10. Overview of Adaptive Immunity

What are the main stages of the adaptive immune response?

• Pathogen invades and proliferates in tissue

• Nearby secondary lymphoid tissue detects infection

• Pathogen-specific B and T cells are activated

• B/T cells proliferate and mature into effector cells

• Antibodies + effector T cells go to infection site
  → Outcomes:

1. Pathogen eliminated → tissue repairs

2. Pathogen persists → death or chronic infection

What are the main innate immune cells?

• Macrophage

• Monocyte

• Neutrophil

• Eosinophil

• Basophil

• NK cell

What are the main adaptive immune cells?

• Lymphocytes:

  • CD4+ T cell (helper)

  • CD8+ T cell (cytotoxic)

  • B cell

  • Regulatory T cell

What makes adaptive immune cells adaptive?

• They react and adapt to specific pathogens

• Their functions are not innate — they are instructed during infection

• (Linked to Paul Ehrlich’s idea of specificity and instruction = side-chain theory → antibodies)

What are the three key principles of immunity?

• Immune recognition – Detect the invader

• Immune protection – Mount a killing response

• Immune regulation – Limit the response to prevent damage

How does adaptive immune recognition differ from innate recognition?

Adaptive receptors:

• ❌ Not inherited in genome

• ❌ Not expressed by all cells

• ❌ No immediate response

• ✅ Highly specific — can distinguish closely related molecules

What are adaptive immune receptors specific to?

• They are antigen-specific (“ANTIbody GENerating” substances)

• Almost anything can be an antigen:

  • Proteins

  • Carbohydrates

  • Nucleic acids

  • Some small molecules

What receptors do B and T cells have?

• B cells: B cell receptor (BCR) / antibody receptor

• T cells: T cell receptor (TCR)

These receptors are ONLY found on B cells or T cells. Unlike TLRs which can be found on many immune cells.

How do B cell receptors recognize antigens?

• BCR = immunoglobin = antibody

• BCRs bind whole, intact antigens

• Bind to whole antigen’s in their natural conformation

  • No need to process antigen

What determines antibody specificity?

• Each antibody binds only one specific antigen

• “Anti-X” = antibody against antigen X

  • e.g., anti-influenza antibody binds influenza antigen, not SARS-CoV-2

What is an epitope?

• A small part of an antigen that a B cell, T cell, or antibody recognizes and binds to.

• Example: A multivalent antigen can have several different epitopes (e.g., circle, triangle, square, butt), each recognized by a different antibody.

  • Tip of the antibody is called the paratope which binds to the epitope

What are the two types of epitopes made during immune response?

• Linear epitope: Sequence of amino acids (primary structure).

  • Antibody still binds even if the protein is denatured.

• Conformational (discontinuous) epitope: Formed only when the protein is folded (secondary/tertiary/quaternary structure).

How do T cell receptors detect antigens?

• TCRs do not bind whole antigens

• They bind processed antigen fragments

• Fragments are presented by antigen-presenting cells (APCs) using MHC molecules

Summarize how T cells recognize antigens.

Pathogen protein → broken down → peptide displayed by MHC molecule → recognized by T cell receptor (TCR)

Immune Protection: Compare innate and adaptive immune responses.

• Killer T-cells → direct killing (similar to NK cells but antigen specific receptor)

• Helper T-cells, B cells → indirect killing (secrete antibodies)

What are the two main T cell types and their roles?

• CD4+ “Helper” T cells: Provide signals which help other immune cells perform functions

• CD8+ “Cytotoxic” T cells: Directly kill infected or mutated cells (cancer cells)

CD4 and CD8 are proteins found on the cell surface.

How do CD8+ T cells detect and kill infected cells?

• CD8 = co-receptor for MHC class I.

• MHC I is expressed on all nucleated cells → allows surveillance of proteins made inside the cell.

• CD8+ T cells scan for foreign (viral or abnormal) peptides displayed on MHC I.

• If MHC I is missing, NK cells will target and kill that cell instead.

• When CD8+ T cell recognizes an infected cell:

  1. TCR binds the antigen–MHC I complex.

  2. The infected cell is programmed to undergo apoptosis (cell death).

  3. Only infected cells are killed — neighboring healthy cells are spared.

How do CD4+ T cells detect antigens and what cells express MHC II?

• CD4 = co-receptor for MHC class II.

• MHC II is expressed only on antigen-presenting cells (APCs):

  • Professional APC: dendritic cells

  • Others: macrophages, B cells

• CD4+ T cells recognize antigens presented on MHC II.

• Function: Enables helper T cells to “talk to” APCs and coordinate immune responses.

• (Extra note: T cells can sometimes express MHC II to interact with other T cells — advanced, not covered here.)

What are the main CD4+ T helper (Th) cell subtypes and their roles?

• Th1: Activate macrophages → antiviral and antimicrobial

  • Type 1 response: IL-12 → Th1 → IgG

• Th2: Activate responses to parasites (cellular + antibody)

  • Type 2 response: IL-4, IL-5 → IgE → mast cells, basophils, eosinophils

  • Can drive allergies if response misfires

• Th17: Enhance neutrophil response → antibacterial

  • Type 3 response: IL-17 → neutrophils

  • Involved in autoimmune responses

• Tfh (follicular helper T cells): Help B cells refine antibodies

  • Can specialize for antiviral or antiparasitic responses

What do B cells do after activation?

• Resting B cells: Have surface antibodies but don’t secrete them yet

• Activation: Triggered by adaptive immune response

• Differentiate into: Plasma cells

• Plasma cell functions:

  • Secrete antibodies that:

    • Bind & neutralize key parts of pathogens

    • Tag pathogens for destruction by innate immune cells

    • Recruit complement proteins (classical pathway) to directly kill pathogen

Where are adaptive immune responses activated?

• Origin: Adaptive immune cells come from bone marrow

• Naïve B/T cells: Reside in secondary lymphoid tissues (lymph nodes, spleen)

• Activation site: Secondary lymphoid tissues

How does the immune system take advantage of space to activate itself?

• Lymph node structure:

  • Follicles at edge: B cells

  • Inside wing: T cells

  • Medullary sinus: exit for immune cells/lymph

• Process:

  • Lymph node collects fluid from tissues → brings antigens to lymphocytes

  • B cells capture antigen → present to T cells → determine activation → initiate adaptive response

How does an adaptive immune response get activated in a tissue infection?

• Battleground: Infection site → macrophages, dendritic cells, neutrophils respond

• Dendritic cells:

  • Capture antigen/bacterial pieces → become activated

  • Enter lymphatics draining the tissue → travel to lymph node

  • Go to T cell area → find antigen-specific T cells → activate them

• B cells:

  • Antigens filter through B cell follicles

  • Bind antigens in native conformation → present to T cells for help → get activated

• Activated lymphocytes:

  • Exit lymph node via lymphatics → enter circulation → protect whole body

  • Example: Infection in left ear → immunity extends to other sites (toe, etc.)

What cell type regulates the immune response?

• Regulatory T cells (Tregs)

• Function: suppress and limit immune responses to prevent tissue damage