2535 - week 7

function and evaluation of the immune system

- primary function is to protect the body against invading pathogens

- evolves and adapts based on exposure to environment

- exhibits: memory, specificity, replicability and redundancy

function and evaluation of the immune system cont.

- specificity indicates that immune system can distinguish between non-cross-reacting antigens

- memory ensures quicker and more vigorous response to similar pathogen

- mobility of elements of the immune system enables local reactions to provide systemic protection

function and evaluation of the immune system cont..

- replication of the cellular component of immune system amplified the immune response

- redundancy refers to immune system's ability to produce components with the same biological effect but produced from diff. cell lines

immunologic disease defined

- immune disease/disorder

- dysfunction of immune system

- characterised in diff ways

- components of immune system are affected

overactive immune system

- mistakenly attack healthy cells

- create autoimmune diseases

underactive immune system

- can't adequately protect body

- immunodeficiency disorders (HIV/AIDS)

- makes body more susceptible to diseases

congenital disease (primary)

- disease present at birth

- genetic factors

acquired disease (secondary)

- disease develops after birth

- due to environmental, infections or medical treatment

methods to distinguish self from non-self

- immune system is designed to attack and destroy a broad spectrum of foreign antigens and pathogens

- self-tolerance is the ability of immune system to distinguish self from nonself

immunological disease

i. body constantly under attack by microbes

ii. system is self-regulated and self-limiting (must be able to distinguish self from non-self)

iii. 2 key activities: defence and attack

2 functional divisions of the immune system

Self:

Tolerance

- immune system recognizes body’s own cells and avoids attacking them

- this ability is critical for preventing autoimmune diseases

Non-Self (Foreign invaders):

Pathogens

- includes viruses, bacteria, fungi, and parasites that can cause infections.

Response

- immune system responds to invaders by initiating defence mechanisms, such as producing antibodies or mobilizing white blood cells to destroy them

innate immune system

- physical and chemical defence are most basic form innate immunity and the first line of defence against invading pathogens

- skin is the largest organ of body and has primary role of physical defence

- alterations in the skin such as burns and abrasions allow portal entry for pathogens

components of innate immunity

- physical barriers (skin, mucous membranes)

- chemical barriers (stomach acid, enzymes in saliva and tears)

- cellular defences (phagocytes - macrophages, neutrophils etc, natural killer (NK) cells)

innate immune response

- invasion of infectious pathogens will lead to innate immunity to halt progression of the infection

- innate immunity is present from birth which uses pre-existing but limited receptors to recognize and destroy pathogens

- innate immune cells include subgroups of leukocytes, specifically monocytes/macrophages, neutrophils, basophils, mast cells and eosinophils

immunoglobulins

- known as antibodies, are specialized produced by the immune system

- primary function is to identify and neutralize foreign objects like bacteria, viruses, and toxins

- critical to the body's defence mechanism, helping to detect and remember pathogens, ensuring a rapid and effective response if they invade again

5 main classes

- IgA, IgD, IgE, IgG and IgM

- each with specific roles in immune response

IgG

- most abundant immunoglobulin

- can combine with antigens to neutralize activity or adhere to antigens to promote phagocytosis

- important for infants

- transmitted across placenta from mother to fetus

- sometimes employs complement activation

function IgG

- neutralization: IgG antibodies can neutralize pathogens like bacteria and viruses by binding to them, preventing their entry into host cells

- opsonization: they tag pathogens for destruction by immune cells, like macrophages and neutrophils

- complement activation: IgG triggers the complement system, a series of protein reactions that lead to the lysis of pathogens

- passive immunity: IgG is the only antibody that can cross placenta, providing fetus with passive immunity during pregnancy

- antibody-dependent cellular cytotoxicity (ADCC): IgG can mediate ADCC, where immune cells kill infected or cancerous cells tagged with IgG

- IgG versatility makes it a vital component of the immune defence mechanism

IgM

- first responder of immune system

- primary resource: first antibody produced in response to an infection

- pentamer structure: its large structure (5 units) makes it highly effective at binding to antigens

- complement activation: IgM efficiently activates the complement system, which helps destroy pathogens

- agglutination: clumps pathogens together, making it easier for the immune system to clear them

- b-cell: IgM acts as a receptor to help initiate the immune response

- these key functions make IgM essential in the early stages of immune defense

IgM cont

- large size

- noteworthy for their large size

- do not readily pass into tissues or across placenta

- develop more quickly than IGG antibodies following antigenic stimulation

- important in controlling: bacteria that enter the bloodstream, agglutination of large foreign substances

IgA

- IgA is like the bodyguard of your mucosal surfaces

- mucosal immunity: found in mucous membranes lining the gut, respiratory tract, and urogenital tract; provides barrier against pathogens

