Immunity, Hypersensitivity, and Autoimmune Disorders

Presentation Overview & Learning Objectives

• Presentation Context:

  • Presenter: Denyce Watties-Daniels, DNP, RN -5.2025

  • Topic: Immunity, Hypersensitivity, and Auto Immune Disorders

• Core Learning Objectives:

  • List the cellular components of the immune system.

  • Describe the pathophysiology of immunity.

  • Compare active and passive immunity.

  • Discuss the types of hypersensitivity.

  • Describe how a diagnosis of AIDS is made.

  • State the treatment, education, and prevention goals of HIV.

Fundamentals of Immunity & Immune Responses

• General Functions of the Immune System:

  • Protects the body against infection-causing microorganisms, foreign substances, and cancerous cells.

  • Acts as the body's third line of defense.

  • Recognizes the body's own cells versus foreign cells, establishing self versus non-self distinction.

  • Antigens are defined specifically as foreign cells.

• Key Characteristics of the Immune System:

  • Memory: The ability to execute an accelerated or heightened response to the presence of an antigen due to previous exposure to that specific antigen.

  • Specificity: The property wherein a specific lymphocyte will only respond to the presence of a specific antigen.

  • Self-Recognition: The capacity to recognize foreign material and distinguish it from host tissue (self vs. non-self).

• Pathophysiology of the Immune Response:

  • Immune system cells continuously survey the body to recognize foreign invasion (antigens) by distinguishing self from non-self.

  • Utilizes components of the inflammatory process to activate specialized cells directed at destroying the invading antigen.

  • Develops antibodies that stand guard over the body to monitor for subsequent invasions of the antigen, remaining prepared to destroy the antigen upon re-exposure.

  • Remembers the antigen, synthesizes specific antibodies against it, and recognizes host healthy cells to avoid attacking self-tissues.

Classifications of Immunity

• Passive Immunity:

  • Artificial Passive Immunity: Acquired through the injection of serum containing ready-made antibodies derived from humans or animals.

  • Natural Passive Immunity: Acquired naturally by infants receiving maternal antibodies across the placenta.

• Active Immunity:

  • Developed through contracting and recovering from a disease, leading to individual antibody synthesis.

  • Active Acquired Immunity: Obtained through exposure to an antigen or through immunization (vaccination), requiring the host's body to synthesize specific antibodies (immunoglobulins) against the antigen.

• Innate Immunity:

  • In-born, non-specific resistance to foreign substances.

  • Does not involve an adaptive immune response.

  • Includes natural antibody protection passed from mother to fetus across the placenta.

• Adaptive Immunity:

  • Detailed in Pathophysiology: Introductory Concepts and Clinical Perspectives by Theresa Capriotti and Joan Parker Frizzell.

  • Allows the body to distinguish between antigens belonging to the host versus antigens originating from an invader.

  • Mechanisms act rapidly, specifically, destructively, and with memory for every individual antigen encountered.

  • Confers long-term immunity.

  • Examples include contracting a disease (such as chickenpox) and developing immunoglobulins followed by recovery, or receiving a vaccine containing the antigen to develop protective antibodies.

Cellular Components of the Immune System

• Lymphocytes:

  • Function as the main effector cells of the immune response.

  • Possess extreme specificity, recognizing only one specific antigen.

• T Lymphocytes (Cell-Mediated Immunity / T Cell Immunity):

  • Represent the foundation of the adaptive immune system and act as direct attackers.

  • Helper T Cells ($CD4$ cells): Turn on the immune system and stimulate the production of other T cells.

  • Suppressor T Cells: Inhibit ongoing immune system responses, providing self-limiting effects to prevent over-activation.

  • Cytotoxic T Cells ($CD8$ cells): Destroy cell membranes or secrete toxic substances that destroy antigens; specifically target non-self cells, including cancer cells, transplanted organ cells, and tissue grafts.

