Infection and Immunity: Pathogens, Diseases, and Immune Responses

Infection

A state of cellular, tissue, and organ destruction resulting from invasion by microorganisms

Pathogens #1

Disease-producing microbes

Pathogens #2

Factors affecting pathogenicity

Pathogens #3

Types of pathogens including obligate versus facultative, bacteria, viruses, rickettsiae, mycoplasmas, Chlamydiae, fungi, protozoa, and helminths

Chain of Infection

The sequence of events that allows for the transmission of infection

Phases of Acute Infection

Exposure, Incubation, Prodrome, Acute clinical illness, Convalescence

Complications of Infection

Septicemia, Bacteremia, Septic shock, Chronic infection

Manifestations of Infection

Systemic symptoms include fever, weakness, headache, malaise, anorexia, nausea; Local symptoms include heat, incapacitation, pain, edema, redness, lymphadenitis, purulent exudate

Laboratory and Diagnostic Tests

White blood cell count, Leukocytosis, Leukopenia, Serum antibody levels, Cultures, Sensitivities

Treatment of Infection

Antimicrobial drugs including antibacterials, antifungals, antivirals; Symptom reduction through fluids, rest, and analgesics

Application of the Concepts of Infection

Conditions such as Acute pyelonephritis, Bacterial meningitis, Tinea, Malaria, Influenza, Viral hepatitis, Tuberculosis, Urinary tract infection

Influenza Pathophysiology

Viral infection of epithelial cells of airway with respiratory droplet transmission and infected epithelial cell necrosis

Influenza Clinical Manifestations

Cough, Sore throat, Nasal congestion/drainage, Shortness of breath, Chills, Fever, Body aches, Weakness, Malaise

Influenza Diagnostic Criteria

History and physical examination, Rapid viral assays

Influenza Treatment

Prevention through handwashing, vaccinations, symptomatic care, hydration, nutrition, analgesics, antiviral drugs

Viral Hepatitis Pathophysiology

Acute or chronic inflammation of the liver caused by infection with one or more hepatitis viruses, transmitted via fecal-oral route or direct contact with infected blood/body fluids

Viral Hepatitis Clinical Manifestations #1

Clay stools, Dark urine, Recovery, Improvement with residual hepatomegaly, Prodrome, Fatigue, Anorexia, Low-grade fever, Icterus, Jaundice, Hepatomegaly

Viral Hepatitis Diagnostic Criteria

History and physical examination, Detection of viral antibodies in blood including Anti-HAV, Anti-HCV, Anti-HDV, Anti-HEV, Other labs like urine bilirubin, serum bilirubin, clotting time

Viral Hepatitis Treatment

Prevention through vaccination, handwashing, avoidance of infected fecal material, blood, body fluids; Symptomatic care including fluids, rest, analgesics, low-fat diet, antiviral drugs

Tuberculosis Pathophysiology #1

Most prevalent and deadly infectious disease worldwide caused by infection with Mycobacterium tuberculosis, transmitted via inhaled airborne droplets

Tuberculosis Clinical Manifestations

90% of those infected are asymptomatic. In 10% with progressive primary disease: Malaise, Weight loss, Fatigue, Anorexia, Low-grade fever, Night sweats, Severe chronic productive cough with hemoptysis (bloody sputum), Site-specific.

Tuberculosis Diagnostic Criteria

Tuberculin skin tests, Chest radiograph, Sputum culture, Sputum nucleic acid amplification.

Tuberculosis Treatment

Antimicrobials: Isoniazid, Rifampin, Pyrazinamide, Ethambutol or streptomycin, Directly observed therapy, Vaccinations, Transmission prevention, Isolation in private room, Negative air pressure, Droplet precautions (masks, respirators).

UTI Pathophysiology

Ascending infection of urinary tract. E. coli most common pathogen. Results in cell necrosis in urinary tract epithelium.

UTI Clinical Manifestations

Dysuria, Urgency, Frequency, Hematuria, Cloudy (purulent) urine.

