Immunology Flashcards
Which form of immunity is described below?
- early response, reacts to microbes and products from injured cells (recognizes PAMPs and DAMPs)
- repeated exposures demonstrate the same reaction
- Involves physical and chemical barriers; neutrophils, macrophages, DCs, NK cells; complement
- Inflammatory cells phagocytose microbes and produce ROS/NOS
- NK cells target viruses
- receptors are encoded within germline
Innate
Which form of immunity is described below?
- specific for distinct molecules
- able to remember and respond more vigorously
- evolved to respond to an initial encounter with a variety of foreign pathogens as well as a potential secondary encounter with the same pathogen
- receptors are produced by somatic recombination (allows greater diversity)
Adaptive
Which form of immunity is described below?
- B lymphocytes secrete Ab to eliminate extracellular microbes
- The response of B-cells to an Ag requires activating signals from CD4+ cells; some activated B-cells will differentiate into Ab-secreting plasma cells
- B-cells also need helper T-cell assistance for class switching and affinity maturation
Humoral
Which form of immunity is described below?
CD4+ and CD8+ T cells defense against intracellular microbes, such as viruses and some bacteria
Cell-mediated
What are ICAMs and how do they work?
What cells are they expressed on?
What cells and other receptors do they bind to?
- Member of Ig superfamily involved in Ca-dependent cellular adhesion
- ICAM-1 (CD54) is expressed on cytokine-activated endothelial cells and many other cell types
- Binds LFA-1 (CD11a/CD18) expressed on leukocytes
- LFA-1 and ICAM-1 binding = synapse between CD8+ T cell and its target
- Also binds Mac-1 (CD11b/CD18) expressed on monocytes
Answer the following questions regarding IL-12:
- IL-12 is produced by what cells?
- IL-12 is produced in response to what stimulus?
- Once produced IL-12, stimulates the synthesis of what other cytokines by T cells and NK cells?
- Enhances cytotoxicity of which cells?
- Stimulates CD4+ TCL differentiation into TH1 cells
- Activates which TF?
- Facilitate what cell differentiation?
- produced by DCs, macrophages and B cells
- in response to IFN-y
- Stimulates synthesis of IFN-y and TNF-a by T-cells and NK cells
- Enhances CTL and NK cell cytotoxicity
- Stimulates CD4+ TCL differentiation into TH1 cells
- Activates STAT4
- Facilitate CD8+ differentiation – shared process with TH1 cells
Answer the following questions regarding IL-2:
- IL-2 is produced by what cells?
- When IL-2 is produced by CD4+ TCLs, what does this stimulate to occur?
- What regulator protein is induced by IL2 which will lead to synthesis of cyclins and degradation of p27, leading to evasion of apoptosis and continued cell cycling?
- IL-2 helps with proliferation and differentiation of which cells?
- IL-2 is required for survival and function of which T cell line?
- IL-2 induces proliferation and activation of what other non-T cell?
- IL-2 enhances cytotoxicity of which cells?
- IL-2 activates which cells?
- produced by T-cells (mainly by activated CD4+, TH1 cells)
- Secreted by CD4+ TCLs when activated by an Ag -stimulates clonal expansion
- Induces Bcl-2, synthesis of cyclins, and degradation of p27 – evasion of apoptosis and continued cell cycling
- Proliferation of T-cells; differentiation into effector and memory cells
- Required for survival and function of Tregs (they don’t produce significant IL-2 on their own, so they rely on CD4+ TCLs)
- Induces proliferation and activation of NK cells
- Enhances CTL and NK cell cytotoxicity, production of LAK cells
- Activates DCs, macrophages, and B cells
- Which inflammatory cytokine is immunosuppressive?
2. What other growth factor and cytokines are also immunosuppressive?
- IL-10
• IL-10 is produced by macrophages and DCs and serves as negative feedback to inhibit their activity - TGF-B and TNF-a are also immunosuppressive
• All suppress anti-tumor response and inhibit DC function
Match which MHC I and MHC II interacts with which T cell:
CD4+
CD8+
MHC class I, expressed on all cells, recognizes CD8+
MHC class II, expressed only on APCs (DCs, macrophages, B-cells), recognizes CD4+
What happens with APC cell and lymphocyte priming?