• B Lymphocytes (Humoral Immunity / B Cell Immunity):

  • Responsible for producing antibodies that attack invading pathogens.

  • Plasma Cells: Specialized cells that secrete immunoglobulins.

  • Memory Cells: Function in acquired immunity to act immediately upon re-exposure to the identical antigen.

• Natural Killer (NK) Cells:

  • Act as surveillance cells that identify and eliminate abnormal host cells.

Immunoglobulins (Antibodies)

• Definition: Immunoglobulins are protein molecules synthesized by B cells (plasma cells) that function as antigen-specific antibodies.

• Primary Classes of Immunoglobulins:

  • $\text{IgG}$

  • $\text{IgA}$

  • $\text{IgM}$

  • $\text{IgE}$

  • $\text{IgD}$

Vaccination & Immunodeficiency

• Vaccines:

  • Formulated using a weakened virus or an injection of pre-formed antibodies.

  • Incapable of causing disease because the genes responsible for pathogenesis are removed.

  • Administered to simulate an antigenic invasion, triggering the body to build specific immunoglobulins.

  • Some vaccinations require multiple administration doses to achieve full protection (e.g., the Hepatitis B vaccine, which requires a $3\text{-dose}$ series).

• Immunodeficiency Overview:

  • Occurs when the immune system fails to activate in the presence of an antigen, leaving the host vulnerable to disease.

  • Can be induced by medications, therapeutic treatments, or underlying systemic illnesses.

Hypersensitivity Reactions

• Definition & General Pathophysiology:

  • An altered, exaggerated immune response to an antigen that results in host tissue damage or harm.

  • Pathophysiologically driven by an overpresentation of the inflammatory response.

  • Includes clinical phenomena such as hay fever, blood transfusion reactions, and organ transplant rejections.

  • Clinical manifestations range from mild symptoms (runny nose, itchy eyes, hives) to severe responses (blood hemolysis, systemic anaphylaxis).

• Classification of Hypersensitivity Types:

  • Type 1 (Immediate Hypersensitivity):

  • $\text{IgE}$-mediated reaction leading to rapid histamine release.

  • Mediators such as leukotrienes and cytokines induce smooth muscle constriction (specifically in the bronchioles) and tissue edema.

  • Type 2 (Cytotoxic Hypersensitivity):

  • $\text{IgG}$ or $\text{IgM}$ mediated immediate cytotoxic reaction.

  • Examples: Blood transfusion reactions, drug reactions, and $\text{Rh}$ incompatibility.

  • Pathology: Target blood cells are lysed and/or hemolyzed.

  • Clinical manifestations: Fever, chills, urticaria, and shock.

  • Type 3 (Immune Complex Hypersensitivity):

  • Driven by the formation of circulating $\text{IgG}$ or $\text{IgM}$ antigen-antibody complexes.

  • These immune complexes deposit into and adhere to the walls of blood vessels, joints, the heart, and other systemic organs.

  • Classic example: Serum sickness.

  • Type 4 (Delayed Hypersensitivity):

  • Cell-mediated immune response involving T lymphocytes (not antibodies).

  • Manifests as a delayed reaction, typically occurring within $24\text{--}48\,\text{hours}$ post-exposure.

  • Examples: Transplant or graft rejection, contact dermatitis (e.g., poison ivy exposure), autoimmune diseases, and the tuberculin (TB) skin test.

• General Pharmacologic Treatment:

  • Antihistamines are utilized to block inflammatory histamine pathways.

Organ Transplant Rejection

• Pathophysiology:

  • The host immune system recognizes the transplanted tissue or organ as non-self and initiates a destructive immune response.

  • Rejection processes can begin as early as $24\,\text{hours}$ following transplantation.

• Types of Transplant Rejections:

  • Hyperacute Rejection: Occurs within $2\text{--}3\,\text{days}$ post-transplant.

  • Acute Rejection: The most common and treatable form; occurs from $4\,\text{days to } 3\,\text{months}$ following transplantation.

