Adaptive Immunity, Hypersensitivity, Autoimmunity, and Vaccination

Adaptive Immunity: Specificity, Memory, and Tolerance

Overview of Adaptive Immunity

Adaptive immunity is a highly specific defense system primarily mediated by B lymphocytes (B cells) and T lymphocytes (T cells). It is characterized by its ability to recognize specific antigens, remember previous encounters, and distinguish self from non-self (tolerance).

• B cells produce antibodies that target extracellular antigens, conferring antibody-mediated (humoral) immunity.

• T cells express antigen-specific T cell receptors (TCRs) and defend against intracellular pathogens, conferring cell-mediated (cellular) immunity.

• Adaptive immunity exhibits specificity (targeting unique antigens), memory (faster, stronger response upon re-exposure), and tolerance (prevention of self-reactivity).

Immune Specificity and Memory

• Innate immunity recognizes broad microbial features (e.g., peptidoglycan, LPS).

• Adaptive immunity targets pathogen-specific antigens.

• Each B or T cell expresses receptors specific for a single antigen.

• Upon first exposure, a primary immune response is generated, leading to the formation of memory cells.

• Subsequent exposures trigger a secondary immune response that is faster and more robust.

Classes of Adaptive Immunity: Active and Passive

• Active immunity: Host produces its own immune response after exposure to antigen (natural infection or vaccination).

• Passive immunity: Host receives antibodies or immune cells from another individual (e.g., maternal antibodies, antiserum).

• Both active and passive immunity can be natural (e.g., infection, maternal transfer) or artificial (e.g., vaccination, injection of antiserum).

B Cells, Antibodies, and Memory

• Each B cell displays ~100,000 identical B cell receptors (BCRs) on its surface.

• Antigen binding to BCR triggers endocytosis and activation.

• Helper T cells (Th cells) stimulate B cells and macrophages.

• Activated B cells differentiate into plasma cells (antibody-secreting) and memory B cells.

• Antibodies block pathogen-host interactions but usually do not directly kill pathogens.

Different Classes of T-Helper Cells

• Th1 cells: Produce IL-2, IFN-γ, TNF-α, and GM-CSF; activate macrophages and promote cell-mediated immunity.

• Th2 cells: Promote B cell activation and antibody production.

• Th17 cells: Important in early immune responses; differentiation is driven by dendritic cell cytokines (IL-6, TGF-β).

Hypersensitivity and Autoimmunity

Types of Hypersensitivity

Hypersensitivity refers to inappropriate or exaggerated immune responses to antigens. They are classified into four types based on immune effectors, antigens, and symptoms:

• Type I (Immediate) Hypersensitivity: Mediated by IgE and mast cells; commonly known as allergy.

• Type II: Antibody-mediated cytotoxic reactions.

• Type III: Immune complex-mediated reactions.

• Type IV (Delayed-Type Hypersensitivity, DTH): Cell-mediated, primarily involving Th1 cells.

Immediate (Type I) Hypersensitivity

• Occurs when mast cells coated with IgE release vasoactive mediators (e.g., histamine, serotonin) upon allergen exposure.

• Symptoms develop within minutes and range from mild (sneezing, hives, watery eyes) to severe (anaphylaxis).

• Common allergens: pollens, molds, animal dander, certain foods.

• Anaphylactic shock involves systemic vasodilation and bronchoconstriction; treated with epinephrine.

• Mild symptoms may be managed with antihistamines or anti-inflammatory steroids.

Delayed-Type (Type IV) Hypersensitivity (DTH)

• Cell-mediated, involving Th1 cells and macrophages.

• Symptoms appear several hours after antigen exposure, peaking at 24–48 hours.

• Common antigens: chemicals that bind skin proteins (e.g., poison ivy), certain intracellular pathogens (e.g., Mycobacterium tuberculosis).

• Results in contact dermatitis and protective immunity against some pathogens.

Autoimmunity

• Normally, self-reactive T and B cells are eliminated during development (tolerance).

• Autoimmune diseases occur when self-reactive lymphocytes are activated, attacking self proteins.

• Some are mediated by autoantibodies (e.g., organ-specific or systemic).

• Systemic lupus erythematosus (SLE): A type III hypersensitivity where autoantibodies target nucleoproteins and DNA.