- During priming, a DC acquires Ag and matures at the site of infection and travels to the draining LN where it enters the T cell area and interacts with T cell residents there.
- DC and T cells both express CCR7- travel to LN due to CCL19 and 21
What are the three methods of MHC loading?
(1) endogenous, (2) exogenous, (3) cross-presentation
all occur before MHC expression on the cell surface
Which MHC loading is being described?
loading MHC class I molecules in APCs – unique to dendritic cells exogenous proteins can be taken up by DCs and presented on MHC class I molecules. At the same time, these DCs present MHC class II peptides to CD4+ T-cells. Enables Ag from one cell (virus or tumor-infected cell) to prime/activate T cells specific for these Ag
Cross-presentation
Which MHC loading is being described?
loads intrinsic proteins onto class I on most cells – intracellular peptides are combined with class I molecules within the ER
Endogenous pathway
Which MHC loading is being described?
loads extracellular peptides class II on APCs – as class II molecules leave the ER in an exocytic vesicle, it fuses with vesicles containing peptides
Exogenous pathway
Which of the MHC loading mechanisms is best used for tumor cells? WHY?
Cross presentation: Since tumor cells are typically not derived from APCs, they lack necessary costimulators for T-cell response. Therefore, they are first taken up by APCs and processed with MHC class I molecules; the APC provides the costimulatory signals to initiate a CD8+ T-cell response.
What are the different molecules that help in the
APC/T-cell recognition and activation?
- Necessary 1st signal for activation
- Second signal for co-stimulation
- Third signal for amplification for T cell response
- recognition of Ag
o DCs and TCLs express CCR7, which colocalizes to lymphatics and T-cell zones of LNs (CCL19 and CCL21)
o Initially, DC interact with T-cells via ICAM (on DC) and LFA-1/2 (on TCLs)
Binding slows movement of DC and brings it in proximity with TCR - CD28 co-stimulatory molecule binds to its ligands, CD80 (B7-1) and CD86 (B7-2), which are present on activated APCs
Results in (1) IL-2 production, which is critical for TCL proliferation/survival, (2) anti-apoptotic proteins Bcl-2 and Bcl-XL - T cell activation increases surface expression of CD154, which binds CD40 on DCs, macrophages, and B-cells
Which factor would help optimize APC presentation?
a. IL-2
b. IL-12
c. GM-CSF
d. G-CSF)
c. GM-CSF
• GM-CSF: produced by T-cells, macrophages, endothelial cells, fibroblasts
o Promotes growth and differentiation of pluripotent progenitor cells
o Stimulates growth of granulocytes, macrophages, and eosinophils
o Activates macrophages and dendritic cells
• GM-CSF used in dendritic cell vaccines to induce differentiation (can also use IL-4)
What is the major difference if B and T cell receptors?
TCR only recognizes peptide fragments bound to MHC (not unprocessed Ag)
BCR can bind to Ag in their native form and can detect unprocessed Ag
This card is just for review of the T-cell receptor
- TCR genes only undergo recombination (not somatic mutation or conversion)
- TCR complex = TCR, CD3 and zeta proteins
- When TCR recognizes MHC-peptide complex, it forms an immunologic synapse (aka SMAC), which contains the TCR complex, CD4 or CD8 coreceptors, costimulatory molecules, and adaptor proteins
- TCR signaling activates NFAT, AP-1, and NF-KB
This card is just for review of the B-cell receptor
- BCR: membrane-bound form of Ig
- Only 2 ITAMs (TCR has 10), but this number increases with cross-linking
- BCR genes can generate diversity through recombination, somatic mutation, or gene conversion
- Transcription factors = Fos, JunB, NF-KB
Which part of the antibody has the effector action?
• C region of heavy chain – this is also what determines the Ab isotype
o Less specifically, the Fc region has effector
function and the Fab region binds Ag
• Since Ab function is determined by binding of the Fc region to the Fc receptor on different cells, each Ab isotype performs different effector functions
