Adaptive Immunity: Specific Defenses of the Host – Study Notes

Adaptive Immunity: Specific Defenses of the Host

Introduction to Adaptive Immunity

Adaptive immunity refers to the specific defense mechanisms that target particular pathogens. This system is acquired through infection or vaccination and is characterized by its ability to remember previous encounters with pathogens, resulting in a more rapid and effective response upon subsequent exposures.

• Primary response: The initial immune response to a specific antigen.

• Secondary response: Enhanced and faster response upon re-exposure to the same antigen due to immunological memory.

Dual Nature of the Adaptive Immune System

Humoral Immunity

Humoral immunity involves the production of antibodies by B lymphocytes (B cells) to combat extracellular pathogens and toxins.

• B cells: Lymphocytes that mature in the red bone marrow and are responsible for antibody production.

• Antibodies: Proteins that specifically recognize and bind to antigens.

Cellular Immunity (Cell-Mediated Immunity)

Cellular immunity is mediated by T lymphocytes (T cells), which recognize and respond to antigenic peptides presented by phagocytic cells. T cells mature in the thymus and use T cell receptors (TCRs) to interact with antigens, leading to the secretion of cytokines.

• T cells: Lymphocytes that mature in the thymus and are involved in cell-mediated immune responses.

• Cytokines: Chemical messengers that regulate immune responses.

Comparison of Humoral and Cellular Immunity

• Cellular immunity: Targets intracellular pathogens (e.g., viruses, some bacteria).

• Humoral immunity: Targets extracellular pathogens and toxins.

Cytokines: Chemical Messengers of Immune Cells

Cytokines are signaling molecules produced by immune cells in response to stimuli. They coordinate the activities of immune cells and mediate inflammation and immune responses.

• Interleukins (ILs): Mediate communication between leukocytes.

• Chemokines: Induce migration of leukocytes.

• Interferons (IFNs): Inhibit viral replication.

• Tumor necrosis factor alpha (TNF-α): Involved in inflammation.

• Hematopoietic cytokines: Regulate development of blood cells.

• Cytokine storm: Harmful overproduction of cytokines.

Antigens and Epitopes

Antigens are substances that provoke an immune response, typically by inducing the production of antibodies. Antibodies recognize specific regions on antigens called epitopes or antigenic determinants.

• Haptens: Small molecules that are not immunogenic by themselves but can elicit an immune response when attached to larger carrier molecules.

Humoral Immunity: Antibodies (Immunoglobulins)

Structure of Antibodies

Antibodies, or immunoglobulins (Ig), are Y-shaped globular proteins composed of two identical heavy chains and two identical light chains joined by disulfide bonds. The variable regions at the tips of the Y bind to specific epitopes, while the constant (Fc) region determines the antibody class.

• Valence: Number of antigen-binding sites (e.g., bivalent antibodies have two sites).

• Five classes: IgG, IgM, IgA, IgD, IgE.

Classes of Immunoglobulins

Class	Structure	Location	Function
IgG	Monomer	Blood, lymph, intestine	Crosses placenta, enhances phagocytosis, neutralizes toxins/viruses
IgM	Pentamer	Blood, lymph, B cell surface	First antibody produced, agglutinates microbes
IgA	Dimer (secretions), monomer (serum)	Mucous membranes, saliva, tears, breast milk	Prevents microbial attachment to mucosa
IgD	Monomer	B cell surface, blood, lymph	Assists in B cell immune response
IgE	Monomer	Mast cells, basophils, blood	Allergic reactions, lysis of parasitic worms

Activation and Clonal Expansion of Antibody-Producing Cells

Major Histocompatibility Complex (MHC)

MHC molecules are cell surface proteins essential for the recognition of self and non-self. Class I MHC molecules are present on all nucleated cells, while Class II MHC molecules are found on antigen-presenting cells (APCs) such as B cells.

