Immunology Flashcards
What vaccines must be conjugated to be very effective? Why?
Vaccines directed against bacteria with polysaccharide capsule antigens as the target:
- Haemophilus influenzae b
- Streptococcus pneumoniae
- Neisseria meningitidis
Polysaccharide antigens cannot be presented to T-cells via MHC
-> need to conjugate to a immunogenic protein (i.e. tetanus toxoid) so that B cells which have B-cell receptor (antibodies) to the polysaccharide can process the toxoid protein and present it on MHC to get T cell activation
Why is T cell activation so important for vaccines? Why is this especially a big deal in children?
Activation by T cells allows antibody class switching (IgM -> IgG) and generation of memory B cells -> longer-lasting and more robust immune response
Furthermore, children have an underdeveloped humoral immunity -> administration of conjugated vaccines is the only way to generate an antibody response
What type of pneumococcal vaccine is generally given to adults vs children?
Adults - Mezzanine - IgM-generating vaccine of polysaccharide capsule not conjugated to anything -> no lasting memory B cell response
Kids - Ground - IgG vaccine conjugated to toxoid -> required for immunogenicity in children
How do you assess if hematuria / proteinuria in endocarditis is due to kidney infarct / abscess vs glomerulonephritis?
Infarct / abscess present with flank pain, while glomerulonephritis generally does not.
Which light chain type rearranges first, and what is the net result of this in terms of circulating Ig? Where does this occur?
Kappa locus rearranges first, and if successful, prevents lambda locus from rearranging (they are on separate chromosomes).
Result is there are about twice as many Kappa Ig molecules vs lambda
This all occurs in the bone marrow
What do V, D, J, and C stand for? Which are not present in light chains?
V = variable D = diversity J = joining C = constant
Diversity segments are not present in light chains
When and how does class switching occur?
After exposure to Ag, somatic rearrangement occurs non-reversibly at the DNA level in response to the cytokine environment (determines optimal Ig class).
What carries the signal that a successful heavy chain has been made, and light chain splicing should begin? What type of receptor is this?
Pre-B cell receptor shuts off surrogate light chain production and starts the light chain rearrangements, while also stopping heavy chain rearrangments.
This is a RTK which, if defective, will arrest all B cells in the pre-B stage (X-linked agammaglobinemia)
What is the main cell type involved in organizing lymphoid tissues?
Reticular cells - fibroblast-like cells which produce Type 3 collagen to provide the framework for spleen, lymph nodes, and lymph nodules
Give an example of a condition where only the cortex of the lymph node would be absent?
Bruton’s agammaglobulinemia -> B cells can never mature from bone marrow if they don’t move on from the pre-B cell stage
-> follicles will be absent
What is the mnemonic for the features of DiGeorge syndrome?
CATCH-22 Cardiac anomalies Abnormal facies Tetralogy of Fallot Cleft palate (not lip) Hypoparathyroidism / hypocalcemia
Explain internal hemorrhoids due to cirrhosis?
Portal HTN slows the drainage of the superior rectal vein, the final branch of the IMA
Superior rectal vein anastamoses with the middle and inferior rectal vein, which are branches of the internal iliac.
Explain the lymph drainage above and below the dentate line?
Above - superior rectal vein to IMA, and middle rectal vein to internal iliac nodes
Below - all lymph goes to superficial inguinal nodes.
What drains the lymph from the superior and inferior portions of the bladder?
Superior - External iliac nodes
Inferior - Internal iliac nodes
Where does the body of the uterus and cervix drain?
External iliac nodes, with the bladder
Where does the prostate, cervix, corpus cavernosum, and proximal vagina drain?
Internal iliac nodes
Where does the distal vagina, vulva, scrotum, and distal anus drain?
Superficial inguinal nodes
Where does the glans penis drain?
Deep inguinal nodes
Does the medial or lateral foot and posterior calf drain into the popliteal nodes?
Lateral tract -> follows the arteries. Ultimately this system drains into the deep inguinal nodes.
Remember the saphenous vein is medial so it drains the medial leg and foot into the superficial system
Where do the kidney lymph nodes drain?
Para-aortic nodes, since renal arteries branch directly from aorta
Where does lymph from the uterine fundus drain to?
Para-aortic nodes, along with the fallopian tubes and ovaries via the gonadal artery distribution
Where are the B and T cells found in the spleen?
T cells - periarteriolar lymphatic sheath - PALS
B cells - follicles within the white pulp
What are four changes seen in the blood post-splenectomy?
- Howell-Jolly bodies - nuclear remnants of RBCs remain in RBCs
- Target cells - lack of removal of excess membrane
- Thrombocytosis + 4. Lymphocytosis -> loss of sequestration in spleen
What are the histologic features of the thymic cortex / medulla on H&E stain?
Cortex - dark basophilic staining, with immature T cells
Medulla - pale staining, with mature T cells and epithelioreticular cells forming Hassall’s corpuscles
What is the pathway for antigen presentation on MHC Class 1? What proteins are involved in translocation to the ER?
