Immunology: Antigen Recognition and Signal Transduction

Cellular Communication and Antigen Recognition

In multicellular organisms, cells must communicate through signals for proper function.
During pathogen invasion, specific recognition mechanisms are essential to alert the immune system.
Antigen recognition is mediated by two main types of receptors:
- Pattern Recognition Receptors (PRRs): Found on innate immune cells and also some adaptive immunity cells.
- B Cell Receptor (BCR) or T Cell Receptor (TCR): Expressed on lymphocytes (cells of the adaptive immune system).
Cells also express receptors for cytokines and chemokines to facilitate communication among themselves.
The immune system often receives multiple signals simultaneously, which must be integrated to produce a single, coordinated cellular response.

Receptor-Ligand Interactions

These interactions are mediated by non-covalent bonds.
For an effective biological response, the interaction must be sustained for a sufficient duration and possess adequate binding energy.
Dissociation constant ( $K_d$ ): A measure of the affinity between a receptor and its ligand.
- $K_d = \frac{[R][L]}{[RL]}$ , where $[R]$ is the concentration of free receptor, $[L]$ is the concentration of free ligand, and $[RL]$ is the concentration of the receptor-ligand complex.
- Typical $K_d$ values:
  - Enzyme/substrate interactions: $10^{-3} - 10^{-5} M$
  - Antigen/antibody interactions: $10^{-12} M$ (indicating a much stronger, high-affinity binding).
- High affinity corresponds to a low $K_d$ value.

Multivalent Interactions and Receptor Clustering

Multivalency: An antibody can mediate interactions with multiple binding sites on an antigen, which enhances the probability of an "ON" state (stable engagement).
Antigens possessing multiple binding sites can induce the clustering of receptors on the cell surface.
This receptor clustering is crucial as it facilitates and amplifies intracellular signaling pathways.

Receptor Diversity

Some receptors are composed of multiple subunits derived from a single chain type, combined with a common chain, enabling the creation of diverse binding sites with varying levels of affinity.
Diversity of BCR and TCR: This diversity is generated through DNA recombination processes (specifically, V(D)J recombination), not by RNA splicing.
Multiple exon copies are recombined in the DNA before transcription occurs, leading to a vast repertoire of unique receptors.

Receptor Expression Levels During Immune Response

The expression levels of receptors can dynamically change throughout an immune response.
Example: Interleukin-2 Receptor (IL-2R):
- Resting lymphocyte: Expresses the intermediate-affinity $IL-2R\beta\gamma$ (beta-gamma chains).
- Activated lymphocyte: Expresses the high-affinity $IL-2R\alpha\beta\gamma$ (alpha-beta-gamma chains).
- Expression of the $IL-2R\alpha$ chain significantly increases on T lymphocytes (highlighted in red in diagrams) following activation.
Responding to physiological levels of IL-2 only occurs at high-affinity binding, which is crucial for preventing activation by irrelevant antigens because the $\alpha$ chain is only expressed after proper antigen-specific activation.

Cell-Cell Interactions and Polarized Secretion

Direct cell-cell interactions can be greatly enhanced by high local concentrations of cytokines.
Example: Polarized secretion of IL-12: Between a dendritic cell (blue) and a T lymphocyte (green), IL-12 (pink) is secreted in a directed manner.
During this process, the secretory system (Golgi apparatus) within the secreting cell redistributes itself towards the target cell, ensuring efficient and localized delivery of cytokines.

Immunoglobulin Domains

The immunoglobulin (Ig) domain is a fundamental structural motif present in a wide array of receptors and adhesion molecules within the immune system.
Examples of molecules containing Ig domains:
- Immunoglobulins (e.g., IgM)
- MHC molecules (Class I and Class II)
- T-cell receptor ( $\alpha\beta$ heterodimer)
- T-cell accessory proteins (CD4, CD8, CD2, CD3, Ig-a, Ig-B, $F_{c}\gamma RI$ )
- Adhesion molecules (VCAM-1, ICAM-1, ICAM-2, LFA-3, Poly-Ig receptor)

Ig Domain Structure and Antigen Binding

The Ig domain is typically composed of several $\beta$ sheets.
Complementarity-Determining Regions (CDRs):
- These regions are characterized by their looser structure and higher variability in amino acid sequence.
- CDRs directly mediate the binding with antigens without disrupting the overall structural integrity of the Ig domain.
- They are critical for the specificity of receptors like the B cell receptor.

