Thymus Anatomy
Where is the Thymus located and is it encapsulated or non encapsulated?
Encapsulated in the anteriorsuperior mediastinum
What are the two main selection checkpoints that developing T cells undergo in the thymus?
Positive and Negative Selection
Failure of negative selection can lead to this category of disease.
Bonus: where does Negative selection occur?
Autoimmunity
Medulla
What is the only immunoglobulin that can be secreted in response to thymus-independent antigens?
IgM
What Does Th1 secrete
IFN-y, IL-2
Which pharyngeal pouch (and wing) gives rise to the thymus?
3rd pouch, ventral wings
Which signaling pathway is crucial for guiding thymus progenitors toward T cell fate?
NOTCH
What genes are essential for initiating VDJ recombination of T cell receptors (TCRs)?
RAG 1 and RAG 2
What are chemotactic agents for a neutrophil?
IL-8 is the primary neutrophil chemoattractant; however, others include leukotriene B4 (LTB4), C5a
Bonus if mention any of these:
the leukotriene precursor 5-HETE, kallikrein, platelet-activating factor, and N-formylmethionyl peptides (from bacterial proteins)
What does Th2 secrete
IL4,5,6,10,13
What part of the thymus consists of immature T cells?
Cortex
What are T cells called when they express both CD4 and CD8 cells?
Double positive
Low levels of what antigen and high levels of what cellular protein allow an immature T cell to be resistant to apoptosis?
Antigen= Fas
Protein= Bcl-2
Which of the following will most likely be underrepresented on flow cytometry in a patient with SCID?
A. CD4
B. CD14
C. CD19
D. CD34
A. CD4
Explanation:
SCID= unable to produce T cells
CD14 found on macrophages
CD19 B cell marker
CD34: hemapoetic stem cells
what induces TH17
IL1,6, TGF B
What part of the thymus contains mature T cells
medulla
Which type of selection causes T cells expressing TCRs with high affinity for self antigens on medullary epithelial cells to either undergo apoptosis or become regulatory T cells?
Negative Selection
The presence of CD4⁺CD25⁺FoxP3⁺ cells in the thymus is essential for the development of this T-cell subtype.
TREGS
A 23-year-old male is brought by ambulance to the emergency department after experiencing sudden onset shortness of breath, dizziness, nausea, and vomiting after being stung by a bee. His boyfriend immediately contacted EMS, and 0.3 mg of intramuscular epinephrine was given en route to the hospital. On arrival, he is alert and oriented to self, place, and time. He reports that his shortness of breath has improved, though he is still feeling nauseous and lightheaded. He denies fevers, cough, urinary symptoms, lower extremity edema, and headache. His boyfriend notes that he has been stung by a bee once before and did not have a reaction to it. On exam, he appears moderately short of breath. Pulmonary auscultation is notable for diffuse, bilateral wheezing. Skin is warm to the touch. Pulses are rapid, weak, and delayed. Vital signs are significant for blood pressure of 85/68 mmHg, heart rate of 110 beats/min, respiratory rate of 24 breaths/min, and temperature of 37.2°C (99.0°F).
Which of the following most likely occurred in the time between the first and second bee-sting?
A. Chemokine- induced inflammation
B. Opsonization of antigen-bound cells
C. Degranulation of mast cells and basophils
D. Class switching to IgE
D. Class switching to IgE
Explanation:
Anaphylaxis is due to a type I hypersensitivity reaction caused by the activation of basophils and mast cells by IgE receptor crosslinking. This patient developed this hypersensitivity due to prior exposure to a bee sting. Upon first exposure, Th2 cells promote antibody class-switching from IgM to IgE via IL-4 and affinity maturation. Subsequent exposure promotes crosslinking of IgE receptors on basophils and mast cells, resulting in degranulation of histamine, leukotrienes (amongst other inflammatory mediators). This causes vasodilation that leads to diffuse erythema and warmth of the skin.
What is T reg inhibited by?
IL 6
The presence of this structure is characteristic of the medulla and unique to the thymus. What is it?
Hassals Corpuscle
What mediates negative selection in the thymus?
Fas ligand binding Fas death receptor (CD95) is what mediates negative selection in the thymus
MHC I presents ____ synthesized antigens to CD8+ cytotoxic T cells
MHC II presents ____ synthesized antigens to CD4+ cells
Endogenously
Exogenously
During a microbiology lecture, a professor reviews the different defense mechanisms of bacteria against the immune system. These virulence factors help evade the immune system by rendering antibodies or complement ineffective. She discusses gram-positive, β-hemolytic, coagulase-positive cocci that form clusters. This organism has a virulence factor that binds the Fc portion of IgG inhibiting complement activation and phagocytosis. Thus, it is highly effective at evading the immune system. She explains that complement is a plasma protein that plays a crucial role in innate immunity and inflammation. She discusses the classical activation pathway and why specific antibody isotypes are better at activating this portion of the immune system.
What is the antibody isotype that is most effective at complement activation? What Bacteria is described in the question stem? What Virulence Factor is this question describing?
IgM, S. Aureus, Protein A
In this lecture, the professor also discusses complement activation via the classical pathway. The classical pathway begins when the C1 protein binds to the Fc region of the IgG and IgM. To become activated, the C1 protein must bind two antibodies. IgM is more effective at activating complement as it travels as a pentamer. IgG [choice D] is less effective as it travels as a monomer.
What inhibits Th2
IFN-y