Adaptive Immunity: Specific Defenses of the Host (Chapter 17 Study Notes)

Adaptive Immunity: Specific Defenses of the Host

Introduction to Adaptive Immunity

Adaptive immunity refers to the host defenses that specifically target pathogens after exposure. This system is characterized by its ability to distinguish "self" from "nonself," its activation following the failure of innate defenses, and its acquisition through infection or vaccination.

• Primary response: The initial immune response to a particular foreign substance.

• Secondary response: Subsequent interactions with the same antigen, which are faster and more effective due to immunological memory.

Dual Nature of the Adaptive Immune System

Humoral Immunity

Humoral immunity is mediated by antibodies produced by B cells. These antibodies combat foreign molecules known as antigens.

• B cells: Lymphocytes created and matured in red bone marrow; recognize antigens and produce antibodies.

• Antibodies: Proteins that specifically bind to antigens, neutralizing or marking them for destruction.

• Location: Once mature, B cells reside in blood and lymphoid organs.

Cellular Immunity (Cell-Mediated Immunity)

Cellular immunity involves T lymphocytes, which recognize antigenic peptides processed by phagocytic cells. T cells mature in the thymus and reside in blood and lymphoid organs.

• T cell receptors (TCRs): Surface molecules that contact antigens, leading to cytokine secretion.

• Function: Best at fighting virus-infected cells and intracellular bacteria.

Comparison of Humoral and Cellular Immunity

• Cellular immunity: Attacks antigens that have already entered cells (e.g., viruses, M. leprae, L. monocytogenes).

• Humoral immunity: Fights invaders and threats outside cells (e.g., extracellular bacteria, toxins, viruses before cell entry).

Cytokines: Chemical Messengers of Immune Cells

Cytokines are protein messengers produced in response to stimuli, facilitating communication and regulation within the immune system.

• Interleukins (ILs): Mediate communication between leukocytes.

• Chemokines: Induce migration (chemotaxis) of leukocytes.

• Interferons (IFNs): Interfere with viral infections of host cells.

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

• Hematopoietic cytokines: Control stem cell development into red and white blood cells.

• Cytokine storm: Overproduction of cytokines, leading to harmful inflammation.

Cytokine	Source	Target Cell(s)	Effect
IL-4	TH2	Naive TH; B cells	Proliferate TH2 cells; Class switching to IgE
IL-12	Dendritic cells, macrophages, neutrophils	Naive TH; NK cells	Stimulates growth and function of TH1 cells; Stimulates IFN-γ and TNF-α
IL-17	TH17	Neutrophils	Inflammation
IL-22	TH17	Epithelial cells	Stimulates epithelial cells to make antimicrobial proteins
Gamma interferon (IFN-γ)	TH1	CTL, macrophages	Promotes phagocytosis; activates macrophages and humoral response
Chemokines	Varies; macrophages and epithelial cells	Neutrophils	Chemotaxis
TNF-alpha (TNF-α)	Macrophages, TH, NK cells	Tumor cells	Inflammation
GM-CSF	Macrophages, T cells, NK cells	Myeloid stem cells	Increase macrophages and granulocytes

Antigens and Epitopes

Antigens

Antigens are substances that provoke the production of antibodies, typically components of invading microbes or foreign substances.

• Examples: Capsules, cell walls, flagella, fimbriae, toxins, viral capsids, viral spikes.

• Nonmicrobial antigens: Egg white, pollen, cell surface molecules.

• Epitopes (antigenic determinants): Specific regions on antigens that antibodies recognize and bind.

• Haptens: Small molecules that are antigenic only when attached to carrier molecules.

Humoral Immunity: Antibodies

Structure and Classes of Immunoglobulins (Ig)

Antibodies are compact, soluble proteins called immunoglobulins (Ig) that recognize and bind specific antigens.

• Valence: Number of antigen-binding sites; bivalent antibodies have two binding sites.

• Structure: Four protein chains (two identical light, two identical heavy) forming a Y shape, joined by disulfide bonds.

• Variable (V) regions: At the ends of the arms, bind epitopes.

• Constant (Fc) region: The stem, identical for each Ig class.

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

Class	Structure	Serum %	Location	Function
IgG	Monomer	80%	Blood, lymph, intestine	Crosses placenta, complement activation, phagocytosis, neutralizes toxins/viruses
IgM	Pentamer	6%	Blood vessels	Agglutination, complement activation, first response
IgA	Monomer/dimer	13%	Mucous membranes, secretions	Prevents microbial attachment
IgD	Monomer	0.02%	Blood, lymph, B cells	Possible role in B cell activation
IgE	Monomer	0.002%	Mast cells, basophils, blood	Histamine release, lysis of parasitic worms, allergies

Humoral Immunity Response Process

B cells interact with antigens in lymphoid organs. Each B cell has numerous surface immunoglobulins serving as antigen receptors.

• Clonal selection: Activation of a B cell when its receptor binds an antigen.

• Clonal expansion: Activated B cell proliferates and differentiates into antibody-secreting plasma cells and memory B cells.

Activation and Clonal Expansion of Antibody-Producing Cells

• T-dependent antigens: Require T helper cell (TH) assistance; both B and T cells must recognize the antigen, and antigen presentation is required.

• T-independent antigens: Do not require TH cell assistance; often polysaccharides from bacterial capsules or LPS.

Major Histocompatibility Complex (MHC)

• MHC Class I: On nucleated cells; identifies cells as "self" and presents antigens to cytotoxic T cells (TC).

• MHC Class II: On antigen-presenting cells (APCs) such as B cells, macrophages, dendritic cells.

The Diversity of Antibodies

Humans can produce approximately $10^{11}$ (100 billion) different antibodies due to gene segment rearrangement in immunoglobulin genes. Clonal deletion removes self-reactive B cells to prevent autoimmunity.

Results of the Antigen-Antibody Interaction

When antibodies bind to antigens, they form an antigen-antibody complex. The strength of this bond is called affinity. This complex protects the host by tagging foreign molecules or cells for destruction.

• Agglutination: Clumping of antigens.

• Opsonization: Coating of antigens to enhance phagocytosis.

• Antibody-dependent cell-mediated cytotoxicity: Destruction of large pathogens by immune cells.

• Neutralization: Blocking of toxins or viruses.

• Activation of the complement system: Cascade leading to pathogen lysis.

Summary Table: Immunoglobulin Classes

Class	Structure	Serum %	Location	Function
IgG	Monomer	80%	Blood, lymph, intestine	Crosses placenta, complement activation, phagocytosis, neutralizes toxins/viruses
IgM	Pentamer	6%	Blood vessels	Agglutination, complement activation, first response
IgA	Monomer/dimer	13%	Mucous membranes, secretions	Prevents microbial attachment
IgD	Monomer	0.02%	Blood, lymph, B cells	Possible role in B cell activation
IgE	Monomer	0.002%	Mast cells, basophils, blood	Histamine release, lysis of parasitic worms, allergies

Key Equations

• Antibody diversity: $10^{11}$

Example

Example: IgG antibodies neutralize toxins and viruses by binding to them, preventing their interaction with host cells. IgM antibodies are the first to respond to infection and are effective at agglutinating pathogens.

Additional info: These notes expand upon the provided slides with definitions, examples, and tables for clarity and completeness, suitable for college-level microbiology exam preparation.