- neutralization: IgA binds to pathogens and toxins, preventing them from adhering to and penetrating epithelial cells

- secretory component: unique aspect of IgA is that it can be secreted in bodily fluids like saliva, tears and breast milk, offering localized protection

- immune exclusion: helps in immune exclusion by trapping pathogen in mucus and facilitating their removal from the body

- antigen transport: IgA plays role transporting antigens across epithelial cells to immune cells, initiating immune responses

- vital player in maintaining integrity of mucosal surfaces and ensuring localized immune protection

IgD

- lesser-known sibling of the antibody family

- B cell receptor: IgD is mostly found on the surface of immature B cells and acts as a receptor to initiate B cell activation and differentiation

- Pathogen interaction: though not as well understood, IgD can bind to pathogens and may play a role in respiratory immune responses

- Regulation: helps in regulating immune responses by controlling cell maturation and antibody production

- while it's not the star of the immune response show, IgD plays a crucial role in starting the immune process and maintaining immune system balance

immunity across the lifespan

- immunity evolves as you age

- Newborns: rely on maternal antibodies passed through the placenta and breast milk, esp IgG, for initial immunity

- Infants: begin developing their own immune responses, vaccinations are crucial during this period to build protection

- Children: immune system becomes more robust, learning to combat a variety of pathogens through exposure and vaccinations

- Adolescence

- Immune maturation: immune system to develop, becoming more efficient and responsive

- Hormonal changes: Puberty can influence function, sometimes temporarily affecting its efficiency

immunity in infancy

- based on maternal IgG for 3-6 months, granting temporary passive immunity, but transferred antibodies have low affinity

- breastfeeding can transfer IgA; vaccinations grant additional protection

- newborns can only respond effectively to protein antigens, NOT glycoproteins or polysaccharides, and many immune functions are limited

immunity in adolescence

- hormonal changes impact the immune system as B cells and macrophages have hormone receptors

- risk for inflammatory and autoimmune diseases increases

- immune dimorphism (sexes respond differently to infection/vaccination)

immunity in older adults

- age reduces immune response in immune senescence

- lower B and T cell production, but increase apoptosis of these cells

- age-related changes are multifactorial

- comorbidity (more than 2 diseases) significantly impacts immunity and autoimmune disorders become more likely due to misinterpretation of signals flooding the body

classification of immunological diseases (immunodeficiency disorders)

PRIMARY:

- genetic disorders present from birth, such as severe combined immunodeficiency (SCID)

SECONDARY:

- acquired later in life due to factors like infection, medication or other diseases

classification of immunological diseases (autoimmune disease)

ORGAN-SPECIFIC:

- these diseases target specific organs or tissues, such as type 1 diabetes (affects the pancreas) and multiple sclerosis (affects nervous system)

SYSTEMIC:

- these diseases affect multiple organs or systems, such as systemic lupus

- erythematosus (SLE and rheumatoid arthritis)

classification of immunological diseases (hypersensitivity reactions)

TYPE I: immediate hypersensitivity (e.g. allergies, anaphylaxis)

TYPE II: antibody-dependant cytotoxic reactions (hemolytic anemia)

TYPE III: immune complex-mediated reactions (e.g. systemic lupus erythematosus)

TYPE IV: delayed-type hypersensitivity (e.g. contact dermatitis)

classification of immunological diseases (allergic diseases)

- conditions like asthma, allergic rhinitis, and atopic dermatitis fall into this category, often involving IgE-mediated responses

classification of immunological diseases (chronic inflammatory diseases)

- diseases characterized by persistent inflammation, such as Crohn's disease and ulcerative colitis

allergy hypersensitivity reactions

too much or inappropriate response to foreign agents

immune deficiency diseases

- too small of a response to foreign agents

- immune deficiency disease and subdivided into: inherited and acquired forms

- deficiency of t and b cell immune systems or BOTH

autoimmune disease

- hypersensitivity reactions to the body own components mediated by lymphocytes and/or antibodies

hypersensitivity reactions

- exaggerated immune responses that cause tissue damage

type I: immediate hypersensitivity

mechanism: IgE antibodies bind to allergens, causing mast cells and basophils to release histamines and other chemicals

examples: allergic rhinitis, asthma, anaphylaxis

symptoms: itching, swelling, bronchoconstriction, anaphylactic shock

type II: antibody-dependent cytotoxic reaction

mechanism: IgG or IgM antibodies target antigens on cell surfaces, leading to cell destruction via complement activation or phagocytosis

examples: hemolytic anemia, goodpastures syndrome, Rh incompatibility in newborns

symptoms: cell and tissue damage, varying based on the affected organ

type III: immune complex-mediated reactions

mechanism: immune complexes (antigen-antibody) deposit in tissues, triggering inflammation and tissue damage

examples: systemic lupus erythematosus, post-streptococcal glomerulonephritis

symptoms: inflammation in affected tissues, such as joints, kidneys or blood vessels

type IV: delayed-type hypersensitivity

mechanism: t cell-mediated response, often taking 48-72 hours to develop

examples: contact dermatitis, tuberculosis skin test, type 1 diabetes

symptoms: localized tissue damage, inflammation, granuloma formation

- these reactions highlight how the immune system can sometimes overreact, leading to harmful effects

hypersensitive reaction (summary)

