Inflammation and Immune Response Overview

Cardinal Signs of Inflammation

• Rubor - redness
• Tumor - swelling
• Calor - heat
• Dolor - pain
• Loss of function (functio laesa)

Leukocyte Adherence to Endothelium

• Blood flow slows
• Wall shear stress decreases
• Peripheral leukocyte positioning
• Margination (neutrophils adhering and aligning to vessels)
• Rolling (cells bind and detach)
• Adhesion molecules (cells adhere via these molecules)

Chemotaxis

• Leukocytes cross endothelium & basement membrane
• Extravascular tissue entry
• Chemotactic gradient followed by cells

Chemotaxis: Continued

• Chemotaxis defined as leukocyte movement to tissue injury
• Bacterial products (e.g., cytokines) are chemotactic
• Leukocyte type depends on stimulus and response timing
• Acute inflammation dominated by neutrophils

Contrast in Inflammation

• Viral infections - lymphocytes first
• Hypersensitivity reactions - lymphocytes & plasma cells
• Allergic reactions - eosinophils dominant

Bacterial vs. Viral Pneumonia

• Bacterial pneumonia - caused by Streptococcus pneumonia
• Immune cells: neutrophils & macrophages
• Viral pneumonia - caused by SARS-CoV-2
• Immune cells: lymphocytes
• Bacteria enter alveoli/begin to grow, capillaries open/ neutrophils combat bacteria, macrophages clear debris.
• Virus multiplies in cells, destroys cells; lymphocytes destroy virus-infected cells/type 2 pneumocytes.

Eosinophils

• White blood cell part of innate immune system
• Protect from allergens and infections (e.g., parasites)
• In response to allergies, hives, parasites, autoimmune responses, medications, etc.

Acute Inflammation: Morphologic Patterns

• Serous inflammation
• Fibrinous inflammation
• Suppurative inflammation
• Abscesses
• Ulcers

Serous Inflammation

• Cell poor fluid in tissues
• Early stage of acute inflammation
• Skin burn results in blisters and serous fluid accumulation

Fibrinous Inflammation

• Increased vascular permeability allows larger molecules to seep
• Fibrinous exudates form when vascular leaks are significant
• Examples: meningitis and pericarditis
• Fibrinous exudates are usually cleared by macrophages
• If not removed, stimulates fibroblasts and blood vessels leading to scarring (organization)
• Example: Fibrinous pericarditis

Purulent Inflammation

• Characterized by pus (neutrophils, necrotic debris, and fluid)
• Same as suppurative inflammation
• Common cause: bacteria
• Example: acute appendicitis

Abscesses

• Localized collections of purulent inflammatory tissue confined to a space
• Central portion is necrosis
• Periphery: zone of preserved neutrophils and fibroblasts

Ulcers

• Local defects on tissue/organ surfaces, due to inflamed necrotic tissue sloughing
• Tissue necrosis is involved
• Example: peptic ulcer disease

Chronic Inflammation Morphologic Features

• Mononuclear cells (macrophages, lymphocytes, plasma cells) dominate
• Lymphocytes (T cells), for example, secrete interferon to activate macrophages
• Interferon gamma is a cytokine (mediator of inflammation) causing tissue destruction
• Healing via fibrosis

Mast Cells

• Involved in insect bites, medication/drug reactions, and allergies

Cellular Adaptation: Hyperplasia and Hypertrophy

• Cells respond to increased demand by proliferation or enlargement (or both)
• Hyperplasia involves cellular proliferation
• Hypertrophy involves cellular enlargement
• Metaplasia is another type of adaptation

Metaplasia Examples

• Columnar to squamous epithelium (bronchial epithelium, in response to toxins, such as cigarette smoking)
• Squamous to columnar epithelium (esophageal epithelium, in response to repeated exposure to acidic gastric contents)
• Biliary tree epithelium in response to stones

Cell Injury Manifestations: Intracellular Accumulations

• These accumulating substances can be normal, abnormal, endogenous, or exogenous

Reversible Cell Injury Microscopic Changes

• Cellular swelling (cytoplasm)
• Fatty change

Irreversible Cell Injury Underlying Processes

• Hypoxia (a common underlying process)

Types of Necrosis

• Coagulative necrosis
• Liquefactive necrosis
• Caseous necrosis
• Fat necrosis
• Fibrinoid necrosis

Patterns of Tissue Necrosis

• Large numbers of cells undergoing necrosis = necrotic tissue or organ
• Distinct patterns exist, giving clues about the underlying cause

Coagulative Necrosis

• Tissue architecture preserved initially
• Protein denaturation, enzymatic changes occur
• Eosinophilic, anucleate cells may persist
• Example: myocardial infarction (localized area of coagulative necrosis)

Liquefactive Necrosis

• Digestion of dead cells resulting in liquid, viscous mass forming pus
• Common in bacterial/fungal infections
• Example: brain tissue ischemia

Gangrenous Necrosis

• Coagulative necrosis in limbs or bowels
• With infection, turns into liquefactive necrosis ("wet" gangrene)
• Dry (coagulative) gangrene is a type of gangrene

