Immunity PDF

Immunity DR. EMILY LAROCQUE GOALS FOR THIS CONCEPT PRESENTATION 1. Define and describe the concepts (immunity, inflammation, infection). 2. Notice risk factors for altered immune functioning. 3. Recognize when an individual has altered immune functioning. 2 COMMON DIAGNOSTIC TESTS  Laboratory tests...

Immunity DR. EMILY LAROCQUE GOALS FOR THIS CONCEPT PRESENTATION 1. Define and describe the concepts (immunity, inflammation, infection). 2. Notice risk factors for altered immune functioning. 3. Recognize when an individual has altered immune functioning. 2 COMMON DIAGNOSTIC TESTS  Laboratory tests  CBC  WBC with differential (subpopulations)  C-Reactive Protein (CRP)  Erythrocyte sedimentation rate (ESR)  Serological tests to detect specific antibodies or viruses  Immunoglobulins  Allergy testing  Genetic testing  Rheumatoid factors (RFs), other  Organ function tests 3 RADIOGRAPHIC STUDIES  MRI  CT  Colonoscopy  X-rays  PET and other scans 4 The normal physiologic response to microorganisms and proteins as well as conditions associated with an inadequate or excessive immune response. IMMUNITY DEFINITION  First line of defense  Innate (natural) (native) immunity  Physical, mechanical, biochemical barriers  Second line of defense  Inflammation  Third line of defense  Adaptive (acquired) (specific) immunity 5 FIRST LINE OF DEFENSE  Physical barriers:  Skin  Linings of the gastrointestinal, genitourinary, and respiratory tracts  Sloughing off of cells  Coughing and sneezing  Flushing—urine  Vomiting  Mucus and cilia  Epithelial cell-derived chemical barriers:  Secrete saliva, tears, earwax, sweat, and mucus  Antimicrobial peptides  Cathelicidins, defensins, collectins, and mannose-binding lectin  Normal microbiome  Each surface colonized by bacteria and fungi that is unique to the particular location and individual 6 SECOND LINE OF DEFENSE  Inflammatory response (first immune response to injury)  Nonspecific  Caused by a variety of materials  Infection, tissue necrosis, trauma, physical or chemical injury, foreign bodies, immune reaction, ischemia, etc.  Local manifestations  Redness, heat, swelling, pain, loss of function  Vascular responses:  Blood vessel dilation  Increased vascular permeability and leakage  White blood cell adherence to the inner walls of the vessels and migration through the vessels 7 INFLAMMATION  Goals:     Limit and control the inflammatory process Prevent and limit infection and further damage Initiate adaptive immune response Initiate healing 8 PLASMA PROTEIN SYSTEMS  Protein systems:  Complement system  Produces biologically active fragments that recruit phagocytes, activate mast cells, and destroy pathogens  Clotting system  Forms a fibrinous meshwork at an injured or inflamed site  Kinin system  Functions to activate and assist inflammatory cells  Primary kinin is bradykinin 9 CELLULAR COMPONENTS OF INFLAMMATION  Cellular components:  Erythrocytes  Platelets  Leukocytes  Granulocytes (neutrophils, eosinophils, basophils)  Nongranulocytes (monocytes, lymphocytes) 10 WBC WITH DIFFERENTIAL  Total leukocytes: 4.5-11.0 x 10 9/L  Neutrophils: 2.5–7.5 x 10 9/L  Lymphocytes: 1.5–3.5 x 10 9/L  Monocytes: 0.2–0.8 x 10 9/L  Eosinophils: 0.04-0.4 x 10 9/L  Basophils: 0.01-0.1 x 10 9/L 11 WHITE BLOOD CELLS  A white blood cell (WBC) count of less than 4.5 x 109/L indicates leukopenia.  Infection  Treatment such as chemotherapy or radiation therapy, or leukemia.  Leukopenia (decrease in WBC) is most often due to a lower number of neutrophils, referred to as neutropenia. Characteristically, the neutrophil count is less than 1.5 x 109/L. [1, 2]  A WBC count of more than 11 x 109/L indicates leukocytosis.  infection, stress, inflammatory disorders (referred to as reactive leukocytosis), or abnormal production as in leukemia. 