Adaptive Immunity: Structure, Function, and Mechanisms (Chapter 16 Study Notes)

Adaptive Immunity

Introduction to Adaptive Immunity

Adaptive immunity is a specialized branch of the immune system that provides targeted defense against specific pathogens. Unlike innate immunity, which is present at birth and acts non-specifically, adaptive immunity develops throughout life and is characterized by its ability to recognize, remember, and respond more effectively to repeated exposures to the same pathogen.

• Pathogen-specific and has memory

• Activated upon infection

• Slow during first exposure but rapid upon re-exposure

• Develops throughout your life

Overview of the Immune System

Innate vs. Adaptive Immunity

• Innate Immunity: Present at birth, always active, non-specific, rapid response.

• Adaptive Immunity: Pathogen-specific, activated upon infection, slower initial response but faster upon re-exposure, develops over time.

Branches of Adaptive Immunity

Humoral (Antibody-Mediated) and Cell-Mediated Immunity

• Humoral Immunity: B cell-based, involves production of antibodies that neutralize pathogens.

• Cell-Mediated Immunity: T cell-based, involves direct action of T cells against infected or abnormal cells.

Attributes of Adaptive Immunity

Five Key Attributes

Attribute	Description
Specificity	Response acts against a specific attacker (pathogen or antigen).
Inducibility	Cells are activated in response to a specific pathogen.
Clonality	Cells of the adaptive immune system form identical cells for many generations.
Unresponsiveness to Self	Does not act against normal body cells (prevents autoimmunity).
Memory	Remembers specific pathogens and responds faster upon re-exposure.

Lymphocytes and Their Development

B Cells and T Cells

• Lymphocytes: Type of white blood cell that acts against specific pathogens.

• B Lymphocytes (B cells): Mature in the bone marrow, responsible for antibody production.

• T Lymphocytes (T cells): Start in the bone marrow but mature in the thymus, responsible for cell-mediated immunity.

• Both types look similar under the microscope but have distinct surface proteins.

The Lymphatic System

Role in Adaptive Immunity

The lymphatic system is essential for the production, maturation, and housing of immune cells. It forms a surveillance system that screens tissues for foreign molecules.

• Lymphatic vessels: Conduct the flow of lymph, a fluid containing immune cells.

• Primary lymphoid organs: Red bone marrow (lymphocyte origin and B cell maturation), thymus (T cell maturation).

• Secondary lymphoid organs: Lymph nodes, spleen, tonsils, and mucosa-associated lymphatic tissue (MALT) where mature lymphocytes migrate and encounter antigens.

Antigens and Their Properties

Definition and Types

Antigens are molecules recognized as foreign and worthy of attack by the immune system. They are identified by three-dimensional regions called epitopes.

• Large foreign macromolecules (5000–100,000 daltons) are the best antigens.

• Proteins or mixtures of protein and sugar are generally the best antigens.

• Structural complexity increases antigenicity.

Types of Antigens

Type	Source	Example
Exogenous	Extracellular microbes	Bacterial toxins, surface proteins
Endogenous	Intracellular microbes	Viral proteins inside infected cells
Autoantigens	Human cells (self)	Normal cell proteins

Major Histocompatibility Complex (MHC)

Structure and Function

• MHC: Glycoproteins in cell membranes that hold and present antigenic determinants (epitopes) to T cells.

• Antigens bind in the antigen-binding groove of MHC molecules.

• Two classes of MHC proteins:

  • MHC Class I: Found on every nucleated cell; displays endogenous and autoantigens.

  • MHC Class II: Found on B cells and other antigen-presenting cells (APCs); displays exogenous antigens.

Antigen Processing and Presentation

Role of Antigen-Presenting Cells (APCs)

• Dendritic cells, macrophages, and B cells regularly present antigens using MHC proteins.

• MHC I displays endogenous and autoantigens; MHC II displays exogenous antigens.

Elements of Adaptive Immunity: T Cells

T Lymphocytes (T Cells)

• Produced in red bone marrow, mature in thymus.

• Circulate in lymph and blood, migrate to lymph nodes, spleen, and Peyer's patches.

• Have T cell receptors (TCRs) on their cytoplasmic membrane.

Specificity of TCR

• TCRs do not recognize epitopes directly; they bind epitopes associated with MHC proteins.

• T cells act against cells harboring intracellular pathogens or producing abnormal surface proteins.

• The human TCR repertoire is estimated to be around $10^{10}$ unique receptors.

Types of T Cells

Type	Function	Markers
Cytotoxic T cells	Kill other cells	CD8, distinctive TCR
Helper T cells	Provide growth factors, regulate cytotoxic T cells	CD4, distinctive TCR
Regulatory T cells	Suppress autoimmune response, prevent autoimmune disease	CD4, CD25

Self-Tolerance and Clonal Deletion

How T Cells Avoid Autoimmunity

• Immature T cells undergo clonal deletion in the thymus.

• Cells that do not recognize body's MHC protein undergo apoptosis.

• Cells that recognize autoantigen die by apoptosis.

• Some self-recognizing T cells become regulatory T cells.

• Cells that recognize MHC protein and foreign epitopes become protective T cells.

Cell-Mediated Immune Responses

Activation and Function of Cytotoxic T Cells

Cell-mediated immunity responds to intracellular pathogens and abnormal body cells, such as viruses, cancer cells, and intracellular bacteria.

• Antigen presentation: Dendritic cell presents antigen to T cell in lymph node.

• Helper T cell differentiation: Helper T cell binds to APC, increasing binding and limiting improper response.

• Clonal expansion: IL-2 from helper T cells triggers cytotoxic T cells to reproduce, making memory and active T cells.

• Self-stimulation: Daughter T cells activate and produce IL-2 receptors and protein, allowing reproduction without APC binding.

Mechanisms of Cytotoxic T Cell Killing

• Cytotoxic T cells have vesicles containing perforin and granzyme.

  • Perforin forms pores in the target cell membrane.

  • Granzyme enters through the pore and induces apoptosis (cell death).

• CD95 cytotoxic pathway: Tc cells use CD95 ligand to activate apoptotic enzymes in the target cell.

Memory T Cells

• Persist for months or years in lymphoid tissues.

• Immediately functional upon subsequent contact with specific epitope.

• Enhanced response to previously encountered antigen is called memory response.

Summary Table: Key Concepts in Adaptive Immunity

Concept	Details
Adaptive Immunity	Specific, inducible, clonal, self-tolerant, and has memory
Lymphocytes	B cells (humoral), T cells (cell-mediated)
Antigens	Exogenous, endogenous, autoantigens; proteins are best antigens
MHC	Class I (all nucleated cells), Class II (APCs)
T Cell Types	Cytotoxic (CD8), Helper (CD4), Regulatory (CD4, CD25)
Clonal Deletion	Prevents autoimmunity by removing self-reactive T cells
Cytotoxic Mechanisms	Perforin/granzyme, CD95 pathway
Memory Response	Faster, stronger response upon re-exposure

Take Home Messages

• Activation of cytotoxic T cells requires antigen presentation, helper T cell differentiation, clonal expansion, and self-stimulation.

• Memory T cells can persist for long periods and reactivate upon antigen re-exposure.

• Cytotoxic T cells use perforin and granzyme to kill infected cells; perforin forms a pore, granzyme induces apoptosis.

Additional info: These notes are based on Chapter 16: Adaptive Immunity, and cover the structure, function, and mechanisms of the adaptive immune system, including lymphocyte development, antigen processing, and cell-mediated responses.