Introduction to the Immune System

Overview of the Immune System

• Immunology studies the immune system and its responses to pathogens.
• The immune system consists of cells, tissues, organs, and molecules.
• It mediates resistance to infection and cancer.
• Immune response is when cells, tissues, and molecules coordinate to tackle infectious microbes and cancer cells.
• The immune system's job is to prevent and eradicate infections.

Immunity

• Immunity is the ability to resist or eliminate harmful foreign materials or abnormal cells.

Activities of Immunity

• Defense against invading pathogens
• Removal of worn-out cells and tissue debris
• Identification and destruction of abnormal or mutant cells
• Rejection of foreign cells (e.g., organ transplants)
• Inappropriate responses like allergies and autoimmune diseases can occur.

Innate vs Adaptive Immunity

• Innate immunity provides a rapid response to a broad range of microbes.
• Adaptive immunity gives a slower response to specific microbes.
• Innate immunity has no lag time and is not antigen-specific, and has no memory.
• Adaptive immunity has a lag period, is antigen-specific, and develops memory.

Types of Innate Immunity

• Species immunity is resistance to pathogens common to all members of a species.
• Racial immunity means that within one species, different races exhibit differences in susceptibility or resistance to infections.
• Individual immunity refers to resistance to infection dependent on individual differences within the same race and species.

Factors Affecting Innate Immunity

• Age: Newborns and the elderly are more susceptible to infections.
• Hormones: Hormonal disorders can increase susceptibility to infections.
• Nutrition: Malnutrition predisposes individuals to bacterial infections and diminishes immune responses.

Innate Immune System: External Defenses

• Anatomical barriers include mechanical, chemical, and biological factors.
• Mechanical factors: skin, mucociliary escalator, flushing action of saliva, tears, and urine.
• Chemical factors: Antimicrobial peptides in sweat, HCl in the stomach, and lysozyme in tears/saliva.
• Biological factors: Normal flora competes with pathogens for nutrients and space.
• Normal flora consists of microbes that exist in many parts of the body with over 1000 bacteria species.

Innate Immune System: Internal Defenses

• Key components of blood that contribute to innate immunity are complement proteins, coagulation proteins, cytokines and WBCs.

White Blood Cells (WBCs)

• Consist of B-lymphocytes, T-lymphocytes, natural killer (NK) cells, macrophages, and mast cells.

Neutrophils in Innate Immune Response

• Neutrophils are the most abundant WBCs (~50-60%).
• Act as efficient phagocytes which find, eat, and digest microbes.
• They are the most important cells of the innate immune system.

Neutrophil Digestion of Microbes

• Neutrophils utilize chemotaxis to adhere microbes so phagocytosis can occur.
• A phagosome is created and fused with lysosomes to digest microbe with digestive enzymes and antimicrobial proteins.
• Resulting in partially digested microbes which are excreted.
• Lysozyme digesting bacteria cell walls is an antimicrobial protein.
• Presentation of the antigen, triggers the inflammatory response.

Monocytes

• Monocytes make up about 5% of WBCs.
• They migrate into tissues and mature into macrophages.
• Macrophages perform phagocytosis of microbes in tissue.
• Macrophages also present antigens.

Natural Killer (NK) Cells

• NK cells are neither B-lymphocytes nor T-lymphocytes.
• They attack virus/bacteria-infected cells and cancer cells.
• They function as important part of innate immune system.
• Releasing granules with perforins and proteases to induce cell death.

Pathogen Recognition in Innate Immunity

• Immune cells like macrophages and dendritic cells recognize pathogens.
• Recognition via pathogen-associated molecular patterns (PAMPs).
• PAMPs interact with pattern-recognition receptors (PRRs) on immune cells.
• TLR is a type of pattern-recognition receptor
• Binding releases cytokines to stimulate further immune response.

Toll-Like Receptors (TLRs)

• TLRs are transmembrane proteins on macrophages and other cells that are conserved across vertebrates.
• They aid the innate immune system, looking out for and binding to microbes to trigger a cascade of events to kill or protect against pathogens.

TLR Response to binding with a Microbe

• Upon TLR binding to a microbe will secrete cytokines/interferon for Inflammation.
• This leads to phagocytosis and/or apoptosis of infected cells

Innate Response Summary (Cellular)

• Neutrophils, monocytes/macrophages, NK cells, and TLRs are key cellular defenses.
• These cellular components come into play when external defenses are breached.

