Module 1 Notes - Infection & Immunity PDF

**Process of Infection and Clinical Course** The process of infection begins with **encounter and transmission** of a pathogen. This can happen through direct contact with an infected individual, exposure to contaminated substances, or bites from animals or insects. Once the pathogen has encountere...

**Process of Infection and Clinical Course** The process of infection begins with **encounter and transmission** of a pathogen. This can happen through direct contact with an infected individual, exposure to contaminated substances, or bites from animals or insects. Once the pathogen has encountered the host, it must **colonize** the host environment, which involves adhering to host cells and surviving and multiplying in the human environment. Next, the pathogen must **invade** or penetrate the host's surface barriers, such as the skin and mucous membranes. This can involve direct penetration, such as through a mosquito bite, or a break in the barrier\'s integrity, such as through trauma. Some microorganisms can directly invade cells. Following invasion, the pathogen may **disseminate** or spread through surrounding tissues or via blood or lymphatic vessels. Finally, the pathogen causes **cellular or tissue damage**, either directly through lysis during replication or toxin production, or indirectly through the host's immune and inflammatory responses. The clinical course of infection occurs in four stages: - **Incubation period:** This stage spans from the initial exposure to the onset of the first symptoms. During this time, the pathogen multiplies but remains insufficient to cause symptoms. - **Prodromal stage:** The prodromal stage marks the appearance of initial, often mild symptoms, including discomfort and tiredness, as the pathogen continues to multiply. - **Invasion or acute illness period:** This stage involves rapid pathogen multiplication, tissue invasion, and triggering of the immune and inflammatory responses. Symptoms may relate to the pathogen or the inflammatory response. - **Convalescence:** In most cases, the immune system successfully eliminates the pathogen, leading to symptom decline. Alternatively, the disease may be fatal or enter a latency phase until pathogen reactivation. **Countering Infectious Diseases** **Antibiotics**, **vaccines**, and **passive immunizations** are crucial tools in countering infectious diseases. - **Antibiotics** target bacteria by disrupting their essential processes, such as cell wall synthesis, protein synthesis, or DNA replication. However, the overuse and misuse of antibiotics have led to the emergence of antibiotic-resistant bacteria. - **Vaccines** work by exposing the immune system to weakened or inactivated pathogens, triggering the production of protective antibodies and memory cells. This allows for a faster and more effective immune response upon subsequent exposure to the actual pathogen. - **Passive immunization** involves administering preformed antibodies to individuals who have been exposed to a pathogen or are at risk of infection. This provides immediate but temporary protection. **Antibiotic Resistance** **Antibiotic resistance** is a growing global health threat. The primary causes include: - **Overuse and misuse of antibiotics:** This creates selective pressure, favoring the survival and proliferation of resistant strains. - **Horizontal gene transfer:** Bacteria can share genetic material, including antibiotic resistance genes, through mechanisms like conjugation and transduction. The consequences of antibiotic resistance include: - **Increased morbidity and mortality:** Resistant infections are harder to treat, leading to prolonged illness, complications, and death. - **Higher healthcare costs:** Treating resistant infections requires more expensive and prolonged therapies. - **Limited treatment options:** The pipeline for new antibiotics is dwindling, leaving fewer options for treating resistant infections. **Acute Inflammation** **Acute inflammation** is a rapid, localized response to injury or infection that aims to neutralize and eliminate pathogens and promote tissue repair. It is initiated within seconds to minutes and typically resolves within days. The process involves a sequence of events: 1. **Detection of foreign material or cell damage:** Immune cells, such as mast cells, macrophages, dendritic cells, and lymphocytes, detect foreign material or cell damage using non-specific receptors. 2. **Activation of local immune cells and release of inflammatory mediators:** Upon activation, local immune cells release inflammatory mediators. Mast cells release histamine, causing vasodilation and increased vascular permeability. Chemokines released by mast cells and macrophages recruit more immune cells. Pro-inflammatory cytokines, such as TNF-α, IL-1, IL-6, and IL-23, activate both resident and recruited immune cells. 3. **Immune cell recruitment and phagocytosis:** Recruited immune cells, primarily neutrophils followed by monocytes/macrophages, engulf foreign material and cellular debris. Neutrophils release reactive oxygen species, which can cause collateral tissue damage, and also release pro-inflammatory cytokines and chemokines. 