IAS60 Acute inflammation

The main chemoattractants include:

• Bacterial products
• Cytokines
• Complements (especially C5a)
• Leukotrienes

Neutrophils move towards the site of injury by recognizing the concentration gradient of chemoattractants and using amoeboid movement to move up the gradient to the source of these chemicals.

C5a causes mast cells to release histamine, leading to vasodilation. It also acts as a chemotactic agent, directing neutrophils to move through diapedesis to the site of injury.

1. Tissue injury leads to complement activation.
2. C5a is released.
3. C5a stimulates mast cell degranulation, resulting in histamine release and vasodilation.
4. C5a acts as a chemotactic agent, directing neutrophils to the injury site.
5. Neutrophils express receptors for C3b and bind to C3b-coated antigens, undergoing chemotaxis toward the injury site.

Acute inflammation is a rapid and immediate response of the body to injury or infection, characterized by the increased blood flow and accumulation of immune cells at the site of damage.

1. Infections (bacterial, viral, fungal)
2. Tissue injury (trauma, burns)
3. Chemical irritants (toxins, allergens)
4. Ischemia (lack of blood supply)

• Neutrophils: First responders to infection or injury.
• Macrophages: Engulf pathogens and debris, release mediators.
• Mast cells: Release histamine and other mediators that promote inflammation.
• Lymphocytes: Involved in the adaptive immune response.

• Histamine: Increases blood vessel permeability.
• Prostaglandins: Promote vasodilation and pain.
• Cytokines: Mediate immune responses and inflammation.
• Leukotrienes: Attract immune cells to the site of inflammation.

1. Vasodilation: Increased blood flow to the area.
2. Increased vascular permeability: Allows proteins and immune cells to exit the bloodstream.
3. Stasis: Slowing of blood flow, leading to accumulation of cells.
4. Emigration of leukocytes: White blood cells move to the site of injury.

• Redness (rubor): Due to increased blood flow.
• Heat (calor): Also due to increased blood flow.
• Swelling (tumor): Caused by fluid accumulation.
• Pain (dolor): Resulting from chemical mediators and pressure on nerves.
• Loss of function: Due to pain and swelling.

Tommy C is a 20-year-old university student with no significant past medical problems. He is a member of the basketball team and is active in hall sports teams.

Tommy experienced vague central abdominal pain after basketball practice.

At 3 am, Tommy felt feverish, experienced intensified pain that prevented him from sleeping, and noted that the pain had moved to the right lower quadrant of his abdomen.

Tommy's physical examination revealed a temperature of 38.5 C and a pulse of 110/min.

The examination showed tenderness over the right lower quadrant of the abdomen, with guarding and rebound tenderness present.

A white blood cell count of 15.0 x 10^9/L is elevated compared to the normal range (4 - 10 x 10^9/L), indicating a possible acute inflammatory response or infection.

A neutrophil count of 80% suggests a strong acute inflammatory response, as neutrophils are typically the first responders to infection or injury.

A haemoglobin level of 13.5 g/dL is within the normal range, indicating that there is no significant anemia present, which can sometimes accompany chronic inflammation.

A platelet count of 420 x 10^9/L is elevated, which can be associated with acute inflammation as platelets play a role in the inflammatory process and tissue repair.

The main causes of tissue damage include:

1. Ischaemia - Reduced blood flow leading to oxygen deprivation.
2. Physical Energy - Damage from physical impacts or trauma.
3. Chemicals - Harmful chemical substances that can cause cellular injury.
4. Infections - Pathogenic organisms that invade and damage tissues.

Cellular stress can lead to different outcomes based on the severity and duration of the stress:

• Normal Cell (Homeostasis): Under normal conditions, cells maintain homeostasis.
• Adaptation: Cells can adapt to mild stress, reverting back to normal if the stress is removed.
• Cell Injury: If the stress is severe, it can lead to cell injury, which can be reversible or irreversible:
  • Reversible Injury: Mild, transient damage that can recover.
  • Irreversible Injury: Severe, progressive damage leading to necrosis or apoptosis.

The determination of reversible vs irreversible injury depends on:

1. Type of injury
2. Duration of the injury
3. Severity of the injury
4. Type of cell involved
5. State of the cell
6. Adaptability of the cell

Neurons can only withstand ischaemia for 5 minutes before irreversible injury occurs.

Heart, liver, and kidney cells can survive ischaemia for 30 minutes to 1 hour before irreversible injury occurs.

Skin and skeletal muscle can survive ischaemia for several hours before irreversible injury occurs.

