Immunology- Pt 2

Antigen Receptors (T cells and B cells)

• T cells require antigen presentation, whereas B cells can approach antigens directly.

Antigen Processing and Presentation (T cells)

• The MHC (major histocompatibility complex) molecule has two classes: MHC1 and MHC2.

Class 1 MHC

• CD8 (cytotoxic T cells) can only recognize antigens presented on MHC1 molecules.
• Every nucleated cell has a class 1 MHC molecule.
• MHC1 takes proteins produced in the cells, breaks them down into peptides, and displays them on the cell surface.

Class 2 MHC

• CD4 (helper T cells) can only recognize antigens presented on MHC2 molecules.
• MHC2 expressing cell types include dendritic cells, macrophages, and B cells.

Naïve T Cell: Activation

• Naïve T cells are fully mature T cells that have not yet interacted with antigens.
• They are located within lymph nodes.
• The activation of naïve T cells is always done by dendritic cells.
• Activation involves proliferation and differentiation into effector and memory T cells.

Naïve T cell: Activation Steps

• Step 1: Immature dendritic cells encounter antigens in the tissue.
• Step 2: Migration to lymphoid tissue and maturation.
• Step 3: Antigen presentation by mature dendritic cells in the lymph nodes.

T Cell Subsets (CD4 and CD8)

• CD4 is known as the helper T cell, involved in the activation of macrophages, B cells, and other cells.
• CD4 has subsets/types: Th1, Th2, Th17.
• CD4+ Th1 cells are involved in cytokine secretion, activation of macrophages, and activation of CTLs (CD8+).
• CD4 expresses surface molecules and secretes cytokines that activate other cells.

CD8

• CD8 is known as the cytotoxic T cell, involved in the killing of infected "target cells" and macrophage activation.
• CD8 has a subset/type: CTLs (cytotoxic T lymphocytes).
• CD8+ CTLs will only kill pathogens and will never produce cytokines.
• CD8+ CTLs induce apoptosis of infected cells.

Apoptosis and Lysis

• Apoptosis is when a cell dies without rupturing the cell membrane, preventing inflammation.
• Lysis allows the pathogen to leave the cell due to the rupturing of the cell membrane, causing inflammation.

Adaptive Immunity: Humoral Response (B cells)

• B cells recognize antigens directly and present them to T cells.
• Antigen recognition is not restricted by MHC presentation.

B cell T-independent activation

• The production of IgM is the only possible response with T-independent activation.
• T-independent activation does not produce memory cells.
• T-independent activation B cells have low-affinity antibodies and short-lived plasma cells.

B cell activation by Th cells

• When T cells activate B cells, they can have responses including antibody secretion, isotype switching, affinity maturation, and memory B cell formation.
• B cell activation by Th cells induces a stronger response than T-independent activation.

Humoral responses involve:

• Immunoglobulins (Ig)
• Ig Isotypes or classes

Ig Isotypes

• Ig isotypes have differences in heavy chain structure, monomeric vs polymeric structure, subclasses, serum concentration, half-life, and functions.

Ig Isotype distribution

• IgM is mainly found in blood and is the major antibody of primary responses.
• IgG is found in blood and tissues and is the major antibody of secondary responses.
• IgA is found in mucous membranes.
• IgE is found in epithelial tissue.

Ig Isotype functions

• IgM activates the classical pathway of complement.
• IgA provides mucosal immunity, neutralizing microbes and toxins within the GI and respiratory tract.
• IgE is involved in eosinophil and mast cell mediated defense against helminths.
• IgG neutralizes microbes and toxins, provides feedback inhibition of B cell activation, neonatal immunity, antibody-dependent cellular cytotoxicity mediated by NK cells, and opsonization of antigens for phagocytosis by macrophages and neutrophils.