Week 2 - Immune System PDF

**1) What are the two types of immune responses/ components of the immune system? Compare and contrast them.** - **Innate immune response** - **Non-specific** - **Very fast- works within minutes** - **Causes fevers** - **No memory** - **Includes:** -...

**1) What are the two types of immune responses/ components of the immune system? Compare and contrast them.** - **Innate immune response** - **Non-specific** - **Very fast- works within minutes** - **Causes fevers** - **No memory** - **Includes:** - **Chemical barriers: lysozymes in tears, low pH in stomach** - **Physical barriers: epithelium in skin and gut, cilia in airways** - **Adaptive immune response** - **Highly specific** - **Diverse** - **Has to be primed/activated to differentiate into right cell** - **Takes weeks to develop** - **Immunologic memory** - **Clonal expansion** - **Clonal deletion -\> survive as memory cells** **2) What are the cells of the immune system and where do they come from?** - **Hematopoiesis = formation of WBCs and RBCs (usually takes place in bone marrow)** - **WBCs (leukocytes)** - **Multipotent hematopoietic stem cell -\> myeloid progenitor cell OR lymphoid progenitor cell** - **Myeloid cells -\> granulocytes (neutrophil, eosinophil, basophil), mast cell, dendritic cell, macrophage, monocyte** - **INNATE** - **Granulocytes contain granules in cytoplasm** - **Lymphoid cells -\> B cells, T cells, NK cells (can travel in/out of tissue in bloodstream)** - **B and T = ADAPTIVE** - **T develops in thymus** - **NK = INNATE** - **B and NK develop in bone marrow** **[3) Review the basic functions of the different immune cells.]** - **Neutrophils = phagocytes** - **Eosinophil and basophil = contain histamine and proinflammatory molecules** - **Eosinophils fight helminthic parasites, worms by poking holes in outer layer of helminths; also involved in allergic reactions (atopic dermatitis, allergic rhinitis)** - **Basophils initiate allergic responses** - **Mast cells = live in tissues, cause inflammation in allergic responses** - **Monocytes, dendritic cells, macrophages = phagocytic, APCs, release cytokines** - **Monocytes are only in blood -\> can migrate into tissues to turn into macrophages** - **Dendritic cells are prototype APC, found in sites that are in contact with external antigens (like skin epithelium and gi cilia)** - **NK = large lymphocytes with granules that target viruses and cancer cells** - **Kill by releasing cytotoxic granules \> punch holes via binding to phospholipids AND by apoptosis (programmed cell death)** - **B cells = bind to specific antigens, do not need antigens to be presented** - **Also display antigens to T cells -\> after presentation will turn into plasma cell -\> secretes antibodies (takes weeks, has same specificity as original B cell, circulate in plasma, tag antigens for destruction** - **T cells = cell-mediated immunity, antigen-specific** - **Matures from APCs** - **CD4 = helper cells, secrete cytokines that coordinate macrophages and B cells, can only see antigens on MHC II** - **CD8 = cytotoxic T cells, kill cells with specific antigen on MHC I** **4) What immune cells are phagocytic?** - **Neutrophils (aka polymorphonuclear cells)** - **Monocytes** - **Dendritic cells** - **Macrophages** **5) Describe in detail the process of phagocytosis. What is a phagolysosome? What is an oxidative burst?** - **Phagocytosis = reach around pathogen with cytoplasm to swallow it whole -\> ends up in phagosome -\> use oxidative burst** - **Phagolysosome = phagosome + cytoplasmic granules** - **Granules lower pH of lysosome to make very acidic (kills 2% of pathogens)** - **Oxidative burst = neutrophils produce ROS (like hydrogen peroxide) that destroy proteins and nucleic acids within phagolysosome -\> pathogen eliminated** **6) Which cells are antigen presenting cells? Why are they important? Review the process.** - **Monocytes** - **Dendritic cells** - **Eat large proteins in interstitial fluid -\> phagocytizes pathogen -\> breaks pathogen into small amino acid chains -\> move through lymph to present antigen to T cells** - **Best at APC because they are only cells that live where pathogens enter and traffic from tissues to lymph nodes (where T cells circulate)** - **Macrophage** - **B cells** - **APCs connect innate and adaptive immune system** **7) What part of the immune system is a natural defense against cancerous growth?** - **NK cells** **8) What is humoral immunity? What is cell-mediated immunity?** - **Humoral immunity = antibodies float freely in blood (antibody mediated immunity)** - **Cell-mediated immunity = adaptive immune system that involves the activation of immune cells to fight off intracellular pathogens** **[9) Describe the series of events that could happen if a pathogen enters the body.]