The consequences of cell death in organs include:

• Loss of organ function
• Leakage of molecules into the bloodstream, detectable in blood tests
• Scarring after dead cells are cleared, affecting organism function
• Dystrophic calcification, leading to hard lumps visible on X-ray
• Potential bacterial infection in the necrotic area

The cardinal features of acute inflammation include:

1. Rubor (Redness)
2. Tumor (Swelling)
3. Calor (Warmth)
4. Dolor (Pain)
5. Loss of function

The cardinal signs of acute inflammation are:

1. Rubor (Redness)
2. Calor (Heat)
3. Tumor (Swelling)
4. Dolor (Pain)
5. Functio laesa (Loss of function)

Aulus Cornelius Celsus was a Roman medical writer known for his works on philosophy, agriculture, medicine, and warfare. He is considered the greatest Roman medical writer and is an important source for present-day knowledge of Alexandrian medicine. He recommended cleanliness and the washing of wounds with antiseptic substances, such as vinegar.

Rudolf Ludwig Carl Virchow, known as the 'Father of modern pathology', was a German physician who made significant contributions to the understanding of disease processes and pathology.

Inflammation is the physiological response of an organism to tissue injury. It is important to note that inflammation is not a disease by itself.

Acute inflammation is an initial and often transient series of tissue reactions to injury, typically lasting around 3 days.

Chronic inflammation is characterized by subsequent and often prolonged tissue reactions following the initial response of acute inflammation.

Acute inflammation is a rapid and early response of the body to injury or infection, characterized by the influx of immune cells and the release of chemical mediators to eliminate the cause of cell injury and initiate healing.

1. Infections (bacterial, viral, fungal)
2. Tissue injury (trauma, burns)
3. Chemical irritants (toxins, allergens)
4. Ischemia (reduced blood flow leading to tissue damage)

• Neutrophils: First responders to sites of infection or injury.
• Macrophages: Engulf pathogens and debris, and secrete mediators.
• Mast cells: Release histamine and other mediators that promote inflammation.
• Lymphocytes: Involved in the adaptive immune response.

• Histamine: Increases blood vessel permeability.
• Prostaglandins: Mediate pain and fever.
• Cytokines: Regulate immune responses and inflammation.
• Chemokines: Attract immune cells to the site of inflammation.

1. Vasodilation: Blood vessels widen to increase blood flow.
2. Increased permeability: Blood vessel walls become more permeable, allowing proteins and immune cells to exit.
3. Stasis: Slowing of blood flow due to increased viscosity and cellular accumulation.

1. Margination: White blood cells move to the periphery of blood vessels.
2. Adhesion: White blood cells adhere to the endothelium.
3. Transmigration: White blood cells exit the blood vessel and migrate to the site of injury.
4. Phagocytosis: Immune cells engulf and destroy pathogens and debris.

• Redness (rubor): Due to increased blood flow.
• Heat (calor): Also due to increased blood flow.
• Swelling (tumor): Caused by fluid accumulation.
• Pain (dolor): Resulting from chemical mediators and pressure on nerves.
• Loss of function: Due to pain and swelling affecting mobility.

The main components involved in acute inflammation include:

1. Tissue damage
2. Chemical mediators
3. Blood vessels
4. Neutrophils

The main blood cells involved in inflammation include:

Neutrophilia indicates a bacterial infection and is characterized by an increased number of neutrophils in the blood.

Lymphocytosis indicates a viral infection and is characterized by an increased number of lymphocytes in the blood.

Eosinophilia indicates an allergic reaction or parasitic infection and is characterized by an increased number of eosinophils in the blood.

The most numerous cells in Tommy's blood smear are red blood cells, which appear as small round discs colored in light pink with a lighter center.

The first step in the process of acute inflammation is tissue damage, which triggers the subsequent inflammatory response.

After tissue damage, there is increased blood flow due to vascular dilation, which is a key event in the acute inflammatory response.

Neutrophils emigrate to the site of inflammation, stimulated by the release of chemical mediators, which can lead to pain and other symptoms of inflammation.

The cardinal signs of acute inflammation include:

1. Rubor (Redness)
2. Calor (Heat)
3. Tumor (Swelling)
4. Dolor (Pain)

1. Margination: Cells adhere to the wall of the vessel.
2. Diapedesis: Cells move through the vessel wall.
3. Chemotaxis: Cells move towards the site of tissue damage.
4. Phagocytosis: Cells destroy bacteria.

