Adaptive Immunity : Specialisation and Memory

Innate immunity

Non‑specific, immediate defense using existing infrastructure like barriers, phagocytes, NK cells, complement, no memory

Adaptive immunity

Specific, antigen‑dependent, slower primary response, faster secondary response, involves T and B lymphocytes, generates memory

T cell receptor (TCR)

Unique receptor on all T cells, composed of αβ (95%) or γδ chains, recognizes antigen presented by MHC

CD3

Expressed on all T cells, transmits signals from TCR into the cell after antigen recognition

CD4

Expressed on helper and regulatory T cells, binds MHC II, co‑receptor for activation, receptor for HIV gp120

CD8

Expressed on cytotoxic T cells, binds MHC I, co‑receptor for recognition of endogenous antigens

CD25

IL‑2 receptor alpha chain, expressed on activated T cells and constitutively on Tregs with FoxP3

CD28

Co‑stimulatory receptor on T cells, binds B7 on APCs, provides signal 2 for activation

CD154 (CD40L)

Ligand on T cells, binds CD40 on B cells, essential for class switching and memory formation

Naïve T helper cell

CD4+, CD3+, TCR+, has not encountered antigen, cannot perform effector functions until activated

Clonal selection

Process where antigen‑specific lymphocytes are recognized, activated, expanded, differentiated into effector and memory cells

Phase 1 recognition

Antigen presentation by APC via MHC‑TCR complex, signal 1 to T cell

Phase 2 activation

Co‑stimulatory signal B7‑CD28, signal 2, induces cytokine production

Phase 3 clonal expansion

IL‑2 production, autocrine proliferation of activated T cells, paracrine activation of other immune cells

Phase 4 differentiation

Polarising cytokines drive differentiation into Th1, Th2, Th17, Tfh subsets or memory cells

Phase 5 effector function

Effector cytokine secretion, eradication of infection, formation of memory cells

Th1 polarising cytokine

IL‑12 from macrophages and dendritic cells

Th1 transcription factor

T‑bet

Th1 secreted cytokines

IFN‑γ and IL‑2

Th1 functions

Promotes cell‑mediated immunity, activates macrophages, CTLs, NK cells, combats intracellular microbes, delayed‑type hypersensitivity

Th1 clinical correlation

Defective response increases susceptibility to intracellular infections like mycobacteria

Th2 polarising cytokine

IL‑4

Th2 transcription factor

GATA3

Th2 secreted cytokines

IL‑4, IL‑5, IL‑13

Th2 functions

Promotes humoral immunity, activates B cells for IgE, recruits eosinophils and mast cells, combats helminths, mediates allergy

Th2 clinical correlation

Overactive response causes allergic diseases such as asthma and atopy

Th17 polarising cytokines

IL‑6, IL‑21, IL‑23, TGF‑β

Th17 transcription factor

RORγt

Th17 secreted cytokines

IL‑17, IL‑21, IL‑22

Th17 functions

Recruits neutrophils, defends against extracellular bacteria and fungi, promotes inflammation

Th17 clinical correlation

Overactive response contributes to autoimmune diseases like psoriasis and rheumatoid arthritis

Tfh polarising cytokine

IL‑6

Tfh transcription factor

BCL‑6

Tfh secreted cytokines

IL‑21 and IL‑4

Tfh functions

Specialized in germinal center B cell help, promotes class switching, affinity maturation, memory B cell formation

Tfh clinical correlation

Defective response leads to poor antibody production and impaired humoral immunity

IL‑2

Produced by activated T cells, promotes clonal expansion, enhances CD8 cytotoxicity

IL‑12

Produced by macrophages and dendritic cells, promotes Th1 and CD8 differentiation, activates NK cells, drives IFN‑γ immunity

IFN‑γ

Secreted by Th1 and CD8 cells, activates macrophages, enhances MHC expression, inhibits viral replication

IL‑4

Secreted by Th2 and Tfh cells, drives Th2 differentiation, promotes IgE class switching

IL‑5

Secreted by Th2 cells, activates eosinophils

IL‑17

Secreted by Th17 cells, recruits neutrophils, promotes inflammation

IL‑21

Secreted by Tfh cells, promotes B cell proliferation, class switching, affinity maturation

Cell mediated immunity

Defense against intracellular microbes, performed by cytotoxic T cells, Th1 cells, NK cells, macrophages

Innate CMI

Phagocytosis by neutrophils and monocytes, NK cell cytotoxicity, ADCC via Fc receptors

Adaptive CMI

CD8 cytotoxic T cells kill virus‑infected, tumor, and foreign cells via perforin, granzymes, Fas‑FasL, cytokines

