Antigens, Epitopes, and Immunity

Innate vs. Adaptive Immunity

• The innate immune system has a generalized response, recognizing general pathogen features.
• A stronger immune response can recognize specific parts of a pathogen for invader identification.
• These specific parts are called antigens, each possessing multiple epitopes.

Antigens and Epitopes

• An antigen (Ag) is a substance triggering an immune response in specific lymphocytes.
• Antigenicity is the property of behaving as an antigen.
• Factors such as foreignness, size, shape, and accessibility contribute to antigenicity.
• Antigens have antigenic determinants also known as epitopes, and they are small molecular groups recognized by lymphocytes.

Molecular Shape, Size, and Antigenicity

• T-cell lymphocytes are activated by protein-based antigens.
• B-cell lymphocytes are activated by protein, sugar, fats, etc. antigens.

Antigen Presentation

• Adaptive Immune System functions include specific responses to epitopes, connection with the innate immune system, continuous antigen processing, T-cell control over immune responses against specific microbes, B-cell antibody production, and creation of memory cells for an enhanced future response.
• Adaptive Immune Response is also known as the Acquired Immune Response.

Processing Bacterial Antigens

• Bacteria gets phagocytosed by a cell like a dendritic cell or macrophage, then it enters a vacuole.
• Lysosomes fuse with vacuole, using acids and enzymes to destroy bacteria.
• Antigens from the bacteria are added to individual Major Histocompatibility Complex II (MHCII) protein "cups."
• The "cups" with antigens move to the cell surface for presentation to the immune system.

Processing Viral Antigens

• A virus growing inside an infected cell uses the host's machinery to make proteins.
• The host cell takes some of these viral proteins and destroys them, separating the viral antigens.
• Antigens are loaded onto a Major Histocompatibility Complex (MHC-I) protein cup.
• The MHC-I "cup" with the antigen moves to the cell surface and is presented.
• All cells except red blood cells have an MHC-I system.

Antigen Presenting Cells

• Dendritic cells contain both MHC-1 and MHC-2.
• Macrophages start as monocytes, transform when activated, and are the main APC contributor.

Lymphocytes

• Lymphocytes, including T and B cells, are the main cells involved in acquired immunity.

T-Cells

• Overall specific immunity is controlled by T-cells by communicating with various cell types. This communication turns cells on, expresses genes, and other functions.
• T-cells are turned on by connecting with the innate cell containing the antigen on its surface.
• Memory cells are created during the first infection, allowing stronger, faster subsequent responses to recurring pathogens.

Activating T-cells

• Innate cells (phagocytes, macrophages, dendritic cells) digest and present various epitopes from an antigen on their surfaces using specific receptors called Major Histocompatibility Complex (MHC).
• Each T-cell has a specific receptor with a specific shape that fits a specific epitope on an antigen.
• The T-cell produces specific cytokines for certain immune responses if the receptor matches.
• An activated T-cell multiplies to create more specific cells and its receptors.
• The activated T-cell makes memory cells for later use.

T-Cell Receptors

• T-cell receptors are formed by genetic recombination, like B cell receptors with constant and variable regions.
• Receptors have 2 parallel polypeptide chains.
• Unlike B-cell receptors, T cell receptors are small, and remain intact on the T cell's surface.

Cytotoxic T-Cells

• Cytotoxic T (TC) cells also known as CD8 cells express CD8 receptors and are activated by antigen/MHC-I.
• They destroy foreign or abnormal cells by secreting perforins and granzymes.
• They destroy transplanted cells and organs.

Helper T-Cells

• T Helper (TH) cells, also known as CD4 cells, express CD4 receptors and are activated by antigen/MHC-II.
• They are the most prevalent type of T cell in blood and lymphoid organs.
• They regulate the immune reaction to antigens, including other T and B cells.
• They are involved in activating macrophages and increasing phagocytosis.

Types of T-cells and Functions

• T helper cells (TH) use CD4, TCR to activate other CD4 and CD8 cells; secrete cytokines and interferon gamma; control immune response with cytokines and MHC-II receptors; activate B cells.
• T cytotoxic cells (TC) use CD8, TCR to destroy a target foreign cell by lysis, are important for the destruction of cancer cells and virus-infected cells, and graft rejection; requires MHC I for function.