12 WBC INTERPRETATION Neutrophilic leukocytosis occurs when neutrophils are greater than 7.5 x 109/L. Common causes are as follows: Eosinophilic leukocytosis occurs when eosinophils are greater than 0.4 x 109/L. Common causes are as follows: Acute bacterial infections Sterile inflammation/tissue necroses seen in MI, burns, crush injuries. Allergic disorders such as asthma, parasitic infections, drug reactions 13  Monocytosis  occurs when monocytes are greater than 0.8 x 109/L. Common causes include the following:  Chronic infections such as tuberculosis, Bacterial endocarditis, Malaria, collagen vascular disease , inflammatory bowel disease  Lymphocytosis  occurs when lymphocytes are greater than 3.5 x 109/L. Common causes are as follows:  Accompanies monocytosis, viral infections such as hepatitis A, cytomegalovirus (CMV), EpsteinBarr virus (EBV) 14 CYTOKINES  Responsible for activating other cells and regulating inflammatory response  Chemokines  Interleukins  Tumor necrosis factor-alpha  Interferon (IFN) 15  Mast cells are cellular bags of granules located in the loose connective tissues close to blood vessels  Skin, digestive lining, and respiratory tract  Contain histamine, cytokines, and chemotaxic factors MAST CELLS AND BASOPHILS  Basophils are found in blood and probably function in same way as mast cells  Chemical release in two ways  Degranulation  The release of the contents of mast cell granules  Synthesis  The new production and release of mediators in response to a stimulus 16 ENDOTHELIUM  Endothelial cells adhere to underlying connective tissue matrix  Interact with circulating cells, platelets, plasma proteins  Regulate circulating inflammatory components  Damage to these initiates platelet adherence 17 PLATELETS  Activated by tissue destruction and inflammation  Activation leads to interaction with coagulation cascade to stop bleeding  Degranulation with serotonin release (acts like histamine) 18  Neutrophils  Also referred to as polymorphonuclear neutrophils (PMNs)  Predominate in early inflammatory responses  Ingest bacteria, dead cells, and cellular debris  Cells are short lived and become a component of the purulent exudate PHAGOCYTES  Eosinophils  Mildly phagocytic  Defense against parasites and regulation of vascular mediators  Basophils  Least prevalent granulocytes  Primary role unknown 19 PHAGOCYTES (CONT.)  Monocytes and macrophages  Monocytes are produced in the bone marrow, enter the circulation, and migrate to the inflammatory site, where they develop into macrophages  Macrophages typically arrive at the inflammatory site 24 hours or later after neutrophils  Phagocytosis  Process by which a cell ingests and disposes of foreign material 20 NATURAL KILLER CELLS  Recognize and eliminate cells infected with viruses  Inhibitory and activating receptors to allow differentiation between normal and abnormal cells  Produce cytokines and toxic molecules 21 ALTERED IMMUNITY What is meant by “altered” immunity? Conditions in which immune responses are either suppressed or exaggerated Suppressed responses are referred to as immunocompromised or immunodeficiency Exaggerated responses are referred to as hypersensitive 22 SUPPRESSED IMMUNE RESPONSE  Primary immunodeficiency  a group of more than 300 rare, chronic disorders in which part of the body’s immune system is missing or functions improperly  Secondary immunodeficiency  Intentional  Adverse effect of treatment 23 CONSEQUENCES OF EXAGGERATED IMMUNE RESPONSE Acute hypersensitive reaction Chronic body-wide system disease Localized effect Destruction of body tissue Systemic effect Abnormal organ growth Change in organ function 24 EXAGGERATED IMMUNE FUNCTIONING Symptoms Clinical Findings  Allergic response Allergic symptoms Fatigue  Mild allergic response  Severe allergic response Pain Fever  Autoimmune disorders  Can range from vague findings to findings associated with organ failure 