The B Cell Receptor (BCR)

The BCR exists in two forms:
- Transmembrane protein: The membrane-bound form on the B cell surface.
- Secreted form: Known as an antibody or immunoglobulin.
The transition from membrane-bound to secreted form is regulated by RNA splicing, which replaces a transmembrane hydrophobic segment with a short hydrophilic one.
Antibodies are secreted only after B cell activation.
Antibody structure: Consists of two identical heavy chains (H) and two identical light chains (L), all connected by disulfide bonds.

Antibody Antigen Binding Site and Hypervariability

Constant regions (C): Provide structural support and mediate effector functions.
Variable regions (V): Determine antigen specificity.
The antigen binding site is located at the N-termini region, formed by the interaction of the heavy and light chains.
CDR regions (highlighted in red in diagrams): These regions exhibit high variability in their amino acid sequences.
This hypervariability within CDR regions allows for the generation of a vast array of binding sites, enabling recognition of an enormous diversity of antigens.
Crystallography analysis, such as that performed on antibody binding to the Influenza HA protein, has confirmed the precise nature of these interactions.

Protease Digestion of Antibodies

Protease digestion can yield distinct functional fragments of an antibody:
- Fc (Fragment crystallizable): Composed solely of the constant regions of the heavy chains. The Fc region mediates effector functions like phagocytosis or complement activation.
- Fab (Fragment antigen binding): Contains one antigen-binding arm, made of one light chain and the N-terminal part of one heavy chain.
- F( $ab^\prime$ )$_2$: Consists of two antigen-binding arms linked by disulfide bonds, larger than Fab.

Antibody Isotypes and Classes

Light Chains: Two main types of constant regions exist: lambda ( $\lambda$ ) and kappa ( $\kappa$ ).
Heavy Chains: Five types of constant sequences (isotypes) are found: alpha ( $\alpha$ ), delta ( $\delta$ ), epsilon ( $\varepsilon$ ), gamma ( $\gamma$ ), and mu ( $\mu$ ).
Different heavy chain types define different antibody classes (isotypes):
- IgA: Uses the $\alpha$ chain
- IgD: Uses the $\delta$ chain
- IgE: Uses the $\varepsilon$ chain
- IgG: Uses the $\gamma$ chain
- IgM: Uses the $\mu$ chain
Developmental expression:
- IgM: Primarily expressed by immature B cells.
- IgD: Primarily expressed by mature, unstimulated B cells.
The generation of different antibody classes (class switching) results from DNA recombination events.

BCR Signaling Mechanism

The B cell receptor (BCR) itself possesses a short cytoplasmic domain and is inherently incapable of transducing intracellular signals independently.
For signaling, the BCR is associated with other proteins, forming a complex that includes CD19, CD21, CD79, and CD81.
CD21 (Co-receptor): Aids in antigen binding to the BCR. Its interaction is often mediated by complement component C3d, which tags antigens for clearance by the innate immune system.
CD79 $\alpha$ / $\beta$ (also known as Ig $\alpha$ /Ig $\beta$ ): These heterodimeric proteins contain Immunoreceptor Tyrosine-based Activation Motifs (ITAMs).
- ITAMs are characterized by tyrosine residues that, upon phosphorylation, create anchoring points for intracellular signaling proteins containing SH2 or PTB domains, thereby initiating downstream signaling cascades.

Antigen Binding and Internalization by BCR

When an external antigen binds to the BCR, it induces a conformational change in the receptor, which in turn triggers intracellular signaling.
Following binding and signaling, the antigen-receptor complex can be internalized by the B cell.
The internalized antigen is then processed (digested into peptides) and presented on MHC class II molecules at the cell surface to T cells, forming a critical link in adaptive immunity.
The BCR is distinctive in its ability to directly bind large entities such as soluble toxins, bacteria, and viruses, which often do not require prior processing before recognition.

The T Cell Receptor (TCR)

The T cell receptor (TCR) is unique in that it only recognizes antigens that have been processed by Antigen-Presenting Cells (APCs).
These antigens are presented as short peptides in the context of Major Histocompatibility Complex (MHC) molecules.
T cells continuously survey the organism for cellular changes indicative of threats like viral infections, malignancy, or the presence of phagocytosed foreign antigens.
Most TCRs comprise two chains: an $\alpha$ chain and a $\beta$ chain.
In certain immunological niches, such as the mucosa and skin, a subset of T cells expressing $\gamma$ and $\delta$ chains may exist, which do not always require MHC presentation for antigen recognition.

