Hypersensitivity Reactions: Types and Examples

Hypersensitivity reactions are immune responses that can cause tissue damage and inflammation. There are four types of hypersensitivity reactions, each with different mechanisms and clinical presentations.

Type I hypersensitivity reaction is an immediate hypersensitivity reaction mediated by IgE in response to an innocuous environmental antigen. Examples of such reactions are allergic rhinitis and systemic urticaria.

Type II hypersensitivity reaction is an antibody-mediated reaction. Cellular injury may result from complement activation, antibody-dependent cell-mediated cytotoxicity or phagocytosis. Examples include incompatible blood transfusions, haemolytic disease of the newborn and autoimmune haemolytic anaemias.

Type III hypersensitivity reaction is an immune complex-mediated reaction. Immune complexes are lattices of antibody and antigen. When these are not cleared from the circulation, they may trigger an inflammatory response. An example of this type of reaction is extrinsic allergic alveolitis, otherwise known as ‘bird fancier’s lung’, a hypersensitivity pneumonitis caused by exposure to bird droppings.

Type IV hypersensitivity reaction is a delayed hypersensitivity reaction involving T helper cells that become activated upon contact with an antigen, which results in a clonal expansion over 1–2 weeks. Repeated exposure to the antigen results in cytokine release from sensitised T-cells, leading to macrophage-induced phagocytosis.

Anaphylaxis is a type I-mediated hypersensitivity reaction, involving the release of inflammatory mediators (such as histamine), which precipitate vasodilatation and oedema. Anaphylaxis is characterised by the rapid onset of respiratory and circulatory compromise.

Understanding the different types of hypersensitivity reactions is important for diagnosis and treatment. Treatment may involve removal of the source of hypersensitivity, immunosuppressive therapy, or administration of epinephrine in the case of anaphylaxis.

Misconceptions about the Pathophysiology of Allograft Rejection

There are several misconceptions about the pathophysiology of allograft rejection. One of them is that hyper-acute allograft rejection is solely caused by class I HLA antibody activation, granulocyte adhesion, and thrombosis. While these factors do play a role, the ultimate result of hyper-acute rejection is thrombosis of the vessels and graft ischaemia, which presents itself as graft swelling once perfusion is reinstated.

Another misconception is that donor MHC I antigens react with host CD8 resulting in direct cytotoxic damage, which is a sequence in the pathophysiology of acute rejection response, not hyper-acute rejection.

Class II HLA antibodies are often thought to be the primary source of activation of the coagulation cascade, but this is not the case. Monocytes are also not activated in this process.

Interstitial fibrosis is often thought to be a mechanism of acute rejection, but it is actually the end-stage mechanism of chronic graft rejection.

Lastly, lymphocyte, killer T-cell, and cytokine activation are often thought to be part of the mechanism of hyper-acute allograft rejection, but they are actually part of the mechanism of action in acute allograft rejection.

It is important to have a clear understanding of the pathophysiology of allograft rejection to properly diagnose and treat patients.

Overview of Complement Deficiencies and Associated Infections

Membrane Attack Complex (MAC) Formation Deficiency
MAC is the final stage of complement activation that leads to the formation of a hole in the bacterial cell membrane, causing cell lysis. Patients with MAC formation deficiency are prone to recurrent bacterial infections, particularly with Neisseria meningitidis or Neisseria gonorrhoeae.

C1 Deficiency
Deficiencies of components of the classical pathway (C1, C2, and C4) are associated with immune complex diseases such as systemic lupus erythematosus (SLE) and an increased risk for bacterial infection. C2 deficiency is associated with an increased risk for bacterial infection, while C3 deficiency increases the risk for infections by encapsulated organisms (e.g., pneumococci, Haemophilus, and meningococci).

C2 Deficiency
Deficiencies of components of the classical pathway (C1, C2, and C4) are associated with immune complex diseases such as SLE and an increased risk for bacterial infection. C2 deficiency is associated with an increased risk for bacterial infection, while C3 deficiency increases the risk for infections by encapsulated organisms (e.g., pneumococci, Haemophilus, and meningococci).

C4 Deficiency
Deficiencies of components of the classical pathway (C1, C2, and C4) are associated with immune complex diseases such as SLE and an increased risk for bacterial infection. C2 deficiency is associated with an increased risk for bacterial infection, while C3 deficiency increases the risk for infections by encapsulated organisms (e.g., pneumococci, Haemophilus, and meningococci).

Immunoglobulin A (IgA) Deficiency
IgA deficiency results in autoimmune diseases, respiratory infections, urinary tract infections, and gastrointestinal infections.

Understanding Hepatitis B: Causes, Symptoms, Complications, and Management

Hepatitis B is a type of virus that contains double-stranded DNA and is transmitted through exposure to infected blood or body fluids. It can also be passed from mother to child during childbirth. The incubation period for this virus is between 6 to 20 weeks. Symptoms of hepatitis B include fever, jaundice, and elevated liver transaminases. Complications of this infection include chronic hepatitis, fulminant liver failure, hepatocellular carcinoma, glomerulonephritis, polyarteritis nodosa, and cryoglobulinemia.