25 SUPPRESSED IMMUNE FUNCTIONING Symptoms Clinical Findings  Report of frequent infections  May appear poorly nourished or have wasting syndrome  Report of poor wound healing  Fatigue  Malaise  Weight loss  May have chronic wounds  May have enlarged lymph nodes  Presence of opportunistic infection 26  Failure of immune mechanisms of self-defense IMMUNE DEFICIENCIES  Primary (congenital) immunodeficiency  Genetic anomaly (Most are the result of a single gene defect)  Generally not inherited  May appear early or late in life  Rare but increasing  Secondary (acquired) immunodeficiency  Caused by another illness  More common 27 ADAPTIVE IMMUNITY  Purposes:  Destruction of infectious microorganisms that are resistant to inflammation  Long-term, highly effective protection against future exposure to the same microorganism  Specific  Long-lived  Has memory 28  Elements:  Antigens  Lymphocytes (T cells, B cells) ADAPTIVE IMMUNITY (CONT.)  Components:  Humoral—immunoglobulins (antibodies)  Bind to antigens on bacteria and viruses  Cellular—T cells  Subpopulations (effector T cells)  Kill target directly  Stimulate other leukocytes  Both produce memory cells 29 Active immunity ADAPTIVE IMMUNITY (CONT.) Exposure to antigen Immunization Passive immunity Preformed antibodies or T cells are administered 30 Antigens ANTIGENS AND IMMUNOGENS Immunogens Haptens 31 cm d ies ep e stl ,o v re T ass o n b n d u T tB ab c n ee d cl lB o sc m eeA ill ll m si m u N m n o m o t u g n eo n c g ie cn s as fa tr ei ral cn y o ti m i b m g ieu n iso n g b g e u w tn in s to h t ANTIBODIES  Immunoglobulins (antibodies)  Classes:  IgG  IgA  IgM  IgE  IgD  Characterized by differences in structure and function 32 ANTIBODY FUNCTIONS  Antibody functions:  Direct  Neutralization  Agglutination  Precipitation  Indirect  Inflammation  Phagocytosis  Complement 33 SECRETORY (MUCOSAL) IMMUNE SYSTEM  Lymphoid tissues that protect the external surfaces of the body  Antibodies present in tears, sweat, saliva, mucus, and breast milk  IgA is the dominant immunoglobulin  Small amounts of IgG and IgM are present 34 SECRETORY (MUCOSAL) IMMUNE SYSTEM (CONT.) 35 T HELPER LYMPHOCYTES  “Help” the antigen-driven maturation of B and T cells  Facilitate and magnify the interaction between APCs and immunocompetent lymphocytes 36 PEDIATRIC IMMUNITY  Maternal antibodies provide protection within the fetal circulation and during the first months of life  Immunologically immature when born with deficiencies in antibody production, phagocytic activity, and complement activity 37 Inflammation: Review/Synopsis INFLAMMATION Inflammation is an immunologic defense against tissue injury, infection, or allergy. Function  Restitution of normal, functioning cells after injury  Fibrous repair when restitution of functioning cells is impossible 39 EXAMPLES OF INJURY CAUSING INFLAMMATION Discuss examples of the types of injury that lead to inflammation. Be sure to think of examples at different stages of the lifespan. Mechanical injury Thermal injury Electrical injury Chemical injury Radiation injury Biological assault 40 CONSEQUENCES OF AN EXCESSIVE OR INEFFECTIVE INFLAMMATORY RESPONSE  Local tissue damage from compression  Development of chronic inflammation  Systemic pathology:  Atherosclerosis  Chronic renal disease  Neurological disorders 41 ACUTE AND CHRONIC INFLAMMATION  Acute  Self-limiting  Local manifestations—result from vascular changes and corresponding leakage of circulating components into the tissue  Heat, swelling, redness, pain  Exudative fluids 42  Serous exudate  Watery exudate: indicates early inflammation  serosanguinous EXUDATIVE FLUIDS  Fibrinous exudate  Thick, clotted exudate: indicates more advanced inflammation  Purulent exudate (suppurative)  Pus: indicates a bacterial infection  Hemorrhagic exudate  Exudate contains blood: indicates bleeding 