Adaptive Immunity: Mechanisms, Cells, and Antibody Responses

Adaptive Immunity

Overview of Adaptive Immunity

The adaptive immune system is a highly specific defense mechanism that develops in response to exposure to antigens. Unlike innate immunity, adaptive responses take longer to mount but provide targeted and long-lasting protection, including immunological memory. Adaptive immunity is divided into two main branches: cellular (T cell–mediated) immunity and humoral (antibody–mediated) immunity.

• Cellular response: Mediated by T cells, targets infected or abnormal cells.

• Humoral response: Mediated by B cells and antibodies, targets extracellular pathogens and toxins.

• Key features: Specificity for particular antigens, memory for faster future responses, and interaction with innate immunity.

Cells of the Adaptive Immune System

• T cells: Produced in the bone marrow, mature in the thymus. Involved in both humoral and cellular immunity.

• B cells: Produced and mature in the bone marrow. Coordinate humoral responses by producing antibodies.

• Antigen-presenting cells (APCs): Dendritic cells, macrophages, and B cells that process and present antigens to T cells.

Stages of Adaptive Immune Response

1. Antigen Presentation: APCs display antigens to T cells. B cells can directly bind antigens without APCs.

2. Lymphocyte Activation: Cytokines activate specific B and T cells after antigen recognition.

3. Lymphocyte Proliferation & Differentiation: Activated lymphocytes undergo clonal expansion and differentiate into effector and memory cells.

4. Antigen Elimination and Memory: Effector cells eliminate the antigen; memory cells persist for rapid future responses.

Antigens and Immunogenicity

Definition and Properties

• Antigen: Any substance (usually protein or polysaccharide) that can trigger an immune response.

• Immunogenicity: The ability of an antigen to provoke an immune response, influenced by size, complexity, and composition.

• Most immunogenic: Proteins > Polysaccharides > Lipids

• Epitope: The specific part of an antigen recognized by B or T cell receptors.

• Haptens: Small molecules that are only immunogenic when attached to a larger carrier.

Antigen Recognition and Self-Tolerance

• T cell receptors (TCRs) and B cell receptors (BCRs): Each lymphocyte expresses thousands of identical receptors, each specific for a single epitope.

• Self-tolerance: Mechanisms ensure immune cells do not attack the body's own tissues. Non-tolerant cells undergo apoptosis.

• T cell screening: Occurs in the thymus, ensures recognition of self-MHC but not self-antigens.

• B cell screening: Occurs in the bone marrow, prevents production of self-reactive antibodies.

T Cells: Types and Functions

Main T Cell Lineages

• T cytotoxic cells (Tc, CD8+): Directly destroy infected, damaged, or cancerous cells.

• T helper cells (Th, CD4+): Most abundant; coordinate immune responses by releasing cytokines and activating other immune cells.

• T helper 1 (Th1): Activate Tc cells, macrophages, and NK cells (cellular response).

• T helper 2 (Th2): Stimulate B cells to produce antibodies (humoral response).

• T regulatory (Treg): Suppress or regulate immune responses to prevent autoimmunity.

Antigen Presentation and MHC Molecules

• MHC I: Found on all nucleated cells; presents intracellular antigens to Tc cells.

• MHC II: Found on APCs; presents extracellular antigens to Th cells.

• Allorecognition: Lymphocytes distinguish self from non-self MHCs, critical in transplantation.

T Cell Activation

• Signal 1: TCR binds to MHC–antigen complex.

• Signal 2: Co-stimulatory proteins (e.g., B7 on APC and CD28 on T cell).

• Cytokines: Direct differentiation into Th1 or Th2 subtypes (e.g., IL-12 and IFN-γ for Th1; IL-2 and IL-4 for Th2).

Mechanism of Cytotoxic T Cell Killing

1. Tc cell recognizes infected cell via TCR and MHC I–antigen complex.

2. Releases perforins (form pores) and granzymes (induce apoptosis).

Superantigens

• Potent activators of T helper cells (e.g., certain bacterial toxins).

• Cause massive cytokine release, potentially leading to shock or death.

B Cells and Antibody-Mediated (Humoral) Immunity

B Cell Activation

• T-dependent antigens: Require Th cell help for full activation (most antigens).

• T-independent antigens: Repetitive antigens that can activate B cells without Th cells; limited memory response.

• Activated B cells proliferate and differentiate into plasma cells (antibody producers) and memory B cells.

Antibody Structure and Isotypes

• Antibody (immunoglobulin, Ig) monomer: 2 heavy chains, 2 light chains, antigen-binding sites at the tips.

• Isotype switching: B cells can change the class of antibody produced.

Isotype	Structure	Location	Function
IgG	Monomer	Blood, all fluids	Main antibody in blood, crosses placenta, opsonin, complement activation
IgA	Monomer/Dimer	Mucous, secretions	Mucosal immunity, neutralization, opsonization
IgM	Pentamer/Monomer	Blood	First produced, agglutination, complement activation
IgE	Monomer	Lungs, skin, mucosa	Allergy, parasite defense
IgD	Monomer	B cell surface	Unclear function, B cell receptor

Antibody Functions

• Neutralization: Block pathogen binding to host cells.

• Opsonization: Coat pathogens to enhance phagocytosis.

• Agglutination: Clump pathogens for easier removal.

• Precipitation: Form complexes for phagocyte removal.

• Complement activation: Trigger classical complement pathway.

Primary vs. Secondary Immune Response

• Primary response: First exposure, slower, mainly IgM then IgG, memory cells formed.

• Secondary response: Faster, stronger, mainly high-affinity IgG, due to memory cells.

Types of Adaptive Immunity

Type	How Acquired	Memory	Duration
Naturally acquired active	Infection	Yes	Long-term
Artificially acquired active	Vaccination	Yes	Long-term
Naturally acquired passive	Maternal antibodies	No	Temporary
Artificially acquired passive	Antiserum/antibody therapy	No	Temporary

Summary Table: Key Immune Cells and Functions

Cell Type	Function	Example
Innate immunity	Immediate, non-specific defense	Mucus traps bacteria
Humoral immunity	Antibody production	Antibodies bind virus
Cellular immunity	Kill infected cells	Cytotoxic T cells destroy infected cells
B cells	Recognize antigens, produce antibodies	Plasma cells secrete antibodies
Dendritic cells	Present antigens to T cells	Engulf pathogen, present to Th cells
Helper T cells (Th)	Activate B cells, CTLs, other immune cells	Release cytokines
Memory cells	Long-term immunity	Respond rapidly to re-exposure
Plasma cells	Produce antibodies	Secrete IgG, IgM, etc.
Cytotoxic T cells (Tc)	Kill infected/cancerous cells	Release perforin, granzyme

Key Mechanisms and Examples

• Clonal expansion: Activated B or T cell divides to produce effector and memory cells.

• Isotype switching: Plasma cell changes antibody class (e.g., from IgM to IgG) during infection.

• Example: After vaccination, rapid IgG response upon exposure to the pathogen.

• Example: IgE elevation in anaphylactic response to bee venom.

Additional info:

• CD8 T cell deficiency impairs response to intracellular pathogens (e.g., viruses like Epstein Barr Virus).

• Absence of thymus (DiGeorge Syndrome) impairs T-dependent but not T-independent B cell responses.

• Superantigens can cause life-threatening immune overactivation.