B-Cells

• B-cells produce antibodies when activated using innate immune cells, antigens on their surface with specific receptors, and T-cells that carry antigens on their surface.
• Memory cells are produced to allow stronger and faster immune responses

Activation of B-cells

• The B-cell's receptor connects with the antigen on the microbe directly.
• If the antigen fits, the B-cell becomes activated.
• The B-cell receptor becomes an immunoglobulin, also known as an antibody; released into the blood to provide humoral immunity.
• The activated B-cell makes copies of itself which are stored as memory cells.

B-Cell T-Cell Dependent Activation

• A T-cell takes antigens from the APC and holds it on a T-cell receptor.
• This T-cell attaches to the B-cell through its receptor to find a match to its receptor.
• The B-cell is activated if it matches which turns B-cell receptors into antibodies, allowing expansion of cell amounts, and creation of memory cells.

Immunoglobulins

• Immunoglobulins are glycoproteins acting like B cells receptors and antibodies.
• It is composed of 4 polypeptide chains with 2 identical heavy chains (H) and 2 identical light chains (L) in a Y-shape.
• A wide range of variable antigen-binding sites are located at the ends of the forks caused by the chains which is caused by the V regions.
• Constant (C) regions do not vary greatly.

Fab Antigen-binding Site

• The antigen-binding site is composed of hypervariable regions with an extremely variable amino acid content.
• The groove has a specific three-dimensional fit for the antigen.
• Specificity of Fab sites is identical for each antigen.

Fc Fragment Function

• The Fc fragment binds to cell membranes of macrophages, neutrophils, eosinophils, mast cells, basophils, and lymphocytes where regions on the Fc portion in certain antibodies fix complements.
• Binding of Fc may cause the release of cytokines.

Classes of Immunoglobulins

• IgG is a monomer produced by plasma cells, crosses placenta, and is most prevalent.
• IgA is a monomer that circulates in the blood and a dimer in mucous and serous secretions.
• IgM contains five monomers and is the first class synthesized following Ag encounter.
• IgD is a monomer acting as a receptor for antigens for B cells.
• IgE is used in allergic responses and parasitic worm infections.
• The differences in these classes are due primarily to variations in the Fc.

Antibody-Antigen Interactions

• Antibodies unite with, immobilize, call attention to, or neutralize the Ag for which it was formed.
• Opsonization is the coating microorganisms or particles with specific antibodies which causes microorganism recognition with a phagocyte; carried out by opsonins.
• Neutralization is when antibodies fill the surface receptors and activate a microbial protein or toxin to prevent interaction or attachment.

T-Cell and B-Cell Receptor Creation

• Immune genes during recombination are randomly recombined to make new T-cell and B-cell receptors (and antibodies); each new recombinant has a different shape to recognize specific antigens.
• Lymphocytes use 500 genes to produce a tremendous specificity.

Genetic Composition of Lymphocytes

• Lymphocyte specificity is genetically preprogrammed, even before an antigen enters the system
• Clone – Each genetically different type of lymphocyte expresses a single specificity
• Undifferentiated lymphocytes contain 150 genes for variable light chains, and 250+ genes for the variable(V) and diversity (D) regions of heavy chains.
• Only a small number of genes code for the constant (C) regions and the joining (J) regions that link segments of the final molecule.

Clonal Selection

• During clonal selection, receptors carrying cells come into contact with a microbe containing antigens, the receptor touches the antigen to see if it fits
  • The cell makes copies of itself if there is a match.
  • The cell will it let other cell receptors touch if there is not a match until a match is made
  • If the receptors recognize a self molecule, the cells are eliminated

Cytokines

• Cytokines are proteins immune cells release, that bind to other immune cells and other cells, and tell them what to do in response to infection.

Monitoring Antibody Production Over Time

• Primary response is a latent period where the IgM antibody occurs early, followed by the IgG activation. then the titer tapers back to low levels.
• Secondary response is a latent period that lacks when lymphocytes respond rapidly which causes a rapid increase in antibody levels.

Natural Killer Cells

• NK cells release perforins, which polymerize, and form a hole in a foreign cell membrane to degrade proteins.
• The foreign cell will die through apoptosis
• The macrophage will engulf and digest the dying cell

Antigen Recall

• Antigens are molecules that stimulate an immune response such as epitopes.

The types of Antigens

• Alloantigens are markers and molecules that occur in some members of the species, for example, blood groups and major histocompatibility profiles.
• Allergens are a type that produces vigorous immune responses where perceived threats by the immune system fight a harmless body

Characteristics of Superantigens

• Superantigens are viral/bacterial virility factors that provoke overwhelming immune responses by a large amount of T cells
  • Cytokine releases
  • Blood Vessel damage
  • Toxic shock
  • Multi-Organ Failure