43 Exudate SEROUS-SEROSANGUINOUS-PURULENT-FIBRINOUS-HEMORRHAGIC 44  Fever  Caused by exogenous and endogenous pyrogens  Act directly on the hypothalamus SYSTEMIC MANIFESTATIONS OF ACUTE INFLAMMATION  Leukocytosis  Increased numbers of circulating leukocytes  Increased plasma protein synthesis  Acute-phase reactants:  C-reactive protein  Fibrinogen  Haptoglobin  Amyloid  Ceruloplasmin, etc. 45  Inflammation lasting 2 weeks or longer CHRONIC INFLAMMATION  Often related to an unsuccessful acute inflammatory response  Characterized by pus formation, suppuration, and incomplete wound healing  Causes of chronic inflammation:  High lipid and wax content of a microorganism  Ability to survive inside the macrophage  Toxins  Chemicals, particulate matter, or physical irritants 46 INFECTION 47 DEFINITION Infection is the invasion and multiplication of microorganisms in body tissues, which may be unapparent, or the result of local cellular injury caused by competitive metabolism, toxins, intracellular replication, or antigen-antibody response. 48 OPPORTUNISTIC INFECTIONS  Candidiasis  Histoplasmosis  Toxoplasmosis  Cytomegalovirus (CMV)  Mycobaterium Aviam Complex (MAC)  Kaposi’s Sarcoma (KS) 49 OTHER DESCRIPTORS OF INFECTION  Location  Localized infection versus disseminated infection versus systemic infection  Duration  Acute infection versus chronic infection  Source  Hospital-acquired/health care–acquired infection versus community-acquired infection  Primary infection versus secondary infection Copyright © 2017, Elsevier Inc. All rights reserved. 50  Endemic infection  when that infection is maintained in the population without the need for external inputs (chicken pox versus zika or malaria) OTHER DESCRIPTORS OF INFECTION (CONT.)  Epidemic infection  rapid spread of infectious disease to a large number of people in a given population within a short period of time, usually two weeks or less (norovirus)  Pandemic infection  is an epidemic of infectious disease that has spread through human populations across a large region; for instance multiple continents, or even worldwide  HIV, H1N1 2009, COVID-19 51 PROCESS OF INFECTION 52 INFECTIOUS PROCESS  Immune responses to bacterial invasion:  B lymphocytes are activated, resulting in the production of antibodies.  T lymphocytes are activated, resulting in phagocytosis.  Bacteria release endotoxins or exotoxins, which damage the cells of the host and initiate an inflammatory response. 53 RISK FACTORS FOR INFECTION: POPULATIONS AT GREATEST RISK  Infections potentially affect all individuals, regardless of age, gender, race, and socioeconomic status.  Populations at greatest risk are the:  Very young  Poor  Uninsured  Residents of geographic areas where an infection is prevalent 54 Infection and Defects in Mechanisms of Defense  Communicability  Ability to spread from one individual to others and cause disease: measles and pertussis spread very easily; HIV is of lower communicability FACTORS FOR INFECTION  Infectivity  Ability of pathogen to invade and multiply in the host  Involves attachment to cell surface, release of enzymes, escape of phagocytes, spread through lymph and blood to tissues  Virulence  Capacity of a pathogen to cause severe disease; for example, measles virus is of low virulence while rabies virus is highly virulent 56 FACTORS FOR INFECTION (CONT.)  