  • Chronic Rejection: Occurs over $4\,\text{months to years}$; characterized by progressive ischemia and eventual fibrosis of the transplanted tissue.

Autoimmune Disorders

• Pathophysiology:

  • The body loses self-tolerance and attacks its own tissues, resulting in sustained cellular damage and chronic inflammation.

  • Autoantibodies directly attack various host tissues, cells, organ groups, or systemic organs.

  • Clinical course is typically marked by alternating periods of remission and relapse.

• Clinical Manifestations & Complications:

  • Manifestations consist of localized and systemic inflammatory symptoms.

  • Complications include significant, irreparable organ damage and an increased risk for cancer development.

• Treatment:

  • Primary management utilizes immunosuppressant drugs to attenuate autoantibody attack.

Immunodeficiency Disorders: Congenital vs. Acquired

• Congenital (Primary) Immunodeficiencies:

  • Severe Combined Immunodeficiency (SCID): Caused by stem cell failure, resulting in the complete absence of both T and B lymphocytes.

  • DiGeorge Syndrome: Stem cell/thymic defect leading to isolated T-cell failure.

  • Selective IgA Deficiency: B-cell lineage failure leading to an inability to produce $\text{IgA}$.

• Acquired (Secondary) Immunodeficiencies:

  • Chemotherapy-induced immunosuppression.

  • Immunosuppressive drug therapy.

  • Acquired Immune Deficiency Syndrome (AIDS).

Pathophysiology & Transmission of HIV

• Properties of Human Immunodeficiency Virus (HIV):

  • HIV is a retrovirus that stores its genetic material as RNA rather than DNA.

  • Specifically targets and destroys helper T cells ($CD4$ cells), suppressing the entire immune cascade and creating generalized immune deficiency.

  • Immune suppression exposes the host body to severe infections by opportunistic pathogens.

• Routes of Transmission:

  • Sexual Transmission: Via infectious semen and cervical secretions.

  • Parenteral Transmission: Via contaminated blood, blood products, or shared needles.

  • Perinatal Transmission: Transmitted from an infected mother to child prenatally, intrapartum, or postpartum.

• Intracellular Replication Cycle:

  • HIV enters the bloodstream or mucosal tissue via blood or semen.

  • The viral particles bind to and invade host T-helper ($CD4$) cells.

  • Reverse transcription alters host cell RNA expression to transcribe reverse-copied viral DNA.

  • The host cell becomes permanently altered, continuously replicating viral RNA.

  • Virions exit the damaged cell, duplicate, and infect surrounding T-helper cells.

Clinical Progression & Systemic Manifestations of HIV/AIDS

• Initial & Generalized Symptoms:

  • Early stage is often asymptomatic.

  • Symptoms emerge and worsen as viral replication accelerates and $CD4$ counts decline.

  • Generalized, vague systemic symptoms: Unexplained weight loss, low-grade fevers, night sweats, generalized lymphadenopathy, and chronic diarrhea.

• Systemic Manifestations by Body System:

  • Systemic: Fever, severe weight loss.

  • Central Nervous System: Generalized malaise, headache, peripheral neuropathy, and progressive dementia.

  • Pulmonary: Chronic cough, dyspnea, and recurrent pneumonia.

  • Pharynx & Upper Airway: Pharyngitis.

  • Mouth: Oral mucosal sores and oral candidiasis (thrush).

  • Esophagus: Esophageal ulcers/sores.

  • Musculoskeletal: Myalgia.

  • Hepatosplenic: Liver enlargement (hepatomegaly) and spleen enlargement (splenomegaly).

  • Lymphatic: Generalized lymphadenopathy.

  • Integumentary: Cutaneous rashes.

  • Gastrointestinal: Nausea and vomiting.

Diagnostic Criteria, Testing, & Disease Progression Timeline

• Diagnostic Distinction: HIV vs. AIDS:

  • HIV Positive: Confirmed presence of host infection with the HIV virus via validated diagnostic tests.