Chemical mediators released from damaged tissue lead to:

• Vasodilation: Widening of blood vessels.
• Increased vascular permeability: Allows substances to pass through vessel walls more easily.
• Attraction of neutrophils: Draws immune cells to the site of injury.
• Initiation of plasma protein-derived mediators: Activates further inflammatory responses.

1. Cell-derived mediators: Derived from cells.
2. Plasma protein-derived mediators: Derived from blood.

• Vasodilation
• Increase vascular permeability

• Origin: Macrophages
• Effect: Increase neutrophil adhesion to endothelium

Chemokines attract neutrophils to the site of tissue damage.

Arachidonic acid metabolites, including Prostaglandins and Leukotrienes, cause vasodilation and increase vascular permeability.

Nitric oxide (NO) is produced by endothelial cells and its effect is to increase vascular permeability.

Histamine is stored in mast cells and basophils. It is released during physical injury, binding of antibodies to mast cells, and is initiated by the complement system.

Histamine causes vasodilation and increases vascular permeability during the inflammatory response.

Mast cells play a crucial role in the immune response by releasing histamines and other inflammatory mediators upon activation. They are involved in allergic reactions and help to initiate inflammation.

Arachidonic acid is an omega-6 polyunsaturated fatty acid that is common in cell membrane phospholipids. It is significant in inflammation as it is converted to prostaglandins and other inflammatory mediators during tissue injury.

Phospholipases act on cell membrane phospholipids to release arachidonic acid, which is a key precursor in the synthesis of various eicosanoids.

COX-1 and COX-2 inhibitors, such as aspirin, inhibit the cyclooxygenase enzyme, which prevents the conversion of arachidonic acid into prostaglandins and thromboxanes, thereby reducing inflammation and pain.

Leukotrienes, such as LTB4, LTC4, LTD4, and LTE4, are involved in various inflammatory responses, including vasoconstriction, bronchospasm, and increased vascular permeability.

Steroids inhibit phospholipases, which prevents the release of arachidonic acid from cell membrane phospholipids, thereby reducing the production of inflammatory mediators.

Prostaglandins and thromboxanes play crucial roles in mediating inflammation, pain, and fever, with specific effects such as vasodilation and increased vascular permeability.

Lipoxins, such as LXA4 and LXB4, are involved in resolving inflammation by inhibiting neutrophil adhesion and chemotaxis, promoting the resolution of inflammatory responses.

COX-1 is responsible for producing prostaglandins that have several key roles:

1. Protects gastric mucosa
2. Maintains renal blood flow
3. Supports platelet aggregation (via TXA₂)
4. Aids macrophage differentiation

The Complement system is activated by:

• Antigen-antibody complexes
• Microbes

Its effects include:

• Kills bacteria
• Recruits neutrophils
• Releases histamine from mast cells

The Kallikrein-kinin system is activated by tissue damage and has the following effects:

• Vasodilation
• Activates complement C5

The Coagulation system is activated by tissue damage and its primary effect is to:

• Create blood clots

The three pathways of complement activation are:

1. Alternative pathway: Initiated by a microbe leading to C3 cleavage.
2. Classical pathway: Initiated by an antibody bound to a microbe, also leading to C3 cleavage.
3. Lectin pathway: Initiated by mannose-binding lectin on a microbe, converging on C3 cleavage.

• C3a: Recruits and activates leukocytes, contributing to inflammation.
• C3b: Opsonizes microbes, coating them for phagocytosis and facilitating their recognition by phagocytes.

The membrane attack complex (MAC), formed by C5 to C9, causes direct lysis of bacteria by creating pores in their membranes, leading to cell death.

C3b facilitates phagocytosis by being deposited on the microbe, which is then recognized by phagocyte C3b receptors, leading to the engulfment and destruction of the microbe.

C5a and C3a are involved in inflammation by recruiting and activating leukocytes, which leads to the destruction of microbes by these immune cells.

Acute inflammation is a rapid and immediate response of the body to injury or infection, characterized by the increased blood flow and accumulation of immune cells at the site of damage.

