Immunology and Viral Vaccines Lecture Notes

Stage 1: Antigen Presentation - Antigens are presented to lymphocytes by Antigen-Presenting Cells (APCs). - Interaction involves an antigen, an APC (which releases cytokines), and a T cell.
Stage 2: Lymphocyte Activation - Activation of specific T cells and B cells. - T cells physically and chemically interact with B cells to fully stimulate a humoral response. - Both T cells and B cells become activated during this phase.
Stage 3: Lymphocyte Proliferation and Differentiation - Proliferation (Clonal Expansion): The activated lymphocytes undergo rapid cell division to produce a large population of identical cells. - Differentiation: - T cells differentiate into Memory T cells and various T effector cell subsets. - B cells differentiate into Memory B cells and Plasma cells (which are effector B cells).
Stage 4: Antigen Elimination and Memory - Antigen Elimination: Effector cells work to eliminate the specific antigen from the body. - Memory: Memory cells (both B and T) reside in lymphatic tissue. They are primed to respond rapidly to later encounters with the same antigen.

Origin: - Pluripotent stem cells develop in the red bone marrow or the fetal liver. - The stem cell line diverges into two distinct pathways.
T Cell Maturation: - T cells differentiate and mature in the Thymus.
B Cell Maturation: - B cells initially develop in the fetal liver. - Maturation primarily occurs in the Red Bone Marrow of adults.
Migration: - After maturation, lymphocytes migrate via the blood to lymphoid tissues, including the spleen and especially the lymph nodes.

Definition of Antigen: Any substance that may trigger an immune response.
Sources of Antigens: These are typically proteins or polysaccharides derived from bacteria, viruses, fungi, or protists.
Immunogenic: A term describing any antigen that successfully triggers an immune response.
Factors Affecting Immunogenicity: - Antigen size. - Overall molecular complexity. - Chemical composition.
Hierarchy of Immunogenicity (from most to least immunogenic): 1. Proteins: The most immunogenic. Examples include hemagglutinin or neuraminidase proteins on influenza virions. 2. Polysaccharides: High immunogenicity. Example: Haemophilus influenzae capsule polysaccharides. 3. Lipids: Lower immunogenicity. Example: Lipopolysaccharide ( $LPS$ ) of Gram-negative bacterial cell walls. 4. Haptens (Incomplete Antigens): Small molecules that are not immunogenic on their own. Example: Various drugs like penicillin. They only become immunogenic when attached to a larger carrier molecule.
Complete Antigens: These are the most effective at causing an immune response.

Definition of Antibody: A protein designed to recognize and bind to a specific antigen. They are either secreted by plasma cells or attached to the surface of a B cell.
Basic Structure: - Composed of four polypeptide chains: two light chains and two heavy chains. - These chains are linked together by disulfide bridges.
Functional Regions: - Variable Regions (V): Located at the ends of the antibody arms. These are responsible for binding to the specific epitope (antigenic determinant site) on an antigen. - Constant Regions (C): These form the "stem" of the antibody and are consistent within each class of antibody.
Valence: - Refers to the number of antigen-binding sites on a single antibody. - A bivalent antibody (a monomer) has exactly $2$ antigen-binding sites.

Disease	Vaccine Type	Recommendation	Booster Info
Chickenpox	Attenuated virus	For infants aged $12$ months	Duration of immunity unknown
Hepatitis A	Inactivated virus	Children at age $1$ year; travelers to endemic areas; specific high-risk groups	Protection estimated at $~10$ years
Hepatitis B	Antigenic fragments	Infants/children; high-risk adults (healthcare workers, etc.)	Duration at least $7$ years; boosters uncertain
Herpes zoster	Attenuated virus	Adults over age $60$	None recommended
Human papillomavirus	Antigenic fragments	Boys and girls ages $11-12$	Duration at least $5$ years
Influenza	Inactivated virus (injected)	Everyone over $6$ months of age	Annual
Measles	Attenuated virus	For infants aged $15$ months	Adults if exposed during outbreak
Mumps	Attenuated virus	For infants aged $15$ months	Adults if exposed during outbreak
Poliomyelitis	Killed virus	For children; adults based on risk	Duration of immunity unknown
Rabies	Killed virus	Biologists, veterinarians, or those bitten	Every $2$ years
Rotavirus	Modified/Attenuated	Oral, for infants up to $8$ months	None recommended
Rubella	Attenuated virus	Infants aged $15$ months; non-pregnant women	Adults if exposed during outbreak

Adjuvants: - Substances that enhance the effectiveness of vaccines. - They may work by improving the response of Toll-like receptors (TLRs). - Historical context: Purified vaccines were found to be less effective once contamination was removed, leading to the discovery that certain "contaminants" (adjuvants) were necessary for a strong response. - Examples: Alums (aluminum salts) and Monophosphoryllipid A (derived from $LPS$ ).
Herd Immunity: - A concept where immunization of a population provides indirect protection to non-immune individuals. - Requirement: Immunization levels must be high (text notes a threshold of more than $20\%$ for initial effectiveness, though usually significantly higher for complete protection).

Sensitivity: The ability of a test to correctly identify those with the disease (true positive rate).

Specificity: The ability of a test to correctly identify those without the disease (true negative rate).