To prevent hepatitis B, children born in the UK are now vaccinated as part of the routine immunization schedule. At-risk groups who should also be vaccinated include healthcare workers, intravenous drug users, sex workers, close family contacts of an individual with hepatitis B, individuals receiving regular blood transfusions, chronic kidney disease patients, prisoners, and chronic liver disease patients. However, around 10-15% of adults may fail to respond or respond poorly to the vaccine.

Testing for anti-HBs is only recommended for those at risk of occupational exposure and patients with chronic kidney disease. The interpretation of anti-HBs levels is as follows: an anti-HBs level of >100 indicates an adequate response, 10-100 indicates a suboptimal response, and <10 indicates a non-responder. Management of hepatitis B includes the use of pegylated interferon-alpha, which reduces viral replication in up to 30% of chronic carriers. Other antiviral medications such as tenofovir, entecavir, and telbivudine are also used to suppress viral replication.

Although it is possible for the man to have been prescribed any of the medications listed, it is evident that he is experiencing angioedema, as indicated by the swelling of his tongue and lips. Ramipril, an ACE inhibitor, is the medication most commonly associated with this side effect. Even if the patient has no history of allergies or negative reactions to ACE inhibitors, angioedema can still occur. While the likelihood of this happening is low, it is important to keep in mind due to the large number of patients taking this type of medication and the potential complications associated with angioedema.

Angiotensin-converting enzyme (ACE) inhibitors are commonly used as the first-line treatment for hypertension and heart failure in younger patients. However, they may not be as effective in treating hypertensive Afro-Caribbean patients. These inhibitors are also used to treat diabetic nephropathy and for secondary prevention of ischaemic heart disease. The mechanism of action of ACE inhibitors is to inhibit the conversion of angiotensin I to angiotensin II. They are metabolized in the liver through phase 1 metabolism.

ACE inhibitors may cause side effects such as cough, which occurs in around 15% of patients and may occur up to a year after starting treatment. This is thought to be due to increased bradykinin levels. Angioedema may also occur up to a year after starting treatment. Hyperkalaemia and first-dose hypotension are other potential side effects, especially in patients taking diuretics. ACE inhibitors should be avoided during pregnancy and breastfeeding, and caution should be exercised in patients with renovascular disease, aortic stenosis, or hereditary or idiopathic angioedema.

Patients receiving high-dose diuretic therapy (more than 80 mg of furosemide a day) are at an increased risk of hypotension when taking ACE inhibitors. Before initiating treatment, urea and electrolytes should be checked, and after increasing the dose, a rise in creatinine and potassium may be expected. Acceptable changes include an increase in serum creatinine up to 30% from baseline and an increase in potassium up to 5.5 mmol/l. Patients with undiagnosed bilateral renal artery stenosis may experience significant renal impairment. The current NICE guidelines provide a flow chart for the management of hypertension.

Understanding Immunoglobulin Deficiencies and Their Symptoms

Immunoglobulin deficiencies are a group of disorders that affect the body’s ability to produce specific types of antibodies, leading to an increased risk of infections and autoimmune diseases. Here, we will discuss the different types of immunoglobulin deficiencies and their associated symptoms.

IgA Deficiency:
This deficiency is characterized by a decrease in immunoglobulin A, which can lead to an increased incidence of mucosal infections, particularly gastrointestinal infections with Giardia. Patients may also experience recurrent ear infections, sinusitis, bronchitis, pneumonia, and urinary tract infections. Additionally, IgA deficiency increases the risk of autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus.

IgE Deficiency:
IgE is responsible for fighting parasitic and helminthic infections, so patients with IgE deficiency are more likely to develop these types of infections. They are also at an increased risk of autoimmune disease and non-allergic reactive airways disease.

IgG Deficiency:
Patients with IgG deficiency are prone to developing infections from encapsulated bacteria, such as Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis. This deficiency can lead to upper and lower respiratory tract infections and meningitis.

IgM Deficiency:
Primary selective IgM deficiency results in increased infections by bacteria, fungi, and viruses, as well as increased autoimmune diseases. However, this deficiency does not have the selectivity for mucosal membrane infections seen in IgA deficiency.

Severe Combined Immunoglobulin Deficiency (SCID):
SCID is a rare disorder that results from abnormal T- and B-cell development due to inherited genetic mutations. Patients with SCID are affected early in life with multiple severe bacterial, viral, and fungal infections, as well as failure to thrive, interstitial lung disease, and chronic diarrhea.

In conclusion, understanding the different types of immunoglobulin deficiencies and their associated symptoms is crucial for prompt recognition and treatment of opportunistic bacterial infections and autoimmune diseases.

