Chapter 17: Adaptive Immunity – Specific Defenses of the Host

Adaptive Immunity: Specific Defenses of the Host

Overview of Adaptive Immunity

Adaptive immunity is the body's induced resistance to specific pathogens, involving specialized cells and processes. Unlike innate immunity, which provides general protection, adaptive immunity targets particular invaders and develops memory for future responses.

• Key Cells: T cells and B cells are central to adaptive immunity.

• Sensitization: Exposure to a pathogen triggers antibody production.

• Vaccination: Deliberate exposure to harmless pathogen versions to induce immunity (e.g., smallpox vaccine).

Historical Context

• Louis Pasteur: Observed immunity in chickens injected with weakened pathogens.

• Von Behring: Discovered antitoxins, Nobel Prize (1901).

• Ehrlich: Identified antibodies in serum.

Dual Nature of Adaptive Immunity

Humoral vs. Cellular Immunity

Adaptive immunity consists of two main branches: humoral and cellular immunity, each with distinct mechanisms and roles.

• Humoral Immunity: Mediated by antibodies produced by B cells. Antibodies circulate in body fluids and target pathogens.

• Cellular Immunity: Mediated by T cells, which interact directly with infected or abnormal cells.

• Antigen-presenting cells (APCs): Recognize and present antigens to immune cells.

• Antibody-producing cells: B cells that differentiate into plasma cells.

Antigens and Antibody Structure

Nature of Antigens

Antigens are substances that provoke an immune response, leading to the production of antibodies or sensitized T cells.

• Sources: Proteins or large polysaccharides from microbial components (capsules, cell walls, flagella, fimbriae, toxins, viral coats) and non-microbial sources (pollen, egg whites, blood cell surface molecules, transplanted tissues).

• Epitopes: Specific regions on antigens where antibodies bind (antigenic determinants).

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

Nature of Antibodies (Immunoglobulins)

Antibodies are globular proteins produced in response to antigens, capable of binding specifically to them.

• Structure: Two identical antigen-binding sites (bivalent).

• Valence: Number of antigen-binding sites; most human antibodies are bivalent.

Classes of Antibodies

Antibody classes are determined by the constant segments of their heavy chains, each with unique functions and characteristics.

Class	Structure	Function	Location
IgM	Pentamer	First responder; main attacker	Blood
IgA	Dimer	Protects before pathogens enter	Tears, saliva, body fluids
IgD	Monomer	B cell sensitization	B cell surface
IgG	Monomer	Most diverse; attacks bacteria/viruses	Blood
IgE	Monomer	Allergic response	Mast cells

Cell Types in Adaptive Immunity

B Cells and Humoral Immunity

B cells are responsible for antibody production and play a central role in humoral immunity.

• T-dependent antigens: Require presentation with MHC to helper T cells, which produce cytokines to activate B cells.

• T-independent antigens: Directly stimulate B cells to produce antibodies without T cell involvement.

• B cell differentiation: Upon activation, B cells become plasma cells (active, antibody-producing) or memory cells (inactive, long-term immunity).

T Cells and Cellular Immunity

T cells mediate cellular immunity, interacting directly with infected or abnormal cells.

• Helper T cells (TH): Activate B cells; express CD4 marker.

• Suppressor T cells (Tsup): Combat autoimmunity.

• Cytotoxic T cells (CTL): Destroy infected or abnormal cells; express CD8 marker; use perforin and granzymes to induce apoptosis.

• Natural Killer (NK) cells: Destroy infected or cancerous cells; act non-specifically; immunological surveillance.

Antigen Presenting Cells (APCs)

APCs are non-lymphocyte cells (macrophages, dendritic cells, B cells) that process and present antigens to T cells.

• Function: Display antigenic fragments on their surface after phagocytosis or infection.

• Location: Found in organs, tissues, fluids, and specialized sites like M cells in Peyer's patches.

M Cells and Peyer's Patches

• M Cells: Microfold cells that transfer pathogens to lymphocytes and APCs in the GI and respiratory tracts.

