Adaptive Immunity: Specific Defenses of the Host

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Adaptive Immunity: Specific Defenses of the Host

Introduction to Adaptive Immunity

Adaptive immunity is a specialized defense mechanism that targets specific pathogens. Unlike innate immunity, which provides general protection, adaptive immunity develops after exposure to antigens through infection or vaccination. It is characterized by specificity and memory, allowing for a more rapid and effective response upon subsequent exposures to the same pathogen.

Primary response: The initial adaptive immune reaction to a novel antigen.
Secondary response: A faster, stronger reaction upon re-exposure to the same antigen, due to immunological memory.

Diagram comparing innate and adaptive immunity, showing cell types and antibodies Syringe and vaccine vial, representing vaccination as an example of adaptive immunity

Dual Nature of the Adaptive Immune System

The adaptive immune system consists of two main components: humoral immunity and cellular immunity. Both systems interact with the innate immune system to provide comprehensive protection.

Humoral immunity: Mediated by B cells, which produce antibodies that neutralize extracellular pathogens and toxins.
Cellular immunity: Mediated by T cells, which recognize and destroy infected or abnormal cells.

Diagram showing the difference between humoral and cell-mediated immunity

Humoral Immunity

B cells: Lymphocytes that mature in the bone marrow and are responsible for antibody production.
Antibodies: Proteins that specifically bind to antigens, marking them for destruction.
Example: Neutralization of bacterial toxins by antibodies.

B cell with membrane-bound antibodies Bursa of Fabricius in chickens, source of B cells

Cellular Immunity

T cells: Lymphocytes that mature in the thymus and are involved in recognizing antigenic peptides presented by other cells.
T cell receptors (TCRs): Surface molecules that bind to specific antigens.
Cytokines: Secreted by T cells to direct immune responses.
Example: Destruction of virus-infected cells by cytotoxic T lymphocytes (CTLs).

Lymphocyte T cell Diagram of T and B cell development from stem cells Cellular immunity process: antigen presentation, T cell activation, and lysis of infected cell

Comparison of Humoral and Cellular Immunity

Humoral immunity: Targets extracellular pathogens (e.g., bacteria, toxins, viruses before cell entry).
Cellular immunity: Targets intracellular pathogens (e.g., viruses, some bacteria inside host cells).

Cytokines: Chemical Messengers of Immune Cells

Cytokines are signaling proteins produced by immune cells in response to stimuli. They regulate the intensity and duration of immune responses by mediating communication between cells.

Interleukins (ILs): Mediate communication between leukocytes.
Chemokines: Induce migration of immune cells to infection sites.
Interferons (IFNs): Inhibit viral replication and activate immune cells.
Tumor necrosis factor alpha (TNF-α): Promotes inflammation, especially in autoimmune diseases.
Hematopoietic cytokines: Stimulate production of blood cells from stem cells.
Cytokine storm: Overproduction of cytokines, leading to tissue damage.

Diagram showing cytokine signaling between cells Cytokine storm: comparison of normal and excessive immune response

Antigens and Antibodies

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

Epitope: The specific part of an antigen recognized by an antibody.
Hapten: A small molecule that is not immunogenic by itself but can elicit an immune response when attached to a carrier protein.

Antibodies binding to epitopes on a bacterial cell Hapten molecules binding to a carrier to form a hapten-carrier conjugate

Structure and Classes of Antibodies (Immunoglobulins)

Antibodies are Y-shaped proteins composed of two heavy and two light chains, with variable regions that bind antigens and a constant region that determines the antibody class.

Valence: Number of antigen-binding sites (most antibodies are bivalent).
Variable (V) region: Binds to the epitope of the antigen.
Constant (Fc) region: Determines the antibody class and mediates effector functions.
Five classes of immunoglobulins: IgG, IgM, IgA, IgD, IgE.

Antibody structure showing variable and constant regions Diagram of immunoglobulin classes: IgG, IgM, IgA, IgD, IgE

Summary Table: Immunoglobulin Classes

Class	Structure	Serum %	Main Functions
IgG	Monomer	80%	Crosses placenta, enhances phagocytosis, neutralizes toxins/viruses, activates complement
IgM	Pentamer	6%	First antibody produced, agglutinates microbes, activates complement
IgA	Monomer/dimer	13%	Protects mucosal surfaces, found in secretions (tears, saliva, breast milk)
IgD	Monomer	0.02%	On B cells, assists in immune response
IgE	Monomer	0.002%	Allergic reactions, defense against parasitic worms

IgM pentamer structure IgA dimer structure with secretory component

Humoral Immunity Response Process

B cells are activated to produce antibodies through interactions with antigens and helper T cells. This process involves antigen presentation, clonal selection, and differentiation into plasma and memory cells.

