Inmunidad contra virus y bacterias

Immunology Class: Understanding Immune Responses

Introduction to Immune Responses

• The class focuses on the interplay between adaptive and innate immunity against viruses and bacteria.

Natural Barriers Against Bacterial Invasion

• The human body is protected by natural barriers such as skin and mucous membranes, which prevent bacterial adhesion to deeper tissues.

• Skin shedding removes bacteria from its surface, while factors like sweat acidity and sebum help inhibit bacterial attachment.

Role of Normal Microbiota

• Normal microbiota in respiratory, digestive, and urogenital tracts compete with pathogens for adhesion sites, preventing infections.

• For instance, vaginal microbiota can lower pH levels to create an inhospitable environment for harmful microorganisms.

Immune Response Activation

• When natural barriers are breached, non-specific immune responses (e.g., fever, inflammation) are activated initially before specific immune responses (e.g., antibodies, T lymphocytes) come into play.

• Various immune cells such as dendritic cells, macrophages, B1 lymphocytes, neutrophils, and natural killer cells patrol tissues for pathogens.

Recognition of Pathogen-associated Molecular Patterns (PAMPs)

• Damaged epithelial or endothelial cells release signals recognized by immune cells that trigger a response against PAMPs found on pathogens like bacteria.

• These include structures unique to bacteria such as flagella and lipopolysaccharides that activate immune cell receptors leading to cytokine production and inflammation.

Cytokine Production and Inflammatory Response

• Activated immune cells produce various cytokines (e.g., TNF-alpha) that initiate local inflammatory responses essential for fighting infections. This includes regulating temperature through the hypothalamus in the brain.

Activation of the Complement System

Mechanisms of Activation

• The complement system is activated through various pathways, notably by lipopolysaccharides and teichoic acid from Gram-positive bacteria. This activation occurs via the alternative pathway, which is one of three pathways for complement activation: classical, alternative, and lectin.

Fragmentation of C3

• Upon activation, C3 is cleaved into fragments C3a, C3b, and C3d. The fragment C3d binds to bacterial surfaces and serves two primary functions: opsonization to enhance phagocytosis by immune cells and activating further components in the complement cascade.

Role of C5 in Immune Response

• The activated form of C5 (C5b) also attaches to cell surfaces, recruiting additional complement proteins to form the membrane attack complex (MAC), leading to pore formation and subsequent lysis of bacteria. Additionally, C3d activates a specific type of B lymphocyte found in mucosal tissues that produces antibodies against polysaccharide capsules on bacteria.

Chemotactic Functions of Complement Fragments

• Other fragments like C3a and C5a have chemotactic properties that attract neutrophils and other phagocytic cells to sites of bacterial replication. These fragments also act as anaphylatoxins causing vasodilation and increased vascular permeability, facilitating immune cell migration from circulation into affected tissues.

Inflammatory Response Mechanisms

Formation of Inflammasome

• The accumulation of immune products at infection sites leads to inflammasome formation, which releases cytokines such as IL-1β and IL-6 that trigger acute phase responses characterized by fever and systemic inflammation. This response includes increased production of reactive proteins from blood vessels as well as coagulation factors like factor XII.

Clinical Symptoms of Inflammation

• Acute inflammation manifests clinically with symptoms including redness (rubor), heat (calor), swelling (tumor), pain (dolor), due to capillary dilation and increased permeability caused by inflammatory mediators acting on endothelial cells. These changes compress nerve endings contributing to pain perception during inflammation episodes.

Role of Neutrophils in Infection Control

Enzymatic Activation During Inflammation

• Neutrophils play a crucial role in inflammation through the activation of intracellular enzymes such as lipoxygenase and cyclooxygenase that produce prostaglandins from arachidonic acid present in cell membranes; these compounds are vital for sustaining inflammatory processes.

Recruitment Mechanisms for Phagocytes

• Chemotactic agents including complement fragments (C3a, C5a) along with bacterial-derived signals guide phagocytes like neutrophils towards injury sites through mechanisms involving vasodilation allowing their exit from circulation into inflamed tissues for effective pathogen clearance.

Phagocytosis Process Overview

Mechanism Behind Phagocytosis

• Phagocytosis involves binding bacteria via receptors for complement fragment C3b or lectins that recognize sugars on microbial surfaces; this facilitates engulfment leading to destruction within lysosomes containing hydrolytic enzymes essential for degrading pathogens effectively without harming host tissue integrity.

Oxygen-dependent vs Oxygen-independent Killing

Immune Response Mechanisms

Antigen Presentation and T Cell Activation

• Specific responses are initiated through antigen presentation involving CD4 and CD8 lymphocytes. Phagocytic cells degrade pathogens into peptides that travel to lymph nodes, where they interact with naive T helper cells (Th0).

• The cytokine environment influences Th0 differentiation. For instance, transforming growth factor-beta (TGF-β) can convert Th0 into Th17 cells, which produce interleukins crucial for antibacterial defense.

Role of Th17 Cells in Defense

• Th17 cells primarily secrete interleukin 17 (IL-17), IL-21, and IL-22, leading to the production of antimicrobial peptides like defensins and cathelicidins that disrupt bacterial membranes.

