The early phases of the host response to infection depends on innate immunity in which a variety of innate resistance mechanisms recognize and respond to the presence of a pathogen. Innate immunity is present in all individuals all the time, does not increase with repeated exposure to a given pathogen, and does not discriminate between pathogens. It is followed by adaptive immunity.
Adaptive Immunity –
Adaptive immuity is the response of antigen-specific lymphocytes to antigen, including the development of immunological memory. Adaptive immune responses are generated by clonal selection of lymphocytes, and are distinct from innate and non-adaptive phases of immunity, which are not mediated by clonal selection of antigen-specific lymphocytes. Also known as acquired immune responses.
Innate immunity and adaptive immunity cooperate, examples include: complement activated opsonization of bacteria, and cytokine signals from T-cells which activate macrophages
Immunoglobulin. Plasma proteins produced by B cells that bind to specific antigens. They bind to and neutralize pathogens or prepare them for uptake and destruction by phagocytes. Each antibody has a unique structure that allows it to bind its specific antigen (variable region), but all antibodies have the same overall structure (constant region).
T Cell Receptor –
TCR. The TCR consists of a disulfide-linked heterodimer of the highly variable a and b chains expressed at the cell membrane as a complex with the CD3 chains. Can bind antigens of bacterial or viral origins. Unlike antibodies, the TCR will only recognize peptides which must be presented to it by MHC molecules.
Thymic Education –
T cells get thymic education so they will not recognize self proteins. Stages happens in: Subcapsular region of thymus Þ cortex Þ cortico-medullary region (touch antigen presenting cells) Þ medulla Þ release into circulation.
MHC Restriction –
Antigen recognition by T cells is MHC restricted, meaning that a given T cell will recognize antigen only when its peptide fragments are bound to a particular MHC molecule. Normally, as T cells are stimulated only in the presence of self MHC molecules, antigen is recognized only as peptides bound to self MHC molecules. However, experimental manipulations can produce T cells that recognize antigen only when its peptide fragments are bound to non-self MHC molecules. Thus, MHC restriction defines T-cell specificity both in terms of the antigen recognized and in terms of the MHC molecule that binds its peptide fragments.
Superantigens
are molecules that stimulate a subset of T cells by binding to MHC class II molecules and Vb domains of TCRs. As such they can falsely activate a large number of T cells without the presence of the appropriate antigen.
MHC class I –
MHC molecules which present peptides generated in cytosol to CD8 T cells.
MHC class II –
MHC molecules which present peptides degraded in cellular vesicles to CD4 T cells.
While MHC class I molecules are found in every cell, MHC class II molecules are expressed on Ag-presenting cells (Macrophages, dendritic cells, and B cells). Expression of class II molecules can be induced on several other cell types, however, including endothelial cells and fibroblasts, by action of IFN-gamma.
Invarient Chain –
MHC class II proteins are assembled in the ER with the invariant chain, which is involved in shielding the MHC class II molecules from binding peptides and in delivering them to cellular vesicles. There the invarient chain is degraded, leaving the MHC class II molecules able to bind peptide fragments of antigen. This prevents the MHC class II molecules from binding intracellular peptides.
HLA –
Human Leukocyte Antigen, is the genetic designation for the human major histocompatibility complex. The HLA region consists of Class I regions (A, B, C) and Class II regions (DP, DM, DQ, DR). The genes may contain a Class III region as well.
TH1 cells –
Inflammatory CD4 T cells activate MF s via IFN-g . Activated by IL-2.
TH2 cells –
Helper CD4 T cells activate B cells via IL-4 and IL-5. Also activated by IL-2.
Why do T cells not recognize self?
When a T cell binds an antigen present cell (APC) it has an additional receptor, CD-28, which attempts to bind surface molecule B7 on the surface of the APC. This sends a co-stimulatory signal which lets the T cell get activated. APCs which present self-peptides will not express the B7 molecule on their surface, thus preventing T cells from recognizing self.
Autoimmunity
– If the above fails the immune system will attack self.
Examples of diseases
: Graves disease - Abs bind TSH-R and upregulate thyroid hormone production, Myasthenia gravis - Abs bind ACh-R and inhibit it, Lupus - several defects in both T and B cells, but mostly Abs against nuclear antigens (i.e. genetic stuff inside cells).