppression In Transplant Pts
 Infection 2nd most impt problem posttransplantation
Pre-transplant Host Factors:
 ongoing medical conditions (HBV, HCV, diabetes)
 prior MO colonization ( Candida, staph)
 prior latent infection (TB, CMV)
 prior medications (i.e. immunosuppressives,
antibiotics)
Common Microbial Etiologies Post-Transplantation
 Bacteria: common gm+ & gm- flora
 Fungi: Candida sp.; Aspergillus sp

28. 5. Immunosuppression in autoimmune
Diseases:
Multiple infection risk factors:
1. functional defect in phagocytic cells.
2. CMI defects: lymphopenia, CD4 - cell
3. reduced Ab levels & low complement levels.
4. functional asplenia.
5. also, corticosteroids & immunosuppressives
increase infection risks.

29. 6. Immunosuppression Related to Steroid Use
 Glucocorticoids (corticosteroids) have inhibitory
effects on T cells and B cells, as well as
phagocytes.
 Infections depend on route of administration,
dose, & duration of therapy.

30. Infections Related to Steroid Use
 increased susceptibility to all types of
infection.
 Prolonged CMI suppression important for
opportunistic infection to occur.
 Fever may be absent
 delayed wound healing & wound infections:
steroids interfere with fibroblast proliferation &
collagen synthesis.

31. 7. Immunosuppression In Asplenic Pts
• lower C3 levels & defective responses to encapsulated
bacterial pathogens
• decreased phagocytosis
• failure to recognize polysaccharide Ag’s.
• impaired IgM synthesis early in infection.
Pathogen:
-S. pneumoniae ,H influenzae ,N. meningitidis
 Sickle Cell
Functionally aspenic (ask about immunizations!)

32. 8. Effect of Aging On Immune Competence
 Declining :
Innate, Humoral & Cellular Immune
Responses
 Increased Susceptibility to Pneumonias &
Chronic Infections

33. During pregnancy:

34. Initial Evaluation of Possible
Immunodeficiency
 Make sure that what seems to be infections are not
really: ATOPY, ALLERGY, ASTHMA
 Exclude other conditions
 Hold off on any live viral vaccines or transfusions until
situation well defined
 Document that there have been multiple infections
 Look for other, non-immune features of
immunodeficiency: rash, hypocalcemia, facial
characteristics
 Family history

35. Initial screening tests for
immunodeficiency
 CBC: WBC,function
 Quantitative immunoglobulins: IgG, A & M
 Total lymphocyte count
 T-cell enumeration, with subsets
CD4, CD8
 Evaluate for current infections:
CULTURES, ESR, CRP, X-RAYS.

36. Tests for B cell,antibody deficiency:
 Total ,lymphocyte count
 Total serum immunoglobulins
 IgG subclasses, Antibodies for pervious vaccination
 Immunoglobulin function& survival
Tests for cellular deficiency:
 Total lymphocyte count
 T-cell enumeration, with subsets CD4, CD8
 Functional assays: antigens response to mitogens,
cytokines assay.
 Delayed hypersensitivity reaction for Tuberculin and
Candida antigen

37. Tests for other deficiency:
Phagocyte:
i. Neutrophil count
ii. NBT test for screening.
Complement:
Total and specific complement
count.

38. Treatment options
 monitor
 Live vaccines are absolutly contraindicated

39. 1. IVIG .( IV infusion of immunoglobulin.)
For : a. agammaglbulinaemia . b. CVI. c. WAS
2. Periodic antibiotic treatment.
3. Bone marrow transplantation .
For : a. SCID . b. WAS.
4. Enzyme replacement .
For : ADA deficiency.
5-CSF.(colony stimulating factor ) For : neutropenia
6. Thymus transplantation .
For : DiGeorge syndrome.
7. IFN – gamma . For : CGD.
8-gene therapy

40. 1) Which one of the following does 3) Which of the following
not predispose to superficial tests may assess
Candida albicans infection?
cellular immune
A Pregnancy
B Lymphoma
dysfunction;
C Diabetes mellitus a) CD4, CD8.
D Vegetarian diet
b) Total serum
2) Which of the following is not
commonly associated with immunoglobulins
marked secondary antibody
deficiency? c) IgG subclasses
a) Multiple myeloma.
d) Immunoglobulin
b) autoimmune diseases.
c) HIV infection. response
d) hypersplinism.