Chapter 24 Omega

Innate immune system

The first, non-specific line of defense including physical barriers, toxic molecules, and phagocytic cells that respond rapidly to many pathogens.

Adaptive immune system

A slower, highly specific system using B and T lymphocytes that produces long-lasting, antigen-specific responses and immunological memory.

Epithelial barriers

Physical and chemical defenses at skin and mucosal surfaces (tight junctions, keratin, mucus, cilia, secreted acids/peptides) that block pathogen entry and adhesion.

Defensins

Positively charged, amphipathic antimicrobial peptides secreted by epithelial cells that bind to and disrupt pathogen membranes.

PAMPs (pathogen-associated molecular patterns)

Conserved microbial molecules (e.g., LPS, dsRNA, CpG DNA) that indicate the presence of microbes and are recognized by the innate immune system.

PRRs (pattern recognition receptors)

Host receptors that detect PAMPs and activate intracellular signaling to initiate innate immune responses and inflammation.

TLRs (Toll-like receptors)

A family of transmembrane PRRs that recognize extracellular or endosomal PAMPs (e.g., TLR3 recognizes dsRNA, TLR4 recognizes LPS).

NLRs (NOD-like receptors)

Cytoplasmic PRRs with leucine-rich repeats that detect intracellular bacterial molecules and can form inflammasomes.

RLRs (RIG-like receptors)

Cytoplasmic RNA-helicase PRRs that detect viral RNA and trigger antiviral responses.

CLRs (C-type lectin receptors)

Cell-surface PRRs that bind carbohydrate structures on microbes in a Ca²⁺-dependent manner.

Inflammatory response

Local vascular and cellular response to infection driven by PRR signaling, producing redness, heat, swelling, pain, leukocyte recruitment, and cytokine release.

Inflammasome

A multiprotein cytosolic complex (assembled by some NLRs) that activates caspase-1 to cleave and release pro-inflammatory cytokines such as IL-1β and IL-18.

Macrophages

Long-lived tissue resident phagocytes that detect pathogens, engulf and kill microbes, secrete cytokines to orchestrate inflammation, and present antigen to adaptive cells.

Neutrophils

Short-lived, highly abundant blood phagocytes rapidly recruited to infection sites to phagocytose microbes, release toxic oxidants and enzymes, and amplify inflammation (then die).

Complement system — classical pathway

Activation initiated by antibodies or C-reactive protein bound to pathogens, leading to C3 activation and downstream complement cascade.

Complement system — lectin pathway

Activation initiated by mannose-binding lectin binding microbial carbohydrates, triggering the complement proteolytic cascade and C3 activation.

Complement system — alternative pathway

A pathway that can be directly activated by pathogen surfaces and serves as an early amplifier of complement activation through C3.

C3b

A covalently binding fragment of C3 that opsonizes pathogen surfaces to promote phagocytosis and contributes to assembly of proteolytic complement complexes.

Complement regulation/shutdown

Complement is limited by instability of activated intermediates, rapid inactivation unless bound to target, and specific inhibitor proteins on host cells (e.g., recruited to sialic acid) that prevent host damage.

Innate viral detection

Innate sensors recognize viral features (e.g., dsRNA, CpG DNA) via PRRs (such as TLR3, TLR9, RLRs), triggering antiviral programs including interferon production.

Type I interferons (IFN-α/β)

Cytokines induced by viral infection that act autocrinely and paracrinely to induce antiviral genes, inhibit protein synthesis, activate RNases, and boost NK cell activity.

Natural killer (NK) cells

Innate lymphoid killer cells that detect and kill cells with abnormally low MHC I or with stress-induced ligands, inducing apoptosis of infected or transformed cells.

Cytotoxic T cells

Adaptive T lymphocytes that use TCRs to recognize viral peptide fragments bound to class I MHC on infected cells and induce apoptosis of those cells.

Dendritic cells

Antigen-presenting innate cells that phagocytose pathogens, process and display peptide-MHC complexes, provide co-stimulation and cytokines, and migrate to lymphoid organs to activate T cells.

B cells

Adaptive lymphocytes that, upon activation, clonally expand and differentiate into plasma cells that secrete antibodies specific to the inducing antigen.

T cells

Adaptive lymphocytes that differentiate into helper, cytotoxic, or regulatory subsets

Clonal selection

The process by which antigen selectively activates preexisting lymphocytes bearing receptors specific for that antigen, leading to their proliferation and differentiation.

Clonal expansion

Rapid proliferation of antigen-specific lymphocytes after activation, generating large numbers of effector and memory cells from a single precursor.

Naïve cell

A mature B or T lymphocyte that has not yet encountered its specific antigen and circulates through peripheral lymphoid organs.

Effector cell

An activated lymphocyte that performs the immune response (e.g., plasma cell secreting antibody, cytotoxic T cell killing infected cells).

