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BIO15 Exam 5 Chapter 19 Disease of the Immune System / Immunopathology Today, we're discussing Chapter 19 , which focuses on diseases of the immune system. Specifically, we're looking at cases where the immune system is activated when it shouldn’t be or when it’s inappropriately activated. Chapter 19 shares similarities with Chapter 17 in terms of activation mechanisms, but there are key differences that you'll need to understand. So, ensure you have Chapter 17 well in hand before tackling Chapter 19. Immunopathology: Chapter 19 deals with immunopathology —the study of diseases caused by the over-activation or inappropriate activation of the immune system. To make studying easier, immunopathology is broken down into four different types of hyperactivity:
- Type 1 : Immediate hypersensitivity (e.g., hay fever, anaphylactic shock, basic allergies)
- Type 2 : Antibody-mediated (e.g., blood type incompatibility)
- Type 3 : Immunocomplex-mediated (e.g., rheumatoid arthritis, serum sickness)
- Type 4 : Cell-mediated cytotoxicity (e.g., contact dermatitis, graft rejection, organ transplant rejection)
Type 1 Hypersensitivity (Allergies, Anaphylaxis, Hay Fever) (1/3) Type 1 hypersensitivity includes conditions like allergies , anaphylaxis , hay fever , and hives. Many of these conditions exhibit symptoms similar to those of a cold or flu: o Coughing, chills, body aches (especially in allergy-induced asthma) o Vomiting o Rashes o Low blood pressure (due to anaphylaxis) o Runny nose, watery eyes (from hay fever) o Hives can also present with symptoms like a cold or flu. Around 30% of the population suffers from allergies. These can be: o Hereditary (genetic predisposition) o Age-related o Environmental , influenced by factors such as location (e.g., more people in Los Angeles suffer from asthma due to poor air quality compared to people in rural areas with fresher air).
Mechanisms of Allergies: Allergies can be triggered by different types of allergens :
- Inhalants : Something you breathe in (e.g., pollen).
- Ingestants : Something you eat (e.g., food allergies).
- Injectants : Caused by something injected (e.g., penicillin, snake bites, bee stings).
- Contactants : Caused by something you touch (e.g., poison ivy, poison oak).
A chart classifies the most common allergens based on how they enter the body. This is for reference; it is not something you need to memorize.
Phases of Type 1 Allergies: Type 1 allergies occur in several phases:
- First Exposure : The first time an allergen is introduced to the body, no signs or symptoms appear. This is known as the sensitizing dose. The immune system reacts as if the allergen is a pathogen, activating similar mechanisms. However, since the allergen is not associated with a pathogen , there is no immediate illness or symptoms. The body produces a small amount of IgE antibodies that bind to mast cells , but the allergen has usually been cleared from the body by this time. The immune system is "primed" but there is no reaction.
- Re-exposure : Upon second exposure , the body recognizes the allergen (thanks to the IgE antibodies on the sensitized mast cells). This results in the degranulation of mast cells, leading to the typical symptoms of allergies.
Antigen vs. Allergen: Antigen : A substance that the immune system recognizes as foreign, often associated with a pathogen. Allergen : A specific type of antigen, but one that is non-pathogenic. The body should not be responding to an allergen as it would to a pathogen.
Immune Response to Allergens: Initial Response :
- The allergen enters the body, and macrophages (or antigen-presenting cells) engulf it through phagocytosis.
- The allergen is processed and presented on MHC II molecules , which are displayed on the cell surface.
- Helper T cells are activated by the MHC II complex displaying the allergen.
- B cells also take up the allergen, process it, and present it on MHC II molecules.
- When the helper T cell interacts with the B cell , the helper T cell releases cytokines (primarily interleukins ) that stimulate the B cell to proliferate and differentiate into plasma cells. IgE Production : o Initially, IgM is produced, but B cells class switch to producing IgE. These IgE antibodies are specific to the allergen, but by this time, the allergen has been mostly cleared from the system. o The IgE antibodies circulate and bind to mast cells , "priming" them (making them ready for a response upon subsequent exposure to the allergen).
They are still based on an antibody-antigen interaction , but this interaction results in activation of the complement system.
Pre-Requisite Knowledge: If you haven’t studied Chapter 16 or if you don’t understand the complement system , especially classical complement activation , pause now and go review Chapter 16. Understanding the complement system is essential to fully grasp how Type II hypersensitivities work.
Main Type II Hypersensitivity Reactions:
- Hemolytic disease of the newborn (a.k.a. erythroblastosis fetalis)
- Hemolytic transfusion reactions (e.g., receiving the wrong blood type)
Blood Typing Basics: Red blood cells have different antigens on their surfaces. The main ones to focus on: o A antigen o B antigen o You can have: Only A → Type A blood Only B → Type B blood Both A and B → Type AB blood Neither A nor B → Type O blood
Mechanism of Type II Hypersensitivity (Using Blood Transfusion as an Example):
- Scenario : o A person with Type B blood receives a transfusion of Type A blood. o Type A blood contains A antigens , which the recipient does not have. o The recipient’s immune system already contains anti-A antibodies.
