Immunology Concepts Quiz

Antigens

• Antigens (Ag) are substances that, when introduced into the body, stimulate the production of an antibody that reacts specifically with the antigen.
• The word "antigen" originates from the idea that these substances stimulate antibody generation.
• An immunogen is a substance that induces a specific immune response.
• An epitope, or antigenic determinant, is the part of an antigen that combines with the products of a specific immune response.
• Tolerogens are antigens that induce immunological tolerance. Immunological tolerance is a series of mechanisms that prevent the immune system from attacking self-antigens.
• Allergens are antigens that induce anaphylaxis, a severe immediate hypersensitivity reaction due to rapid mast cell granulation. Examples include some medications, pollen, and seafood.
• Tumor antigens are presented by MHC I molecules on the surface of tumor cells. These antigens may only be present on tumor cells and not normal cells; these are called tumor-specific antigens (TSAs) and typically result from a tumor-specific mutation.
• Autoantigens are normal proteins that are recognized by the immune system of patients with autoimmune diseases. Under normal conditions, these antigens are not targets of the immune system, but genetic and environmental factors can cause a loss of immunological tolerance to them.
• Vaccines are antigen preparations that induce a protective immune response against microbes and prevent diseases. Killed vaccines, like the rubella vaccine, and attenuated vaccines, like the measles vaccine, are used. Toxoids, like the tetanus toxoid, are also used.
• Antibodies (Ab) are specific proteins produced in response to an immunogen; they react with the antigen.
• Immunogenicity is the ability of a molecule/microbe/cell to be recognized by the host's immune cells and elicit an immune response.
• Antigenicity is the ability of a molecule to bind/react with the products of an immune response (antibodies or lymphocytes).
• Antigens can be classified as complete or incomplete. Incomplete antigens are also known as haptens; they are non-immunogenic, but they can react with the products of a specific immune response. Haptens are small molecules that do not induce an immune response when given alone, but when given with a carrier molecule they can induce an immune response.
• Antigens can also be classified based on their chemical nature (proteins, polysaccharides, nucleic acids, lipids) or their source (exogenous, or endogenous).
• Exogenous antigens have entered the body from the outside (e.g., by inhalation, ingestion, or injection), while endogenous antigens are generated within the cell, as a result of normal metabolism or infection.
• T-dependent antigens require the help of T cells to stimulate antibody production by B cells; most proteins act as T-dependent antigens. T-independent antigens directly stimulate B cells to produce antibodies, and are mainly carbohydrates, especially in polymeric or repetitive structure.
• Superantigens are potent T-lymphocyte mitogens that simultaneously bind to class II MHC molecules. They stimulate a polyclonal T-cell response, leading to a large release of cytokines. Examples include staphylococcal enterotoxins, the toxic shock toxin, and exfoliating toxins.

Factors influencing Immunogenicity

• Foreignness - The immune system typically differentiates between self and non-self, meaning only foreign substances are immunogenic.
• Size - Larger molecules are generally more immunogenic.
• Chemical composition - More complex substances are usually more immunogenic. Complex proteins are potent immunogens.
• Physical form - Particulate antigens tend to be more immunogenic than soluble ones, and denatured antigens are more immunogenic than their native counterparts.
• Degradability - Antigens that are easily phagocytosed are generally more immunogenic. This is because, for T-dependent antigens, immune response development requires phagocytosis, processing, and presentation to helper T cells by an antigen-presenting cell (APC).
• Genetic factors - The host's receptor genes and the ability of APCS to present antigen affect immunogenicity.
• Age - Younger and older individuals tend to have reduced immunogenic responses.
• Method of administration - The dose and route of antigen administration can impact immunogenicity. Adjuvants increase the immune response to an immunogen.