Type I (IgE mediated):

- immediate, local or systemic

- occurs when T helpers stimulate B cells to produce IgE that sensitizes mast cells and basophils; requires repeated exposure to large doses of allergen

Type II (cytotoxic hypersensitivity):

- immediate (usually), targets single cell

- IgG or IgM antibodies bind to antigen on individual’s own cells, triggering antibody production in macrophages

- cell lysis occurs due to activation of complement and phagocytosis

Type III (immune complex-mediated):

- delayed, local or systemic

- circulating antigen-antibody complexes accumulate in tissue, triggering the complement system’s inflammatory response

Type IV (delayed hypersensitivity):

- delayed, two phases: sensitizing and effector

- cell-mediated (T cells), not antibody-mediated; antigen presentation results in cytokine release, severe tissue injury, and fibrosis

type I hypersensitivity reactions

caused by release of vasoactive amines, producing:

- contraction of most nonvascular smooth muscle

- vasodilation

- increased vascular permeability

- stimulation of secretory activity of some glands

typical lab finding:

- increase in eosinophils in blood or tissue

- increase in IgE in plasma

- potential atopic allergens may be evaluated by skin-testing

asthma-primary involves type I hypersensitivity

Mechanism

Sensitization Phase: Initial exposure to an allergen (e.g., pollen, dust mites) causes B cells to produce IgE antibodies specific to that allergen.

IgE Binding: These IgE antibodies bind to receptors on mast cells and basophils.

Re-exposure: Upon subsequent exposure to the same allergen, the allergen cross-links the bound IgE on mast cells and basophils.

Degranulation: This triggers the mast cells and basophils to release inflammatory mediators such as histamines,

- leukotrienes, and cytokines

asthma continued

Effect

Bronchoconstriction

- release of mediators causes the smooth muscles in the bronchi to contract, narrowing the

airways and making it difficult to breathe

Inflammation

- inflammatory mediators lead to swelling and increased mucus production in the airways, further

obstructing airflow

Symptoms

- this results in classic asthma symptoms such as wheezing, coughing, shortness of breath, and chest tightness

- various allergens can trigger this hypersensitivity reaction and is a key component of the pathophysiology of asthma

allergic rhinitis - type I

- allergic rhinitis, commonly known as hay fever, is another example of a Type I (immediate) hypersensitivity reaction

Mechanism

Sensitization Phase:

- initial exposure to an allergen (like pollen or dust mites) prompts B cells to produce IgE antibodies

specific to that allergen

IgE Binding:

- these antibodies attach to receptors on mast cells and basophils within the nasal mucosa

Re-exposure:

- upon subsequent encounters with the allergen, it cross-links the bound IgE on these cells

Degranulation:

- this triggers the release of inflammatory mediators such as histamine, leukotrienes, and prostaglandins

allergic rhinitis - type I cont.

Effects

Vasodilation and Increased Permeability - these mediators cause blood vessels in the nasal passages to widen and become more permeable, leading to nasal congestion.

Increased Mucus Production:

- mucous glands are stimulated to produce more mucus, contributing to runny nose and postnasal drip.

Nerve Stimulation:

- histamine and other mediators irritate sensory nerves, resulting in itching and sneezing.

allergic rhinitis (symptoms)

- sneezing: sudden and repetitive due to irritation of nasal

passages

- itchy nose and eyes: caused by the irritation and inflammation

of mucosal surfaces

- runny nose: excess mucus production

- congestion: swelling of nasal tissues makes breathing difficult

- this cascade of events highlights the body's rapid response to allergens, leading to the characteristic symptoms of allergic rhinitis

urticaria - type I hypersensitivity

- urticaria, commonly known as hives, is a skin reaction that results in itchy, raised,

red or skin-coloured welts (wheals) on the skin's surface

- it's typically associated with a type I

hypersensitivity reaction.

