3. Principles of the adaptive immunity

28/01/2026

Three lines of defence

1) Physical or chemical barriers (skin, mucus), 2) Innate immunity (complement, cells, cytokines

Adaptive immunity position

Third line of defence in the body

Main cells of adaptive immunity

B cells and T cells (lymphocytes)

Innate immunity characteristics

Non

PAMPs

Pathogen

PRRs

Pattern Recognition Receptors, receptors on leukocytes (macrophages, dendritic cells) that recognize PAMPs

Antibody repertoire size

100 billion different antibodies in humans

Genes available for antibody production

Only about 300 genes (1% of ~30,000 total genes)

How antibody diversity is achieved

Through gene rearrangement (V(D)J recombination) despite limited genes

Adaptive immunity key differences

Specific to pathogen, slower (takes days), lymphocyte involvement, creates immunological memory, gene rearrangement of TCR/BCR allows millions of antigens to be targeted

Three main advantages of adaptive immunity

1) Precise targeting, 2) Memory cells, 3) Recognize 'new' pathogens

BCR structure

B cell receptor, Y

Antibody structure

Soluble form of immunoglobulin, lacks hydrophobic membrane

TCR structure

T cell receptor, membrane protein made of two chains (alpha and beta), has one antigen

Where immune cells originate

Haematopoietic stem cells in bone marrow

Where T cells mature

Thymus (migrate from bone marrow to thymus for maturation)

Where T cells are activated

Lymph nodes (peripheral lymphoid organs)

Where B cells mature

Bone marrow (stay there for maturation)

Where B cells are activated

Spleen or other secondary lymphoid organs

Gene rearrangement definition

V(D)J recombination in B and T lymphocytes, somatic recombination of variable (V), diversity (D), and joining (J) gene segments

Purpose of gene rearrangement

Generates vast diversity of antigen receptors, allows finite genome to encode receptors for almost unlimited range of antigens including previously unencountered pathogens

Specificity in adaptive immunity

Individual lymphocyte clones recognize distinct antigenic epitopes

Clonal selection

Only lymphocytes with receptors that bind antigen are activated and expanded

Consequence without gene rearrangement

Lymphocytes would express identical or highly limited receptors, severely compromising antigen recognition, immune memory, and ability to mount tailored responses

B and T cell activation mechanism

Two

Result of two

signal activation

Tolerance definition

The process of clearing self

Central tolerance

T cells undergo negative and positive selection in the thymus to eliminate self

Positive selection in thymus

T cells must be reactive to MHC (if not, they die)

Negative selection in thymus

T cells must NOT be reactive to self

Thymus structure for T cell development

T cells progress through cortex to medulla, potentially undergoing apoptosis if they fail selection processes

Step 1 of naive T cell activation

Dendritic cells carry antigen from infection site to lymph node

Step 2 of naive T cell activation

T cells recognize pathogen fragments, DC takes up and degrades pathogen, proteins cut into peptides, peptides bind MHC and go to cell surface, TCRs bind peptide:MHC complexes

Antigen processing

Macromolecular structures are unfolded and cleaved into short peptide pieces

Antigen presentation

Antigens displayed on cell surface in context of MHC molecules

How T cells recognize antigens

T cells can only recognize small peptide fragments (antigens) when presented on MHC molecules via peptide:MHC complexes

MHC Class I location

All nucleated cells

MHC Class II location

Antigen presenting cells (APCs) only

MHC Class I function

Presents antigens from intracellular infections (cytosolic compartment)

MHC Class II function

Presents antigens from extracellular sources (vesicular compartment)

T cell role in B cell activation

T helper cells provide co

CD40

CD40L interaction

Requirement for T cell help to B cells

B cell must act as APC, presenting antigen that T cell can recognize

Regulatory T cells (Tregs) function

Suppress naive T

Th1 cells function

Release IFN

Th2 cells function

Release IL

Th17 cells function

Release IL

T follicular helper cells (Tfh)

