What is the major difference between how CMI and humoral immunity are elicited by antigen?
Unlike the IgM B-cell antigen receptor, the T-cell receptor (TCR) is not secreted. Immunity must be conferred via direct contact between cells.
Cell-mediated immunity is mainly directed against what two major types of cells?
- Cells with intracellular microorganisms
2. Aberrant, endogenous cells such as cancer cells
Persons with a deficiency in cell-mediated immunity are prone to which types of infections?
Infections with viruses, fungi, Mycobacterium, and other intracellular organisms
What are the two types of naive Th cells? What are their functions?
- Th1 cells mediate the inflammatory process and activate macrophages.
- Th2 cells inhibit both the inflammatory process and macrophage activation and aid in helminth immunity and ab production
List the major steps in Th1-cell-mediated macrophage activation:
- Antigen-presenting cells (APCs) present antigen to naive Th cells, leading to Th1-cell differentiation and sensitization in lymph nodes
- Transit of Th1 cells to site of antigen release (ie, site of infection).
- Th1 cell activation of macrophages.
Name the different types of APCs. What two signals are needed to activate a Th cell. What cytokine do APCs secrete to induce Th1-cell differentiation?
B cells, macrophages, and dendritic cells. APC’s major histocompatibility complex II (MHC-II) molecule with ag binds to TCR/CD4 and APC’s B7 protein binds to Th cell’s CD28, providing the necessary costimulation for activation. IL-12 and y-IFN differentiates naive Th cells into Th1 cells.
Th1 cells migrate to source of antigen (infection) and activate macrophages that present the antigen of interest through what three signals?
- Interaction of MHC-II with bound antigen and TCR/CD4
- CD40 on macrophage with CD40L on the TH1 cell
- IFN-y released from Th1 cell with IFN-y receptor on macrophage
What are the functions of macrophages?
Macrophages present antigens, produce cytokines and perform phagocytosis
What functions of macrophages are enhanced in T cell activation of macrophages?
Activated macrophages kill phagocytosed microbes via H2O2, O2- and NO; trigger acute inflammation; and facilitate tissue repair by phagocytosis of necrotic tissue
Delayed-type hypersensitivity (DTH, type IV) is the only cell-mediated hypersensitivity reaction. Describe it and name some examples:
Previously sensitized T cells reencounter the intital antigen and trigger macrophage activation, a process that develops over 24-48 hours. Examples include acute transplant rejections, tuberculosis (TB) skin tests, and contact dermatitis.
Describe the histopathology of a granuloma. In what instances are granulomas produced?
Granulomas are composed of a central core of activated macrophages surrounded by lymphocytes and are formed in response to persistent antigen stimulation of CML
Activated macrophages in a granuloma are also called epitheliod cells due to morphological changes. What cytokine triggers this change?
y-IFN
How are Tc cells activated?
Tc cells require APC with MHC-I with antigen of interest binding to TCR/CD8 on Tc cell and costimulation by either B7/CD28 or cytokines (IL-2) from TH cells
How do activated Tc cells recognize infected cells?
Through presentation of the antigen of interest on the infected cell by the MHC-1 molecule
How do activated Tc cells kill infected cells?
Perforins (create holes in the cell membranes, disrupts osmotic balance), granzymes (activate apoptosis through caspases), and FasL on Tc cells binds Fas on target cells also resulting in apoptosis
Cell-mediated immunity (CMI) and humoral immunity are the two aspects of adaptive immunity. What mediates CMI?
T-helper cells (CD4+/CD8-; Th cells), cytotoxic T cells (CD8+/CD4-; Tc cells), macrophages, and natural killer (NK) cells
