Immunopathology and immune system by Dr. Garima S.
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- 2. NUMBER NAME 1. GENERALIMMUNOLOGY 2. HYPERSENSITIVITY REACTION 3. AUTOIMMUNITY 4. IMMUNODEFICIENCY DISORDERS 5. AMYLOIDOSIS CHAPTERS INCLUDED
- 3. Immune system Immunity refersto the body’s ability to recognize, resist, and defend itself against harmful substances such as pathogens (bacteria, viruses, fungi, parasites), toxins, and foreign bodies. The immune system is the body’s defense network made up of cells, tissues, organs, and molecules that work together to protect the body from harmful invaders. Key Components of the Immune System: WHITE BLOOD CELLS • LYMPHOCYTES • PHAGOCYTES LYMPHOID ORGAN • BONE MARROW • THYMUS • SPLEEN LYMPHATIC SYSTEM Molecules and Proteins • Antibodies . • Cytokines. • Complement system
- 4. IMPORTANT CELLS &FUNCTIONS • Engulf and kill bacteria (phagocytosis) • First responders at infection site • Kill parasites (esp. worms) • Involved in allergic inflammation • Circulate in blood and become macrophages • Phagocytose microbes and debris • Release histamine in allergic reactions • Initiate inflammation • Engulf and digest pathogens • Activate other immune cells (APC) • Kill virus-infected and tumor cells • Release cytotoxic granules • Mediate allergic responses • Release histamine and cytokines • Capture antigens and present to T cells • Bridge innate and adaptive immunity NEUTROPHILS MAST CELLS BASOPHILS DENDRITIC CELLS EOSINOPHILLS MONOCYTE MACROPHAGE NATURAL KILLER
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- 8. What is Hypersensitivity? Protective vs. Injurious While the immune response is generally a protective process, hypersensitivity refers to conditions where this response becomes excessive, causing harm to the sensitized host. Exaggerated Reactions It is defined as an exaggerated state of the normal immune response, resulting in adverse effects such as tissue damage, disease, or even death. Types of Hypersensitivity Reactions Immediate Type Occurs within seconds to minutes. mediated by humoral antibodies (B cell mediated). This includes Type I, II, and III reactions. Delayed Type Slower in onset. developing within 24-48 hours. This type is mediated by cellular responses (T cell mediated). specifically Type IV reactions.
- 9. Type I (Anaphylactic) •Rapidly developing immunological reaction, commonly known as allergy. Type II (Cytotoxic) • Involves antibody-mediated destruction of cells. Type III (Immune Complex) • Caused by the formation and deposition of immune complexes. Type IV (Delayed or Cell-Mediated) • Slower, T-cell mediated response. The Four Main Types!!
- 10. Type I: Anaphylactic(ALLERGIC) Reaction This is a rapidly developing immunological reaction occurring within seconds to minutes, commonly referred to as an allergy. It involves a specific sequence of events upon initial exposure to an antigen. Mediators of Anaphylaxis Upon subsequent exposure to the antigen, mast cells degranulate, releasing various potent inflammatory mediators. These substances are responsible for the immediate and severe symptoms of anaphylaxis. Other important mediators include chemotactic factors for neutrophils and eosinophils, and platelet-activating factor, all contributing to the widespread effects observed in anaphylactic reactions. Histamine Serotonin Vasoactive Intestinal Peptide (VIP) Leukotrienes & Prostaglandins Antigen Contact Antigen is captured by antigen-presenting cells. T-cell Differentiation Antigen is presented to T cells, which differentiate into TH2 cells. B-cell Activation TH2 cells release IL-3, IL-4, and IL-5, with IL-4 activating B cells. IgE Production Activated B cells differentiate into IgE-secreting plasma cells. Mast Cell Binding IgE antibodies bind to Fc receptors on mast cells.
- 11. Effects of AnaphylacticAgents • The released agents from mast cells have widespread effects on the body, leading to the characteristic symptoms of anaphylaxis. These effects can range from localized reactions to life-threatening systemic responses. Vascular Permeability Increased vascular permeability leads to fluid leakage and swelling. Shock Severe cases can lead to anaphylactic shock, a life- threatening systemic reaction. Nasal & Lacrimal Secretions Increased secretions from the nose and eyes, common in allergic rhinitis. Smooth Muscle Contraction Contraction of smooth muscles, particularly in the airways, causing bronchoconstriction. Vasoconstriction/ Vasodilation Early vasoconstriction followed by widespread vasodilation, contributing to a drop in blood pressure. Gastric Secretion Increased gastric secretion, potentially leading to gastrointestinal symptoms.
- 12. Type I: Anaphylactic(ALLERGIC) Reaction Antigen Contact Antigen is captured by antigen-presenting cells. T-cell Differentiation Antigen is presented to T cells, which differentiate into TH2 cells. B-cell Activation TH2 cells release IL-3, IL-4, and IL-5, with IL-4 activating B cells. IgE Production Activated B cells differentiate into IgE-secreting plasma cells. Mast Cell Binding IgE antibodies bind to Fc receptors on mast cells. Type II: Antibody-Mediated (Cytotoxic) Reaction Antigen Contact Antigen is captured by TARGET cells. B-cell Activation Circulating b cells get activated and differentiate to form plasma cells IgG & IgM Production Plasma cells forms antibodies. AG-AB Complex Formed Activation of serum complement pathway and C3B formation Phagocytosis Activated C3b bound to the target cells act as an opsonin
- 13. Type III: Immunecomplex mediate (ARTHUS) Reaction Soluble Antigen Antigen is soluble. B-cell Activation Antigen is presented to B cells, which differentiate into Plasma cells. IgG & IgM Production Plasma cells forms antibodies. Formation of immune complex on tissue Fc component of antibody links with the complement and forms Ca3 Ca5 and membrane attack. Inflammatory reaction Resulting in cell injury. Type IV: Delayed hypersensitivity (T Cell Mediated) Reaction Antigen Contact Antigen is captured by Antigen presenting cells. Migration of APC to Lymph Node APC migrates to lymph node where antigen is presented to helper T cell.( TH1) Release of cytokines TH1 cells releases cytokines (TNF – ALPHA, IFN- G,IL-2 Granuloma Formation These cytokines take one specific cells from blood and form granuloma.
