Immunology Flashcards
Where are the B cells made?
Bone marrow
Where are the T cells made?
The thymus
What are the secondary or peripheral lymphoid organs?
Spleen
Lymph nodes
Organ-associated lymphoid tissue
-gut-associated lymphoid tissue (GALT), Peyer’s patches
mucosa-associated lymphoid tissue (MALT)
What is the Innate/Intrinsic Immune system?
Present from birth
Specificity is “pre-programmed”
Includes non-immunological cells (e.g. skin and cilia)
What is the adaptive immune system?
Develops during life with exposure to infection
Increases affinity with experience
Two compartments:
-Cellular- Mediated by cells (T cells)
-Humoral-Mediated by soluble factors (antibodies)
What makes up the most prevalent Inborn Error of Immunity subgroup (65%)?
Antibody deficiencies (65%)
What makes up the second most prevalent Inborn Error of Immunity subgroup (15%)?
Combined cellular and antibody deficiencies (15%)
What makes up the third most prevalent Inborn Error of Immunity subgroup (10%)?
Phagocytic deficiencies (10%)
What are the ten warning signs of immunodeficiency?
- Four or more ear infections within one year
- Two of more serious sinus infections within one year
- Two or more months on antibiotics with little effect
- Two or more pneumonias within one year
- Failure of an infant to gain weight or grow normally
- Recurrent, deep skin or organ abscesses
- Persistent thrush in mouth or fungal infection on skin
- Need for intravenous antibiotics to clear infections
- Two or more deep-seated infections including septicemia
- A family history of PI
How do you Assess Integrity of Adaptive Immune Function?
- CBC with leukocyte differential
- Total IgG, IgA, IgM, IgE
- Total T cells, B Cells, NK cells by flow cytometry
What Immune disorder is on the NBS?
Severe Combined Immunodeficiency (SCID)
What is one method of functionally assessing Immune function?
Vaccine titers to tetanus and pneumonia vaccine
What are the general principles of Treatment in Inborn Errors of Immunity?
- Prophylactic antivirals, antibiotics, antifungals
- Intravenous immunoglobulins
- Immunomodulation
-Glucocorticoids and biologics - Bone marrow transplantation if indicated
- Screening for malignancy (especially lymphoma)
-Skin cancers are also common in certain forms of SCID and CID
What is the phenotype of SCID?
Susceptibility to all infectious organism
FTT
Chronic diarrhea
Erythrodermia or other skin eruptions
What is the diagnostic criteria in SCID?
Lymphopenia in most
Diminished or absent T cells in most (maternal T cell engraftment may confuse the picture)
Poor/absent in vitro mitogen induced T cell proliferation in all
What are some types of SCID?
Adenosine deaminase deficiency
Common gamma chain deficiency (Xlinked SCID)
RAG1/RAG2 deficiency
IL7Ra deficiency
Reticular dysgenesis
Omenn
What is a treatment for SCID?
Bone Marrow Transplant
What are patients with Common Variable Immune Deficiency susceptible to?
Bacteria, common respiratory and enteroviruses (including vaccine strains), rotavirus, giardia,
cryptosporidium
What are the clinical features of Common Variable Immune Deficiency?
Recurrent sinopulmonary infections
Bronchiectasis
Diarrhea
Arthritis
Giardiasis
Autoimmunity (20%)
Asthma (10%)
lymphoproliferative disease
gastric cancer and lymphoma
How do you diagnose Common Variable Immune Deficiency?
Hypogammaglobulinemia (low IgG plus low IgA, or IgM), B cells present
Low class switched memory B cells
Impaired antibody response
Clinical Definition:
* IgG <2SD + low IgA and/or low IgM
* Inappropriate vaccine responses
* Rule out secondary causes
What are the top non-infections comorbidities in CVID?
Chronic lung disease (functional/structural)
Bronchiectasis
Autoimmunity (ITP, AIHA)
Gastrointestinal disease (malabsorption, IBS)
Liver disease/hepatitis (Hep C, liver granuloma)
What is a treatment in CVID?
IVIG
What are some CVID disorders where B lymphocytes are absent
X-linked agammaglobulinemia:
BTK
AR:
IGHM, CD79A, CD79B, BLNK, IGLL1, NI, PIK3R1
AD:
TCF3
What are the three most common genetic causes of CVID?
PIK3CD
LRBA
CTLA4
What cancer is screened for in CVID?
non-Hodgkin’s lymphoma
What is the treatment Abatacept used for?
CTLA-4 and LRBA haploinsufficiency
What is the treatment Leniolisib used for?
PI3KCD
What is the treatment Tocilizumab used for?
JAK inhibs for STAT3 GOF
What is the phenotype of X-linked agammaglobulinemia (XLA)?
Immunodeficiency characterized by failure to produce mature B lymphocytes
Associated with a failure of Ig heavy chain rearrangement.
What is the genetic cause of X-linked agammaglobulinemia (XLA)?
Mutations in the BTK gene
What disorder is caused by biallelic mutations in MEFV?
Familial Mediterranean Fever
What is the phenotype for Familial Mediterranean Fever?
Recurrent episodes of painful inflammation
Fever
Rash
Headache
Can lead to kidney damage
What is the gene associated with SCID (Artemis type) and in what populations is there a founder mutation?
DCLRE1C
Navajo and Apache
