Untitled Flashcards Set

Introduction to Leukocytes

• Leukocytes are the only formed elements in blood that are complete cells, comprising less than 1% of total blood volume, with a normal count of 4800-10,800 WBCs/μl.

• They play a crucial role in protecting the body against pathogens such as bacteria, viruses, parasites, toxins, and tumor cells.

• Leukocytes can exit the bloodstream through a process called diapedesis to mount an immune or inflammatory response.

• An increase in leukocyte count, known as leukocytosis, occurs in response to infections, with counts exceeding 11,000/μl, potentially doubling within hours during acute infections.

• Leukocytes are categorized into two main groups: granulocytes and agranulocytes.

Types of Leukocytes

• Granulocytes: These include neutrophils, eosinophils, and basophils, characterized by their lobed nuclei and visible cytoplasmic granules when stained.

• Agranulocytes: Comprising lymphocytes and monocytes, these cells lack visible granules and have spherical or kidney-shaped nuclei.

Key Functions of Leukocytes

• Neutrophils are the most abundant leukocytes (>50%) and act as phagocytes, ingesting and destroying bacteria, particularly during acute infections like meningitis and appendicitis.

• Eosinophils (2-4% of leukocytes) combat parasitic infections by surrounding them and releasing digestive enzymes, also playing a role in allergies and asthma.

• Basophils are the rarest leukocytes (0.5%) and release histamine, which acts as a vasodilator, increasing blood vessel permeability and attracting other WBCs.

Leukocyte Development and Disorders

Leukopoiesis

• Leukopoiesis is the process of producing leukocytes, regulated hormonally based on the body's needs.

• Interleukins and colony-stimulating factors are hormones that stimulate the production of various leukocytes.

• The process begins with hemocytoblasts differentiating into myeloid and lymphoid stem cells, leading to committed cells like myeloblasts and lymphoblasts.

Lifespan and Storage of Granulocytes

• Granulocytes have a short lifespan, ranging from 0.25 to 9 days, with most dying in the line of duty during immune responses.

• Bone marrow stores mature granulocytes, typically containing about ten times more than found in the bloodstream.

Leukocyte Disorders

• Leukemia: A cancer of WBCs characterized by the proliferation of unspecialized cells, leading to severe anemia and clotting issues. Treatment may involve irradiation, anti-leukemic drugs, or bone marrow transplants.

• Infectious Mononucleosis: Caused by the Epstein-Barr virus, it results in an increase of enlarged lymphocytes, often mistaken for monocytes, leading to symptoms like fatigue and sore throat.

• Leukopenia: An abnormally low WBC count, often due to medications like glucocorticoids or chemotherapy.

Immune System Mechanisms

Innate vs. Adaptive Immunity

• The immune system is divided into innate (nonspecific) defenses and adaptive (specific) defenses, each playing distinct roles in immune response.

• Innate defenses provide immediate protection against foreign substances without specific identification, utilizing generalized markers on cell surfaces.

Activation of the Innate Immune System

• The innate immune system can be activated by pathogens entering the body (PAMPs) or by tissue damage (DAMPs).

• PAMPs are molecular patterns associated with pathogens, recognized by Toll-like receptors on phagocytic cells, leading to phagocytosis and inflammation.

• DAMPs are molecules that indicate tissue damage, such as DNA found in the cytoplasm, triggering immune responses.

Summary of Key Terms

• PAMPs (Pathogen-Associated Molecular Patterns): Recognized by the immune system as indicators of infection, leading to an immune response.

• DAMPs (Damage-Associated Molecular Patterns): Signals of tissue damage that activate the immune system, even in the absence of pathogens.

Overview of Immune Responses

Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs)

• PAMPs are molecular patterns found in pathogens, such as bacterial cell walls, that are not normally present in the body. They are recognized by Toll-like receptors (TLRs) on phagocytic cells, leading to phagocytosis and triggering an inflammatory response.

• DAMPs are molecules that indicate damage within the body, such as DNA found in the cytoplasm. They signal the innate immune system without the need for specific pathogen recognition.

• Both PAMPs and DAMPs play crucial roles in alerting the immune system to potential threats, facilitating a rapid response to injury or infection.

Innate Defenses

• The innate immune system includes physical barriers like skin and mucous membranes, which are the first line of defense against pathogens.

• Chemical defenses include:

• Acidity: Skin and secretions deter bacterial growth.

• Enzymes: Lysozyme in saliva and respiratory mucus breaks down bacterial cell walls.

• Mucin: Traps microorganisms in digestive and respiratory tracts.

• Defensins: Antimicrobial peptides secreted by mucous membranes and skin.

• Other chemicals, such as lipids in sebum and dermicidin in sweat, also contribute to the antimicrobial environment.

Inflammatory Response

Mechanisms of Inflammation

• Inflammation is a protective response to injury characterized by four key signs: redness, heat, swelling, and pain.

• It serves multiple functions:

• Prevents the spread of pathogens.

• Disposes of cell debris and pathogens.

• Sets the stage for tissue repair.

• Alerts the adaptive immune system to the presence of pathogens.

• Inflammatory chemicals such as histamine and prostaglandins are released by damaged cells, promoting blood flow and attracting immune cells to the site of injury.

Pain and Benefits of Inflammation

• Pain during inflammation is caused by the release of inflammatory mediators that sensitize nerve endings.

• Inflammation is beneficial as it helps to isolate and eliminate pathogens, facilitates healing, and activates the adaptive immune response.

• Key terms:

• Margination: The process by which leukocytes adhere to the endothelium of blood vessels.

• Diapedesis: The movement of leukocytes through the blood vessel wall into tissues.

• Chemotaxis: The movement of cells towards the site of injury or infection in response to chemical signals.

Interferon and Complement System

Interferon Mechanism

• Interferons are proteins secreted by virus-infected cells that help protect neighboring cells by blocking protein synthesis and degrading viral RNA.

• They play a role in activating macrophages and mobilizing natural killer (NK) cells, contributing to anti-cancer effects.

• Interferons are crucial in the body's response to viral infections, even before the virus is specifically recognized.

Complement System

• The complement system consists of over 20 plasma proteins that circulate in an inactive form.

• Upon activation, these proteins enhance the inflammatory response and promote opsonization, which marks pathogens for destruction.

• C3b is a key component that acts as an opsonin, facilitating phagocytosis by immune cells.

Adaptive Immune Mechanisms

Key Players in Adaptive Immunity

• The adaptive immune system involves three main types of cells:

• B lymphocytes: Responsible for humoral immunity and antibody production.

• T lymphocytes: Involved in cell-mediated immunity, targeting infected or cancerous cells.

• Macrophages: Act as antigen-presenting cells, crucial for activating T cells.

Lymphocyte Development and Activation

• Lymphocytes originate from hemocytoblasts in the red bone marrow and undergo maturation to become either B or T cells.

• T cells mature in the thymus, where they acquire immunocompetence and self-tolerance, with only about 2% successfully passing this process.

• B cells mature in the bone marrow and develop unique receptors to recognize specific antigens.

B-Cells and Humoral Immune Response

Activation and Function of B-Cells

• B-cells are activated upon encountering their specific antigen, typically in the spleen or lymph nodes.

• Upon activation, B-cells differentiate into plasma cells that produce antibodies at a rate of approximately 2000 molecules per second.

• Antibodies bind to antigens, marking them for destruction, while some B-cells become memory cells, providing long-term immunity.