1. Infection (bacterial, viral, fungal)
2. Tissue injury (trauma, burns)
3. Chemical irritants (toxins, allergens)
4. Ischemia (lack of blood supply)

The principal cells involved in acute inflammation include:

• Neutrophils: First responders to infection
• Macrophages: Clear debris and secrete mediators
• Mast cells: Release histamine and other mediators
• Endothelial cells: Line blood vessels and regulate permeability

Key mediators of acute inflammation include:

• Histamine: Increases blood vessel permeability
• Prostaglandins: Mediate pain and fever
• Cytokines: Regulate immune responses
• Leukotrienes: Attract immune cells to the site of inflammation

The sequence of vascular events in acute inflammation includes:

1. Vasodilation: Increased blood flow to the area
2. Increased vascular permeability: Allows proteins and immune cells to exit the bloodstream
3. Stasis: Slowing of blood flow, leading to accumulation of cells
4. Emigration of leukocytes: White blood cells move to the site of injury

The cardinal signs of acute inflammation are:

• Redness (rubor)
• Heat (calor)
• Swelling (tumor)
• Pain (dolor)
• Loss of function (functio laesa)

Blood vessels play a crucial role in acute inflammation through two main processes:

1. Vasodilation: This process increases blood flow to the affected area, leading to redness and warmth.

2. Increased vascular permeability: This allows proteins and immune cells to exit the bloodstream and enter the tissue, contributing to the inflammatory response.

During vasodilation in acute inflammation, the vessel diameter increases, allowing greater blood flow through the inflamed area. This influx of oxygenated blood causes the tissue to become red and warm, explaining the cardinal signs of rubor (redness) and calor (heat).

The cardinal signs of acute inflammation associated with vasodilation are rubor (redness) and calor (heat).

Mediators involved in vasodilation during acute inflammation include:

• Histamine
• Prostaglandins
• Complements
• Bradykinin
• Etc.

According to Starling's Law, increased vascular permeability leads to an increase in fluid being pushed out from the vessel into the surrounding tissue.

In the early phase of acute inflammation, transudate is characterized by:

1. Endothelial gaps are small, allowing only low-molecular-weight plasma proteins to pass through.
2. The leaked fluid is called transudate.
3. Its composition is mostly water and electrolytes with minimal protein.
4. It appears clear and watery.

In the later phase of acute inflammation:

1. Endothelial gaps enlarge, allowing large-molecular-weight proteins to escape.
2. Leukocytes migrate out of the blood vessel.
3. The fluid becomes protein-rich and cell-rich, referred to as exudate.

The key differences between transudate and exudate are as follows:

During the retraction of endothelial cells, gaps appear between them, allowing substances to leak out into the surrounding tissue. This process mainly occurs in venules and is induced by mediators such as histamine and nitric oxide. It is rapid and short-lived, lasting only minutes.

Endothelial injury occurs in arterioles, capillaries, and venules, and is caused by factors such as burns and some microbial toxins. This type of injury leads to the death of endothelial cells, allowing substances from within the blood vessel to pass unrestricted into the surrounding tissue. It is rapid and may last for hours to days.

Leukocyte-mediated vascular injury occurs in venules and pulmonary capillaries, typically associated with the late stages of inflammation. In this process, hyperactive white blood cells attack and kill endothelial cells, compromising the integrity of the vessel wall. This type of injury is long-lived, lasting for hours.

Vasodilation causes blood to flow slower, leading to stasis where vessels are packed with slow-moving red cells. This allows neutrophils to move to the peripheral zone of the blood vessel, facilitating their migration out of the vessel.

During vasodilation, plasma fluid escapes into tissues, resulting in increased blood viscosity.

Margination is the redistribution of leukocytes toward the endothelial surface due to stasis and increased viscosity, allowing prolonged contact between neutrophils and the endothelium for later adhesion and emigration.

Vasodilation slows down blood flow, causing stasis which allows neutrophils to shift from the central flow toward the vessel wall, aiding their migration out of the blood vessel.

Increased vascular permeability allows immunoglobulins and coagulation proteins to move into damaged tissue, which helps in:

• Destroying invading microorganisms through immunoglobulins.
• Facilitating blood clot formation through coagulation proteins.

The key steps in neutrophil emigration include:

1. Neutrophil surface molecules: Neutrophils have binding sites like Sialyl-Lewis X glycoprotein and integrins for interaction with endothelial cells.
2. Endothelial counter-receptors: Endothelial cells express selectins that bind to neutrophils, initiating attachment.
3. Chemokine influence: Chemokines increase the stickiness of neutrophils, activating integrins into a high-affinity form.
4. Firm adhesion: Activated integrins bind to ICAM-1 on endothelial cells, anchoring neutrophils.
5. Emigration/Transmigration: Neutrophils migrate through the endothelial wall into surrounding tissue, driven by a chemokine gradient.
6. Role of cytokines: Cytokines like TNF enhance the expression of adhesion molecules on endothelial cells, improving neutrophil attachment and migration.