Mechanism

Allergen Exposure:

- when an allergen (like certain foods, medications, or insect stings) enters the body, it triggers the production of IgE antibodies

IgE Binding:

- these antibodies bind to mast cells and basophils in the skin

Re-exposure:

- upon re-exposure to the allergen, it cross-links the IgE on these cells

Histamine Release:

- this leads to the release of histamine and other inflammatory mediators from the mast cells and basophils

Vasodilation and Increased Permeability: - these mediators cause blood vessels in the skin to widen and become more permeable,

leading to fluid leakage into the surrounding tissues and the formation of wheals

urticaria (symptoms)

Wheals: Raised, red, itchy welts that can appear anywhere on the body

Angioedema: Swelling beneath the skin, often around the eyes, lips, and throat

Duration: Wheals typically last less than 24 hours but can recur

Management

Avoiding Triggers: Identifying and avoiding known allergens

Antihistamines: Medications like cetirizine or loratadine can help reduce symptoms

Corticosteroids:

- for severe cases, corticosteroids may be prescribed to reduce inflammation

- urticaria is a common manifestation of hypersensitivity reactions and highlights how the immune system can sometimes overreact to harmless substances

angioedema - type I hypersensitivity

- angioedema is a deeper form of swelling beneath the skin and mucous membranes, often associated with hypersensitivity

reactions

Mechanism

Allergen Exposure:

- an allergen (food, medication, insect sting, etc.) triggers the production of IgE antibodies

IgE Binding:

- these antibodies attach to mast cells and basophils.

Re-exposure: When the body encounters the allergen again, it cross-links the bound IgE.

Histamine Release: This leads to the degranulation of mast cells and basophils, releasing histamine and other inflammatory mediators.

Vasodilation and Increased Permeability: These chemicals cause blood vessels to widen and become more permeable,

leading to fluid accumulation in the deeper layers of the skin and mucous membranes

angioedema (symptoms)

Swelling:

- deep, nonpitting swelling, often around the eyes, lips, tongue, and sometimes the throat, which can cause breathing difficulties.

Pain or Discomfort:

- affected areas might feel tight, swollen, and painful

Triggers

Allergens:

- foods (nuts, shellfish), medications (penicillin, aspirin), insect stings

Non-Allergic Triggers:

- physical factors (heat, cold, pressure), stress, infections

angioedema (management)

Avoiding Triggers:

identifying and steering clear of known allergens.

Medications: antihistamines, corticosteroids, and in severe cases, epinephrine (adrenaline) for life-threatening situations like anaphylaxis

Chronic Cases:

- long-term management might involve medications to reduce the frequency and severity of episodes.

- angioedema can be serious, especially if it involves the airways, and requires careful management

anaphylaxis - type I hypersensitivity

- anaphylaxis is the most severe form of a Type I hypersensitivity reaction, potentially life-threatening if not treated promptly

Mechanism

Allergen Exposure: common triggers include foods (peanuts, shellfish), medications (penicillin), insect stings, and latex

IgE Binding:

IgE antibodies, formed during previous exposures, attach to mast cells and basophils.

Re-exposure:

when re-exposed to the allergen, it cross-links the IgE on these cells.

Degranulation:

this causes the release of large amounts of histamine and other inflammatory mediators

anaphylaxis (effects)

Systemic Vasodilation: widespread expansion of blood vessels leads to a sudden drop in blood

pressure (hypotension).

Bronchoconstriction: constriction of airways makes breathing difficult.

Increased Permeability: leads to fluid leakage from blood vessels, causing swelling (angioedema) and urticaria (hives).

Cardiovascular Symptoms: Rapid heartbeat, weak pulse, and potential collapse.

anaphylaxis (symptoms)

Skin: Hives, itching, flushing.

Respiratory: Shortness of breath, wheezing, throat tightness.

Gastrointestinal: Nausea, vomiting, abdominal pain.

Circulatory: Low blood pressure, dizziness, fainting.

anaphylaxis (management)

Epinephrine:

- first-line treatment; an injection rapidly constricts blood vessels, relaxes airways, and reverses the effects of anaphylaxis

Antihistamines and Corticosteroids:

- used to manage symptoms and prevent late-phase reactions.

Emergency Response:

- immediate medical attention is crucial; patients at risk should carry an epinephrine auto-injector (e.g., EpiPen).

- anaphylaxis underscores the potential dangers of hypersensitivity reactions and highlights the importance of quick intervention

GI food allergies - type I

- food allergies and hypersensitivity reactions in GI tract can cause a range of symptoms, often making it challenging to diagnose

GI food allergies: IgE-Mediated Food Allergies

Mechanism: Involves IgE antibodies binding to allergens, leading to the release of histamine and other mediators from mast cells and basophils

Symptoms: Rapid onset (minutes to hours) after ingestion, including abdominal pain, vomiting, diarrhea, and in severe cases, anaphylaxis

Common Allergens: Peanuts, tree nuts, milk, eggs, soy, wheat, fish, and shellfish

GI food allergies: Non-IgE-Mediated Food Allergies

Mechanism: These reactions do not involve IgE antibodies and are often delayed, taking hours to days to manifest

Symptoms: Primarily gastrointestinal, such as chronic diarrhea, vomiting, and failure to thrive in infants

Examples: Food protein-induced enterocolitis syndrome (FPIES), food protein-induced allergic proctocolitis (FPIAP).