TCR Co-receptors and Co-stimulation

CD4 and CD8: These co-receptors interact directly with the MHC molecules presenting the antigen, significantly increasing the avidity (overall binding strength) of the TCR for its target cell.
- CD4: Binds to MHC Class II molecules, typically found on APCs and associated with T helper cells recognizing extracellular antigens.
- CD8: Binds to MHC Class I molecules, found on most nucleated cells and associated with cytotoxic T cells recognizing intracellular antigens.
Full TCR activation (co-stimulation) requires additional signals: The interaction of CD28 (on the T cell) with CD80 or CD86 (on the presenting cell, APC).
- CD80 and CD86 are typically expressed only by APCs and their expression is upregulated after antigen uptake.
- This co-stimulatory mechanism is crucial because it prevents non-specific activation of the TCR by self-peptides, which are also loaded onto MHC molecules, thereby ensuring self-tolerance and specific immune responses.

TCR Signaling Mechanism

Similar to the BCR, the TCR has a short cytoplasmic domain and cannot transduce intracellular signals directly.
CD3 complex: Associated with the TCR, this complex is responsible for transducing the signal intracellularly.
- The CD3 complex is composed of three dimers: $\delta\varepsilon$ , $\gamma\varepsilon$ , and $\zeta\zeta$ (or $\zeta\eta$ ).
- The subunits of the CD3 complex contain ITAMs, whose tyrosine residues are phosphorylated upon TCR engagement to initiate downstream signaling.
Other accessory molecules are also involved in the intricate T cell signaling pathways.

Innate Immunity Receptors (PRRs)

The innate immune system serves as the first line of defense, capable of eliminating pathogens before the adaptive immune system is fully activated.
Innate immune cells utilize Pattern Recognition Receptors (PRRs) to detect pathogens.
Innate cells can also secrete cytokines that modulate and influence the adaptive immune response.
The specific types of cytokines secreted depend on which particular PRR has been activated.
Key contrast between PRRs and BCR/TCR:
- BCR / TCR: Exhibit clonal expression, meaning each lymphocyte clone expresses a unique receptor specific to one antigen.
- PRRs: Are expressed by many different cell types, including B and T cells. Unlike BCR/TCR, multiple different PRRs can be expressed on the same cell, and different cells can express the same PRRs to recognize common pathogen features.

PAMPs Recognized by PRRs

PRRs are expressed by a wide range of cell types, including adaptive immune cells like B and T cells.
PRRs recognize Pathogen-Associated Molecular Patterns (PAMPs).
PAMPs are molecules that are critical for pathogen survival and thus are less likely to change significantly over evolutionary time, making them conserved targets for innate immunity.
PAMPs commonly consist of repeating molecular motifs or "patterns" (e.g., bacterial lipopolysaccharide, viral double-stranded RNA).

Cytokines - Overview

Definition: Secreted proteins that facilitate communication between immune cells, although they are also utilized by other cell types.
Function: Act in either a paracrine (local effect on nearby cells) or endocrine (systemic effect via the bloodstream) manner.
There are six major families of cytokines.
Chemokines: A specific family of cytokines primarily involved in chemoattraction, guiding cell movement.
Currently, over 39 interleukins (IL-1 to IL-39) have been identified, demonstrating the vastness of the cytokine network.

Cytokine Properties

Pleiotropy: A single cytokine can exert a variety of effects on different target cells or tissues.
Redundancy: Different cytokines can produce the same or similar biological effects.
Synergy: The combined effect of two or more cytokines can be greater than the sum of their individual effects.
Antagonism: One cytokine can inhibit or counteract the effects of another cytokine.

Interleukin-1 Family

Primary role: Facilitates communication between leukocytes (inter-leukocytes).
Secretion: Secreted early during immune responses by dendritic cells, monocytes, and macrophages.
Function: Predominantly pro-inflammatory.
Synthesis: Synthesized as inactive pro-IL-1 forms:
- Pro-IL-1 $\alpha$ is active upon release.
- Pro-IL-1 $\beta$ requires cleavage by caspase-1 (a component of the inflammasome complex) to become active.
Acts as an intermediate molecule, secreted by innate immune cells to activate B and T cells, thereby bridging innate and adaptive immunity.

Modulation of IL-1 Signaling

The signaling of IL-1 can be finely regulated by several mechanisms:
- Antagonists: Such as IL-1Ra (IL-1 Receptor Antagonist), which binds to the IL-1 receptor but does not trigger a downstream signal.
- Non-activating receptors: E.g., IL-1RII, which can bind IL-1 but does not initiate intracellular signaling.
- Soluble forms of the receptor: These circulating receptors can bind to the cytokine in the extracellular space before it can reach and activate membrane-bound receptors, effectively reducing its availability.
Similar modulatory mechanisms are observed for other IL-1 family members like IL-18 and IL-33.