  • AIDS Criteria: Formally diagnosed when HIV has significantly depleted helper T cells, meeting specific quantitative or clinical thresholds:

  • Absolute $CD4$ T-cell count drops below $200\,\text{cells}/\mu\text{l}$ (declining from normal reference levels of approximately $1,200\,\text{cells}/\mu\text{l}$).

  • Patient develops specific immunodeficient diagnostic opportunistic conditions (e.g., Pneumocystis pneumonia [PCP], Tuberculosis [TB], invasive cervical cancer, or Kaposi sarcoma).

• Diagnostic Testing Modalities & Timeline:

  • Window Period:

  • The time interval between initial viral contraction and detectable host antibody synthesis.

  • The host remains "seronegative" during this period.

  • Standard screening tests (ELISA) produce negative results during the window period.

  • Seroconversion:

  • The transition from antibody-negative status to antibody-positive status.

  • Typically occurs between $2\,\text{weeks}$ and $6\,\text{months}$ post-exposure.

  • Diagnostic Assay Types:

  • ELISA / Western Blot Test: Detects host anti-HIV antibodies; standard antibody confirmation methodology.

  • HIV RNA Level (Viral Load Measurement): Directly quantifies the number of viral particles in the blood; represents the EARLIEST diagnostic test capable of detecting HIV infection.

• Clinical Pathway to AIDS Diagnosis Flowchart:

  1. Exposure and viral infection occur.

  2. Window period begins (body begins producing antibodies while initial tests remain negative).

  3. Time elapses; patient visits a healthcare provider.

  4. Provider offers screening and patient consents to an HIV test.

  5. Blood sample is drawn and analyzed.

  6. Antibodies detected; patient returns to the doctor to receive an HIV-positive diagnosis alongside clinical counseling.

  7. Seroconversion continues as viral load multiplies and $CD4$ levels progressively drop from $1,200\,\text{cells}/\mu\text{l}$ toward $200\,\text{cells}/\mu\text{l}$.

  8. Upon reaching a $CD4$ count below $200\,\text{cells}/\mu\text{l}$ or upon the presentation of opportunistic infections, an official AIDS diagnosis is documented.

Clinical Management, Monitoring Schedule, & Opportunistic Infections

• Common AIDS-Defining Opportunistic Infections:

  • Tuberculosis (TB)

  • Pneumocystosis (PCP)

  • Toxoplasmosis

  • Candidiasis

  • Cytomegalovirus (CMV)

  • Herpes zoster

  • Kaposi sarcoma

• Long-Term Success Goals for HIV Management:

  • Maintaining a sustained, undetectable viral load.

  • Achieving a stigma- and discrimination-free environment.

  • Minimizing treatment toxicity and clinical monitoring burden.

  • Optimizing health-related quality of life.

  • Establishing lifelong integration of multidisciplinary healthcare.

  • Ensuring every individual living with HIV can achieve long-term success.

• Pharmacologic Management Principles:

  • HIV is managed as a chronic illness.

  • Antiretroviral regimens utilize multiple agents targeting different stages of the HIV replication life cycle, including antiretroviral drugs that alter viral DNA/RNA synthesis.

• Routine Laboratory & Monitoring Schedule:

  • $CD4$ Count: Measured every $3\text{--}6\,\text{months}$.

  • Viral Load: Measured every $3\text{--}6\,\text{months}$ and following any modification in antiretroviral therapy.

  • Diagnostic Screening: Monitor PPD (tuberculin skin test), RPR (syphilis screening), CMV, toxoplasmosis, and PAP smears every $6\,\text{months}$.

  • Immunizations: Administer indicated preventative vaccines, specifically Pneumococcal and Hepatitis B (HepB) vaccines.

Questions & Discussion

• Interactive Learning Prompt:

  • Participants are asked to reflect: "Name one thing you learned today from the lecture that you did not know before."

  • Open floor maintained for clinical questions and answers.