Proteins are degraded by the proteasome. TAP-1 and TAP-2 transport the broken down proteins from the proteasome to the RER, where fragments become associated with the newly formed MHC Class 1. These peptides will be presented on the surface of the cell.
TAP1 = transporter associated with antigen processing
What is the mechanism of MHC Class 2 presentation?
MHC Class 2 is assembled in ER and stabilized by invariant change.
Invariant chain degrades to CLIP after vesicle ships from Golgi.
Phagocytosed and acid-digested vesicle (acidified endosome) fuses with MHC vesicle, and CLIP is removed.
The immunodominant protein fragment will bind
What chromosome is HLA found on and how do you remember this? This relates to hemochromatosis somehow.
Chromosome 6. Remember this because hemochromatosis is associated with HLA-A3, and must be in linkage disequilibrium since Chromosome 6 is also where the HFE gene is.
Which HLA’s are associated with Addison’s disease?
HLA-B8, DR-3, and DR-4
Think Graves + rheuatoid arthritis
Which HLA is associated with myasthenia gravis?
Sadly, same MHC class 1 as Graves disease
HLA-B8.
What HLA is associated with pernicious anemia?
Same as Hashimoto’s thyroiditis - HLA-DR5. High five luke!
How are NK cells and macrophages in a positive feedback loop?
Macrophages release IL-12 -> activates NK cells
NK cells release IFN-y (part of the lymphoid line, but still innate immunity) -> activates macrophages
How are natural killer cells activated in response to viral infection?
TLR-3 binds dsRNA -> upregulates local IFNalpha / IFNbeta synthesis
- > IFNalpha / IFNbeta activate NK cells
- > they also upregulate MHC class 1 to improve presentation of viral peptides to CD8 T cells.
How does ADCC occur?
CD16 (Fc receptor for IgG) binds to the base of immunoglobulin, activating NK cell to use perforin and granzymes to induce apoptosis of viral infected / tumor cells.
What is Stage 1 of T cell development? What takes place in the thymic cortex / medulla?
Bone marrow cells arrive at the thymus as double negative (CD4-CD8-).
Cortex - Positive selection, where TCRs capable of binding self-MHC survive
Medulla - Negative selection, mediated by AIRE. TCRs with high affinity for self antigens undergo appoptosis.
What selection takes place during the double positive stage (stage 2)? This follows the double negative stage where TCR rearrangement occurs and both CD4 / CD8 become expressed.
Positive selection - T cells bind with weak affinity to self MHC
Negative selection - T cell binding is too strong - recognition of self = apoptosis
Death by neglect - unreactive T cells to MHC die via apoptosis after neglect.
-> MHC type which they have the best affinity for determines if they will become CD4 or CD8 cell (other receptor is downregulated).
List the cytokines needed to induce formation of Th1 vs Th2 vs Th17 vs Treg cells? What cells are releasing these cytokines?
Th1 - IL-12 (macrophages), IFN-y
Th2 - IL-2, IL-4
Th17 - TGF-beta, IL-6
Treg - TGF-beta
Cytokines are released my antigen presenting cells to induce a specific subset differentation
List the cytokines which inhibit the formation of Th1 vs Th2 cells.
Th1 - IL-4, IL-10 (Th2 line)
Th2 - IFN-y (Th1 line)
What cytokines does the Th1 subset secrete and what does this do?
Secretes IFN-y -> activates macrophages, induces class switching to IgG3, suppresses Th2 response
Secretes IL-2 -> T cell growth factor and stimulator of CD8 cells (costimulator for cytotoxic cells which encounter their MHCI)
What cytokines does the Th2 subset secrete and what does this do?
Secretes IL-4, IL-5, IL-10 and IL-13
IL-4 - Class switching to IgE and IgG, inhibits Th1
IL-5 - Eosinophil chemotactic agent, class switching to IgA
IL-10 - Inhibits Th1
IL-13 - similar to IL-4
What is the function of Treg cells and what cytokines do they produce?
Suppress activation of immune response via production of TGFb and/or IL-10
They also express CTLA4 and bind B7, preventing the interaction betwen CD28 and B7 on CD4 cells.
What syndrome does Foxp3 mutation cause? Symptoms?
IPEX Immune dysregulation, Polyendocrinopathy - thyroiditis and pancreatitis -> destruction of pancreatic islets -> diabetes Enteropathy - diarrhea X-linked - (diabetes in males infants)
Also has dermatologic manifestations i.e. dermatitis / nail dystrophy
What is the process by which T cells are activated by antigen presenting cells?
- Signal 1 - APCs present peptides to TCRs via MHC Class 1 or 2
- Signal 2 - APCs send costimulatory signal by by having their B7 (CD80/86) bind CD28 of T cells.
What is the process by which T cells induce class switching in B cells?
- Signal 1 - B cell presents processed peptide via MHC Class 2 to CD4 T cell
- Signal 2 - CD40L of T cells bind CD40 receptor of B cells to induce class switching of B-cell as costimulation.
- Signal 3 - Cytokine released by T cell induces the class
IgE - IL-4
IgA - IL-5
IgG - IL-6