Class 1 Cytokines (Hematopoietin Family)

Structural homology: Members of this family share a common four- $\alpha$ helix bundle structure.
Diverse origins and targets: Exhibit a wide range of cellular sources and target cells.
- IL-2: Crucial for lymphocyte proliferation and survival.
- IL-4: Plays a key role in the regulation and differentiation of T helper (TH) cells.
- IL-6: Promotes the differentiation of B cells into antibody-secreting plasma cells.
Receptor structure: Typically involves an $\alpha$ subunit responsible for cytokine binding, with signaling mediated by other associated subunits (e.g., $\beta$ and $\gamma$
chains).
X-linked severe combined immunodeficiency (X-SCID): This severe immunodeficiency is caused by a defect in the $\gamma$ c gene (common gamma chain), located on the X chromosome. This defect leads to a significant impairment in the generation of functional T cells, as the common gamma chain is part of the receptors for several vital Class 1 cytokines (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21).

Class 2 Cytokines (Interferons and IL-10)

Interferons (IFNs) - Antiviral Response: Primarily involved in antiviral immunity and upregulate MHC expression to enhance antigen presentation.
- Type I Interferons (IFN- $\alpha$ , IFN- $\beta$ ):
  - Secreted by macrophages and dendritic cells.
  - Induce the expression of RNase enzymes to destroy viral RNA, thereby inhibiting viral replication.
- Type II Interferon (IFN- $\gamma$ ):
  - Secreted by T cells and Natural Killer (NK) cells.
  - Potently activates macrophages, enhancing their ability to kill intracellular pathogens.
  - It is a key cytokine of TH1 responses, essential for activating cytotoxic immune responses.
- Type III Interferon (IFN- $\lambda$ ):
  - Induces the upregulation of genes involved in controlling viral replication.
IL-10: A cytokine primarily known for its role in regulating and suppressing immune responses, helping to prevent excessive inflammation and autoimmunity.

Tumor Necrosis Factor (TNF) Family

Structure: Both ligands and receptors in this family typically form trimers.
Ligands: Can be either membrane-bound or soluble.
TNF (TNF- $\alpha$ ): A major pro-inflammatory cytokine involved in responses to infection, inflammation, and cellular stress.
LT- $\alpha$ (lymphotoxin-alpha): Produced by activated lymphocytes; acts as an activation signal and increases MHC expression.
LT- $\beta$ (lymphotoxin-beta): Involved in the differentiation and organization of lymphocytes.
CD40L (CD40 Ligand) / CD40 interaction: CD40L, expressed on T cells, binds to CD40 on B cells, which is crucial for B cell differentiation, activation, and antibody class switching.
FasL (CD95L): Induces apoptosis (programmed cell death) in cells expressing its receptor, Fas (CD95), playing a role in regulating immune responses and eliminating infected or cancerous cells.
Clinical Significance: Many anti-TNF drugs (e.g., Humira, Enbrel) are widely used in the market to treat various inflammatory diseases.

Interleukin-17 Family

Secretion: Primarily secreted by specialized T cells known as TH17 cells, as well as CD8+ T cells, $\gamma\delta$ T cells, NKT cells, LTi-like cells, neutrophils, and Paneth cells.
Function: This is the most recently discovered cytokine family. Its members largely function to promote neutrophil accumulation and activation at sites of infection or inflammation, and they are generally pro-inflammatory.
They activate a variety of cells, including neutrophils, keratinocytes, and non-lymphoid cells, to secrete other pro-inflammatory cytokines.
Representative Members and Functions:
- IL-17A: Induces proinflammatory cytokine expression, neutrophil recruitment, and antimicrobial peptide induction; promotes T-cell priming and antibody production (Secreted by TH17 cells, CD8+ T cells, etc.).
- IL-17B: Induces proinflammatory cytokine expression and neutrophil recruitment (Secreted by chondrocytes, neurons).
- IL-17C: Induces proinflammatory cytokine expression and neutrophil recruitment (Secreted by TH17 cells, DCs, macrophages, keratinocytes).
- IL-17D: Promotes proinflammatory cytokine production (Secreted by TH17 cells, B cells).
- IL-17E (IL-25): Induces TH2 and TH9 responses; suppresses TH1 and TH17 responses; promotes eosinophil recruitment (Secreted by TH17 cells, CD8+ T cells, mast cells, eosinophils, epithelial cells, endothelial cells).
- IL-17F: Critical for neutrophil recruitment and immunity to extracellular pathogens; induces proinflammatory cytokine expression (Secreted by TH17 cells, CD8+ T cells, $\gamma\delta$ T cells, NK cells, NKT cells, LTi-like cells, epithelial cells).