GI food allergies (food intolerances)

Mechanism:

- unlike allergies, food intolerances do not involve the immune system

- they are often due to enzyme deficiencies (e.g., lactose intolerance) or reactions to food additives

Symptoms:

- bloating, gas, diarrhea, and abdominal pain, but not life-threatening

GI food allergies (management)

Avoidance: Identifying and avoiding trigger foods is key.

Medications: Antihistamines for mild allergic reactions, epinephrine for anaphylaxis, and enzyme supplements for intolerances.

Dietary Adjustments:

- For intolerances, modifying the diet to exclude problematic foods or using lactase supplements for lactose intolerance

- Understanding the differences between these conditions can help in managing symptoms effectively

type 2 - cytotoxic hypersensitivity

- cytotoxic hypersensitivity, also known as Type II hypersensitivity, involves the immune

system mistakenly targeting the body's cells

Mechanism

Antibody Production: The body produces IgG or IgM antibodies against antigens on the surface of its own cells or tissues.

Antigen-Antibody Binding:

These antibodies bind to the target cells.

Complement Activation: The binding activates the complement system, leading to cell lysis.

Phagocytosis: Immune cells like macrophages engulf and destroy the marked cells.

Antibody-Dependent Cellular Cytotoxicity: Natural killer (NK) cells recognize and destroy the antibody-coated cells.

cytotoxic hypersensitivity (examples)

Autoimmune Hemolytic Anemia: The immune system destroys red blood cells, leading to anemia.

Goodpasture's Syndrome: Antibodies target the basement membrane of the kidneys and lungs.

Myasthenia Gravis: Antibodies attack acetylcholine receptors at the neuromuscular junction, leading to muscle weakness.

cytotoxic hypersensitivity (symptoms)

Symptoms

Hemolytic Anemia: Fatigue, pallor, shortness of breath.

Goodpasture's Syndrome: Blood in urine, coughing up blood.

Myasthenia Gravis: Muscle weakness, difficulty swallowing, drooping eyelids.

- type II hypersensitivity showcases how a misguided immune response can lead to the destruction of healthy cells.

erythroblastosis fetalis

- erythroblastosis fetalis, also known as hemolytic disease of the newborn, is a condition where the mother's immune system attacks the red blood cells of the fetus

- this happens due to a blood group incompatibility, specifically the Rh factor

Mechanism

Rh Factor Incompatibility: If the mother is Rh-negative and the fetus is Rh-positive (inherited from the father), the mother's immune system may recognize the fetal red blood cells as foreign

Antibody Production: The mother produces IgG antibodies against the Rh-positive red blood cells

Placental Transfer: These antibodies cross the placenta and enter the fetal circulation

Hemolysis: The antibodies bind to the fetal red blood cells, leading to their destruction (hemolysis)

erythroblastosis fetalis (symptoms)

Anemia: The fetus may develop severe anemia due to the destruction of red blood cells

Jaundice: Excess bilirubin from the breakdown of red blood cells can cause jaundice

Hydrops Fetalis: Severe cases can lead to fluid accumulation in the fetus, causing heart failure and other complications

erythroblastosis fetalis (prevention and treatment)

Rho (D) Immune Globulin (RhIg): Administered to Rh-negative mothers during pregnancy and after delivery to prevent the formation of Rh antibodies

Intrauterine Transfusions: In severe cases, blood transfusions may be given to the fetus while still in the womb

Postnatal Care:

- Newborns may require blood transfusions, phototherapy for jaundice, and other supportive treatments

- Erythroblastosis fetalis is a serious condition, but with proper prenatal care and preventive measures, it can be managed effectively

blood transfusion reactions

- a blood transfusion reaction occurs when the body has an adverse response to the transfused blood

blood transfusion reaction (types of reaction)

Acute Hemolytic Reaction

Cause: ABO incompatibility, where the donor's red blood cells are attacked by the recipient's antibodies.

Symptoms: Fever, chills, back pain, dark urine, low blood pressure, and shock

Febrile Non-Hemolytic Reaction

Cause: Reaction to white blood cells or cytokines in the transfused blood.

Symptoms: Fever, chills, headache, and nausea.

Allergic Reaction

Cause: Allergic response to plasma proteins in the donated blood.

Symptoms: Itching, hives, and sometimes anaphylaxis.

blood transfusions reactions

Transfusion-Related Acute Lung Injury (TRAI)

Cause: Antibodies in the donor plasma react with the recipient's leukocytes.

Symptoms: Acute respiratory distress, fever, and hypotension.

Transfusion-Associated Circulatory Overload (TACO)

Cause: Volume overload due to rapid or high-volume transfusion.

