IMMUNOLOGY Flashcards
HLA associated with diseases:
HLA-A3
Hemochromatosis
HLA associated with diseases:
HLA-B27
PAIR
- Psoriasis
- Ankylosing spondylitis
- Inflammatory bowel disease
- Reactive arthritis (Reiter’s)
HLA associated with diseases:
HLA-DR3
DM1
HLA associated with diseases:
HLA-DR4
Rheumatoid arthritis
DM1
Follicular Dendritic cells
- not from bone marrow
- No MHC II and not APC
- only in lymph follicle
- help mature B cells
Characteristic finding on electron microscopy of a dendritic cell with Langerhans cell histiocytosis
- Birbeck granules (Tennis rackets), immature dendritic cells from monocyte lineage;
- do not stimulate T lymphocytes via antigen presentation.
- Express S-100 and CD1a
Site of negative selection for T-lymphocytes
- Corticomedullary junction of the thymus
- T-cells expressing TCR’s with high affinity for self undergo apoptosis
- Cells become either CD4 or CD8 T-cells
IL-12
- Induces helper T cell to become Th1 cell
- Virally infected cells secrete IL-12.
- More Th1 secrete IL-2 which stimulates cytotoxic T cells to kill virally infected cells
- IL-2 is the most important cytokine in activating antigen primed helper T cells
How do interferons work?
- induce production of ribonucleus that degrades viral mRNA (alpha and beta)
- Increase expression of MHC I and MCH II (gamma interferon) and antigen presentation
- Activate NK cells to kill virally infected cells
Macrophages of bone?
osteoclasts
gene complex RAG 1 and RAG 2
- gives rise to a protein that initiates VDJ recombination in B and T cell development
- Recognize Recombination Signal Sequences that flank VDJ sequences
- Rearrangement begins at breaks in the dsDNA located at the RSS
- Mutations in RAG genes lead to inability for VDJ recombination and arrest B and T cell development
When is passive immunity necessary?
To Be Healed Rapidly
- Tetanus toxoid
- Botulinum toxin
- HBV
- Rabies, (RSV for babies, once a month vaccine)
Screening for SLE?
Antinuclear antibodies (ANA)
nonspecific
Anti-dsDNA, anti-smith
More specific for SLE + Renal disease
Antihistone autoantibody
90% Drug induced lupus
Hydralazine
Seen in 50% of patients with SLE
Given the following features, what type of graft rejection is occuring?
Obliterative vascular damage
(Fibrosis of the graft tissue and blood vessels)
- Chronic rejection
- Months-years
- Class I MHCnon-self perceived by CTLs as class I MHCself presenting non-self antigens
- Irreversible
- T-cell and antibody mediated damage
Given the following features, what type of graft rejection is occuring?
Vasculitis of graft vessels with dense interstitial lymphocytic infiltrate
- Acute rejection
- Weeks
- Cell mediated due to CTLs reacting against foreign MHCs
- Reversible with immunosuppresants
Given the following features, what type of graft rejection is occuring?
Macupapular rash, jaundice, diarrhea, hepatosplenomegaly
- GVHD
- Timeframe Varies
- Grafted immunocompetent T cells proliferate in the irradiated immunocompromised host and reject cells with “foreign” proteins resulting in severe organ dysfunction
- Usually occurs when organs rich in lymphocytes are donated: Bone and liver
Given the following features, what type of graft rejection is occuring?
Occlusion of graft vessels causing ischemia and necrosis
- Hyperacute rejection
- Within minutes!
- Antibody mediated (type II) due to presence of preformed anti-donor antibodies in transplant recipient
$ Types of Hypersensitivities
ACID
- Anphylactic and Atopic (type I) - free antigen cross links IgE on presensitized mas cells and basophils, releasing vasoactive amines acting on postcapillary venules.
- Cytotoxic (antibody mediated) (type II) - IgM, IgG bind and fix cell leading to lysis, recruit neutrophils and macrophages do most damage.
- Immune complex (type III) - Antigen-antibody (IgG) complexes activate complement, attracts neutorphils -> release lysosomal enzymes
- Delayed (cell mediated) (type IV) - Sensitized T lymphocytes encounter antigen and then release lymphokines (leads to macrophage activation; no antibody)
4 T’s of Type IV hypersensitivity
- T lymphocytes
- Transplant rejections
- TB skin tests
- Touching ( contact dermatitis)
What causes more eosinophils in circulation?
DNAAACP + IL-5 (snot interleukin)
- Drugs
- Neoplastic
- Asthma , Atopic, Allergic processes, Churg strauss
- Addison’s
- Acute interstitial nephritis
- Collagen vascular diseases
- Parasites (invasive)
$$$ Bruton Agammaglobulinemia
- X-linked (Boys)
- B cell deficiency -> defective tyrosine kinase gene (BTK) -> low levels of all immunoglobulins
- Recurrent Bacterial infections after 6 months
- Absent thymic shadow
$$$ Thymic plasia (DiGeorge)
- 3rd and 4th pouches fail to develop
- No thymus -> No T cells
- No parathyroids -> low Ca2+ -> tetany
- Congenital defects in heart/great vessels
- Recurrent viral, fungal protozoal infections
- 90% have a chrom 22q11 deletion (detect with FISH)
- Absent thymic shadow on CXR
$$$ Triad seen in SCID
_1. Severe recurrent infections _
- Chronic mucocutaneous Candidiasis
- Fatal or recurrent RSV, VZV, HSV, measles, flu, parainfluenza
- PCP pneumonia
2. Chronic diarrhea
3. Failure to thrive
$$$ Whatis SCID?