Memory cell

Long-lived lymphocytes produced after an immune response that rapidly respond and differentiate into effectors upon re-exposure to the same antigen.

Primary immune response

The initial adaptive response to first encounter with an antigen characterized by a lag phase, clonal expansion, and generation of effector and memory cells.

Secondary immune response

A faster, larger, and more efficient response upon re-exposure to the same antigen due to preexisting memory cells and circulating antibodies.

Lymphocyte recirculation

The continual movement of naïve and memory B and T cells between blood, peripheral lymphoid organs, lymph, and back to blood so rare antigen-specific cells can encounter antigen.

Thoracic duct

The main lymphatic vessel that collects lymph (and migrating lymphocytes) from most of the body and returns it to the bloodstream.

Postcapillary venules

Specialized small veins in lymphoid organs where lymphocytes leave the bloodstream by first rolling and then adhering to endothelium.

Selectins

A family of cell-surface lectins on lymphocytes and endothelium that mediate the initial weak rolling interactions during lymphocyte homing.

Integrins

Cell-surface adhesion proteins on lymphocytes that, once activated by chemokines, mediate firm adhesion to endothelium and arrest rolling.

Chemokines

Secreted signaling proteins from endothelial or stromal cells that activate integrins and guide lymphocytes into and within lymphoid tissues.

CD31 (PECAM-1)

A cell adhesion molecule used by lymphocytes to crawl between endothelial cells and exit the bloodstream into lymphoid tissues.

Efferent lymphatic vessel

The vessel by which lymphocytes and lymph leave a lymph node after percolating through it.

Lymph node microanatomy — B cell follicles

Regions within a lymph node where B cells are guided by specific chemokines to form follicles and germinal centers.

Lymph node microanatomy — paracortex

The T cell–rich region of a lymph node where naïve T cells encounter dendritic cells.

Dendritic-cell antigen transport

Activated dendritic cells pick up antigen at peripheral sites and migrate via lymph to lymph nodes to present antigen to naïve T cells.

Homing receptors

Lymphocyte surface receptors (including selectins/integrins) that mediate tissue-specific entry into lymphoid organs.

Retention after activation

When a lymphocyte’s specific antigen is encountered in a node it upregulates adhesion molecules that trap it for clonal expansion and differentiation.

Immunological self-tolerance

The collection of mechanisms that prevent adaptive immune cells from attacking the body’s own tissues.

Receptor editing

A central tolerance mechanism in developing B cells where self-reactive BCRs are altered by further light-chain rearrangement to eliminate self-reactivity.

Clonal deletion

Apoptotic removal of developing B or T cells that strongly recognize self antigens during maturation (central tolerance).

Clonal inactivation (anergy)

Functional inactivation of mature self-reactive lymphocytes when they encounter antigen without appropriate co-stimulation (peripheral tolerance).

Clonal suppression (Treg-mediated)

Regulatory T cells suppress potentially self-reactive lymphocytes via inhibitory cytokines and cell-surface molecules (peripheral tolerance).

Failure of tolerance

When tolerance mechanisms fail, autoimmune diseases can result (examples: myasthenia gravis, type I diabetes).

B cell receptor (BCR)

A membrane-bound immunoglobulin (with associated Igα/Igβ invariant chains) that recognizes native antigen and initiates B cell signaling.

Igα and Igβ

Invariant transmembrane signaling subunits associated with the BCR that contain ITAMs and transmit activation signals.

Antibody (general structure)

A Y-shaped protein of two identical heavy and two identical light chains with variable antigen-binding regions (Fab) and a constant Fc tail that mediates effector functions.

Variable and constant regions

The variable (V) regions form the antigen-binding sites

Fc region

The constant tail of an antibody that binds Fc receptors on immune cells and activates complement — mediates effector functions.

BCR → antibody transition

Activated B cells differentiate into plasma cells that secrete soluble antibodies with the same antigen specificity as their membrane BCR.

IgM structure and role

First antibody made by immature B cells and early responses

IgD role

Co-expressed with IgM on mature naïve B cells as a BCR

IgG functions

The major serum antibody in secondary responses

IgA functions

Principal antibody in secretions (saliva, tears, mucosal fluids)

IgE functions

Antiparasite and allergy antibody that binds Fcε receptors on mast cells/basophils and triggers histamine release upon antigen binding.

Stages of B cell development

Progression from pro-B → pre-B → immature B (IgM+) → mature naïve B (IgM+IgD+) with central tolerance checkpoints in bone marrow.

Class switching

A DNA rearrangement in activated B cells that changes antibody heavy-chain constant region (e.g., IgM→IgG) to alter effector function while keeping antigen specificity.

Somatic hypermutation

Mutation of Ig variable region in germinal centers that, with selection, increases antibody affinity (requires T cell help).