4. **Neutrophil extracellular trap (NET) formation:** Neutrophils can produce NETs by unraveling and extruding their DNA into the extracellular space. These NETs trap microorganisms, contain antimicrobial agents, and serve as danger signals to other immune cells. 5. **Antigen presentation and adaptive immunity:** Professional antigen-presenting cells (APCs) present fragments of foreign material to T helper cells, initiating the adaptive immune response. This leads to a specific and long-lasting immune response, including the production of memory cells for faster responses upon secondary exposure. 6. **Resolution and tissue repair:** If the threat is neutralized, inflammation subsides, and immune cells coordinate tissue repair. Local manifestations of acute inflammation include heat, swelling, pain, and redness caused by vasodilation, increased vascular permeability, edema, and activation of pain fibers by mediators like prostaglandins and bradykinin. Systemic manifestations include fever, leukocytosis (increased circulating leukocytes), and increased plasma protein synthesis, particularly acute-phase reactants like C-reactive protein and fibrinogen. **Chronic Inflammation** **Chronic inflammation** persists for two weeks or longer and is characterized by excessive immune cell infiltration, particularly lymphocytes and macrophages. Unlike acute inflammation, chronic inflammation is not productive and can cause significant tissue damage and promote cancer development. Chronic inflammation can result from: - **Unsuccessful acute inflammatory response**. - **Pathogen evasion mechanisms** allowing persistence. - **Persistent tissue damage from toxins** even after pathogen elimination. - **Continuous exposure to irritants**, such as chemicals, particulate matter, or physical agents. - **Idiopathic causes** with no known cause. **Comparing and Contrasting Acute and Chronic Inflammation** **Feature** **Acute Inflammation** **Chronic Inflammation** -------------------------- ----------------------------------------------------------------------- ---------------------------------------------------------------------------------------------- **Duration** Short-term (typically resolves within days) Long-term (persists for 2 weeks or longer) **Immune cells** Primarily neutrophils, followed by monocytes/macrophages Lymphocytes and macrophages predominate **Outcome** Usually productive, leading to pathogen elimination and tissue repair Non-productive, causing excessive tissue damage and potentially promoting cancer development **Local manifestations** Heat, swelling, pain, redness Less prominent, may include tissue fibrosis and scarring **Systemic effects** Fever, leukocytosis, increased acute-phase reactants May contribute to fatigue, anemia, weight loss **Granuloma Formation** During chronic inflammation, **granulomas** may form as a way to contain persistent irritants that the body cannot eliminate. Granulomas are organized collections of macrophages that have differentiated into epithelioid cells, surrounded by lymphocytes and fibroblasts. These structures wall off the irritant, preventing its spread but also contributing to tissue damage. **Adaptive Immune Responses** Professional APCs, like macrophages, dendritic cells, and B cells, play a critical role in initiating **adaptive immune responses**. These cells capture, process, and present antigens to T helper cells (Th cells) via major histocompatibility complex (MHC) molecules. Th cells then orchestrate the development of humoral and cell-mediated immunity. **Humoral immunity** is mediated by B cells that differentiate into plasma cells, which produce antibodies. Antibodies target extracellular antigens, neutralizing pathogens and toxins and activating complement and phagocytes. **Cell-mediated immunity** is primarily conducted by T cytotoxic cells (Tc cells), which target intracellular antigens presented on MHC class I molecules. Tc cells destroy infected or abnormal cells through mechanisms like perforin and granzyme release, Fas-FasL interactions, and antibody-dependent cellular cytotoxicity (ADCC). **Comparing Humoral and Cell-Mediated Immunity** **Feature** **Humoral Immunity** **Cell-Mediated Immunity** --------------------------- -------------------------------------------------------------------------------- -------------------------------------------------------------------------------------------------------------------- **Mediating cells** B cells, plasma cells Tc cells, NK cells, macrophages **Antigen target** Extracellular antigens (e.g., pathogens, toxins) Intracellular antigens (e.g., viruses, intracellular bacteria, cancer cells) **Mechanisms of defense** Antibody production, neutralization, opsonization, complement activation, ADCC Direct cell killing through perforin/granzyme, Fas-FasL, and ADCC; macrophage activation; delayed hypersensitivity **Sensitization in Hypersensitivity Reactions** **Sensitization** refers to the initial exposure to an allergen that triggers the development of an allergic response. During sensitization, the immune system becomes primed to recognize and react to the allergen upon subsequent exposures. This often involves the production of allergen-specific IgE antibodies that bind to mast cells and basophils \[You may want