Severe Combined Immunodeficiency (SCID)
- Defect in early stem cell differentiation
- Can be caused by at least 7 different gene defects:
- IL-2 receptor (most common, X-linked) -> T cells don’t activate
- Adenosine deaminase deficiency - increased adenine is toxic to B and T cells
- Failure to synthesize MHC II antigens
- Last defense is cytotoxic NK cells
- TRIAD - Recurrent infection, CD, FtT
- No thymic shadow on newborn CXR
- Treatment: Bone marrow transplant
$$$ Chronic Mucocutaneou Candidiasis
- T cell dysfunciton v. C. albicans
- Recurent RSV, VZV, HSV
- Rx: Ketoconazole
$$$ What are the X-linked Immunodeficiencies?
X-linked are “WBC H”
- Wiskott-Aldrich
- Bruton Agammaglobulinemia
- Chronic Granulomatous Disease (+/-)
-
Hyper-IgM syndrome (3 types), all increased IgM and reduced Ig
- X-linked -> No CD ligand
- AR -> no CD40
- -NEMO deficiency
$$$ Wiskott Aldrich
“WAITER”
- Wiskott
- Aldrich
- Immunodeficiency - pregressive deletion of B and T cells
- Thrombocytopenia and purpura
- Eczema
-
Recurrent pyogenic infections
- No IgM v. capsular polysacchraides of bacteria - Strep, Staph, Haemophilus, Moraxella
- Low IgM, high IgA, IgE
- X-linked
- Triad = TIE: Thrombocytopenic purpura, Infections, Eczema
$$$ Ataxia-Telangiectasia
Triad: AAA
Cerebellar defects (Ataxia)
Spider Angiomas (telangiectasia)
IgA** deficiency**
- Defects in ATM gene - codes for DNA repair enzymes
- Cerebellar ataxia, and poor smooth pursuit of moving target w/ eyes
- Telangiectasias of face > 5yo
- ↑ cancer risk: lymphoma & acute leukemias
- Radiation sensitivity (avoid X-Rays)
- ±↑_A_FP in chlidren >8m
- Average age of death: 25 y/o
$$$ Selective Immunoglobulin Deficiencies
IgA deficiency is most common
- Defect in isotype switching
- Most appear healthy
- Sinus and lung infections
- 1/600 European descent
- Associated with atopy, asthma
- Possible anaphylaxis to blood transfusions and blood producs with IgA
$ IL-12 receptor deficiency
Mycobacterial infections
Reduced Th1 response -> reduced IFN-gamma
$$$ Phagocyte Deficiencies
- Chronic granulomatous disease
- Chediak-Higashi syndrome
- Job syndrome
- Leukocyte adhesion deficiency syndrome
$$$ Chronic Granulomatous Disease (CGD)
- Lack of NADPH oxidase activity -> impotent phagocytes
- Susceptible to organisms with catalase (S. aureus, E. coli, Klebsiella spp., Aspergillus spp., Candida spp.)
- Dx: (-) nitroblue tetrazolium (NBT) dye - No yellow to blue-black oxidation (healthy phagocytes oxidize yellow dye to blue)
- Prophylactic TMP-SMX
- INF-gamma also helpful
$$$ Chediak-Higashi Syndrome
- Defective LYST gene (lysosomal transport)
- Defective phagocyte lysosome (microtubule dysfunciton in phagosome-lysosome fusion) -> giant cytoplasmic graules in PMNs are diagnostic
- Presentation triad:
- Partial albinism
- Recurrent respiratory tract and skin infections - Pyogenic infections by staph, strep
- Neurologic disorders - Peripheral neuropathy, seizures
$$$ Hyperimmunoglobulin E Syndrome
Job Syndrome - “FATED”
- coarse Facies
- cold (noninflamed) staphylococcal Abscesses
- retained pirmary Teeth
- ↑ IgE
- Dermatologic problems (eczema)
- Hyperimmunoglobulin E syndrome
- Deficient INF-gamma (T-cells don’t make any)-> PMNs fail to respond to chemotactic stimuli (C5a, LTB4)
- High levels of IgE and Eosinophils
- Presentation triad:
- Eczema
- Recurrent cold (no IL-1) staph. aureus abscesses (think of bibilical Job with boils
- Course facial features: broad nose, prominent forehead (“frontal bossing”), deep set eyes, and “doughy” skin
- Also common to have retained primary teeth resulting in 2 rows of teeth
$$$ Leukocyte Adhesion Deficiency Syndrome
- Abnormal integrins (Defect in LFA-1 integrin (CD18) protein on phagocytes -> Inability of phagocytes to exit circulation
- Delayed separation of umbilicus
- **Recurrent bacterial infections **
- Absent pus formation
- Neutrophilia
Child with staph abscesses, if the neutrophils fail to respond to chemotactic stimuli, what is the most likely diagnosis?
Job Syndrome (Hyperimmunoglobulin E syndrome)
Which embyonic germ layer is the thymus derived from?
Endoderm
Newborn with chronic diarrhea, failure to hrive and chronic Candida
SCID
Child with eczema, course facial features, cold abscesses
Hyper-IgE Syndrome (job syndrome)
Child with partial albinism, peripheral neuropathy, and recurrent infections
Chediak-Higashi Syndrome