T cell vs B cell responses (key differences)

T cells recognize peptides presented on MHC and act mainly by cell contact and cytokines

Major T cell classes

Cytotoxic CD8 T cells (kill infected cells), Helper CD4 T cells (coordinate immune responses), Regulatory T cells (suppress immunity).

T cell receptor (TCR) structure

An Ig-like heterodimer (most commonly α and β chains) with variable and constant domains that recognize peptide-MHC complexes.

γδ T cells

A minority T cell population with γ and δ chains that often reside in epithelia and have restricted ligand recognition independent of classical MHC.

Dendritic cell activation of naïve T cells

Activated dendritic cells present peptide-MHC plus co-stimulatory molecules and adhesion proteins to naïve T cells in lymphoid organs to initiate T cell responses.

Co-stimulation (B7-CD28)

B7 proteins on APCs bind CD28 on T cells to provide essential second signals required for naïve T cell activation and survival.

MHC class I — function and expression

Expressed on almost all nucleated cells, presents peptides from cytosolic proteins (8–10 aa) to CD8 cytotoxic T cells.

MHC class II — function and expression

Expressed mainly by professional APCs, presents peptides derived from endocytosed extracellular proteins (12–20 aa) to CD4 helper T cells.

Class I antigen processing

Cytosolic proteins are degraded by proteasomes, peptides transported into the ER by TAP, loaded onto class I MHC and exported to cell surface.

Class II antigen processing

Exogenous proteins are endocytosed, degraded in endosomes, class II MHC (with invariant chain) loads peptides in endosomal compartments and traffics to surface.

Invariant chain (Ii) role

Blocks premature peptide binding to class II MHC in the ER and guides class II MHC into endocytic pathway

Cross-presentation

A process by which dendritic cells present exogenous antigens on class I MHC to activate CD8 T cells (important for viral/tumor immunity).

CD4 co-receptor

Expressed on helper and regulatory T cells, binds invariant regions of class II MHC and recruits Lck to aid T cell activation.

CD8 co-receptor

Expressed on cytotoxic T cells, binds invariant regions of class I MHC and recruits Lck to strengthen TCR signaling and focus killing.

Lck and signaling

Lck is a Src family tyrosine kinase associated with CD4/CD8 cytoplasmic tails that phosphorylates ITAMs to initiate TCR signaling.

Thymocyte positive selection

Process in thymic cortex that selects thymocytes whose TCRs weakly recognize self-MHC (ensures MHC restriction).

Thymocyte negative selection

Deletion of thymocytes that bind too strongly to self peptide-MHC in the thymic medulla to eliminate self-reactive T cells (central tolerance).

AIRE (autoimmune regulator)

A thymic medullary epithelial transcription factor that induces expression of tissue-restricted antigens in thymus to allow negative selection and prevent autoimmunity.

Purpose of negative selection

To remove highly self-reactive T cells during development and reduce the risk of autoimmune disease.

Immunological synapse

The focused interface between a killer/effector T cell and its target cell where receptors, adhesion molecules, and secretory machinery are organized.

Perforin

A pore-forming protein released by cytotoxic T cells and NK cells that creates membrane pores in target cells to allow granzymes entry.

Granzymes

Serine proteases delivered into target cells via perforin pores that activate caspases and trigger apoptosis.

Fas-FasL killing

An alternative cytotoxic mechanism where Fas ligand on killer cells binds Fas on target cells to trigger caspase-dependent apoptosis.

Helper T cell assistance

CD4+ helper T cells provide cytokines and co-stimulatory signals (e.g., CD40L) to activate B cells, macrophages, and sustain dendritic cells.

TFH cells (follicular helper)

A helper T subset that localizes to follicles and provides help (CD40L, IL-21) for B cell proliferation, class switching, and affinity maturation.

TH1, TH2, TH17 functions

TH1 (IFN-γ: activate macrophages, cell-mediated)

Regulatory T cells (Treg)

Suppress immune responses via IL-10/TGF-β and inhibitory surface molecules

Invariant chains for antigen receptors

BCRs associate with Igα/Igβ signaling chains

Early B cell signaling events

Antigen clustering of BCR → Src family kinase (e.g., Lyn) phosphorylates ITAMs on Igα/Igβ → Syk recruitment → downstream signaling for activation.

Antigen activation of helper T cell vs B cell

A T cell recognizes peptide-MHC on APC

Co-stimulatory help to B cells (CD40L)

Tfh cells express CD40L that binds CD40 on B cells to provide essential signals for B cell proliferation, class switching, and germinal center reactions.

Vaccine type — whole microbe

Vaccines containing whole pathogens (live-attenuated or inactivated) that typically induce strong immune responses due to PAMPs.

Vaccine type — subunit/adjuvanted

Vaccines composed of selected microbial components

Vaccine type — nucleic acid/viral vector

Vaccines delivering DNA or RNA or viral vectors encoding antigen proteins that induce host cells to produce antigen and trigger immune responses.