Pathogenicity  Ability of an agent to produce disease  Success depends on communicability, infectivity, extent of tissue damage, and virulence  Portal of entry  Route by which a pathogenic microorganism infects the host     Direct contact Inhalation Ingestion Bites of an animal or insect  Toxigenicity  Ability to produce soluble toxins or endotoxins, factors that greatly influence the pathogen’s degree of virulence 57 Incubation period  The period between exposure to an infection and the appearance of the first symptoms 58 BACTERIAL DISEASE  Staphylococcus aureus  Life threatening  Major cause of nosocomial infection  Common on normal skin and nasal passages  Opportunistic  Biofilms associated with colonization  Secretes exotoxins  Antibiotic resistance is a major problem 59  Most common affliction of humans  Replication depends on ability to infect host cell  Simple organism, not living  Usually self-limiting VIRAL DISEASE  Transmission:  Aerosol  Infected blood  Sexual contact  Vector (the vector may assist in multiplying, isolating, or expressing the foreign DNA insert) 60 METHICILLIN RESISTANT STAPHYLOCOCCUS AUREUS  MRSA is methicillin-resistant Staphylococcus aureus, a type of staph bacteria that is resistant to several antibiotics. In the general community, MRSA most often causes skin infections. In some cases, it causes pneumonia (lung infection) and other issues. If left untreated, MRSA infections can become severe and cause sepsis  In a healthcare setting, such as a hospital or nursing home, MRSA can cause severe problems such as bloodstream infections, pneumonia and surgical site infections. If not treated quickly, MRSA infections can cause sepsis and death. 61  Bacterium that causes inflammation of the colon, known as colitis.  People who have other illnesses or conditions requiring prolonged use of antibiotics, and the elderly, are at greater risk of acquiring this disease. CLOSTRIDIUM DIFFICILE (CDIFF)  The bacteria are found in the feces.  Symptoms  Watery diarrhea (at least three bowel movements per day for two or more days)  Fever  Loss of appetite  Nausea  Abdominal pain/tenderness 62 BACTERIAL VIRULENCE AND INFECTIVITY  Bacteremia (presence) or septicemia (growth)  A result of a failure of the body’s defense mechanisms  Usually caused by gram-negative bacteria  Endotoxins released into the blood activate the complement and clotting systems, leading to a degree of capillary permeability sufficient to permit escape of large volumes of plasma into surrounding tissue, contributing to hypotension and, in severe cases, cardiovascular shock 63 VIRAL REPLICATION  Not capable of independent reproduction  Need permissive host cell  Attachment  Penetration  Uncoating  Replication  Assembly  Release 64  Influenza, commonly known as ‘the flu’  A respiratory illness caused by influenza A or B viruses that can be mild or serious  Symptoms usually last 7-10 days, sometimes longer in the elderly  Cough and fatigue can last weeks  Influenza is very contagious, you can spread the disease 24 hours before you become symptomatic and for about 5 days after symptom onset 65 MODES OF TRANSMISSION  Respiratory Droplet Transmission  Droplets are generated when a sick person coughs or sneezes  droplets can travel up to two meters in distance  Droplets need to be inhaled by nearby individuals or land on their mouth, eyes or nose to transmit the virus  Contact Transmission  Respiratory droplets can also contaminate surfaces or objects  the flu virus can survive up to 48 hours on hard, non-porous surfaces such as stainless steel  If an individual touches a surface or object contaminated with the flu virus and then touches their mouth, nose or eyes the virus can be transmitted 66 WHO IS MOST VULNERABLE TO THE FLU?  Adults and children with underlying health conditions  Residents of LTCHs and other chronic care facilities  People > 65 years of age  Children < 60 months of age  Pregnant women  Indigenous peoples 67 SYMPTOMS – COLD VS. FLU 68 COLD FLU Lung infections Throat infections Ear infections Sinus infections Pneumonia Pre-existing health conditions getting worse (such as asthma) Hospitalization Death COMPLICATIONS OF A COLD VS. THE FLU 69 CONFIRMING DIAGNOSIS  Nasopharyngeal (NP) Swab  Should be obtained from the most severe and most recently ill residents (i.e. during the first 4 days of their illness) 