Adaptive Immunity Overview

Adaptive Immunity Lecture Notes

• Adaptive immunity is not innate, but develops over a lifetime.
• Adaptive immunity is slower than innate immunity but highly specific.
• It has a memory function.

Learning Objectives

• Features of adaptive immunity
• The 3 Rs of adaptive immunity to describe the mechanism (Recognize, Respond and Remember)
• Clonal selection
• Cell-mediated immunity
• 3 main types of T cells
• Antigen presentation
• Antibody-mediated (humoral) immunity
• B cells
• Structure and functions of antibodies
• Primary and secondary antibody responses

Features of Adaptive/Acquired Immunity

• Not present at birth, develops throughout life
• Slower to respond than the innate immune system
• High specificity for antigens
• Has a memory function

Cells Involved

• Lymphocytes are key cells
• B lymphocytes produce antibodies
• T lymphocytes are involved in cell-mediated immunity
• T cells mature in the thymus, B cells mature in bone marrow

Principles of Adaptive Immunity

• Each cell has a specific receptor for a particular antigen.
• Innate immune system cells help with antigen recognition.
• Recognition is followed by clonal selection.
• Adaptive immunity responds by:
  • Cytokine secretion
  • Antibody production
  • Direct cell killing

Clonal Selection

• Introduced by Burnett in 1957
• Each lymphocyte has receptors to bind one specific antigen.
• The immune system is diverse - many lymphocytes with varying antigen receptors.
• Very few lymphocytes are specific to any one antigen.
• When a lymphocyte encounters its antigen, it becomes activated.
• The activated lymphocyte divides rapidly to create copies (a clone) and cells that destroy antigens.
• It also makes memory cells to protect against future encounters.

Clonal Selection Diagram

• Primary response (first encounter): antigen binding, clone formation, antibody production, memory cell development
• Secondary response (later encounter): faster response, higher antibody titre, mainly IgG, more specific antibodies, affinity maturation

Cell-mediated Immunity

• T cells need antigen-presenting cells (APCs) to introduce the antigen to them.
• APCs include phagocytes (e.g., macrophages, dendritic cells, neutrophils).
• APCs use MHC (Major Histocompatibility Complex) to display fragments of digested antigens on their surface.

Antigen Presentation Process

• Phagocyte engulfs a microbe antigen.
• Parts of the bacteria (antigens) are transported to the phagocyte's surface.
• Phagocyte presents the antigen to the helper T cell.
• This presents the T cell with information necessary to trigger a response.

Antigen Presentation Summary

• Antigen invades the body.
• Phagocytosis occurs by an antigen-presenting cell.
• Antigen is digested into particles.
• Particles are transported to the cell surface.
• The Major Histocompatibility Complex displays the antigen on the cell surface.

Cell-mediated Immunity - T cell types

• Regulatory T cells (Tregs): suppress the immune response, produce anti-inflammatory cytokine interleukin (IL)-10
• Helper T cells: produce cytokines to increase activity of B cells, macrophages, and other T cells
• Cytotoxic T cells: kill foreign or infected host cells, use perforin/granzyme system

T cell counts

• Normal T cell count range is 600-1200 cells/µl
• AIDS: count < 200/µl

B Cells & Antibodies (humoral immunity)

• B cell receptors (BCR) are antibodies
• BCRs bind to the antigen directly
• BCRs recognize specific epitopes (parts) on the antigen.
• Following clonal selection and expansion, B cells create antibodies with the same antigen-binding specificity

Antibodies (Immunoglobulins)

• Consist of two heavy chains and two light chains arranged in a "Y" shape.
• Two identical antigen-binding sites (Fab).
• The stem (Fc region) binds to Fc receptors on cells to mediate the effects of antibodies.

Antibody (immunoglobulin) structure details

• Four polypeptide chains (two heavy and two light chains)
• Each chain has a variable region (determines antigen specificity) and a constant region.
• Antigen-binding sites (Fab) composed of the variable regions of heavy and light chains.
• Fc region is made up of remaining heavy and light chain regions.

Antibody (Immunoglobulin) isotypes

• Five types of heavy chains (γ, μ, α, δ, ε), leading to 5 isotypes (IgG, IgM, IgA, IgD, IgE)
  • IgG, IgE and IgD each have one Y unit
  • IgA often has 2 Ig units (dimer)
  • IgM has 5 Ig units (pentamer).

Antibody class details

• IgG: 70-75% of circulating immunoglobulins, 4 subclasses, can cross the placenta.
• IgM: Exists as a pentamer, important early response antibody, does not cross the placenta.
• IgA: Often exists as a dimer, predominates in secretions.
• IgD: Found in low concentrations, primarily on B cells.
• IgE: Involved in allergies, binds to mast cells and basophils.
• Antibodies perform various functions, such as neutralizing microbes/toxins, opsonization, and antibody dependent cellular cytotoxicity.

Antibody functions

• Neutralization of microbes and toxins
• Opsonization and phagocytosis of microbes
• Antibody-dependent cellular cytotoxicity (ADCC)
• Complement activation
• Inflammation

Primary vs Secondary Antibody Response

• Primary response (first exposure): takes 5-10 days, low antibody titre, mainly IgM.
• Secondary response (later exposure): faster (1-3 days), much higher antibody titre, mainly IgG, more specific antibodies, affinity maturation

Immunological Memory

• Second exposure to an antigen leads to a faster, larger, and more effective antibody response than the primary response.
• This is due to memory cells, which are long-lived and provide quicker recognition and response to the antigen.

Summary of Main Points

• Adaptive immunity is slower but highly specific, adaptable, and has memory.
• Clonal selection creates a large number of antigen-specific lymphocytes.
• T cells need APCs to present antigen.
• B cells bind antigen directly and produce antibodies matching their BCR.
• 5 isotypes (IgG, IgM, IgA, IgD, IgE) exist with diverse roles.
• Secondary antibody response is stronger and faster.

Explore the principles of adaptive immunity, including its features, mechanisms, and key cells involved. This quiz will guide you through the specifics of how adaptive immunity develops, functions, and remembers pathogens. Understand the roles of T cells and B cells in establishing a robust immune response.