3 - Introducción a la inmunidad adaptativa

Introduction to Adaptive Immunity

In this section, the speaker introduces the concept of adaptive immunity as the second pillar of the immune system, contrasting it with innate immunity. The discussion highlights key differences in response times and efficiency between innate and adaptive immunity.

Adaptive vs. Innate Immunity

• Adaptive and innate immunity are interconnected in various stages of the immune response, influencing each other.

• Innate immunity provides a rapid response upon pathogen detection, while adaptive immunity takes several days to mount a response but is more versatile and efficient once initiated.

• Adaptive immunity can eliminate pathogens that evade innate immune responses due to its enhanced efficiency.

• Adaptive immunity generates immunological memory, leading to faster and more effective responses upon subsequent encounters with the same pathogen.

Recognition Strategies

• Innate immunity relies on pattern recognition receptors to detect pathogen-associated molecular patterns (PAMPs), allowing broad recognition across various pathogens.

• Adaptive immunity utilizes antigen-specific receptors like T cell receptors (TCR) and B cell receptors (BCR), which provide specificity but limit recognition diversity compared to innate immunity.

Receptor Specificity

• Cells of innate immunity express diverse pattern recognition receptors for broad pathogen recognition, expanding their scope.

• Lymphocytes in adaptive immunity express unique antigen-specific receptors that recognize a limited range of antigens but collectively form a diverse repertoire for comprehensive antigen recognition.

Antigen Recognition by B Cells

This segment delves into how B cells recognize antigens through their B cell receptors (BCRs), emphasizing the ability of BCRs to identify antigens in their native conformations.

B Cell Receptor Functionality

• BCR can recognize antigens in their native conformations, enabling them to identify specific regions within folded proteins for targeted immune responses.

Antigen Recognition Mechanism

Understanding Antigen Recognition

In this section, the discussion revolves around the variable portion of B-cell receptors (BCRs) known as epitopes. It delves into how antigens are recognized by BCRs and T-cell receptors (TCRs), emphasizing the distinction between linear and conformational epitopes.

Epitope Recognition

• The variable portion of BCR is termed an epitope, which is the part of the antigen recognized by the anti-hygienic receptor.

• Antigens are linear in nature, consisting of sequential amino acids that T-cells recognize after processing into peptides.

• Peptides derived from antigens are crucial for recognition by TCRs within the context of histocompatibility molecules.

• Conformational epitopes present in native proteins can only be recognized by BCRs, characterized by specific arrangements of amino acids.

• Linear epitopes consist of adjacent amino acids in a protein's primary structure, recognizable by both BCRs and TCRs.

Initiation of Adaptive Immune Response

This segment explores the activation and differentiation processes common to adaptive immune responses. It highlights effector cells' role in combating pathogens and memory cells' significance for rapid and efficient future responses.

Adaptive Immune Response Steps

• Upon antigen recognition by T-cells or B-cells, adaptive immune cells undergo activation, proliferation, and differentiation.

• Differentiation leads to effector cell formation responsible for pathogen elimination and memory cell generation for enhanced future responses.

Initiation of Adaptive Immune Response in Lymphoid Organs

The discussion focuses on how adaptive immune responses commence specifically within secondary lymphoid organs. It elaborates on antigen transport via lymphatic vessels to lymph nodes for initiating immune reactions.

Initiation in Lymphoid Organs

• Adaptive immune responses always initiate within secondary lymphoid organs despite infections occurring elsewhere in the body.

• Antigens reach lymph nodes through lymphatic vessels directly or via dendritic cells that process them before transporting to secondary lymphoid organs.

Role of Dendritic Cells in Immune Response Initiation

Dendritic cells play a pivotal role as intermediaries between innate and adaptive immunity. Their ability to detect pathogens due to extensive surface coverage initiates adaptive immune responses effectively.

Dendritic Cell Functionality

• Dendritic cells act as bridges between innate and adaptive immunity, facilitating pathogen detection from infected tissues to secondary lymphoid organs.

• Immunofluorescence images depict dendritic cell distribution with their distinctive extensions aiding broad tissue surveillance for pathogen detection.

Detailed Overview of Immune System Processes

In this section, the lecturer discusses various receptors and mechanisms involved in the immune system's response to pathogens.