Symptoms: Respiratory distress, hypertension, and pulmonary edema.

blood transfusions reactions (management)

Acute Hemolytic Reaction: Stop the transfusion immediately, provide supportive care, and

treat shock

Febrile Non-Hemolytic Reaction: Administer antipyretics and continue transfusion if mild

Allergic Reaction: Administer antihistamines; for severe cases, use epinephrine

TRALI: Provide oxygen therapy and supportive care; avoid further transfusions with plasma

TACO: Slow the rate of transfusion and use diuretics

- careful blood typing, cross-matching, and monitoring during transfusion can help prevent these reactions

autoimmune hemolytic anemia and thrombocytopenia-type 2 (mechanism)

- autoimmune hemolytic anemia occurs when the immune system mistakenly targets and destroys the body's own red blood cells

- this can lead to a shortage of red blood cells, causing anemia

Mechanism

Antibody Production: The body produces antibodies (IgG or IgM) against its own red

blood cells

Red Blood Cell Destruction: These antibodies bind to the red blood cells, marking them for destruction by the immune system

Complement Activation: The binding activates the complement system, leading to the lysis (destruction) of red blood cells

Phagocytosis: Immune cells like macrophages engulf and destroy the marked red blood cells

autoimmune hemolytic anemia (symptoms)

Fatigue and Weakness: Due to reduced oxygen delivery to tissues

Jaundice: Yellowing of the skin and eyes from the breakdown of red blood cells

Dark Urine: Resulting from the release of hemoglobin from destroyed red blood cells

Shortness of Breath: Especially during physical activity

thrombocytpenia - type 2 (mechanism)

- thrombocytopenia is a condition characterized by a low platelet count, which can lead to increased bleeding and bruising

Mechanism

Reduced Platelet Production: the bone marrow produces too few platelets

Increased Platelet Destruction: platelets are destroyed faster than they are produced, often due to autoimmune conditions, infections, or medications

Sequestration: platelets may be sequestered (trapped) in an enlarged spleen

thrombocytpenia - type 2 (symptoms)

Easy Bruising: Due to reduced platelet count

Prolonged Bleeding: From cuts or injuries

Petechiae: Small red or purple spots on the skin caused by minor bleeding

Nosebleeds and Bleeding Gums: Due to impaired blood clotting

autoimmune hemolytic anemia and throbocytopenia (management)

Autoimmune hemolytic anemia: Treatment may include corticosteroids to suppress the immune response, immunosuppressive drugs, and in severe cases, blood transfusions

Thrombocytopenia: Treatment depends on the underlying cause and may include platelet transfusions, medications to increase platelet production, and treating any underlying conditions

- both conditions highlight how the immune system can sometimes target the body's cells, leading to significant health issues

immune complex sensitivities - type 3 (mechanisms)

- immune complex sensitivities, also known as Type III hypersensitivity reactions, occur when the immune system forms complexes of antigens and antibodies that can deposit in various tissues and cause inflammation

Mechanism

Antigen Exposure: The body is exposed to an antigen (a foreign substance)

Antibody Production: The immune system produces antibodies against the antigen

Complex Formation: The antibodies bind to the antigens, forming immune complexes

Deposition: These immune complexes can circulate and deposit in tissues such as blood vessels, kidneys, joints, and the skin

Inflammation: The deposited immune complexes trigger the complement system, leading to inflammation and tissue damage

immune complex sensitivities - type 3 (examples)

Systemic Lupus Erythematosus (SLE): Immune complexes deposit in various organs, causing widespread inflammation

Rheumatoid Arthritis: Immune complexes form in the joints, leading to pain and swelling

Post-Streptococcal Glomerulonephritis: Immune complexes deposit in the kidneys, causing kidney inflammation and damage

immune complex sensitivities - type 3 (symptoms)

Inflammation: Redness, warmth, and swelling in affected areas

Pain: Joint pain and tenderness

Organ Dysfunction: Kidney problems, lung involvement, and other organ-specific symptoms

immune complex sensitivities - type 3 (management)

Anti-inflammatory Medications: To reduce inflammation and pain

Immunosuppressive Drugs: To decrease the immune response and prevent further immune complex formation

Plasma Exchange: In severe cases remove immune complexes from the blood. Understanding immune complex sensitivities helps in diagnosing and managing conditions where the immune system's response leads to tissue damage.

glomerulonephritis - type 3 (mechanism)

- glomerulonephritis is a type of kidney disease that involves inflammation of the glomeruli, the tiny filters in the kidneys that remove waste and excess fluids from the blood

- it can be caused by various factors, including immune complex hypersensitivity reactions (Type III hypersensitivity)

Mechanism

Antigen Exposure: body is exposed to an antigen, such as a bacterial infection (e.g., streptococcus)

Antibody Production: immune system produces antibodies against the antigen

Immune Complex Formation: antibodies bind to the antigens, forming immune complexes