Determinants recognized by the innate immune system

• The innate immune system recognizes highly conserved sets of molecules shared by pathogens (pathogen-associated molecular patterns, or PAMPs).
• These conserved molecular patterns are recognized by pattern recognition receptors (PRRs) on cells of the immune system.
• PRRs initiate a variety of responses including opsonization, complement activation, and phagocytosis.
• Toll-like receptors (TLRs) are a class of PRRs. Different TLRs recognize different PAMPs, leading to distinct pathways and anti-pathogen responses.
• TLRs are conserved in many species from plants and fruit flies to mammals
• These pathways lead to responses as opsonization, complement cascade activation, and phagocytosis, etc.

Antigen processing and presentation

• Antigen processing involves the interaction of PAMPs and PRRs, followed by digestion of the foreign substance by phagocytic cells.
• Antigen presentation is the process of displaying peptides of the antigens associated with MHC molecules to a T cell.
• The path leading to the association of protein fragments with MHC molecules differs for class I and class II MHC.
• MHC class I molecules present degradation products derived from intracellular (endogenous) proteins in the cytosol.
• MHC class II molecules present fragments derived from extracellular (exogenous) proteins that are located in an intracellular compartment.

Cell Receptors or Markers

• Cell receptors confer specificity and identity to cells.
• Major functions of receptors are to recognize nonself or foreign molecules, to recognize self-molecules, to receive and transmit signals between cells, to aid in cellular development.
• Major Histocompatibility Complex (MHC) are receptors found on all cells except RBCs.
• HLA are another name for MHC
• MHC plays a role in recognizing self and rejecting foreign tissue

Lymphatic Receptors

• Lymphocytes use hundreds of genes to produce a varied set of receptors.
• Undifferentiated lymphocytes undergo multiple divisions and genetic changes, which creates many different cell types.
• Each cell has a particular/unique specificity.

Lymphocyte Development

• Lymphocytes differentiate into either B or T cells in the bone marrow; B cells stay in the bone marrow, while T cells migrate to the thymus, then both migrate to secondary lymphoid tissue.

Clonal Selection Theory

• Lymphocytes use many genes to create varied receptors.
• Undifferentiated lymphocytes undergo divisions and genetic changes, generating many cell types.
• Each lymphocyte has a specific receptor.
• Exposure to an antigen selects a specific lymphocyte to expand into a clone of cells that react to that antigen.

Antibody (or immunoglobulin)

• Immunoglobulins (Ig) are large glycoproteins produced from activated B-cells (plasma cells) in response to an antigen.
• They can combine with the triggering antigen.
• They are made of 4 polypeptide chains: 2 identical heavy chains and 2 identical light chains
• Each chain has variable and constant regions: variable regions of the Fab fragments bind to an antigen, and Fc regions interact with various cells and molecules.
• Hinge regions allow flexibility for antibody to bind to antigen.
• Enzymatic digestion can break antibody into fragments, such as Fab fragments and Fc fragments, which each have different functions.
• Five classes of Immunoglobulins are recognized—IgG, IgA, IgM, IgD,and IgE.

Immunoglobulin G (IgG)

• IgG constitutes about 75-85% of total immunoglobulins in the body.
• The subclasses of IgG—IgG1, IgG2, and IgG3—differ in structure, biological function, and fixation by complement.
• IgG can cross placenta and provides immunity to fetus and newborn.
• it has a longest half-life of 23 days.

Immunoglobulin M (IgM)

• IgM is the first class synthesized upon antigen encounters.
• It has the highest molecular weight and maximum sedimentation coefficient (19S).
• It is mainly found in blood or intravascular compartments.
• IgM has both monomeric and pentameric forms.
• Monomeric IgM forms exist on B-cells' surfaces, acting as receptors; pentameric forms are present in secreted form.

Immunoglobulin A (IgA)

• IgA is the second most abundant immunoglobulin class.
• It exists in both monomeric and dimeric forms, with the dimeric form being the predominant form in mucosal and serous secretions.
• IgA in serum is predominantly in monomeric form.
• It's a key component in local or mucosal immunity, protecting the body's mucosal surfaces (intestinal tract)

Immunoglobulin E (IgE)

• IgE has the lowest serum concentration in the body and the shortest half-life.
• It's primarily involved in type I hypersensitivity reactions (allergic responses) and is elevated during helminthic infections.