ADCC

Antibody binds target cell epitope, NK cell Fc receptor recognizes IgG, releases perforin, granzymes, cytokines, induces apoptosis

Cytotoxic T cell effector function

Bind target via TCR‑MHC I, kill using perforin/granzymes, Fas‑FasL apoptosis, TNF and IFN‑γ inhibit viral replication

Perforin mechanism

Forms pores in target cell membrane allowing granzymes to enter and induce apoptosis

Granzyme mechanism

Serine proteases entering via perforin pores, activate caspases, trigger apoptosis in target cell

Fas‑FasL mechanism

CD8 T cell FasL binds Fas on target cell, activates caspase cascade, induces apoptosis

Cytokine mechanism

CD8 T cells secrete TNF and IFN‑γ, inhibit viral replication and promote apoptosis

Humoral immunity

T cell independent and T cell dependent B cell responses, antibody production, class switching, memory formation

T cell independent B cell response

Triggered by polysaccharides, LPS, lipid antigens, produces IgM only, no memory formation

T cell dependent B cell response

Triggered by protein antigens, requires CD40‑CD40L and cytokines, produces IgG, IgA, IgE, memory cells, affinity maturation

B cell activation phase 1

Recognition via BCR binding antigen, signal 1

B cell activation phase 2

Activation via TCR+MHC II and CD40‑CD40L, signal 2

B cell activation phase 3

Clonal expansion via IL‑21, proliferation

B cell activation phase 4

Differentiation via IL‑21 and IL‑4, signal 3, plasma cells and memory cells formed

B cell activation phase 5

Effector functions including antibody secretion, class switching, affinity maturation, memory formation

Antibody structure

Two heavy chains, two light chains, variable region for antigen binding, constant region for effector functions, hinge region for flexibility

IgM key features

First antibody produced, pentamer, part of BCR, primary immune response

IgM functions

Neutralisation, agglutination, complement activation, opsonisation, clearance of apoptotic cells

IgM clinical correlation

Deficiency impairs primary immune response, recurrent infections

IgG key features

Produced after class switching, most abundant, secondary immune response, crosses placenta

IgG functions

Neutralisation, opsonisation, ADCC, complement activation, maternal transfer of immunity

IgG clinical correlation

Deficiency causes recurrent bacterial infections, neonatal immunity relies on maternal IgG

IgA key features

Produced after class switching, found in mucosal secretions (saliva, tears, respiratory, intestinal)

IgA functions

Neutralisation, mucosal immunity, prevents colonisation of bacteria on mucosal surfaces

IgA clinical correlation

IgA deficiency causes recurrent mucosal infections and predisposes to autoimmune disease

IgE key features

Produced after class switching, low serum concentration, binds mast cells and basophils

IgE functions

Neutralisation, mediates allergy, mast cell and basophil degranulation, eosinophil ADCC against parasites

IgE clinical correlation

Type I hypersensitivity reactions such as asthma, anaphylaxis, allergic rhinitis

IgD key features

Co‑expressed with IgM on mature B cells, lowest molecular weight, part of BCR

IgD functions

Activates B cells during adaptive immune response, does not activate complement, cannot cross placenta

IgD clinical correlation

Minor role clinically, marker of mature B cells

Class switching

Process where B cells change heavy chain constant region, mediated by CD40‑CD40L and cytokines IL‑21, IL‑4, requires AID enzyme, antigen specificity unchanged

Affinity maturation

Occurs in germinal centers, driven by Tfh cells, somatic hypermutation generates higher affinity antibodies, selected B cells differentiate into plasma and memory cells

Immunologic memory

Long‑lived T and B cells formed after antigen exposure, rapid and strong response upon re‑exposure, basis of vaccination

Memory T cells

Generated during differentiation, functionally inactive but long‑lived, rapid effector response on re‑exposure

Memory B cells

Formed in germinal centers with Tfh help, undergo affinity maturation, produce high‑affinity antibodies on re‑exposure

Adaptive immune response humoral arm

Antibody neutralisation, complement activation, allergy defense

Adaptive immune response cell mediated arm

Direct killing of tumor, virus‑infected, foreign cells

Adaptive immune response combined

ADCC and opsonisation using antibody plus CMI

HIV infection

Targets CD4+ T cells via gp120 binding, causes immunodeficiency

IL‑12 deficiency

Impaired Th1 response, susceptibility to disseminated mycobacterial infections

Hyper‑IgE syndrome

Defective Th17 response, recurrent staphylococcal abscesses, eczema, high IgE

X‑linked Hyper‑IgM syndrome

Defective CD40L, no class switching, only IgM produced, recurrent infections

Vaccination

Relies on immunologic memory, secondary response faster and stronger, produces high affinity IgG