Treating Autoimmunity

• Organ-specific diseases may be easier to treat than systemic ones.

• Monoclonal antibodies are emerging as targeted therapies.

• Genetic factors, especially major histocompatibility proteins, influence susceptibility and severity.

Vaccination and Immunization

Principles of Vaccination

Vaccination (immunization) is the deliberate exposure to an antigen to induce adaptive immunity and protect against future infection. The immunogen used is called a vaccine.

• Natural passive immunity: Infants receive maternal antibodies via placenta and breast milk, providing temporary protection.

• Vaccination replaces passive immunity with long-lasting active immunity.

• Effective vaccines have dramatically reduced the incidence of diseases like measles and mumps.

Types of Vaccines

• Killed (inactivated) vaccines: Pathogens are killed by heat or chemicals; safe but may induce weaker, short-lived immunity.

• Live attenuated vaccines: Use weakened pathogens; generally induce stronger, longer-lasting immunity.

• Toxoid vaccines: Inactivated toxins (e.g., tetanus, diphtheria) induce antibody-mediated protection without infection risk.

• Conjugate vaccines: Combine poorly immunogenic polysaccharides with protein toxoids to enhance immune response.

Synthetic and Genetically Engineered Vaccines

• Synthetic peptide vaccines: Use engineered peptides corresponding to pathogen antigens.

• Recombinant vaccines: Genes encoding antigens are cloned and expressed in vectors (e.g., vaccinia virus).

• Plant-based vaccines: Pathogen genes are transferred to plants (e.g., via Agrobacterium tumefaciens) to produce antigens.

Nucleic Acid Vaccines

• DNA vaccines: Plasmids encoding antigen genes are injected; host cells produce antigen, inducing immunity.

• mRNA vaccines: Engineered mRNA encoding antigens is delivered; host cells translate mRNA, producing antigen and triggering immune response.

• Advantages: No risk of infection, controlled protein expression, and strong immunogenicity.

Attenuation

• Attenuation is the reduction or loss of pathogen virulence, often occurring during laboratory culture.

• Attenuated strains are used in vaccine production (e.g., viral vaccines).

• Attenuation may be reversible if the organism is reintroduced into a host, but sometimes the loss of virulence is permanent.

• First demonstrated by Louis Pasteur with the rabies vaccine.

Herd Immunity

• Not all individuals need to be immunized for effective disease control; herd immunity protects the population when a high percentage is immune.

• The required percentage for herd immunity depends on pathogen infectivity and virulence.

Table: Types of Hypersensitivity

Type	Immune Effector	Antigen	Example	Onset
I (Immediate)	IgE, Mast cells	Soluble allergens	Allergic rhinitis, anaphylaxis	Minutes
II (Cytotoxic)	IgG, IgM	Cell surface antigens	Hemolytic anemia	Hours
III (Immune Complex)	Immune complexes	Soluble antigens	Systemic lupus erythematosus	Hours
IV (Delayed-Type)	T cells (Th1)	Modified self or foreign proteins	Contact dermatitis, TB test	24–48 hours

Key Terms and Definitions

• Antigen: A molecule capable of inducing an immune response.

• Antibody: A protein produced by B cells that binds specifically to an antigen.

• Autoantibody: An antibody directed against self antigens.

• Immunogen: Any substance capable of eliciting an immune response.

• Epitope: The specific part of an antigen recognized by an antibody or TCR.

• Memory cell: A long-lived lymphocyte that responds rapidly upon re-exposure to its specific antigen.

• Attenuation: The reduction of virulence in a pathogen.

• Herd immunity: Population-level protection resulting from a high proportion of immune individuals.

Example: mRNA Vaccines

mRNA vaccines (such as those developed for COVID-19) deliver engineered mRNA encoding a viral antigen (e.g., spike protein) into host cells. The host cells translate the mRNA, produce the antigen, and stimulate both antibody and T cell responses, providing immunity without risk of infection from the vaccine itself.

Additional info:

• Some content, such as the detailed mechanisms of T cell selection and tolerance, is referenced but not fully described in the source; standard immunology knowledge was used to clarify these points.

• Table 28.1 and Table 27.4 are referenced but not provided; a summary table of hypersensitivity types is included based on standard classification.