Cells and Signals of the Immune System Flashcards
Adaptive Immunity is composed of two responses. What cells mediate each response?
- Humoral immunity is mediated by B lymphocytes
2. Cell-mediated immunity is mediated by T lymphocytes (also macrophages, NK cells)
B and T cell proliferation in early lymphocte maturation is stimulated by which cytokine?
IL-7
What interacts with the T-cell receptor (TCR) of an immature, double positive T cell (CD4+/CD8+ to signal differentiation into a single positive cell? In what organ does this occur?
Interaction with either major histocompatibility complex I (MHC I) (CD8+) or MHC II (CD4+) in the coretex of the thymus
What two processes eliminate immature T cells lacking proper antigen receptor specificities?
- Positive selection selects for lymphocytes with TCRs that recognize self-MHC proteins, ensuring that only T cells with TCR that recognize MHC mature.
- Negative selection eliminates autoreactive T cells that bind to MHC with high affinity.
What mechanism drives cell elimination in positive selection?
T cells that cannot bind to self-MHC molecules undergo apoptosis
Apoptosis of T-helper cells (CD4+, Th) or cytotoxic T cells (CD8+, Tc) bearing TCRs for self-proteins is the result of what process?
Tolerance, which prevents autoimmune reactions
What cytokine released by activated Th further stimulates Th-cell survival/proliferation?
IL-2. It binds to the IL-2receptor on Th cells causing further proliferation
Name the two signals that are needed to activate T cells:
- The first signal is the MHC/antigen complex interaction with a TCR specific for that antigen
- The second is the costimulatory signal of the CD28 protein on the T cell with the B7 protein on the antigen presenting cells (APC)
What is the result of an interaction between a T cell and an APC in the absence of costimulation?
Anergy or unresponsiveness of T cells
What T-cell protein displaces CD28 from B7, inhibiting T-cell activation and ensuring T cell homeostasis?
Cytotoxic T lymphocyte antigen 4 (CTLA-4)
Which MHC class molecule presents processed antigens from organisms that have been phagocytosed? What cells possess this MHC class?
MHC-II complexes on professional APC present extracellular, phagocytosed proteins to Th cells
What cells function as professional APCs?
Dendritic cells, macrophages, and B cells
What is the source of antigen presented by MHC-I molecules? What cells possess this class?
MHC-I complexes on ALL nucleated cells present intracellular proteins proteins to Tc cells
What is the cluster of polypeptides present in all T cells that is important in signal transduction by the TCR?
CD3 complex
Induction of which of the T-cell helper lines (Th1 or Th2) elicits a more effective response against intracellular pathogens such as Mycobacterium tuberculosis?
Th1 cells are more effective against intracellular pathogens
Which cytokine released by Th1 cells is involved in macrophage activation?
gamma-Interferon (y-INF)
What other signaling pathway results in macrophage activation?
The interaction of CD40 on macrophages with CD40L on T cells
What transcription factor is involved in both INF-y and CD40/CD40L signaling?
Nuclear factor-kB
How do macrophages respond to y-INF and CD40/CD40L signaling?
Cytokine release, increased microbicidal activity, increased phagocytic activity (through upregulation of B7and MHC II)
Once activated, what are the major cytokines released by macrophages?
Tumor necrosis factor (TNF) IL-1 IL-8 (leukocyte recruitment) IL-6 (lymphocyte activation IL-12 (Th1 differentiation)
What are the microbicidal substances produced by activated macrophages?
Reactive oxygen species, nitric oxide, and lysosomal enzymes
What are the main effector cells and cytokines of delayed hypersensitivity?
Macrophages induce differentiation of naive Th cells into Th1 cells by secretion of IL-12. IL-12 acts on NK cells to produce y-INF which also promotes Th1 differentiation. Th1 cells in turn release y-INF, activating macrophages
Against what pathogens is delayed hypersensitivity needed?
Intracellular pathogens (eg. M tuberculosis, Salmonella typhimurium, and Histoplasma)
Patients with T-cell deficiencies are most susceptible to what families of pathogens?