Receptors Involved in Immune Response

• The lecture delves into the role of different receptors in recognizing pathogens and antigens.

• It highlights how cells utilize receptors like lectin types to identify carbohydrates present in microorganisms.

• The discussion extends to receptors for oxidized lipoproteins, emphasizing their role in antigen internalization by dendritic cells.

Antigen Internalization Mechanisms

• The process of macro pinocytosis by dendritic cells is explained as a receptor-independent mechanism for antigen internalization.

• Dendritic cells are equipped with an array of receptors facilitating the uptake of various pathogens and proteins from extracellular spaces through processes like phagocytosis.

Migration and Activation of Dendritic Cells

This segment focuses on how dendritic cells capture, process, and transport antigens to lymphoid organs for immune activation.

Antigen Processing and Migration

• Dendritic cells recognize pathogens through receptor-mediated or receptor-independent mechanisms before processing them within tissues.

• After capturing antigens, dendritic cells migrate via afferent lymphatic vessels to secondary lymphoid organs for further maturation.

Dendritic Cell Maturation States

• The lecture distinguishes between immature dendritic cells located peripherally and mature ones found in secondary lymphoid organs based on their functions and characteristics.

• Immature dendritic cells exhibit high antigen-processing capabilities but low histocompatibility molecule expression, crucial for detecting microorganisms effectively.

Dendritic Cell Maturation Process

This part elucidates the transition of dendritic cells from an immature to a mature state upon encountering pathogens.

Maturation Signaling Pathways

• Upon pathogen recognition, dendritic cell maturation is triggered, enhancing antigen presentation capacity while upregulating key molecules like chemokine receptor 7 (CCR7).

Understanding Immune Response Activation

This section delves into the process of immune response activation, focusing on the maturation of dendritic cells and the initiation of adaptive immune responses.

Dendritic Cell Maturation and Antigen Recognition

• Dendritic cells mature in tissues upon recognizing antigens they have previously encountered.

• Immature dendritic cells in tissues recognize antigens, mature, and transport them to secondary lymphoid organs for adaptive immune response initiation.

• Antigens reach secondary lymphoid organs via lymphatic vessels, while naive lymphocytes enter these organs through the bloodstream.

• Lymphocytes exit secondary lymphoid organs via the thoracic duct to enter venous circulation.

Lymphocyte Trafficking and Endothelial Interactions

• Lymphocyte extravasation into secondary lymphoid organs occurs through high endothelial venules expressing adhesion molecules.

• High endothelial venules contain specific adhesion molecules that interact with corresponding ligands on lymphocytes for cell recruitment.

Cellular Interactions in Adaptive Immunity

This section explores cellular interactions crucial for initiating adaptive immune responses, focusing on adhesion molecule interactions between endothelial cells and lymphocytes.

Adhesion Molecule Interactions

• Endothelial cells express adhesion molecules that bind to ligands on naive T cells, facilitating their migration into secondary lymphoid organs.

• Initial interaction between L-selectin on T cells and HLA molecules on high endothelial venules initiates T cell homing to secondary lymphoid organs.

Activation of Dendritic Cells and T Cells

This segment discusses the activation process of dendritic cells within secondary lymphoid organs leading to T cell activation and differentiation.

Activation Mechanisms

• Rolling motion of T cells over endothelium is followed by integrin conformational changes promoting stable adhesion via ICAM1 binding.

• Chemokine recognition by T cells induces integrin conformational changes facilitating firm adhesion through ICAM1 interaction.

Antigen Presentation and T Cell Activation

The focus here is on antigen presentation by dendritic cells leading to T cell activation within secondary lymphoid organs.

Antigen Recognition

• Mature dendritic cells carrying processed antigens migrate to secondary lymphoid organs attracting naive T cells for activation.

Understanding Lymph Node Structures and Antigen Recognition

In this section, the discussion revolves around the fibrous conduits in the cortical area of lymph nodes that facilitate interactions between dendritic cells, T cells, and antigens.

Fibrous Conduits in Lymph Nodes

• Fibrous conduits in the cortical area of lymph nodes are formed by stromal cell structures.

• These conduits allow dendritic cells to be supported by them and enable T cells to navigate through them.