** - **Pathogen breathed in -\> penetrate epithelia of lungs -\> bacteria divide -\> resident macrophage in lung tissue ingests it and releases cytokines -\> make blood vessels leaky and attract basophils, eosinophils, mast cells that amplify inflammation -\> neutrophils in blood and from bone marrow will join** - **Immature dendritic cells residing under epithelium will digest pathogen and move to lymph node to present MHC II to naive T cell** - **If no dendritic cell presents -\> then B cell will present it to CD4 T cell -\> clonal expansion -\> cytokines -\> B cell -\> plasma cell -\> antibodies in bloodstream** **10) What are the key features of the innate immune system? Review the components of innate immunity.** - **Cells are nonspecific** - **Response is fast** - **There is no memory** - **Includes chemical barriers and physical barriers** **11) What is the complement system and what are the possible pathways by which it can be activated? What are the outcomes of the complement system?** - **Complement system = 9 proteins that act as a cascade to cleave bacteria into functional fragments** - **Chemotaxis: attract immune cells -\> release ROS** - **Opsonin\'s: mark target to phagocytose** - **Membrane attack complexes: create a hole** **12) What is the purpose and goal of the inflammatory process? What events can initiate a local inflammatory response? What subtypes of inflammation are there and what are their respective time courses?** - **Inflammatory process = innate, nonspecific, immediate, defensive mechanism that helps protect the body against infection and injury** - **Goal = respond to stimuli and restore balance** - **Initiate:** - **External triggers = bacteria, viruses, fungi, allergens, toxins, irritants** - **Internal triggers = cellular injury** - **Subtypes:** - **Acute = several days** - **Subacute = 2-6 weeks** - **Chronic = months- years** **[13) What are the vascular and cellular events of acute inflammation and in what sequence do they occur?]** - **Vascular response** - **Changes to capillaries, arterioles, venules** - **Transient vasoconstriction of local blood vessels** - **Vasodilation from NO released by endothelial cells -\> increases blood flow to site of injury, redness, warmth** - **Increased permeability of capillaries -\> inflammatory exudate leaks into interstitial space (less proteins inside means a decrease of capillary osmotic pressure and increase in interstitial osmotic pressure) -\> local swelling** - **Cellular response** - **Macrophages do phagocytosis and release inflammatory mediators like histamine, kinins, prostaglandins, leukotrienes, and cytokines -\>** - **Attract neutrophils (extravasation) which get there in 6-12 hours to phagocytose invading pathogens/foreign substances and dead cells** - **Monocytes come in 3-7 days where they turn into macrophages** - **Dendritic cells, macrophages, naive B cells act as APCs to present to T cells which release more cytokines to attract NK, cytotoxic T cells, B cells** **14) What is inflammatory exudate? What the types of exudate?** - **Inflammatory exudate = fluid that leaks and accumulates in tissue during inflammation** - **Serous: clear, thin, watery** - **Sanguinous: fresh blood due to rupture of blood vessel** - **Serosanguinous: mixture of serous and sanguineous; pink, thin, watery** - **Purulent: thick, opaque; WBCs, dead cels, pathogens, tissue debris** - **Fibrinous: fibrin and fibrinogen** - **Catarrhal: rich in mucus; upper respiratory tract** **15) Describe the process of tissue repair.** - **Macrophages eat dead and dying cells so that new cells can take place ad also release growth factors (angiogenesis -\> new blood vessels that regress once healed)** - **Fibroblasts synthesize collagen o help wound healing** - **Mild tissue damage return to healthy state** - **Severe damage -\> non-functional fibrous scar** **16) What are the 5 cardinal signs of inflammation and what caused them?** - **1) redness (rubor) from vasodilation and increased blood flow** - **2) heat (calor) from increased cell metabolism** - **3) pain (dolor) from inflammatory mediators (histamine, bradykinin, prostaglandins)** - **4) swelling (tumor) from increased vascular permeability and increased fluid** - **5) loss of function (functio laesa) from pain/swelling** **17) What are the key features of the adaptive immune system?** - **Acquired throughout life** - **Slower** - **Specific** - **Long-lived (does not forget previous exposures to pathogens)** - **Active and passive** **[18) What cells make up adaptive immunity? Where do they come from? What functions do they serve?]