Deposition: immune complexes circulate and deposit in the glomeruli of the kidneys

Inflammation: deposited immune complexes trigger the complement system, leading to inflammation and damage to the glomeruli

glomerulonephritis - type 3 (symptoms)

Hematuria: Blood in the urine, which may appear pink or cola-colored

Proteinuria: Excess protein in the urine, causing foamy or bubbly urine

Edema: Swelling in the legs, ankles, or around the eyes due to fluid retention

Hypertension: High blood pressure resulting from kidney dysfunction

Reduced Kidney Function: Fatigue, nausea, and decreased urine output

glomerulonephritis - type 3 (managment)

Anti-inflammatory Medications: To reduce inflammation and immune response

Immunosuppressive Drugs: To decrease antibody production and immune complex formation

Blood Pressure Control: Medications to manage hypertension

Dietary Changes: Low-sodium diet to reduce fluid retention and swelling

Dialysis or Kidney Transplant: In severe cases, to support kidney function

polyarteritis nodosa (mechanism)

- polyarteritis nodosa (PAN) is a type of vasculitis, which means blood vessel inflammation

- it primarily affects medium-sized arteries and can lead to damage in various organs

- while PAN is not typically classified as a hypersensitivity reaction, it can be associated with immune system dysfunction

Mechanism

Immune Response: the exact cause of PAN is unknown, but it is thought to involve an abnormal immune response; this can be triggered by infections, drugs, or other factors

Inflammation: immune system attacks the walls of medium-sized arteries, causing inflammation and damage

Necrosis: inflammation can lead to the death of tissue in the affected arteries (necrosis), which can disrupt blood flow to various organs

polyarteritis nodosa (symptoms)

Skin: rashes, ulcers, and nodules

Muscles and Joints: pain, tenderness, and muscle aches

Nervous System: peripheral neuropathy, causing pain, burning, tingling, or weakness in the hands or feet

Kidneys: high blood pressure, blood in the urine, and kidney failure

Other Organs: fatigue, weight loss, and abdominal pain due to involvement of other internal organs

polyarteritis nodosa (management)

Corticosteroids: to reduce inflammation and suppress the immune response

Immunosuppressive Drugs: to further control the immune system and prevent relapse

Supportive Care: managing symptoms and complications, such as blood pressure control and dialysis if kidney function is severely affected

- PAN is a serious condition that requires prompt medical attention and ongoing management.

type 4 cell-mediated hypersensitivities (mechanism)

- type IV hypersensitivity, also known as delayed-type hypersensitivity (DTH), involves cell-mediated immune responses rather than antibody-mediated ones - it’s a slow reaction, typically taking 48-72 hours to develop

Mechanism

Sensitization Phase: upon first exposure to an antigen (like poison ivy, certain metals, or tuberculin in TB tests), antigen-presenting cells (APCs) process and present the antigen to t helper cells

T Cell Activation: t helper cells get activated and proliferate, creating memory t-cells specific to that antigen

Re-exposure: on subsequent exposures, these memory t-cells recognize the antigen

Cytokine Release: t-cells release cytokines, signalling other immune cells like macrophages to the site

Inflammation and Damage: recruited immune cells cause inflammation and tissue damage at the site of antigen exposure

type 4 cell-mediated hypersensitivities (examples)

Contact Dermatitis: caused by substances like poison ivy, nickel, and latex. Results in red, itchy, blistering skin

Tuberculin Skin Test: reaction to the tuberculin antigen injected into the skin, used to test for TB infection

Granulomatous Inflammation: in chronic infections like tuberculosis, activated macrophages form granulomas to contain the infection

Autoimmune Diseases: conditions like Type 1 diabetes and multiple sclerosis involve Type IV hypersensitivity mechanisms

type 4 cell-mediated hypersensitivities (symptoms)

Localized Inflammation: redness, swelling, and warmth at the site of antigen exposure

Blisters and Rash: especially in contact dermatitis

Tissue Damage: prolonged reactions can lead to significant tissue damage and scarring

- type IV hypersensitivity underscores the critical role of t-cells and cell-mediated immunity in responding to certain antigens and pathogens

contact dermatitis (mechanism)

- contact dermatitis is an inflammatory skin condition caused by direct contact with an irritant or allergen

Mechanism

Irritant Contact Dermatitis: more common type, caused by direct damage to the skin from substances like soaps, detergents, or acids; it doesn’t involve the immune system

Allergic Contact Dermatitis:

- involves an immune response

- upon exposure to an allergen (like poison ivy, nickel, or certain cosmetics), the body’s immune system reacts, leading to inflammation

contact dermatitis (symptoms)