Immunoglobulin D (IgD)

• IgD is found on the surface of B cells along with IgM and acts as a B-cell receptor.
• It has a high carbohydrate content.

Function of Immunoglobulins

• Antigen binding (by Fab region)
• Protection of the host
• Interaction with antigens
• Valency of an antibody refers to the number of Fab regions an antibody has.
• Effector functions (by Fc region):
  • Fixation of complement (leads to lysis of target cell)
  • Binding to various cell types (e.g., phagocytes)
  • Transfer across placenta (IgG)

Cooperation in Immune Reactions to Antigens

• The basis for most immune responses is the encounter between antigens and white blood cells.
• Lymph nodes and spleen concentrate antigens to facilitate interactions with lymphocytes.

Antigen processing and presentation to lymphocytes

• T-dependent antigens must be processed by phagocytes called antigen-presenting cells (APCs).
• APCs modify the antigen and move it to the surface, where it's bound to an MHC receptor.
• Antigen presentation to lymphocytes involves direct collaboration between an APC and a T helper cell. Interleukin-1 is secreted by APC to activate Th cells; Interleukin-2 is secreted by TH cells to activate B and other T cells.

T helper cells

• T helper cells (CD4) are crucial mediators of the immune response.
• They activate other CD4 and CD8 cells, and secrete various cytokines (e.g., IL-2, TNF, IFN-γ).
• They regulate delayed hypersensitivity, and participate in B cell proliferation.

Cytotoxic T cells

• Cytotoxic T cells (CD8) destroy foreign cells and abnormal cells.
• They do so by secreting perforins, which create pores in the target cell membrane, allowing granzymes to enter and induce apoptosis(programmed cell death).

Natural killer cells (NK cells)

• NK cells are part of the innate immune system and lack specificity; they circulate through the spleen, blood, and lungs.
• They destroy a variety of foreign cells and abnormal cells without prior sensitization or antigen presentation (similar mechanism to cytotoxic T cells)

T cells and superantigens

• Superantigens are virulence factors that trigger overwhelming immune responses by stimulating numerous T cells and releasing large amounts of cytokines.
• This can lead to blood vessel damage, toxic shock, and multi-organ damage.

Disorders in immunity

• Allergy
  • Exaggerated, misdirected reactions to harmless substances (allergens)
• Immunodeficiency
  • Deficient immune responses due to absence or malfunction of immune cells or components
• Autoimmunity
  • Immune system attacks the body's own tissues
• Cancer
  • Malignant growth of abnormal cells within the body.

Hypersensitivity reactions

• Type I
  • Immediate hypersensitivity; IgE-mediated;
  • Atopy is localized reactions, while anaphylaxis is systemic
• Type II
  • Antibody-mediated; involves antibodies and complement;
  • Blood type incompatibility
  • Rh factor incompatibility
• Type III
  • Immune complex mediated; involves antigen-antibody complexes that deposit in tissues
  • Arthus reaction (local)
  • Serum sickness (systemic)
• Type IV
  • Cell-mediated; delayed reactions; T-cell mediated
  • Contact dermatitis

Immune system and cancer

• New growths of abnormal cells may be benign (non-spreading) or malignant (spreading throughout the body).
• Genetic changes can lead to disruption of the normal cell cycle.
• Immune surveillance mechanisms help to keep cancer in check.

Autoimmunity

• The immune system loses tolerance to its own tissues and reacts against them.
• Autoantibodies and sensitized T cells attack self-tissues. This can lead to the disruption of organ or systemic function.
• Sequestered antigen theory, forbidden clones, receptor gene defects, molecular mimicry, infections can all contribute to the origins of autoimmune diseases.