Understanding Allergic Reactions: Types and Symptoms

Allergic reactions can take many forms, each with its own set of symptoms and causes. Anaphylaxis is a severe and potentially life-threatening reaction that can occur in response to drugs, insect stings, or certain foods. It is characterized by rapid onset of airway, breathing, and circulation problems, as well as skin and mucosal changes. Systemic mastocytosis is another type of allergic reaction that can cause symptoms such as itching, abdominal cramping, and even shock. Pseudoallergy, on the other hand, can mimic true allergies but has different underlying causes, such as altered histamine metabolism or food intolerance.

Serum sickness is a self-limited allergic reaction that occurs after exposure to foreign proteins. It is a type III hypersensitivity reaction that can cause fever, skin rash, and joint symptoms. Contact dermatitis is an inflammatory skin reaction that can be caused by either an irritant or an allergen. Allergic contact dermatitis is a type IV delayed hypersensitivity reaction that occurs after sensitization and subsequent re-exposure to an allergen, while irritant contact dermatitis is an inflammatory response that occurs after damage to the skin by chemicals.

It is important to recognize the symptoms of these different types of allergic reactions and seek medical attention if necessary. Anaphylaxis, in particular, is a medical emergency that can lead to death if not treated promptly. By understanding the different types of allergic reactions and their causes, we can take steps to prevent them and manage their symptoms effectively.

Differential diagnosis of immunodeficiency in an adolescent with weight loss and recurrent infection

Malnutrition, primary immunodeficiency, cytomegalovirus (CMV) infection, human immunodeficiency virus (HIV) infection, and diabetes mellitus are among the possible causes of immunodeficiency in an adolescent with weight loss and recurrent infection. Malnutrition can suppress the immune system and is often associated with anorexia nervosa, which can be characterized by a very low body mass index (BMI), lanugo hair growth, hypothermia, bradycardia, and hypotension. Primary immunodeficiency syndromes, which are usually inherited as single-gene disorders, tend to present in infancy or early childhood with poor growth and weight gain and recurrent, prolonged, severe, or atypical infections. Cytomegalovirus (CMV) is a herpes virus that can cause serious complications in immunocompromised individuals or congenital cases, but is usually asymptomatic in immunocompetent individuals. Human immunodeficiency virus (HIV) infection can result in immunodeficiency by infecting and destroying CD4 cells, and should be suspected in individuals with prolonged, severe, or recurrent infections, particularly if they are a member of a high-risk group. Diabetes mellitus, especially type I, can also cause dysfunction of the immune system and increase the risk of infection. However, in an adolescent with a low BMI, type II diabetes would be very unlikely.

Overview of Viral Hepatitis: Types, Transmission, and Risk Factors

Viral hepatitis is a group of infectious diseases that affect the liver and can cause serious health complications. There are five main types of viral hepatitis: A, B, C, D, and E. Each type has its own unique characteristics, transmission routes, and risk factors.

Hepatitis A is transmitted via the faecal-oral route and is most common in developing countries. It can cause symptoms similar to other types of viral hepatitis, but is less severe. Hepatitis B is transmitted via blood-to-blood and bloody fluid contact, and is most prevalent in migrant populations from certain regions. Hepatitis C is highly infectious and is commonly transmitted through shared needles or other injecting paraphernalia used for illicit drugs. Hepatitis D is a rare type of viral hepatitis that can only occur in patients with existing hepatitis B infection. Hepatitis E is also transmitted via the faecal-oral route, but is less common and usually only causes mild illness.

If a healthcare professional sustains a needlestick injury or other high-risk exposure to hepatitis C, they should have blood tests taken at specific intervals to confirm active infection. Hepatitis B vaccination is recommended for individuals working in high-risk clinical areas, and can also prevent hepatitis D infection. Chronic infection is rare for hepatitis E, unless the affected person is immunocompromised.

Understanding the different types of viral hepatitis, their transmission routes, and risk factors is important for preventing and managing these infections.

Patients who are immunosuppressed, such as those taking azathioprine, should not receive live attenuated vaccines including BCG, MMR, oral polio, yellow fever, and oral typhoid.

Types of Vaccines and Their Characteristics

Vaccines are essential in preventing the spread of infectious diseases. However, it is crucial to understand the different types of vaccines and their characteristics to ensure their safety and effectiveness. Live attenuated vaccines, such as BCG, MMR, and oral polio, may pose a risk to immunocompromised patients. In contrast, inactivated preparations, including rabies and hepatitis A, are safe for everyone. Toxoid vaccines, such as tetanus, diphtheria, and pertussis, use inactivated toxins to generate an immune response. Subunit and conjugate vaccines, such as pneumococcus, haemophilus, meningococcus, hepatitis B, and human papillomavirus, use only part of the pathogen or link bacterial polysaccharide outer coats to proteins to make them more immunogenic. Influenza vaccines come in different types, including whole inactivated virus, split virion, and sub-unit. Cholera vaccine contains inactivated strains of Vibrio cholerae and recombinant B-subunit of the cholera toxin. Hepatitis B vaccine contains HBsAg adsorbed onto aluminium hydroxide adjuvant and is prepared from yeast cells using recombinant DNA technology. Understanding the different types of vaccines and their characteristics is crucial in making informed decisions about vaccination.