• These cationic peptides bind to negatively charged bacterial cell walls, forming pores that result in bacterial lysis. This response enhances neutrophil production and activates epithelial cells to release prostaglandins, initiating inflammation.

Differentiation of T Helper Cells

• Dendritic cells producing interleukin 12 (IL-12) can drive the transformation of naive T cells into Th1 cells. These Th1 cells activate transcription factors for genes coding for IL-2 and interferon-gamma (IFN-γ).

• IFN-γ is pivotal in activating dendritic and macrophage cells while also stimulating B cell activity. Importantly, it enhances cytotoxic activity against intracellular bacteria by promoting the formation of epithelioid macrophages around pathogens like Mycobacterium tuberculosis.

Memory Responses and Regulation

• Interleukin 23 (IL-23) plays a role in stimulating memory Th1 lymphocytes. If antigen-presenting cells produce both IL-12 and IL-4, this leads to a shift towards a Th2 response characterized by increased production of various interleukins.

• In a Th2 response, antibodies neutralize toxins from bacteria rather than directly destroying them. They also activate complement pathways and opsonize bacteria for easier phagocytosis by immune cells.

Antiviral Responses

• During viral infections, type I interferons (IFN-alpha and IFN-beta), produced by infected nucleated or epithelial cells, protect neighboring uninfected cells from viral replication.

• Natural Killer (NK) cells recognize infected host cell proteins on their surface; they induce apoptosis in these compromised cells as part of the innate immune response against viruses.

Understanding Antiviral Responses

Role of Infected Cells and Antibody Formation

• Infected cells play a crucial role in antiviral responses, particularly through the stimulation of lymphocytes that lead to antibody formation. This process acts as a final line of defense after innate mechanisms are activated.

Mechanisms of Viral Neutralization

• Key antiviral mechanisms include interferons, natural killer (NK) cells, CD4+ T helper type 1 (Th1) responses, cytotoxic T lymphocytes, and antibodies. These components work together to neutralize viral particles effectively.

Fever as an Antiviral Defense

• Upon viral infection, mucosal cells respond by producing interleukin-1 (IL-1), which is responsible for inducing fever. Fever serves as an important antiviral defense mechanism since many viruses replicate poorly at elevated body temperatures.

Interferon Production and Function

• Interferons are critical in the body's response to viral infections. They act when a virus enters a cell, leading to the production of double-stranded RNA (dsRNA), which triggers interferon synthesis.

Mechanism of Action for Interferons

• When dsRNA is produced during viral replication within an infected cell, it activates transcription factors that lead to the production of interferons alpha and beta. These proteins are secreted and taken up by neighboring cells to enhance their antiviral defenses.

Types of Interferons and Their Sources

• There are three types of interferons:

• Type I includes alpha (produced by B lymphocytes, epithelial cells, monocytes, macrophages, and immature dendritic cells) and beta (produced mainly by fibroblasts).

• Type II is gamma interferon produced by activated T lymphocytes.

• Type III includes lambda interferon produced by epithelial and endothelial cells.

Interferon's Role in Neighboring Cells

• Once secreted into neighboring uninfected cells, interferons prevent viral entry and replication by inhibiting protein synthesis necessary for forming new virions.

Induction of Apoptosis in Infected Cells

• If antiviral mechanisms fail within an infected cell, interferon can trigger apoptosis—programmed cell death—to eliminate the cellular machinery required for virus replication.

Summary on Interferon Activation Triggers

• The presence of dsRNA from viral replication stimulates the production of interferons. This process involves copying viral RNA into complementary strands that serve as templates for further genetic material generation.

Mechanisms of Viral Defense and Immune Response

Role of Interferons in Immune Response

• Interferons signal the nucleus to produce two crucial proteins: one that prevents the formation of prison-like proteins, and another that activates RNA enzymes capable of destroying viral mRNA.

• Type 1 interferons assist natural killer (NK) cells and CD8 T lymphocytes in destroying infected cells, enhancing their ability to combat viral infections.

Antigen Presentation and T Cell Activation

• Interferons increase the expression of major histocompatibility complex (MHC) molecules on infected nucleated cells, facilitating antigen presentation to CD4 T lymphocytes for an effective immune response.

• Antibodies formed from activated lymphocytes recognize epitopes on viral capsid proteins, blocking their binding to cellular receptors and preventing infection.

Phagocytosis and Viral Clearance

• Infected cells degrade capsid proteins into peptides that are transported into the endoplasmic reticulum, where they bind to MHC class I molecules for presentation.

• Once presented on the cell surface, CD8 T lymphocytes recognize these peptide-MHC complexes via their specific receptors, leading to activation.

Cytotoxic Activity of CD8 T Lymphocytes

• Activated CD8 T lymphocytes produce perforins that lyse infected cells and release granzymes inducing apoptosis in those cells.

• This cytotoxic mechanism is critical when viruses evade extracellular defenses like antibodies by establishing persistent infections.

Memory Cells and Secondary Immune Response

• Upon re-exposure to a virus, memory cells rapidly activate without needing extensive activation mechanisms, quickly producing neutralizing antibodies against the virus.