- 15. AUTOIMMUNITY Introduction Group ofdisorders in which tissue injury is caused by humoral (by auto- antibodies) or cell mediated immune response (by auto-reactive Tcells) to self antigens. Normally → a protective mechanism called tolerance→ immune system does not attack self antigens. Autoimmune diseases → Any breach in tolerance mechanisms → immune system attack self-cells.
- 16. TOLERANCE Immunological Tolerance Anergy In thethymus for T cells Peripheral Tolerance Central Tolerance In the bone marrow for B cells Apoptosis By AICD Phenotypic Skewing Regulatory T Cells (Treg Cells) Sequestration of self- antigen 1 2 1 5 4 2 3
- 17. 3. Apoptosis By AICD 2.Phenotypic Skewing 1. Anergy Unresponsiveness to antigenic stimulus. Self-reactive T cells interact with APCs presenting self antigen. B7 molecules on APC bind to CTLA- 4molecules on T cells instead of CD28 Molecules. Co-stimulatory signal is blocked. No activation Self-reactive T cells interacting with APCs presented with self-antigens. Activation of T cells. Secrete non- pathogenic cytokines and chemokine Activation-induced cell death Self-reactive T cells interacting with APCs presented with self- antigens. Activation of T cells. Induces upregulation of Fas ligand. Interacts with death receptor Fas Apoptosis
- 18. 4. Regulatory TCells (Treg Cells) 5. Sequestration of self-antigen Certain self-antigens can evade immune recognition by sequestration in immunologically privileged sites. e.g. corneal and lens proteins, testicular antigens and antigens from brain. Treg cells Secrete cytokines (e.g., IL-10 and TGF- B) or killing by direct cell to cell contact Down regulate self-reactive T cells
- 19. Mechanisms of Autoimmunity Breakdownof T Cell Anergy Failure of AICDs Molecular Mimicryg Loss of Treg cells Release of Sequestered Antigens 1 5 4 2 3 • Autoimmunity results due to breakdown of one or more of the mechanisms of immunological tolerance. Molecular Mimicry Microorganisms which share antigenic determinants (epitopes) with self- antigens entre human body Molecular Mimicry Antibodies are produced for micro- organism Antibodies cross-react with self-antigen Eg. → T cell • Shigella fleneri and HLA B27 • Mycobacterium tuberculosis and joint membranes • Coxsackie B virus and myocardium • Streptococcus bacteria and RHD
- 20. IMMUNODEFICIENCY DEFINITION Immunodeficiency isa state where defence mechanisms of body are impaired > enhanced susceptibility to microbial infections and certain forms of cancer. CLASSIFICATION Primary immunodeficiency diseases Secondary immunodeficiency diseases
- 21. CLASSIFICATION • Primary immunodeficiencydiseases inherited defects affecting immune system development. • Secondary immunodeficiency diseases secondary to some other disease process that interferes with the proper functioning of the immune system (e.g. infection, malnutrition, aging, immunosuppression, autoimmunity, or chemotherapy). • Bruton disease (X-linked agammaglobulinemia) • Common variable immunodeficiency • Isolated IgA deficiency • Hyper-IgM syndrome • DiGeorge syndrome (thymic hypoplasia) • Chronic mucocutaneous candidiasis • Purine nucleoside phosphorylase (PNP) deficiency • Severe combined immunodeficiencies • Cytokine receptor mutation • Adenosine deaminase (ADA) deficiency Humoral immunodeficiency (B cell defects) Cellular immunodeficiencies (T cell defects) Combined immunodeficiencies (B and T cell defects)
- 22. AMYLOIDOSIS Introduction Amyloidosis refersto a variety of condition in which amyloid proteins are abnormally deposited extracellularly between the cells in various organs / tissues. Amyloid is a protein that has an alteration in its secondary structure which imparts it a particular insoluble form
- 23. NATURE OF AMYLOIDS CLASSIFICATION Physicalnature CHEMICAL NATURE OF AMYLOID Electron microscopy : • Nonbranching fibrils with diameter 7.5-10 nm and indefinite length Amyloid protein chains i) AL (amyloid light chain) protein ii) AA (amyloid associated) protein iii) Other proteins
- 24. DIAGNOSIS DIAGNOSIS OF AMYLOIDOS •The most definitive investigation for amyloidosis is Biopsy. • The best sites for biopsy are rectum and abdominal fat pad (abdominal fat pad aspiration biopsy). • Other sites of biopsy are salivary glands, gingiva, skin, tongue, bone marrow and stomach.
- 25. SPLEEN Two patterns ofdeposition is seen - i) Sago spleen → Amyloid deposition is limited to splenic follicles (White pulp) - produces topioca like granules. ii) Lardoceous spleen → Amyloid depositon spares the follicles and involves the walls of the splenic sinuses (Red pulp). • It is the most common form of systemic amyloidosis. • It is the most serious form of organ involvement. • The earliest pathological change seen in renal amyloidosis is thickning of the glomerular basment membrane. • Amyloid is primarily deposited in the glomeruli, but interstitial peritubular tissue, arteries and arterioles are also affected. Results in abnormal increase in permeability of the glomerular capillaries → proteinuria and nephrotic syndrome KIDNEYS
- 26. Strong immunity, strongyou.... THANK -YOU