Major histocompatibility complex (MHC): Glycoproteins on cell surfaces that present antigen fragments to T cells.
Class I MHC: Present on all nucleated cells; recognized by CD8+ T cells.
Class II MHC: Present on antigen-presenting cells (APCs) such as B cells, macrophages, and dendritic cells; recognized by CD4+ T cells.
Clonal selection: Activated B cells proliferate and differentiate into antibody-producing plasma cells and memory cells.
Clonal deletion: Elimination of self-reactive B cells to prevent autoimmunity (via apoptosis).

Antigen presentation and B cell activation Clonal selection and differentiation of B cells

T-Dependent and T-Independent Antigens

T-dependent antigens: Require helper T cells for B cell activation; generate strong, long-lasting immunity with memory cell formation.
T-independent antigens: Activate B cells without T cell help; usually polysaccharides; provoke a weaker response, mainly IgM, and do not generate memory cells.

T-independent antigen activation of B cell

Results of Antigen-Antibody Interaction

When antibodies bind to antigens, several protective mechanisms are triggered to eliminate the pathogen:

Agglutination: Clumping of antigens, enhancing phagocytosis.
Opsonization: Coating of antigens to enhance phagocytosis.
Neutralization: Blocking of pathogen attachment or toxin activity.
Antibody-dependent cell-mediated cytotoxicity (ADCC): Destruction of large pathogens by immune cells.
Activation of the complement system: Leads to cell lysis.

Cellular Immunity Response Process

Cellular immunity is mediated by T cells, which recognize and respond to intracellular pathogens. T cells mature in the thymus and are classified based on their surface markers and functions.

CD4+ T cells (Helper T cells): Activate B cells, other T cells, and macrophages via cytokine secretion.
CD8+ T cells (Cytotoxic T lymphocytes, CTLs): Destroy infected or abnormal cells by inducing apoptosis.
T regulatory cells (Treg): Suppress immune responses to maintain self-tolerance and prevent autoimmunity.

Diagram showing CD4+ and CD8+ T cells and their functions Activation of CD4+ T helper cells

Subsets of Helper T Cells

TH1 cells: Activate macrophages and promote cell-mediated immunity.
TH2 cells: Stimulate B cells to produce IgE and activate eosinophils.
TH17 cells: Recruit neutrophils and promote inflammation.

Antigen-Presenting Cells (APCs)

Dendritic cells: Capture and present antigens to T cells; found in tissues and blood.
Macrophages: Engulf pathogens and present antigens to T cells; activated by cytokines.
B cells: Present antigens to helper T cells for further activation.

Different types of antigen-presenting cells: dendritic cell, macrophage, B cell

Apoptosis

Definition: Programmed cell death, a mechanism to eliminate infected or harmful cells without causing inflammation.

Diagram of apoptosis: normal cell to phagocytosis

Nonspecific Cells and Extracellular Killing

Natural killer (NK) cells: Destroy cells lacking MHC class I molecules, such as virus-infected or tumor cells, by inducing lysis or apoptosis. NK cells are not antigen-specific.
Antibody-dependent cell-mediated cytotoxicity (ADCC): Immune cells recognize and kill antibody-coated target cells, important for defense against large parasites.

Immunological Memory

Immunological memory is the ability of the adaptive immune system to respond more rapidly and effectively to pathogens that have been encountered previously.

Primary response: Initial exposure to an antigen; slower and less robust.
Secondary (anamnestic) response: Subsequent exposure; faster, stronger, and longer-lasting due to memory cells.
Antibody titer: Measurement of antibody concentration in serum, reflecting the strength of the humoral response.

Cartoon of a memory T cell

Types of Adaptive Immunity

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

Type	How Acquired	Example
Naturally acquired active	Infection	Recovery from measles
Naturally acquired passive	Maternal antibodies	Antibodies via placenta or breast milk
Artificially acquired active	Vaccination	MMR vaccine
Artificially acquired passive	Injection of antibodies	Gamma globulin injection

Syringe and vaccine vial, representing artificial active immunity