Redness: affected area becomes red and inflamed

Itching: intense itching is common

Blisters: small, fluid-filled blisters can develop

Cracking: skin may crack or become scaly if the reaction is prolonged

Swelling: area may swell, particularly in severe cases

contact dermatitis (diagnosis and management)

Patch Testing: identifies specific allergens causing the reaction

Avoidance: key to managing contact dermatitis is avoiding known irritants or allergens

Topical Steroids: helps reduce inflammation and itching

Moisturizers: protect the skin barrier and prevent dryness

Antihistamines: alleviate itching in allergic cases

- identifying and steering clear of triggers, along with appropriate treatment, can help manage and alleviate contact dermatitis effectively

immune deficiency (primary: congenital)

- immune deficiency refers to a state where the immune system's ability to fight infections and diseases is compromised or entirely absent

- this can lead to frequent infections and more severe health issues

Genetic Disorders:

- these are inherited and present from birth.

- examples: Severe Combined Immunodeficiency (SCID) and X-linked agammaglobulinemia

Symptoms: recurrent infections (bacterial, viral, fungal), poor growth, and autoimmune disorders

immune deficiency (secondary: acquired)

Causes: factors like infections (HIV/AIDS), medications (chemotherapy, immunosuppressants), malnutrition, and chronic diseases (diabetes, cancer)

Symptoms: similar to primary immunodeficiency but develop later in life and often related to the underlying cause

Management

Antibiotics and Antiviral Treatments: to manage infections

Immunoglobulin Therapy: to provide necessary antibodies

Stem Cell Transplants: severe cases like SCID

Managing Underlying Conditions:

- treating the cause of secondary immunodeficiency to restore immune function

- understanding and managing immune deficiencies can significantly improve health outcomes

autoimmune disease (mechanism)

- autoimmune diseases occur when the immune system mistakenly attacks the body’s own tissues

- instead of defending against harmful invaders, it targets healthy cells

Mechanism

Loss of Self-Tolerance: immune system fails to recognize the body’s own cells as “self” and perceives them as foreign

Antibody Production: produces antibodies against its tissues, known as autoantibodies

Immune Cell Activation: t-cells and b-cells are inappropriately activated, leading to an immune response against the body’s own tissues

Inflammation and Damage: resulting immune response causes chronic inflammation and tissue damage

autoimmune diseases (examples)

Rheumatoid Arthritis: immune system attacks the joints, causing inflammation, pain, and eventual joint damage

Systemic Lupus Erythematosus (SLE): targets multiple organs, leading to widespread inflammation and damage

Type 1 Diabetes: immune system destroys insulin-producing cells in the pancreas

Multiple Sclerosis: attacks the myelin sheath covering nerve fibres in the central nervous system, disrupting communication between the brain and the rest of the body

autoimmune diseases (symptoms)

Chronic Inflammation: persistent swelling, redness, and pain in affected areas

Fatigue: constant tiredness is common in many autoimmune diseases

Organ Dysfunction: depending on the target, it can affect the function of organs like the heart, kidneys, or lungs

Systemic Effects: fever, weight loss, and general malaise

autoimmune disease (management)

Immunosuppressive Drugs: medications like corticosteroids and biologics to reduce immune activity

Anti-inflammatory Medications: to manage symptoms and reduce inflammation

Lifestyle Adjustments: diet, exercise, and stress management to support overall health

Monitoring and Regular Checkups: important for managing chronic conditions and preventing complications

systemic lupus erythematosus (causes)

- Systemic Lupus Erythematosus (SLE), commonly known as lupus, is a chronic autoimmune disease where the immune system attacks the body's own tissues

Causes

Genetic Factors: family history can increase the risk

Environmental Triggers: sunlight, infections, certain medications, and stress can trigger symptoms

Hormonal Factors: more common in women, especially during childbearing years, suggesting hormones like estrogen may play a role

systemic lupus erythematosus (symptoms)

Fatigue: persistent tiredness is a common symptom

Joint Pain and Swelling: arthritis-like symptoms are frequent

Skin Rash: classic “butterfly rash” appears across the cheeks and nose

Fever: unexplained fevers without infection

Kidney Problems: lupus nephritis can lead to kidney inflammation and damage

Other Symptoms: mouth ulcers, hair loss, photosensitivity, and chest pain upon deep breathing

systemic lupus erythematosus (diagnosis)

Blood Tests: to detect antibodies like ANA (antinuclear antibodies) and anti-dsDNA

Urinalysis: check for kidney involvement

Biopsy: sometimes a kidney or skin biopsy is needed.

systemic lupus erythematosus (treatment)

Medications: anti-inflammatory drugs, corticosteroids, and immunosuppressants to control inflammation and the immune response

Lifestyle Changes: protecting skin from sun exposure, maintaining a healthy diet, and managing stress

Regular Monitoring: regular check-ups to monitor disease activity and adjust treatment as needed