1. Rolling: Neutrophils express Sialyl-Lewis X-modified glycoprotein and integrins, allowing loose adhesion to P-selectin and E-selectin on endothelial cells.

2. Integrin activation by chemokines: Chemokines activate integrins on the leukocyte.

3. Stable adhesion: Activated integrins bind strongly to ICAM-1 on endothelial cells.

4. Migration through endothelium: Neutrophils migrate through the endothelial layer using PECAM-1 (CD31).

5. Transmigration: Neutrophils pass through the endothelium into surrounding tissue.

Adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) on endothelial cells and LFA-1 on leukocytes, facilitate the binding of leukocytes to endothelial cells. They are increased during inflammation and function like a lock and key to ensure stable adhesion of leukocytes to the endothelium.

PECAM-1 (CD31) is crucial for the migration of neutrophils through the endothelial cell layer, allowing them to cross the endothelial barrier and enter the surrounding tissue during the inflammatory response.

During phagocytosis, neutrophils:

• Attach to C3b-labeled microbes (opsonized pathogens).
• Engulf and destroy these microbes.

The two main opsonins involved in phagocytosis are C3b and Fc.

The first step in the process of phagocytosis is that antibodies (Ab) bind to the antigen (Ag).

Fc receptors on the phagocytic cell bind to the antibody-antigen complex, facilitating the engulfment of the complex.

After the pseudopodia engulf the complex, a phagosome is formed, which then fuses with a lysosome for intracellular destruction.

The final outcome of phagocytosis is intracellular destruction of the engulfed pathogens.

1. Recognition and attachment of the microbe
2. Engulfment of the microbe
3. Killing and degradation

Neutrophils undergo self-destruction as they are considered suicide cells after killing the microbes.

The first step is the conversion of oxygen (O₂) to superoxide (O₂⁻) via the NADPH oxidase pathway.

The bactericidal agents produced are:

• Superoxide (O₂⁻)
• Hydrogen peroxide (H₂O₂)
• Hypochlorous acid (HOCl)

Myeloperoxidase (MPO) converts hydrogen peroxide (H₂O₂) into hypochlorous acid (HOCl), which is a bactericidal agent.

Acute inflammation is a rapid and immediate response of the body to injury or infection, characterized by the increased blood flow and accumulation of immune cells at the site of damage.

1. Infection (bacterial, viral, fungal)
2. Tissue injury (trauma, burns)
3. Chemical irritants (toxins, allergens)
4. Immune reactions (allergic responses, autoimmune diseases)

The principal cells involved in acute inflammation include:

• Neutrophils: First responders to infection or injury.
• Macrophages: Engulf pathogens and debris, and secrete mediators.
• Mast cells: Release histamine and other mediators that promote inflammation.

Key mediators of acute inflammation include:

• Histamine: Increases blood vessel permeability.
• Prostaglandins: Promote vasodilation and pain.
• Cytokines: Regulate immune responses and inflammation.
• Leukotrienes: Attract immune cells to the site of inflammation.

The sequence of events includes:

1. Vasodilation: Increased blood flow to the affected area.
2. Increased permeability: Allows plasma proteins and leukocytes to exit the bloodstream.
3. Leukocyte migration: Neutrophils and other immune cells move to the site of injury.
4. Phagocytosis: Immune cells engulf and destroy pathogens and debris.

The cardinal signs of acute inflammation are:

• Redness (rubor): Due to increased blood flow.
• Heat (calor): Also due to increased blood flow.
• Swelling (tumor): Caused by fluid accumulation.
• Pain (dolor): Resulting from chemical mediators and pressure on nerves.
• Loss of function: Due to pain and swelling affecting mobility.

The systemic effects of acute inflammation include:

• Fever: An increase in body temperature.
• Tiredness: A general feeling of fatigue or malaise.
• Loss of appetite: Decreased desire to eat.
• Leucocytosis: An increase in the number of white blood cells in the bloodstream.

The suffix '-tosis' indicates an increase in number in medical terminology. For example:

The possible outcomes of acute inflammation include:

• Resolution: Complete healing without residual effects.
• Suppuration: Formation of pus.
• Repair and organization, fibrosis: Replacement of damaged tissue with scar tissue.
• Chronic inflammation: Prolonged inflammation that can lead to tissue damage.