• Peyer's Patches: Lymphoid tissue in the small intestine protecting against bacteria from the large intestine.

Major Histocompatibility Complex (MHC)

MHC Classes and Immune Response

MHC molecules are essential for antigen presentation and immune cell activation.

• Class I MHC: Present on all nucleated cells; signal abnormality to CD8+ cytotoxic T cells; leads to cell lysis.

• Class II MHC: Present only on immune cells; signal danger to CD4+ helper T cells; leads to antibody production.

• =8 Rule: CD8 x MHC1 = 8; CD4 x MHC2 = 8.

Antigen-Antibody Interactions

Binding and Protective Mechanisms

Antibodies bind to antigens with high specificity and affinity, neutralizing threats through various mechanisms.

• Agglutination: Antibodies cause antigens to clump, facilitating phagocytosis.

• Opsonization: Antigen coated with antibodies and complement, enhancing ingestion and lysis.

• Complement Fixation: Formation of membrane attack complex (MAC) to create pores in pathogen membranes.

• Antibody-Dependent Cell-Mediated Immunity: Destruction of target cells via exocytosis.

• Neutralization: IgG antibodies block attachment of microbes to host cells and neutralize toxins.

Immune Cell Activation

CD4+ T Cell Activation Steps

• APC ingests microorganism and processes antigen.

• Antigen combines with MHC II and is displayed on cell surface.

• CD4+ T cell receptor binds to MHC-antigen complex.

• APC secretes costimulation molecules, activating helper T cells.

• Helper T cells produce cytokines, proliferate, and develop function.

Cytotoxic T Cell Activation

• Virally infected or cancerous cells present abnormal antigens via MHC I.

• CD8+ T cells recognize these antigens and become cytotoxic T cells.

• Cytotoxic T cells induce apoptosis in infected cells.

Chemical Messengers: Cytokines

Types and Functions of Cytokines

Cytokines are signaling molecules that regulate immune cell communication and responses.

• Interleukins: Communication between leukocytes.

• Chemokines: Induce migration of leukocytes to infection sites.

• Interferons: Protect cells from viral infections.

• Tumor Necrosis Factor (TNF): Induces inflammation and autoimmune diseases.

• Hematopoietic Cytokines: Control stem cell development (RBC, WBC).

• Cytokine Storm: Excessive cytokine production, causing tissue damage.

Immunological Memory

Primary and Secondary Immune Responses

The immune system remembers previous encounters with antigens, enabling faster and stronger responses upon re-exposure.

• Primary Response: Slow antibody production after initial antigen contact; detectable after 7-10 days, peaks at 10-17 days.

• Secondary Response: Rapid, robust antibody production by memory cells; peaks in 2-7 days.

• Antibody Titer: Measurement of antibody concentration in serum.

Types of Adaptive Immunity

Natural and Artificial Immunity

Immunity can be acquired naturally or artificially, and can be active or passive.

Type	How Acquired	Example
Naturally Acquired Active Immunity	Exposure to antigens, illness, recovery	Chickenpox infection
Naturally Acquired Passive Immunity	Transfer of antibodies from mother	Placenta, breast milk
Artificially Acquired Active Immunity	Vaccination (antigens introduced)	Flu vaccine
Artificially Acquired Passive Immunity	Injection of antibodies	Antiserum for rabies

Key Terms and Definitions

• Epitope: Specific region of an antigen recognized by antibodies.

• Hapten: Small molecule that becomes antigenic when attached to a carrier.

• Cytokine: Chemical messenger for immune cell communication.

• Plasma Cell: Activated B cell producing antibodies.

• Memory Cell: Inactive B cell retaining antigen memory for rapid response.

• Clonal Selection: Process of developing clones of B and T cells specific to an antigen.

• Apoptosis: Programmed cell death, often induced by cytotoxic T cells.

Additional info:

• Formula for Antibody Titer: $\text{Antibody Titer} = \frac{\text{Amount of Antibody}}{\text{Volume of Serum}}$

• Clonal Selection Theory: Each lymphocyte bears a single type of receptor with unique specificity; upon binding antigen, it proliferates into clones.