to independently verify this information as it is not from the provided sources\]. **Comparing and Contrasting Hypersensitivity Reactions** Hypersensitivity reactions are classified into four types based on the underlying immune mechanisms: **Type** **Immune Cells Involved** **Pathophysiological Mechanisms** **Consequences** -------------- ------------------------------------------------------------------------ --------------------------------------------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------ **Type I** Mast cells, basophils, IgE antibodies Allergen cross-linking IgE on mast cells and basophils, leading to degranulation and release of histamine, leukotrienes, and prostaglandins Immediate hypersensitivity reactions, such as allergic rhinitis, asthma, anaphylaxis **Type II** IgG or IgM antibodies, complement, phagocytes Antibodies binding to cell surface antigens, leading to complement activation, opsonization, and phagocytosis or cell lysis Cytotoxic reactions, such as autoimmune hemolytic anemia, Goodpasture syndrome **Type III** Immune complexes (antigen-antibody complexes), complement, neutrophils Immune complex deposition in tissues, leading to complement activation and neutrophil recruitment, causing inflammation and tissue damage Immune complex-mediated diseases, such as systemic lupus erythematosus, serum sickness **Type IV** T cells (Th1 cells, Tc cells) Delayed-type hypersensitivity mediated by T cells, leading to cytokine release, macrophage activation, and cytotoxic T cell responses Delayed hypersensitivity reactions, such as contact dermatitis, tuberculin skin test, transplant rejection **Immunodeficiency** refers to the failure of the immune system to protect the body against infection. This leads to an increased susceptibility to infections, particularly opportunistic infections caused by microorganisms that typically do not cause disease in healthy individuals. **Primary immunodeficiency** is caused by genetic defects affecting immune system development or function. It is often sporadic and presents early in life. **Secondary immunodeficiency** arises from an underlying condition or external factor that impairs immune function. It is more common than primary immunodeficiency and can be caused by malnutrition, HIV infection, immunosuppressive medications, or cancer treatments. **HIV and AIDS** **Human immunodeficiency virus (HIV)** targets CD4+ T helper cells, which are crucial for adaptive immunity. The virus infects these cells by binding its gp120 envelope protein to the CD4 receptor on the cell surface. Following attachment, HIV inserts its RNA genome into the host cell and uses the viral enzyme reverse transcriptase to convert RNA into DNA, which is then integrated into the host cell genome by the viral enzyme integrase. This allows HIV to remain dormant for many years. The clinical course of HIV infection involves: - **Acute HIV infection:** Occurs 2-4 weeks after exposure, often with flu-like symptoms. Viral load is high, and CD4+ T cell numbers decline. - **Clinical latency (chronic HIV infection):** Viral replication continues, but the immune system can replenish infected cells, leading to a slow decline in immune function. This stage can last for years or decades with antiretroviral therapy. - **Acquired immunodeficiency syndrome (AIDS):** Occurs when CD4+ T cell counts drop below 200 cells/µL or when opportunistic infections or certain cancers develop. This stage marks severe immune suppression, making individuals highly susceptible to life-threatening infections. **Cytokines and Fever** **Fever** is a systemic response to infection or injury characterized by an elevated body temperature. It is triggered by **cytokines**, such as TNF-α, IL-1, IL-6, and interferons, released by immune cells in response to infection. These cytokines act on the hypothalamus, resetting the body's thermostat to a higher level. This leads to increased heat production and conservation, resulting in fever. **Causes and Consequences of Cachexia** **Cachexia** is a complex metabolic syndrome characterized by muscle wasting, weight loss, and anorexia. It is often seen in chronic inflammatory conditions, such as cancer, HIV infection, and chronic obstructive pulmonary disease \[You may want to independently verify this information as it is not from the provided sources\]. The causes of cachexia are multifactorial and include: - **Increased pro-inflammatory cytokines:** Cytokines, such as TNF-α, IL-1, and IL-6, contribute to muscle protein breakdown and suppress appetite. - **Metabolic alterations:** Cachexia involves changes in glucose, lipid, and protein metabolism, leading to energy imbalance and tissue wasting. - **Hormonal dysregulation:** Imbalances in hormones, such as insulin and growth hormone, can contribute to muscle wasting and metabolic dysfunction. The consequences of cachexia are significant and include: - **Reduced quality of life:** Muscle wasting and fatigue limit physical activity and overall well-being. - **Increased morbidity and mortality:** Cachexia weakens the body, making individuals more susceptible to infections and complications. - **Treatment resistance:** Cachexia can reduce the effectiveness of cancer treatments and other therapies.