Cytokines

• Cytokines are small proteins regulating immune cell behavior and are critical in both innate and adaptive immunity.
• Cytokines are signaling molecules secreted by immune system cells.

Cytokine Release

• Neutrophils and macrophages release cytokines when encountering pathogens.
• TLRs release cytokines upon binding to microbes.
• NK cells release cytokines when encountering infected cells.
• Lymphocytes release cytokines upon activation.

Examples of Cytokines

• Interferons
• Interleukins
• Tumour necrosis factor (TNF)

Interferons (IFN)

• These are signalling proteins produced by virus-infected monocytes and lymphocytes.
• Secreted proteins acts as key antiviral.
• They interfere with virus replications which warns neighboring cells.

Mechanism of Interferons

• Released dsRNA goes through Induction activation of inactive host to activate cascade of event.
• Resulting in host protein synthesis inhibition disrupting, viruses cannot replicate.

Interleukins

• Interleukins range from 1-37 and are not stored inside cells.
• They are quickly synthesized and secreted at infection, they modulate behavior of the immune cells secreted by T-lymphocytes & macrophages.

Role of Interleukins

• Stimulation of proliferation and activation of immune cells.
• Increasing antibody production.
• Causing inflammation at infected cells.

Tumor Necrosis Factor (TNF)

• TNF is a cytokine that induces fever, inflammation and killing of cancer.

Complement System

• The complement system involves numerous plasma proteins (C1-C9) that react with each other.
• Complement proteins bind to and coat microbes and form essential components of the innate immune response, enhances adaptive immunity.

Role of Complement Proteins

• Facilitation of phagocytosis
• Direct lysis of pathogens
• Causing inflammation

Complement Facilitation of Phagocytosis

• Opsonization of bacteria with complement (C`).
• The neutrophils receptor binds to the C`.
• Beginning phagocytosis of bacteria/pathogens.

Complement's Lyse Pathogens by Forming a Bacteria Membrane Attack

• C` (proteins) are activated forming a complex of proteins that creates holes in the bacterial cell wall.
• Water and salt diffuse into the cell causing the bacterium swells and eventually bursts.

Coagulation Proteins

• Coagulation, involving the function of Platelets and Vitamin K is the mechanism to stop after injury to the blood vessels.

Delicate Balance of Coagulation

• Coagulation proteins work with Inflammation causing platelet clumping and Apoptosis (cellular self-destruction).
• Anticoagulation prevents coagulation by inhibiting inflammation and apoptosis which need a balance to be maintained.

Coagulation and Innate Immunity

• Increased inflammation and increased apoptosis of infected cells, is triggered by the introduction of pathogens.

Inflammation

• Inflammation is a complex biological process in response to pathogens and irritants.
• It is characterized by tissue swelling and serves as a key player in the innate immune response.

All Roads Lead to Inflammation

• Neutrophils, monocytes /macrophages, NK cells proteins, vascular changes, complement proteins and TLRs all attribute to Inflammation

Inflammation and Vascular Changes

• Vasodilation which is widening blood vessels.
• Increased capillary permeability leads the blood vessels to become more leaky.

Signs of Inflammation

• Heat/redness, swelling, pain, and fever are all signs attributed to inflammation.

Role of Inflammation in Innate Immunity

• Inflammation initiates phagocytosis, limits the spread of infection.
• It is there to enhance or assist adaptive immune response and Initiate tissue repair.

Response to Tissue Breakdown

• Inflammatory stimulus through cytokine release from monocytic cells.
• These stimulate the activation of acute phase proteins (CRP) with hormonal (cortisol) and metabolic, Hematologic, and Biochemical responses.

The Good and Bad News About Inflammation

• Short term inflammation, can deal with frostbite, cuts, etc for Progressive wound healing.
• Long Term inflammation, is very bad causing heart issues, plus neurological and autoimmune disorders.

Harmful Effects of Chronic Inflammation

• Chronic inflammation is identified by damage of the injured tissues.

• Macrophages release the toxins damaging Reactive oxygen species and (ROSs) which causes destruction in tissues.

Chronic Inflammation

• Incorrect protein folding, is responsible activation of immune cells.
• That in turn can reduce function of the tissue by initiating a killing of host cells, that ends up damaging.

Chronic Inflammation and Cancer

• The introduction of reactive oxygen species to the DNA, can cause inflammation related cancers.

Summary: Defenses When External Defenses Fail

• When internal defenses fail, innate responses that happen are phagocytic cells, antimicrobial proteins, Inflammatory Response, Natural Killer Cells, and complement all play increasing role.