70 CORONAVIRUSES (COV)  Coronaviruses are a large family of viruses that can cause illness in animals or humans  In humans, several known coronaviruses can cause respiratory infections  Ranging from the common cold to more severe diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and coronavirus disease 2019 (COVID-19) COVID-19: TRANSMISSION  The primary transmission of COVID-19 is from person to person through respiratory droplets  Droplets are released when someone talks, sneezes, or coughs  Infectious droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs  COVID-19 may also be spread if you touch contaminated objects and surfaces  Data also suggests transmission by people who are not showing symptoms COVID-19: SYMPTOMS ▪ Wide range of symptoms reported          Fever or chills Cough Shortness of breath or difficulty breathing Headache Nasal congestion or runny nose Muscle or body aches Sore throat New loss of smell or taste Diarrhea (may be present in some patients) Estimated incubation period: 2 to 14 days Community spread means some people have been infected and it is not known how or where they became exposed. 74 COVID-19: EVERYDAY PREVENTATIVE ACTIONS  Avoid touching your eyes, nose, and mouth  Avoid close contact with people who are sick  Remember that people without symptoms can still spread the virus  Stay at home when you are sick  Cover your cough or sneeze with a tissue, then dispose of it properly  Use a face covering when physical distancing is difficult or when going into closed spaces  Clean and disinfect frequently touched objects and surfaces  Perform hand hygiene with soap and water or use alcohol-based hand rub COVID-19 TESTING Viral Testing Antibody Testing PCR (polymerise chain reaction) – viral genetic material Antigen – protein on virus 76 Large microorganisms with thick, rigid cell walls without peptidoglycans (resist penicillin and cephalosporins) Eukaryotes Exist as single-celled yeasts, multicelled molds, or both Reproduce by simple division or budding FUNGAL INFECTION 77  Diseases caused by fungi are called mycoses  Superficial, deep, or opportunistic FUNGAL INFECTION (CONT.)  Fungi that invade the skin, hair, or nails are known as dermatophytes  The diseases they produce are called tineas (ringworm)  Tinea capitis, tinea pedis, and tinea cruris  Pathogenicity  Adapt to host environment  Wide temperature variations, digest keratin, low oxygen  Suppress the immune defenses  Usually controlled by phagocytes, T lymphocytes 78 FUNGAL INFECTION (CONT.)  Candida albicans  Most common cause of fungal infections  Opportunistic  Found in normal microbiome of skin, GI tract, vagina of many individuals  Localized infection if overgrowth occurs  Disseminated infection if immunocompromised  May involve deep infection  High mortality rates 79 PARASITIC INFECTION  Symbiotic  Unicellular protozoa to large worms (helminths)  Flukes, nematodes, tapeworms  Protozoa include malaria, amoebae, flagellates  More common in developing countries  Spread human to human via vectors  Usually ingested  Tissue damage is secondary to infestation itself with toxin damage or from inflammatory/immune response 80 ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS)  Syndrome caused by a viral disease  Human immunodeficiency virus (HIV)  Depletes the body’s Th cells  Incidence:  Worldwide: 37.9 million (2021)  United States: about 36,801 (2021) www.hiv.gov www.cdc.gov 81 ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) (CONT.)  Effective antiviral therapies have made AIDS a chronic disease  Epidemiology  Blood-borne pathogen  Heterosexual activity is most common route worldwide  Women affected more often 82 HUMAN IMMUNODEFICIENCY VIRUS (HIV) (CONT.)  Clinical manifestations  Serologically negative, serologically positive but asymptomatic, early stages of HIV, or AIDS  Window period  Th cells