All severe T-cell deficiencies leave patients particularly susceptible to mycobacterial, viral and fungal infections
What is the result of superantigen activation of Th cells?
Massive Th-cell activation and cytokine release, resulting in shock
Which cytokine induces naive Th cells into mature Th2 cells?
IL-4
What cytokines do Th2 cells produce? What properties do these cytokines share?
IL-4, IL-5, IL-10, and IL-13. All are anti-inflammatory and antagonize Th1 cells
Which cytokines aid B cells in antibody production?
IL-4 and IL-5
What functions do IL-4 and IL-5 from Th2 cells serve in helminth immunity?
IL-4 induces hellminth specific immunoglobulin (IgE) abs and IL-5 activates eiosinophils
Which cytokine is implicated as a mediator of asthma (airway hyperresponsiveness)?
IL-13
By what two main methods do CD8+ cells kill virus-infected, graft, and tumor cells?
Cytotoxic T cells can lyse infected cells or induce apoptosis
Which mature immune cell has receptors for while, unprocessed antigens and does not require MHC presentation?
B cells, which actually present antigens themselves via MHC II to CD4+ helper cells in the process of activation, can recognize soluble or cell-associated antigens
Which types of antigens can induce ab production by B cells without the aid of helper T cells (ie, T-cell independent response)?
Multivalent antigens (bacterial capsule polysaccharides, DNA, RNA, and lipids) bind many IgM (immunoglobulin M) molecules and cross-link IgM receptors on B cells
Where does B cell differentiation occur?
Bone marrow
What is the predominant ab released in the initial stages of the primary humoral response?
IgM. Following a lag phase either IgG, IgA or IgE appear in the secondary response
What is class switching of antibodies?
The process that changes IgM to IgG, IgA or IgE
What cells and signals are involved in class switching?
Th-cell CD40 ligand interacts with B-cell CD40, inducing the release of IL-4, IL-5, and INF-y which signals class switching
X-linked hyper-IgM syndrome is an inherited disorder where the CD40 ligand on T cells is defective. How would this affect B cells?
Inability to perform isotype switching resulting in hypersecretion of IgM
How would the same syndrome (hyper IgM) affect macrophages?
The CD40-CD40L interaction is necessary for macrophage activation by T cells. Macrophages cannot be activated, resulting in susceptibility to intracellular microbes
What are the main steps in B-cell presentation to antigens to helper T cells?
Antigen-specific B cells bind to native antigen with membrane-bound immunoglobulin molecules. After internalization and processing of the antigen in an endosome, epitopes are presented on the B-cell surface via an MHC-II molecule where it is then presented to T cell
One of the causes of severe combined immunideficiency (SCID) is a lack of functional IL-7 receptors. What cells are depleted? How is immunity affected?
Since T cells require IL-7 for development, both cell mediated and humoral responses would be diminished
What would be different about the T cells in a patient with DiGeorge syndrome compared to that of a person without it? (DiGeorge syndrome results in thymic hypoplasia)
T cell differentiate in the thymus; abnormal thymic structure would result in a lack of T cells
What immune cell kills infected cells lacking MHC-I proteins?
NK cells destroy infected cells that lose the ability to synthesize MHC-I proteins
NK cells are activated by which cytokines?
IL-12 and y-INF
Which cytokines are responsible for the increased production of C-reactive protein during an acute-phase response in innate immunity?
IL-1, TNF-a, and IL-6 induce the liver to produce C-reactive protein
What cytokine is chemotactic for neutrophils?
IL-8 along with a complement component (C5a)
Which cytokine has a similar function to granulocyte-macrophage colony stimulating factor (GM-CSF)?
IL-3 is made by activated Th cells and supports growth and differentiation of bone marrow stem cells
The two types of immunity are innate and adaptive immunity. What cells mediate innate immunity?
Monocytes/Macrophages, neutrophils, natural killer (NK) cells, gamma-delta T cells
