Immunology: Immune Cell Recruitment

Global Recognition System

• Pattern recognition receptors (PRRs) function to identify pathogens globally.
• PRRs do not trigger responses to self, reflecting a healthy immune state.
• Essential for initiating the adaptive immune response through interactive mechanisms.

Immune Cell Recruitment and Trafficking

• Leukocytes exit the bloodstream to reach infection sites via a stepwise process.
• Infection detection leads to resident cells producing cytokines and chemokines.
• Cytokines promote adhesion molecules (E- and P-selectin) on endothelial cells.
• Leukocytes express selectin ligands, enabling initial adhesion to endothelial cells.
• Endothelial cells display chemokines on proteoglycans for leukocyte attraction.
• Leukocytes transition integrins (LFA-1, VFA-4) from low to high affinity states.
• This results in stronger interactions, leading to leukocyte arrest and migration through endothelial junctions.
• Cells navigate toward tissue using chemokine gradients and complement fragments.

Adaptive Immune System

• Takes several days to initiate a response and is characterized by specificity and diversity.
• Requires activation of naïve T and B cells in secondary lymphoid tissue.
• Features include clonal expansion and immunological memory, developed through "education" to avoid autoimmunity.

Lymphoid Tissue

• Primary lymphoid organs include the bone marrow (B cell maturation) and thymus (T cell maturation).
• Secondary lymphoid organs consist of lymph nodes, spleen, and mucosa-associated tissues.

Lymphatic System

• Lymphatics are specialized vessels that facilitate fluid drainage and immune response.
• Antigen-presenting cells like dendritic cells transport antigens to lymph nodes via lymphatics.
• Free antigens also pool in lymph nodes and are processed by macrophages and dendritic cells.

Lymph Nodes

• Comprise distinct zones for B and T cells.
• Lymph enters through afferent lymphatic vessels while naïve lymphocytes migrate via high endothelial venules.

Naïve Lymphocytes

• Circulate continuously through secondary lymphoid tissues.
• Naïve T cells enter lymph nodes using high endothelial venules, influenced by selectin ligands and chemokines.

Antigens, Epitopes, and Peptides

• Antigens elicit immune responses and include proteins, lipids, and polysaccharides.
• Epitopes are specific regions on antigens recognized by lymphocyte receptors.
• Cognate T and B cells respond to the same antigen, with T cell receptors primarily recognizing proteins.

B Cells vs. T Cells

• B cells can detect free-floating antigens, while T cells recognize antigens presented by MHC.
• CD8 T cells (cytotoxic) kill infected cells via MHC-I, whereas CD4 T cells (helper) assist other immune cells through MHC-II.

MHC and T Cell Activation

• MHC-I presents intracellular peptides to CD8 T cells, activated to destroy infected cells.
• MHC-II presents extracellular peptides to CD4 T cells, aiding macrophages and B cells.
• Naïve T cells require signals from mature antigen-presenting cells for activation through MHC recognition and co-stimulatory signals.

Clonal Selection and Memory

• Diversity of T and B cells ensures a wide range of antigen recognition.
• Specific T or B cells proliferate upon pathogen encounter, leading to clonal expansion; some become memory cells for future attacks.

Microbial Disease

• Recognition of various causative agents and their links in the infectious disease chain.
• Understanding how disrupting any link can help control outbreaks.
• The evolution from Miasma theory to Germ theory, establishing the causative role of microbes in disease.

Infectious Disease Chain Principle

• Reservoirs of disease include inanimate objects, animals, and symptomatic or asymptomatic humans.
• Transmission occurs through direct contact and other means, influencing disease spread.

Microbial Virulence

• Virulence measures a microbe’s ability to cause disease, indicated by pathogenicity and mortality rates.
• Virulence factors enable microbial survival, spread, and evasion of host defenses.

Host Susceptibility

• Affected by factors such as age, socio-economic status, and immune status, impacting disease resistance.

Infectious Dose

• Successful infection involves both the initial microbial dose and host susceptibility.

Pattern Recognition Receptors (PRRs)

• Expressed by various cell types, essential for innate immune response.
• Located on cell surfaces, endosomes, and cytoplasm, with five primary families: TLRs, CLRs, NLRs, RLRs, and CDSs.

Pathogen Associated Molecular Patterns (PAMPs)

• Common structures in pathogens recognized by PRRs, distinct from healthy cells.
• DAMPs indicate danger signals released from damaged cells.

PRRs in Immune Response

• PRR engagement triggers a signaling cascade, promoting inflammation, cytokine production, cellular apoptosis, and adaptive immune stimulation.