IL-17 Receptor-Ligand Structure

IL-17 cytokines: Typically exist as homodimers (e.g., IL-17A/A, IL-17F/F) or heterodimers (e.g., IL-17A/F).
IL-17 receptors: Can form diverse structures, including homodimers (e.g., IL-17RA/RA), heterodimers (e.g., IL-17RA/RC), or even heterotrimers, by combining five different receptor chains (IL-17RA, IL-17RB, IL-17RC, IL-17RD, IL-17RE).

Chemokines

Function: Chemokines are chemoattractant cytokines that guide immune cells, causing them to move towards increasing concentrations of the chemokine (following a gradient).
Chemotaxis: This directed cellular movement in response to chemical signals is called chemotaxis.
Structure: Chemokines contain conserved cysteine residues that form intrachain disulfide bonds, which are crucial for their tertiary structure and function.
Different chemokine families are defined by the number and spacing of these conserved cysteines, as well as surrounding amino acid residues.
During an immune response, chemokine receptor expression is often upregulated on T lymphocytes, facilitating their directed movement towards secondary lymphoid organs (for antigen encounter) and sites of infection.

Chemokine Signaling via G Protein-Coupled Receptors (GPCRs)

Chemokines signal through G protein-coupled receptors (GPCRs), which are serpentine receptors embedded in the cell membrane.
Inactive State: In the absence of a chemokine, the GPCR is associated with an inactive heterotrimeric G protein (composed of G $\alpha$ , G $\beta$ , and G $\gamma$ subunits), with GDP bound to the G $\alpha$ subunit.
Chemokine Binding: When a chemokine binds to the GPCR, it induces a conformational change in the receptor.
Activation: The activated GPCR then catalyzes the exchange of GDP for GTP on the G $\alpha$ subunit, leading to the dissociation of the G $\alpha$ -GTP complex from the G $\beta\gamma$ dimer.
Downstream Signaling: Both the G $\alpha$ -GTP and G $\beta\gamma$ subunits become active and can interact with various intracellular effector proteins (e.g., adenylyl cyclase, phosphoinositide 3-kinase, phospholipase C), initiating diverse downstream signaling cascades (e.g., changes in cAMP levels, activation of kinases).
Physiological Responses: This intracellular signaling ultimately triggers a range of physiological responses, including chemotaxis, cell survival, apoptosis, and changes in gene transcription.

Signaling in Immune Cells - General Principles

Ligand binding to a receptor typically induces a conformational change in the receptor structure.
This conformational change triggers a cascade of intracellular signals, often culminating in changes in gene expression and the synthesis of new proteins.
Many of these signaling pathways share similarities with those observed in other cellular systems that utilize receptor tyrosine kinases (RTKs).

JAK-STAT Pathway

This pathway is critically utilized by receptors for Class 1 and Class 2 cytokines, including various interleukins, interferons, and some growth factors.
Mechanism:
1. Ligand Binding and Receptor Dimerization: The binding of a cytokine ligand induces the dimerization (or oligomerization) of its receptor.
2. JAK Activation: Janus kinases (JAKs), which are constitutively associated with the cytoplasmic tails of the receptor subunits, become activated upon receptor dimerization.
3. Tyrosine Phosphorylation: Activated JAKs then phosphorylate specific tyrosine residues on the cytoplasmic domains of the receptor subunits.
4. STAT Docking: These phosphorylated tyrosine residues serve as docking sites for STAT (Signal Transducer and Activator of Transcription) proteins, which contain SH2 domains.
5. STAT Phosphorylation: The recruited STAT proteins are subsequently phosphorylated by the activated JAKs.
6. STAT Dimerization: Phosphorylated STATs then dimerize, forming an active transcription factor complex.
7. Nuclear Translocation: These dimeric STAT complexes translocate from the cytoplasm into the nucleus.
8. Gene Activation: In the nucleus, STAT dimers bind to specific DNA sequences in gene promoters, thereby activating gene expression.