- Immune Response : o The anti-A antibodies (IgG or IgM) bind to the A antigens on the transfused red blood cells. o The Fc region of the bound antibodies becomes available.
- Complement Activation : o This triggers the classical complement pathway : C1 binds the Fc region → cleavage of C4 and C2 → activation of C3 → formation of the Membrane Attack Complex (MAC). o Lysis of the transfused red blood cells occurs.
💡 In Chapter 16, the target cell for complement-mediated lysis was a microbe. Here, it’s the donor blood , which makes this an inappropriate immune response — a hypersensitivity.
Consequences if Untreated: Massive hemolysis Systemic shock Kidney failure (due to overwhelmed filtering) Symptoms : fever, anemia, jaundice If caught early, dialysis can help filter the blood and may save the patient’s life. 📺 A YouTube video posted on Canvas provides animations and more detail. Highly recommended before the exam.
The Rh Factor (Rhesus Factor): The Rh factor (discovered in rhesus monkeys) is another antigen that may be present on red blood cells. o Rh-positive : has the Rh factor o Rh-negative : does not have the Rh factor
Rh Incompatibility and Hemolytic Disease of the Newborn:
- Scenario : o Father is Rh-positive o Mother is Rh-negative o First baby inherits Rh-positive blood
- First Pregnancy : o Typically safe because the mother hasn’t been exposed to Rh antigen before. o However, during delivery, baby’s blood may enter mother’s circulation. o Mother then produces anti-Rh antibodies through a normal immune response.
- Subsequent Pregnancies : o If baby #2 is also Rh-positive , maternal IgG antibodies can cross the placenta. o These antibodies attack the fetal red blood cells, causing: Erythroblastosis fetalis Oxygen deprivation Stillbirth, premature birth , or severe birth defects
Prevention – RhoGAM Therapy: RhoGAM is administered to Rh-negative mothers :
o C3b binds to target cells and acts enzymatically. o C3a and C5a stimulate mast cell degranulation. o Neutrophils also degranulate, contributing to tissue breakdown.
Clinical Manifestations: Depends on deposition site : o Blood vessels → leaky vessels, heart damage o Joints → rheumatoid arthritis, inflammation o Skin → skin lesions o Kidneys → nephritis ⚠️ A common misconception is that antibodies first bind to tissue, then antigen—but the correct order is:
- Antibody binds antigen in the plasma
- Complex then deposits in tissue
Key Difference from Type II Hypersensitivity: Type II : Antibodies bind directly to cell-associated antigens (e.g., red blood cells). Type III : Antibodies bind to free-floating antigens , and complexes deposit on tissues.
Type IV Hypersensitivity – Cell-Mediated Reactions Overview: Also known as delayed-type hypersensitivities. Involves T cell activation , not antibodies. Both cytotoxic T cells and helper T cells may be activated. Results in cytokine release and tissue damage.
Classic Examples:
- Poison ivy/poison oak sensitivity
- Type I diabetes
- Tuberculosis (TB) skin test
Mechanism – Poison Ivy Example:
- Initial Exposure : o Oils from poison ivy/oak deposit on skin.
o Oil alone is not antigenic , but when it complexes with skin proteins , it's recognized as foreign. o These oils act as haptens (small molecules that become immunogenic when bound to proteins).
- Immune Response (develops in 48–72 hours): o Dendritic cells/macrophages phagocytose the hapten-protein complex. o Present antigen on MHC II. o Helper T cells recognize this and produce interleukins. o Interleukins recruit more: Helper T cells Dendritic cells Neutrophils o Neutrophils degranulate , causing tissue damage.
- Memory Formation : o Helper T cells form memory cells. o Upon re-exposure, the reaction is faster and more intense , causing the rash to develop sooner.
Type I Diabetes Mechanism: Cytotoxic T cells and macrophages are activated. Cytotoxic T cells recognize specific antigens and: o Release granzymes and perforins o Induce apoptosis Inflammation, edema , diapedesis , and margination occur. Results in a raised lump or lesion.
TB Skin Test – Application of Type IV Hypersensitivity: A small amount of TB antigen is injected under the skin. If previously exposed (via infection or vaccine): o Cytotoxic T cell response occurs. o A fluid-filled vesicle or lesion forms at the site. Does NOT indicate active TB , only prior exposure. Follow-up chest x-ray is required to confirm presence of tuberculoids. 📺 A video on Canvas provides animation and a detailed walkthrough—highly recommended.
Summary of Hypersensitivities:
Final Notes: Watch the four YouTube videos posted in Canvas for visual explanations. You do not need to memorize every cytokine or helper T cell subtype. o Just understand when/where they are released and what they do.