The potential outcomes of acute inflammation include:

1. Resolution - The injurious agent is destroyed, and normal tissue function is restored.
2. Suppuration - Formation of pus, often seen in infections.
3. Repair and Organisation - Healing of tissue through regeneration or scar formation.
4. Fibrosis - Excessive scar tissue formation leading to loss of function.
5. Chronic Inflammation - Persistent inflammation that can lead to further tissue damage.

A brain abscess is a collection of bacteria and neutrophils that forms a localized infection in the brain. It is characterized by a well-defined capsule and purulent material. The presence of a brain abscess can lead to raised central cranial pressure, which can have serious neurological consequences.

Multiple lung abscesses are pockets of pus and necrotic material found throughout lung tissue. They can significantly interfere with respiration, leading to respiratory distress and other complications. The presence of these abscesses indicates a severe inflammatory response in the lungs.

The beneficial effects of acute inflammation include:

1. Destroying invading microorganisms
2. Delivering oxygen and nutrients to the injured tissue
3. Delivering drugs (e.g. antibiotics) to the site of infection

The harmful effects of acute inflammation include:

1. Destruction of normal tissue (non-specific)
2. Swelling (oedema) that can be harmful in certain anatomical sites:
   • Infection of the epiglottis (acute epiglottitis) can block the airway.
   • Cerebral oedema can lead to brain herniation.

Central abdominal pain in Tommy's case is caused by:

• Acute inflammation of the appendix leading to oedema, which stimulates the pain fibers in that area.
• Pain in the midgut is referred to the central abdomen, known as 'referred pain' or 'visceral pain'.

Tommy experiences pain that moves to the right lower quadrant because:

• The inflammation starts to affect the outer layer of the peritoneum, which stimulates pain fibers in the abdominal wall.

Fever is caused by cytokines, especially prostaglandins, entering the bloodstream, which then signal the brain (specifically the hypothalamus) to set a higher body temperature.

The appendix is likely inflamed due to being blocked by a faecalith, leading to an overgrowth of bacteria trapped there, resulting in infection, tissue injury, and ultimately acute inflammation.

A normal appendix shows tissue stained pink and purple with visible cellular structures, including long and flat smooth muscle fibers and a normal cellular distribution.

The microscope view of an acute appendicitis case shows densely packed purple cells, indicating a high concentration of inflammatory cells, particularly neutrophils, suggesting a significant inflammatory response.

The presence of too many inflammatory cells, especially neutrophils, indicates a strong inflammatory response, which is characteristic of acute appendicitis and suggests tissue damage and the need for medical intervention.

The cardinal signs of acute inflammation are redness, swelling, pain, and heat.

Lymphangitis is the secondary inflammation of lymphatics, indicated by the presence of red streaks near a skin wound, which is a telltale sign of infection.

Conditions that lead to recurrent infections include:

1. Cancer patients with low neutrophil counts.
2. Leukocyte adhesion deficiency (Type 1) - mutations in the β chain of CD11/CD18 on cells.
3. Leukocyte adhesion deficiency (Type 2) - mutation in the enzyme needed to make the receptor for neutrophils on the vessel wall.
4. Chronic granulomatous disease - decreased oxidative burst, leading to ineffective macrophage response.
5. Chediak-Higashi Syndrome - mutations affecting lysosomal membrane tethering, causing delayed fusion of phagosomes with lysosomes and resulting in infections and albinism.

Chediak-Higashi Syndrome is characterized by mutations in the protein needed for lysosomal membrane tethering, leading to:

• Delayed fusion of phagosomes with lysosomes in leukocytes.
• Side effects include autophagocytosis of melanosomes in melanocytes, resulting in albinism, and granular defects in NK cells and platelets.
• A mnemonic for this syndrome is CHINA: Chediak Higashi, Infections, Neuropathy, Albinism.

C2 deficiency is the most common complement deficiency, leading to bacterial infections. However, some patients may be asymptomatic due to the alternate pathway being able to cope with the deficiency.

Patients with C5-9 deficiencies are prone to bacterial infections, particularly from Neisseria, due to its thin cell wall.

C1 inhibitor deficiency is more common than C2 deficiency and blocks the activation of C1. It also inhibits Factor XII and the kallikrein system, leading to unregulated production of kallikrein, which can cause hereditary angioedema.

Defects in these enzymes can lead to excess production of complement, which may destroy red blood cells, resulting in paroxysmal nocturnal hemoglobinuria (PNH).

Many anti-inflammatory agents block the action of COX-1 and/or COX-2, which are involved in the inflammatory response.

In patients with a1-antitrypsin deficiency, proteases released by neutrophils are not destroyed, leading to excess tissue destruction.