Lipid Rafts in Signaling

Definition: Lipid rafts are specialized, dynamic microdomains within the plasma membrane that are enriched in cholesterol and sphingolipids.
Function: They serve as platforms for organizing and concentrating specific signaling proteins.
Example: The tyrosine kinase Lyn, a member of the Src family, is often associated with lipid rafts.
Role in BCR Signaling: Antigen binding to the B cell receptor induces its oligomerization and increases its affinity for these lipid rafts.
This movement of the BCR into the raft brings it into close proximity with raft-associated kinases like Lyn.
Lyn then phosphorylates critical tyrosine residues on the ITAMs of the BCR complex, thereby activating the downstream signaling cascade.
Similar mechanisms involving lipid rafts are also observed in T cell receptor (TCR) signaling.

Src Family Tyrosine Kinases

Description: The Src family comprises small, non-receptor tyrosine kinases that are fundamental regulators of intracellular signaling in immune cells.
Key Members: Important examples include Lyn in B cells and Lck in T cells.
Activity Regulation: The activity of Src family kinases is rigorously controlled by phosphorylation at specific tyrosine residues:
- Inhibitory Phosphorylation: Phosphorylation at a C-terminal inhibitory tyrosine residue keeps the kinase in an inactive (OFF) state.
- Activating Phosphorylation: Dephosphorylation of the inhibitory site and concomitant phosphorylation at an activating tyrosine residue within the kinase's activation loop switches the kinase to an active (ON) state.
Example: Csk (C-terminal Src kinase) phosphorylates Lyn at tyrosine residue $Y508$ , maintaining Lyn in an inactive state.

Adapter Proteins and Downstream Signaling Cascades

Adapter proteins: These are non-enzymatic proteins that lack intrinsic enzymatic activity but are crucial for assembling larger signaling complexes by providing multiple docking sites for other signaling molecules.
Key downstream pathways initiated by ITAM phosphorylation:
- Phospholipase C $\gamma$ (PLC $\gamma$ ) Activation: Activated PLC $\gamma$ hydrolyzes $PIP_2$ (phosphatidylinositol 4,5-bisphosphate) into two secondary messengers: DAG (diacylglycerol) and IP3 (inositol 1,4,5-trisphosphate).
  - DAG: Stays in the membrane and activates PKC (Protein Kinase C), leading to diverse cellular responses.
  - IP3: Diffuses into the cytoplasm and triggers an increase in intracellular $Ca^{2+}$ by promoting its release from endoplasmic reticulum stores.
    - $Ca^{2+}$ binding to calmodulin: Activates the phosphatase calcineurin.
    - Calcineurin: Dephosphorylates NFAT (Nuclear Factor of Activated T cells).
    - NFAT: Upon dephosphorylation, NFAT translocates into the nucleus and activates specific genes involved in immune responses.
- SOS binding to Ras: Activates the small GTPase Ras.
  - Ras activation: Initiates the MAPK (Mitogen-Activated Protein Kinase) cascade (e.g., Raf $\to$ MEK $\to$ ERK).
  - ERK phosphorylation of AP-1: ERK (Extracellular signal-Regulated Kinase) phosphorylates and activates the transcription factor AP-1.
  - AP-1: Activates gene expression, particularly for genes involved in cell proliferation and differentiation.

Outcomes of Antigen Recognition

Up-regulation of proteins: Antigen recognition leads to the increased expression of various proteins, such as chemokines and chemokine receptors.
- This is important for guiding dendritic cells to tissues and lymph nodes, where they can process and present antigens to T cells.
Activation of innate cells: Triggers rapid responses, including the oxidative burst in phagocytic cells like neutrophils and macrophages, which generates reactive oxygen species to kill pathogens.
In many cases, the robust activation of innate cells may be sufficient to eliminate pathogens without the need for an adaptive immune response.
Cytokine-mediated inflammation: Cytokines released upon antigen recognition increase vasodilation and enhance the movement of immune cells and fluid into tissues (capillary leakage).
These processes—vasodilation, capillary leakage, cytokine secretion, and cellular infiltration—collectively characterize inflammation, which manifests as heat, redness, swelling, and pain.
Inflammation: Represents a crucial local innate immune response that recruits essential immune cells to the site of infection or injury.
Adaptive Cell Activation and Survival: Activation by antigen significantly increases the survival and extends the half-life of B and T cells (often through pathways like the PI3K/Akt pathway, which promotes cell survival).
Proliferation and Differentiation: Antigen recognition also stimulates the robust proliferation (clonal expansion) and subsequent differentiation of B and T cells into effector cells (which perform immune functions) and long-lived memory cells.