Clinical Immunology - Broides Flashcards
What is caused by a deficiency in:
- B cells?
- T-helper cells?
- Cytotoxic T-cells?
- Regulatory T-cells
- NK cells
- Antibody deficiency
- HIV-like diseases (low CD4)
- Skin diseases (and viruses)
- Immune deficiency (Autoimmune Polyendocrine Syndrome- IPEX)
- Recurrent Herpes Infection
What is the cause of chronic granulomatous disease?
Intracellular killing of phagocytosed microbes by ROS and NO is defective
Extracellular phagocytosis is intact
Manifests as chronic early severe bacterial and fungal infections and granulomas on skin.
What is caused by a deficiency in:
- Mannose binding lectin complement activation pathway?
- Factors C7, C8 or C9?
- Factors C1 through C4?
- Nothing! 15-20% of people.
- Recurrent meningococcal disease
- Lupus-like disease
What do innate deficiencies cause in:
- IL12?
- IFN-gamma?
- IRAK4 pathway?
Adaptive immunity:
- IL2?
- Exaggeration of IL4/IL9?
- Intracellular bacteria infection like candidiasis, mycobacterium and salmonella
- Macrophage activation issues, Mycobacterium, leichmania, listeria, vaccinia infection
- Recurrent pneumococcal infection (signals TLR and T-cells)
- Severe Combined Immune Deficiency (SCID)
- No class switching, allergies
What are PAMPS (pathogen associated molecular patterns) and how are they associated with Toll Like Receptors (TLRs)?
PAMPS- Unique molecular structure that occurs in pathogens but not in humans. Allows for the identification of pathogens and initiation of innate immune response.
TLRs- Receptors that recognize PAMPS and initiate the immune response
What is caused by a deficiency in:
- TLR 3?
- TLR 4?
- Recurrent Herpes Encephalitis
- Recurrent pneumococcal disease and gram negative sepsis
What is caused by a deficiency in:
- MHC II deficiency?
- XLP deficiency
- Bare lymphocyte syndrome
- X-linked lymphoproliferative disease, die of EBV
What cells present:
- CD34
- CD3
- CD4
- CD8
- CD14
- CD19,20,21
- CD56,57
- pluripotent stem cells
- T cells
- MHC class 2 restricted T cells (T Helper), monocytes, macrophage. (Primary receptor for HIV)
- MHC Class 1 restricted T cells
- Monocytes and macrophage, granulocytes.
- B cells
- NK cells
What are the possibilities in SCID for cell defects? (T, B, NK)
What are the causes of each?
T-B-NK- : Reticular dysgenesis, ADA deficiency
T-B-NK+: RAG1, RAG2, Artemis deficiencies
T-B+NK- : γ C, JAK 3 (though B cells dysfunctional)
T-B+NK+ : IL-7 Rα deficiency
What are types of combined immunodeficiency?
SCID
Purine nucleosidephosphorylase deficiency
IL-2 R (CD25) mutation
Cartilage- hair hypoplasia
Omenn syndrome
MHC class I and II
Wiskott-Aldrich syndrome
-Triad of eczema, thrombocytopenia with small platelets and immune deficiency with low MCV
Ataxia telangiectasia
-No p53- usual cause of death
What is the manifestation of X-linked Agammaglobulinemia?
What is treatment?
Clinical features:
- Normal IgG at births (tranplacental transfer of IgG from the mother).
- Infections begin usually after 3 months.
- Bacterial infections- Strep. Pneumoniae, H. influenzae, Staph Aureus and Pseudomonas. All require antibody for opsinization to achieve efficient phagocytosis.
- Chronic sinusitis, chronic lung disease, bronchiectasis and other bacterial infections.
- Viral infections- intact immune response except against enteroviruses. Vaccine associated polio and chronic meningoencephalitis
- Lack of palpable lymph nodes and absent or very small tonsills
Treatment: IVIG
May be given killed vaccines to specify T cells
What is the cause of IgM syndromes?
How do they present?
- CD40 or ligand deficiency
- X-lnked
- No class switching
- AID DEFICENCY. (ACTIVATION INDUCED CYTEDINE DEAMINASE DEFICIENCY)
- URACIL DNA GLYCOSYLANE DEFICIENCY (UNG)
- causes Uracil to be in the DNA
- NEMO (Nuclear Factor Kappa B Essential Modulator) MUTATIONS
- Vulnerability to pneumocystis pneumonia
Treatment- IVIG, sometimes GCSF, Stem Cell transplant.