Caseous Necrosis

• Friable, white cheese-like appearance
• Necrosis with inflammatory foci (granulomas)
• Often encountered in tuberculosis

Fat Necrosis

• Focal areas of fat destruction
• Common in inflamed pancreas/trauma to breast

Fat Necrosis with Dystrophic Calcification

• Fat necrosis resulting in calcification

Fibrinoid Necrosis

• Immunological reactions in blood vessels
• Fibrin deposition is a feature

Two Types of Immunity

• Innate (non-specific): basic elements, readily available
• Acquired (specific): more specialized elements

Hematopoiesis

• Development of blood & derived cells in bone marrow, lymph nodes, tissues
• Lymphoid lineage: lymphocytes (B cells, T cells, NK cells)
• Myeloid lineage: granulocytes, macrophages, erythrocytes, megakaryocytes

Antigen-Presenting Cells (APCs)

• Dendritic cells, macrophages, B lymphocytes
• Take up and digest antigens (pathogens or foreign proteins)
• Digested fragments displayed on MHC class II molecules
• Presentation to CD4+ T cells (e.g., causing antibody production)

Lymphocyte Recirculation

• Immune cells searching for pathogens via lymph, blood, & lymphatic vessels
• Cells pick up exogenous antigens and bring to the draining lymph node
• Specific immune response follows

The Big Picture (Immune Response)

• Primary response & APC presenting antigen to T cells
• Transitions from innate to adaptive (especially concerning APC's)

Requirements for Immunogenicity

• Foreignness: not self-reacting (exception: autoimmune diseases); more foreign = more immunogenic
• Size: > 6 kDa generally immunogenic; < 1 kDa not
• Chemical complexity: homopolymers of amino acids are not immunogenic
• Degradability: susceptibility to enzymatic degradation; stability important for antigen presentation
• Dosage: insufficient dosage creates tolerance; repeated administration required for response

Major Classes of Antigens

• Carbohydrates (immunogenic as part of glycoproteins)
• Lipids (rarely immunogenic)
• Nucleic acids (not immunogenic, except in systemic lupus erythematosus)
• Proteins/glycoproteins (very immunogenic)

Cross-reactivity

• Antibodies specific to one antigen can react with a second antigen (especially antigens that are closely related)
• Example: toxins versus toxoids

Five Major Antibody Classes

• IgG, IgA, IgM, IgD, IgE

IgG Subclasses

• Important differences in occurrence, half-life, complement binding, and placental passage
• Vary in their ability to bind monocytes
• Key feature: placental passage

IgG: Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC)

• IgG-mediated activation of complement
• Toxin/viral neutralization
• Bacterial immobilization

Antibody Levels Early in Life

• IgM first to rise from fetus
• IgG rises (passively transferred/maternal)
• IgA rises later

IgM

• First antibody produced in response to infection/immunization
• Efficient in complement fixation

IgA

• Primarily found in secretions (tears, saliva, etc.)
• Important part of respiratory and mucosal surfaces' first line defense
• Antibacterial/antiviral activities

IgE

• Mediates Type I hypersensitivity reactions
• High levels during parasitic infections

HLA Genes and Inheritance

• MHC genes inherited from both parents as a haplotype
• Individuals expressing particular combinations of HLA genes may have greater disease susceptibility/resistance
• The inheritance of genes in combination determines the outcome for particular diseases

HLA Class I & II Expression

• HLA genes expressed in professional APCs (dendritic cells, macrophages, B cells)
• HLA class II expression can be induced by cytokines (e.g., interferon gamma)

MHC Class I Antigen Processing Pathway

• Endogenous antigens (e.g., viral proteins) are processed and presented to CD8+ T cells

MHC Class II Exogenous Antigen Processing Pathway

• Exogenous proteins taken into the cell, degraded into peptides
• Peptides presented to CD4+ T cells

Cross-Presentation

• Dendritic cells carry exogenous antigens to MHC I, activating cytotoxic T cells from extracellular sources

Chronic Inflammation Cells

• Lymphocytes (microbes/environmental antigens activate and propagate inflammation)
• Macrophages (professional phagocytes, activated by classical/alternative pathways; secrete factors for angiogenesis and fibrosis)
• Eosinophils (granules containing toxic proteins against parasites/epithelial cells)

Granulomatous Inflammation

• Cells (macrophages & lymphocytes) form collections to contain an offending agent
• This inflammation contains central necrosis sometimes

Tuberculosis

• Granulomatous disease caused by mycobacteria infection

General Inflammation Take Aways

• Excessive inflammation can lead to disease & increase infection risk
• Inflammation targets malignant cells for therapeutic interventions

This quiz covers the critical aspects of inflammation, including the cardinal signs, leukocyte behavior, and chemotaxis mechanisms. You'll explore the differences in immune responses to bacterial and viral infections, as well as the types of leukocytes involved. Test your knowledge on these fundamental concepts in immunology.