Ativação de Linfócitos | IMUNOLOGIA (Vídeo 8)

Introduction to Lymphocyte Activation

Overview of the Course

• The course on immunology continues, focusing on T and B lymphocyte activation.

• This is the penultimate lesson in basic immunology, with the next session covering effector mechanisms of immunity.

Key Concepts in Lymphocyte Activation

• The activation of T lymphocytes requires two signals: one from an antigen presented by an antigen-presenting cell (APC), such as a dendritic cell, via MHC.

• A co-stimulatory signal is also necessary for full activation; this occurs in lymph nodes where APCs present antigens to T cells.

Cytokine Secretion and Clonal Expansion

Initial Response to Antigen Recognition

• Upon recognizing an antigen, activated T cells secrete IL-2 cytokine, leading to clonal expansion.

• The type of infection influences which profile of T cells gets activated based on environmental cytokines during clonal expansion.

Profiles of Helper T Cells

TH1 vs. TH2 Profiles

• Two main profiles are TH1 and TH2; their activation depends on the immune context and cytokines present.

• TH1 cells focus on combating bacteria and viruses with inflammatory responses, while TH2 cells target parasites and allergens.

Mechanism Behind TH1 Activation

Dendritic Cell Role in Infection Response

• Dendritic cells recognize pathogens like viruses or bacteria and transport processed antigens to lymph nodes for presentation.

• During this process, dendritic cells secrete IL-12 when recognizing specific infections, guiding T cell differentiation towards the TH1 profile.

Cytokine Functions in Immune Response

Key Cytokines Secreted by TH1 Cells

• Activated TH1 cells primarily secrete TNF-alpha, interferon-gamma (IFN-gamma), and IL-2 to enhance immune response against infections.

• TNF-alpha activates macrophages while IFN-gamma prolongs their activity against pathogens.

Interactions Between Cytokines and B Cells

Impact on Antibody Production

• IFN-gamma promotes class switching in B cells towards IgG3 antibodies that effectively opsonize pathogens.

Recruitment of Immune Elements

Comprehensive Immune Strategy

• The actions of TH1 cytokines recruit both innate and adaptive immune elements for effective bacterial and viral combat.

Transitioning to TH2 Profile

Shift in Immune Focus

• In cases involving parasites or intestinal pathogens, dendritic cells activate a different response through IL4 secretion promoting a shift toward the TH2 profile.

Characteristics of TH2 Activation

Unique Features of IL4

• Unlike previous profiles, initial IL4 production's source remains unknown but is crucial for activating more TH2 lymphocytes once initiated.

Additional Cytokines from TH2 Cells

Role of Other Cytokines

• IL5 stimulates B cell production of IgA antibodies effective against gastrointestinal bacteria.

• IL13 enhances mucus production as a physical barrier against pathogen invasion.

Overview of T Lymphocyte Activation Process

Requirements for Successful Activation

• Successful activation occurs within secondary lymphoid organs like lymph nodes requiring:

• Antigen recognition via MHC-TCR interaction,

• Co-stimulation through CD28 binding with B7 molecules (CD80/CD86).

Formation of Immunological Synapse

Mechanisms Leading to Proliferation

• An immunological synapse forms during activation allowing proliferation into effector or memory T cells post-infection resolution.

Self-Antigen Recognition Prevention

Mechanisms Preventing Autoimmunity

• Self-reactive lymphocytes are typically eliminated during maturation; if they mistakenly recognize self-antigens without co-stimulation they enter anergy state preventing autoimmunity.

Downregulation Post-Infection

CTLA4 Functionality

• As infection resolves , CTLA4 expression increases inhibiting further activation signals thus reducing immune response intensity.

Migration Towards Infection Site

Final Steps in Immune Action

• Once at the infection site , activated T-cells can act independently without needing additional co-stimulatory signals from APC’s .

Transitioning to B Lymphocyte Activation

Overview Of B Cell Functionality

• Naïve B-cells express IgM/IgD antibodies; upon antigen recognition they undergo clonal expansion transforming into plasma cells secreting antibodies.

Types Of Antigens Affecting B Cell Responses

Timodependent vs Timoindependent Antigens

• Protein antigens require helper T-cell involvement (timodependent).

• Non-protein antigens can activate directly without helper involvement (timoindependent).

Cross-Linking Requirement For Activation

Mechanism Behind Timoindependent Antigen Recognition

• Multiple antibody bindings required for cross-linking non-protein antigens triggering second signal via other receptors like toll-like receptors or complement receptors.

Conclusion & Next Steps

Summary And Future Lessons

This session concludes discussions on lymphocyte activation; upcoming lessons will cover effector mechanisms within immunity.