Function of Fibrous Conduits

• The conduits serve as structures in secondary lymph nodes facilitating interactions between dendritic cells and naive T cells.

• Both dendritic cells and T cells rely on these conduits for support during their movement within the lymph node.

Antigen Recognition Mechanism

• Chemokines present on the surface of fibrous reticular conduits guide dendritic cells and T cells to encounter each other.

• The T cell receptor (TCR) recognizes antigens presented by dendritic cells through its variable region, initiating signal transduction for T cell activation.

Molecular Basis of Antigen Presentation

This segment delves into the processing of antigens by dendritic cells, loading onto MHC molecules, and subsequent recognition by T cell receptors.

Antigen Processing and Presentation

• Antigens are processed by dendritic cells, generating peptides loaded onto MHC molecules for recognition.

• Interaction between peptide-loaded MHC molecules and TCR triggers intracellular signaling cascades essential for T cell activation.

Major Histocompatibility Complex (MHC) Class I vs. Class II

• MHC class I molecules consist of alpha chains with three domains along with a beta2 microglobulin, while MHC class II molecules have alpha and beta chains.

Peptide Binding to MHC Molecules

• Peptides interact with specific residues on MHC molecules' binding grooves, determining which peptides can bind based on structural compatibility.

Functional Role of Histocompatibility Molecules

This part elucidates how histocompatibility molecules bind processed peptides for immune response efficiency.

Peptide Binding Specificity

• Histocompatibility molecules bind processed peptides derived from protein processing to expose them on cell surfaces for recognition by T lymphocytes.

Affinity Impact on Immune Response

• Varying affinities between peptides and MHC molecules influence immune response efficiency; higher affinity enhances response effectiveness against pathogens.

Indispensable Factors for Effective Signaling in Immunology

The discussion delves into the crucial role of T cells in effective signaling through the TCR. It highlights how CD4+ T cells recognize MHC class 2 molecules, while CD8+ T cells identify MHC class 1 molecules.

Factors Affecting Immune Response

• The MHC determines the peptides presented to T cells, influencing the immune response. Individuals capable of presenting a wide range of peptides tend to generate stronger responses.

• Evolutionary strategies such as polymorphism and co-dominance increase the expression of MHC molecules in populations, enhancing antigen presentation diversity.

• Each individual possesses multiple genes for MHC molecules (e.g., HLA-DR, HLA-DP, HLA-DQ for class 2), contributing to immune system variability and adaptability.

Genetic Diversity and Immune System Functionality

This segment explores the genetic complexity within the human major histocompatibility complex (MHC), emphasizing its impact on immune function and pathogen elimination.

Genetic Variability in MHC

• The human MHC region encodes various genes responsible for both classical class 2 (HLA-DP, HLA-DQ) and class 1 (HLA-A, HLA-B, HLA-C) molecules, enabling diverse antigen presentation capabilities.

• Higher MHC molecule diversity correlates with increased antigen presentation capacity to T cells, enhancing pathogen clearance efficiency within individuals.

Population-Level Polymorphism and Allelic Variants

Discusses population-level genetic variation impacting immune responses through polymorphism and allelic diversity within MHC genes.

Polymorphism Impact on Antigen Presentation

• Thousands of allelic variants exist for both class 1 and class 2 MHC molecules across populations due to polymorphic characteristics.

• Individual heterozygosity allows for dual allelic expression per gene due to co-dominance, leading to extensive antigen presentation possibilities within individuals.

Inheritance Patterns and Genetic Combinations

Explores inheritance patterns affecting allele combinations and their implications on immune system functionality through genetic diversity.

Inheritance Dynamics

• Polymorphism predominantly manifests in the peptide-binding groove regions of both class 1 (alpha chains) and class 2 (beta chains), influencing antigen recognition specificity.

Heritage of Histocompatibility Molecules

In this section, the discussion revolves around the inheritance of histocompatibility molecules and its significance in transplantation.

Understanding Inheritance Variants

• Four electric variants exist, two from each parent, with distinct options crucial for understanding histocompatibility molecule inheritance.

Implications on Transplantation

• Difficulty in finding donors for transplants stems from these variations, a topic to be explored further towards the course's end.