** - **WBCs (lymphocytes) = B and T cells** - **B cells** - **Produced in bone marrow** - **Mature in bone marrow** - **Circulate in blood, lymph node or spleen until they encounter an antigen -\> become memory B cells/plasma cells -\> secrete antibodies against antigen** - **T cells** - **Produced in bone marrow** - **Mature in thymus** - **Helper T cells** - **Regulatory T cells: inhibit or suppress the immune response, decrease risk of autoimmune diseases (self vs non-self)** - **Cytotoxic T cells** **19) Describe the process of activation and action of the adaptive immune system (B and T cells response).** - **B and T cells mount a particular response to specific pathogens** - **APCs engulf and digest pathogen -\> MHC II presented to T helper cells -\> activate and proliferate -\> release cytokines to attract immune cells like cytotoxic T, neutrophils, NK** - **T helper cells also make naive B cells rapidly multiply and differentiate into plasma cells to secrete antibodies/immunoglobulins that bind and neutralize antigens** **20) Define and compare passive immunity to active immunity.** - **Active:** - **Antibodies produced by own immune system following exposure to a particular antigen** - **Humoral response (antibodies secreted by B cells)** - **Cell-mediated response (T cells)** - **Passive:** - **Ready-made antibodies reach person who does not have their own antibodies** - **Infants have when born from mother** - **Vaccines** **21) Describe the structure of an antibody. What classes exist. Compare and contrast them.** - **2 heavy chains, 2 light chains with fragment-antigen binding (Fab) at the tips of both; constant fragment (Fc) is base; 2 heavy chains are linked via disulfide bonds** - **IgD** - **Less than 1%** - **Monomer** - **On mature B cell and signels when they are ready to leave bone marrow** - **IgA** - **20%** - **Monomer** - **Opsonin for phagocytes like eosinophils, neutrophils, some macrophages** - **Main immunoglobulin in mucosal sites like saliva, tears, breast milk, semen** - **Swept away by cilia, excreted out, degraded by enzymes** - **Babies receive a lot in breastmilk (neutralize pathogens in gi)** - **IgE** - **Associated with allergic and anti-parasitic responses** - **Monomer** - **0.004%** - **Mast cells, eosinophil, basophil** - **Made to non-pathogenic targets as well like peanuts** - **Plays role in atopic dermatitis, seasonal allergies, asthma** - **Causes sneezing, mucus production, vascular permeability -\> swelling and smooth muscle contraction -\> wheezing** - **IgM** - **1^st^ antibody response made** - **Monomer when serving B cell receptor** - **When secreted by plasma cell -\> pentamer held together by J chain** - **Works against carbohydrate and lipid antigens** - **Most effective at activating complement pathway** - **4%** - **IgG** - **Produced most abundantly (75%)** - **Monomer** - **B cell receptor** - **Serves as opsonin to help phagocytes grip bacteria** - **Activates classical complement pathway** - **Works with NK to perform antibody dependent cell mediated cytotoxicity (ADCC)** - **Crosses placenta so newborn babies are born with maternal IgG which provides protection during the first 6 months of life** **22) Review the key features and functions of all the classes of antibodies.** - **See above** **23) What is herd immunity? How is it achieved?** - **Herd immunity = enough people vaccinated in population -\> entire population has resistance** - **Achieved when enough people are vaccinated** **24) How are vaccines administered? What types of vaccines exist? Define, compare, and contrast them.** - **Administered: IM, intradermal, subq, orally** - **4 types:** - **Live attenuated** - **Whole cell** - **Live, but weakened pathogen so that it can still replicate** - **MMR-V, rotavirus, smallpox, yellow fever** - **Inactivated** - **Whole cell** - **Pathogen has been killed using heat or formalin** - **Response is humoral or antibody mediated** - **No cellular immunity** - **Plasma cells make antibodies** - **Immune response is not as strong as live (may need booster shots)** - **Hep A, polio, rabies, influenza** - **Subunit** - **Fractionated (one part of pathogen)** - **Contain polysaccharides or proteins of pathogen that are most immunogenic** - **Polysaccharides of S. pneumoniae** - **Conjugation sometimes used** - **T cell independent** - **Not effective in kids under 2 because young kids needs T cell involvement** - **Repeated doses are needed** - **HIB, hep B, HPV, pertussis, step pneumoniae, Neisseria meningitidis, varicella zoster** - **Toxoid** - **Fractionated** - **Fixed or inactivated using formalin (same structure, no disease)** - **Vaccines against toxins** - **Tetanus, diphtheria** - **Combined with others (i.e. TDAP)** - **Conjugation increases immunogenicity** - **Adjuvants can also increase immune response (aluminum and monophosphorylate lipid A)** - **Enhance APC and T cell activation** **25) What is a hypersensitivity reaction? What subtypes exist? Define, compare and contrast them.