Found in lymphoid tissue, interact with B cells, regulate antibody production

T cytotoxic cells

Typically CD8+ T cells, kill other cells, defend against intracellular pathogens in cytosol

Memory T cells types

Central memory (TCM), effector memory (TEM), tissue

Memory T cells characteristics

More sensitive to specific antigen, respond rapidly on re

B cells as effector cells

Involved in adaptive immune response with highly specific receptors/antibodies

B cells as APCs

Can act as antigen presenting cells similar to macrophages and dendritic cells, presenting antigens elicits T cell help for activation

B cell multi

functionality

Complement receptor (CR) as co

receptor

Innate

adaptive immunity link

B cell surface antibodies

B cells have antibodies on their surface that serve as receptors (BCR)

Antibody specificity

Antibodies are highly specific to their target antigens

Antibody definition

Soluble effector molecules of adaptive immune response

Five antibody isotypes

IgA, IgG (primary effector), IgM (naive antibody), IgE, IgD (naive antibody)

Antibody constant regions

Blue regions, determine antibody class and effector functions

Antibody variable regions

Red regions, make the antigen

Antibody hinge region

Provides flexibility to the Y

Antibody bivalence

Two identical antigen

Antibody heavy chains

Two identical heavy chains (green) form backbone of antibody

Antibody light chains

Two identical light chains (yellow), either lambda or kappa type

Antibody improvements during infection

Antibodies improve through somatic hypermutation and class switching over course of infection

Follicular B cells

Circulate between secondary lymphoid organs searching for antigen, differentiate into plasma cells once antigen found

Marginal zone B cells

Respond quickly without T cell signaling, BCR has low affinity but polyreactive, only produce IgM

Germinal centre B cells

B cells in germinal centre undergoing rapid proliferation, not yet differentiated to plasma or memory cells

Plasma cells

Terminally differentiated B lymphocytes, main antibody

B memory cells

Mediate immunological memory, more sensitive to specific antigen, respond rapidly on re

B regulatory cells

Immunosuppressive cells, support anti

Memory cell production

During primary infection, clonal expansion produces both effector cells and memory cells

Memory cell advantages

More numerous than original clone, more quickly activated, patrol tissue to detect infection early

Memory B cell antibodies

Already somatically mutated (higher affinity), already class

Primary vs secondary response

Memory cells make faster and stronger responses upon re

Autoimmunity examples

Rheumatoid arthritis, lupus, chronic non

Allergy and hypersensitivity examples

Asthma, anaphylaxis, allergic rhinitis (hay fever)

Allergic rhinitis mechanism

Innocuous environmental antigens (allergens) trigger inappropriate immune responses, B cells produce IgE that binds allergen and triggers mast cells to release inflammatory mediators

Transplant rejection

Adaptive immune responses attack transplanted organs/tissue as non

Viruses targeting adaptive immunity

HIV infects CD4+ T cells, Epstein

Disadvantages of adaptive immunity

Can cause autoimmunity, allergies, hypersensitivity, makes transplantation difficult, cells can be viral targets

Adaptive immunity inheritance

Changes occur during lifetime but are not inherited

B cells vs T cells antigen recognition

B cells recognize native antigens directly, T cells are MHC restricted (require antigen presentation)

Antibody functions

Neutralize pathogens, opsonize pathogens for phagocytosis, activate complement, facilitate antibody

Summary point 1

Adaptive immune responses mediated by lymphocytes (T and B cells)

Summary point 2

Gene rearrangement and somatic mutation produce vast range of pathogen receptors

Summary point 3

Individual lymphocytes express receptors of unique antigen

Summary point 4

B cells recognize native antigens, T cells are MHC restricted

Summary point 5

T helper cells can help activate B cells as co

Summary point 6

B cells differentiate into plasma cells and secrete soluble antibodies that neutralize and opsonize pathogens

Summary point 7

Subtypes of both B and T cells have specific roles in adaptive response

Summary point 8

Adaptive immunity changes during lifetime but changes are not inherited

Summary point 9

Adaptive response can go wrong causing disease (autoimmunity, allergy, transplant rejection