Genetic Diversity and Expression

This part delves into genetic diversity impacting molecule expression and inheritance patterns.

Impact on Descendants

• Genetic diversity influences offspring possibilities in MTC inheritance, highlighting individual and population-based polymorphisms.

Role of Polymorphism

• Polymorphism dictates diverse molecule expressions within individuals, showcasing how multiple genes contribute to compatibility variations.

Gene Copy Numbers and Compatibility

Exploring gene copies' role in determining histocompatibility molecule diversity.

Gene Multiplicity Effects

• Presence of three genes per molecule type leads to multiple compatibility types due to polymorphism effects.

Combining Polymorphisms and Heterozygosity

Discussing the impact of combining polymorphisms and heterozygosity on histocompatibility molecules.

Diverse Variant Combinations

• Interaction between polymorphisms and heterozygosity results in six different compatibility variants when an individual is heterozygous for various alleles.

Cellular Expression of Histocompatibility Molecules

Examining cellular expression patterns of histocompatibility molecules across different cell types.

Cellular Distribution

• Histocompatibility molecules are expressed by most body cells except erythrocytes, with professional antigen-presenting cells like dendritic cells playing a key role.

Antigen Presentation Pathways

Delving into pathways through which antigens are presented by specialized cells.

Antigen Presentation Cells

Understanding Antigen Processing and Presentation

In this section, the process of antigen processing and presentation is discussed, focusing on how antigens are processed into peptides by the soma complex in the cytosol and then presented on the cell surface through interactions with class 1 histocompatibility molecules.

Antigen Processing in the Cytosol

• The antigen is processed into peptides by the soma complex present in the cytosol.

• These peptides generated in the cytosol need to access the endoplasmic reticulum for further processing.

• Interaction with class 1 histocompatibility molecules occurs within the endoplasmic reticulum.

Peptide Generation and Transport

• Peptides generated from antigens in the cytosol are transported to the endoplasmic reticulum via a process mediated by a receptor called TAP.

• Once inside the endoplasmic reticulum, these peptides interact with class 1 histocompatibility molecules for further processing.

Histocompatibility Molecules Interaction

• Class 1 histocompatibility molecules get loaded with peptides inside the endoplasmic reticulum.

• Loaded class 1 histocompatibility molecules travel to the cell surface for presentation.

Antigen Presentation Pathways

This section delves into different pathways of antigen presentation, including endogenous and exogenous pathways, highlighting how antigens are processed differently based on their origin and subsequent loading onto histocompatibility molecules.

Endogenous Antigen Processing

• Antigens originating intracellularly undergo processing within early or late endosomes.

• Late endosomes contain numerous active proteases that degrade antigens into peptides.

Exogenous Antigen Processing

• Extracellular antigens are internalized and processed through early endosomes before maturing into late endosomes where proteases generate peptides.

Loading onto Histocompatibility Molecules

• Peptides generated within late endosomes are loaded onto class 2 histocompatibility molecules.

Understanding Antigen Processing and Presentation

In this section, the process of antigen processing and presentation is discussed, focusing on how antigens are processed within cells and presented to the immune system.

Antigen Processing Mechanism

• The antigen phage initially resides in a famous Mao but escapes into the cytosol, where it is processed by the proteome to generate peptides that follow a biosynthetic pathway. This distinguishes between synthetic life and natural life.

Cross-Presentation of Antigens

• In cross-presentation, the protein is originally located in the cytosol in biosynthetic pathways. Contrarily, in cross-presentation, the protein starts in a phagosome and needs to escape into the cytosol before being processed by proteases.

Role of Autophagy

• Autophagy plays a crucial role in antigen cross-presentation. It is a cellular process used for recycling nutrients or degrading damaged organelles. In this context, an antigen initially present in the cytosol can be engulfed by autophagosomes through a series of processes involving membrane structures derived from the endoplasmic reticulum.

Formation of Autophagosomes

• The antigen originally loose in the cytosol can be enclosed within one or more autophagosomes – membrane structures originating from the endoplasmic reticulum but enclosing a portion of the cytosol. This encapsulation leads to degradation processes within lysosomes upon fusion with endosomes or lysosomes.

Proteasomal Degradation Process