B Cell Activation

Inactive B cells bind antigens via surface immunoglobulins, internalize and process them, and present antigen fragments on MHC class II molecules. T helper cells recognize these fragments and secrete cytokines, activating B cells to proliferate and differentiate.

Clonal Selection and Differentiation

Activated B cells undergo clonal selection, differentiating into antibody-producing plasma cells and memory cells. Clonal deletion removes self-reactive B cells to prevent autoimmunity.

T-Dependent and T-Independent Antigens

• T-dependent antigens: Require T helper cell assistance for antibody production.

• T-independent antigens: Stimulate B cells directly, usually producing a weaker IgM response without memory cell formation.

Results of Antigen-Antibody Interaction

When antibodies bind to antigens, they form antigen-antibody complexes that protect the host by tagging foreign molecules for destruction through various mechanisms:

• Agglutination: Clumping of antigens for easier removal.

• Opsonization: Coating antigens to enhance phagocytosis.

• Antibody-dependent cell-mediated cytotoxicity: Targeting large pathogens for destruction.

• Neutralization: Blocking pathogen attachment or toxin activity.

• Activation of the complement system: Leading to cell lysis.

Cellular Immunity Response Process

T Cell Maturation and Activation

T cells mature in the thymus, where thymic selection eliminates non-functional cells. Mature T cells migrate to lymphoid tissues and recognize antigens via T cell receptors (TCRs).

Antigen Entry and Presentation

Pathogens entering the gastrointestinal tract are transported by M cells over Peyer's patches to lymphocytes and APCs for immune processing.

Antigen-Presenting Cells (APCs)

• Dendritic cells: Engulf and present antigens to T cells; found in various tissues.

• Macrophages: Activated by cytokines or antigen ingestion; present antigens to T cells in lymph tissues.

Classes of T Cells

• CD4+ T helper cells (TH): Interact with MHC class II molecules on APCs and B cells; coordinate immune responses via cytokine signaling.

• CD8+ Cytotoxic T lymphocytes (CTL): Bind MHC class I molecules; kill infected or altered self-cells.

T Helper Cells (CD4+)

TH cells recognize antigen-MHC II complexes on APCs, become activated, and differentiate into various subtypes:

• TH1 cells: Activate macrophages, enhance complement, promote phagocytosis.

• TH2 cells: Activate B cells to produce IgE and eosinophils.

• TH17 cells: Produce IL-17, contribute to inflammation.

• Memory cells: Provide long-term immunity.

T Regulatory Cells (Treg)

Treg cells are a subset of CD4+ cells that suppress immune responses against self-antigens, protect beneficial intestinal bacteria, and help maintain tolerance during pregnancy.

Cytotoxic T Lymphocytes (CD8+)

CTLs are activated by antigen presentation and costimulatory signals. They recognize and kill infected or altered self-cells by releasing perforin and granzymes, inducing apoptosis (programmed cell death).

Nonspecific Cells and Extracellular Killing

Natural killer (NK) cells are granular leukocytes that destroy cells lacking MHC class I self-antigens, including virus-infected and tumor cells. They induce lysis or apoptosis by forming pores in target cells.

Antibody-Dependent Cell-Mediated Cytotoxicity

Large pathogens such as protozoans and helminths are targeted by antibodies that coat their surface. Immune cells bind to the Fc region of these antibodies and release chemicals that lyse the target cell.

Immunological Memory

Immunological memory ensures a more rapid and robust response upon re-exposure to an antigen. Class switching from IgM to other antibody classes occurs during secondary responses, which are characterized by higher antibody titers and longer duration.

• Antibody titer: The concentration of antibodies in serum, reflecting the intensity of the humoral response.

Types of Adaptive Immunity

Adaptive immunity can be acquired naturally or artificially, and can be active or passive:

	Active	Passive
Naturally acquired	Infection-induced antibody production	Maternal antibodies via placenta or colostrum
Artificially acquired	Vaccination (immunization)	Injection of preformed antibodies