** +-----------------+-----------------+-----------------+-----------------+ | **Type of | **Mechanism of | **Prototypic | **Description | | Hypersensitivit | Immune attack** | Disorder** | of Disorder** | | y** | | | | +=================+=================+=================+=================+ | **Immediate | **Production of | **Hay fever | **Hay fever | | (type I) | IgE antibodies | allergies, | allergies -- | | hypersensitivit | against | anaphylaxis** | IgE against | | y** | antigen, IgE | | antigens of | | | binds to Mast | | various pollens | | | cells and | | causes varying | | | sensitizes | | degrees of | | | them, upon | | local and | | | first | | systemic | | | appearance of | | inflammatory | | | antigen Mast | | responses | | | cells | | including | | | degranulate and | | itching, | | | initiate | | painful, and | | | inflammatory | | red eyes, nose, | | | response** | | and throat or | | | | | systemic | | | | | effects like | | | | | fever and | | | | | fatigue** | | | | | | | | | | **Anaphylaxis | | | | | -- an acute and | | | | | severe systemic | | | | | type I reaction | | | | | to an allergen. | | | | | Can be life | | | | | threatening** | +-----------------+-----------------+-----------------+-----------------+ | **Antibody-medi | **Circulating | **Autoimmune | **The | | ated | antibodies | hemolytic | development of | | (type II) | (IgM, IgG) bind | Anemia** | anemia (↓ RBCs) | | hypersensitivit | to antigen on | | as a result of | | y** | target cell or | **-MG, Graves, | accelerated RBC | | | tissue | pernicious | destruction | | | promoting | anemia** | (i.e. | | | either | | hemolysis). | | | phagocytosis by | | Hemolysis is a | | | leukocytes | | result of the | | | (IgG) or cell | | presence of | | | lysis by | | autoantibodies | | | complement | | that bind to | | | system (IgM)** | | RBCs and | | | | | stimulate | | | | | immune | | | | | attack.** | +-----------------+-----------------+-----------------+-----------------+ | **Immune | **Circulating | **Post | **Inflammatory | | complex-mediate | antigen-antibod | streptococcal | damage of | | d | ies | glomerulonephri | glomerular | | (type III) | complexes | tis** | membranes | | hypersensitivit | deposit in | | brought on by | | y** | tissues and | **-Lupus** | the deposition | | | initiates an | | of | | | inflammatory | | antigen-antibod | | | response which | | y | | | causes tissue | | complexes | | | damage at site | | occurring after | | | of deposition** | | or along | | | | | streptococcal | | | | | infection.** | +-----------------+-----------------+-----------------+-----------------+ | **Cell-mediated | **Antigen | **Transplant | **Immune attack | | (type IV) | activation of T | rejection** | of grafted or | | hypersensitivit | lymphocytes | | transplanted | | y** | which causes | **-MS, T1D, RA, | tissue/organs. | | | tissue damage | GB** | The target for | | | through: 1) | | the attack | | | activation of | | (antigen) is | | | inflammation | | for the most | | | and recruitment | | part the | | | of phagocytic | | donor's Major | | | cells (also | | Histocompatibil | | | called delayed | | ity | | | type | | Complex | | | hypersensitivit | | proteins.** | | | y) | | | | | and/or 2) | | | | | direct | | | | | cytotoxic T | | | | | cell killing of | | | | | antigen | | | | | carrying | | | | | cells** | | | +-----------------+-----------------+-----------------+-----------------+ **26) What is central vs. peripheral tolerance? What is autoimmunity?** - **Central tolerance = clonal deletion wherein immature lymphocytes that bind to self peptide strongly will undergo apoptosis** - **Peripheral tolerance = regulatory T cells (also play a role in suppressing immune responses)** - **Any self reactive lymphocytes that escaped central tolerance will undergo apoptosis or anergy (can no longer respond to antigens)** - **Autoimmunity = immune system perceives the body's own cells or proteins as foreign antigens and triggers and immune response that can cause organ damage and systemic inflammation** **27) What is thought to be the cause or causal factors behind autoimmunity?** - **Unknown** - **Believed risk factors** - **Modifiable** - **Various meds (procainamide, hydralazine)** - **Nonmodifiable** - **AFAB** - **Over 50 years old** - **Personal or family history** - **Hormonal changes during major endocrinological transitions (puberty, menopause)** **28) What types of autoimmune disorders exist? Define, compare, and contrast them.** - **Systemic: affect multiple organ systems** - **RA, lupus, scleroderma** - **Localized: target a specific system/organ** - **Disorders that affect blood: hemolytic anemia, immune thrombocytopenic purpura** - **CNS: GB, MS** - **Endocrine: Hashimoto\'s, graves, T1D** - **Other: uveitis (eye), rheumatic fever (heart), celiac\'s, IBS** - **Muscles: MG**