UTI Diagnostic Criteria

History and physical examination, Urinalysis and urine culture, Leukocyte esterase dip test.

UTI Treatment

Antibiotic drugs, Increased fluid intake.

Acute Pyelonephritis Pathophysiology

Bacterial infection of kidneys (often E. coli). Risk factors: Urinary obstruction (renal calculi), Incomplete bladder emptying, causing urine stagnation, Frequent intercourse, irritating urethra, Exposure to sexually transmitted infections, Hormonal changes, reducing ureteral peristalsis.

Acute Pyelonephritis Clinical Manifestations

Fever, Costovertebral angle pain, Nausea or vomiting, Dysuria, Urinary frequency, hesitancy, or urgency, Lower abdominal pain, Blood in urine.

Acute Pyelonephritis Diagnostic Criteria

Presence of symptoms, Urinalysis and microscopic evaluation, Urine culture, Imaging studies.

Acute Pyelonephritis Treatment

Intravenous fluids, Antibiotics, Analgesics, Surgery.

Bacterial Meningitis Pathophysiology

Inflammation of the meninges of the brain and spinal cord. Commonly caused by N.

Respiratory droplet transmission

Mechanism for entry into CNS unknown

Bacterial Meningitis Clinical Manifestations

Rapid and severe onset, severe headache, photophobia, nuchal rigidity, decreased alertness, loss of consciousness, changes in mental status, vomiting, seizures, fever, leukocytosis, anorexia

Bacterial Meningitis Diagnostic Criteria #1

History and physical examination, Kernig sign, Brudzinski sign, blood cultures, CSF analysis and cultures

Bacterial Meningitis Treatment

Vaccination, antibiotics, corticosteroids, fluids, treatment of close contacts

Tinea Pathophysiology

A group of fungal infections transmitted via direct contact; dermatophyte attaches to and produces thickening of keratinized cells

Tinea Clinical Manifestations #1

Variable depending on type (location): Corporis (body): 'ringworm', Versicolor (skin): hypopigmentation, Capitis (scalp): hair loss/breakage, Pedis (feet): maceration between and around toes, Cruris (groin): erythema, itching, Unguium (nails): nail thickening, discoloration

Tinea Diagnostic Criteria

History and physical examination, microscopic examination, fungal cultures, Wood light examination

Tinea Treatment

Prevention, proper hygiene, avoidance of contact with those infected, antifungal drugs (topical and oral)

Malaria Pathophysiology

Caused by infection with Plasmodium protozoa, transmitted by mosquito, incubation period of 1 month from exposure, currently eradicated in United States, worldwide, >1 million deaths per year, common in children from sub-Saharan Africa

Malaria Clinical Manifestations

Headache, shivering and chills, high fever, excessive sweating, cough, fatigue, malaise, joint/muscle aching

Malaria Diagnostic Criteria

Lactate dehydrogenase level, lymphocytes, peripheral blood smears, history of travel to an endemic area, physical examination, laboratory testing, hemoglobin level, platelet counts, liver function tests

Malaria Treatment

Prevention, avoiding mosquitoes, using a bed net during sleep, wearing long-sleeve clothing, using insect repellants (with DEET), antimalarial drugs, quinolines, antifolates, artemisinins, antimicrobials, antipyretics

Immune Defense

Third line of defense; Recognition and neutralization of foreign substances; Specific immune response; Immunologic memory.

Cellular Components of Immunity

Includes lymphoid progenitor cells, T lymphocytes (cytotoxic, helper, suppressor), B lymphocytes (differentiate into plasma cells for antibody production), and natural killer cells.

Lymphatics

Important in establishing the immune response; includes central organs (bone marrow and thymus) and peripheral organs (spleen, lymph nodes, and lymphoid tissue).

Innate immunity

Nonspecific immune response involving inflammatory processes.

Adaptive immunity

Targeted to a specific antigen and involves T and B lymphocytes.

Active immunity

Development of antibodies to an antigen achieved by having a specific disease or vaccine.

Passive immunity

Immunity transfer from host to recipient, achieved via mother-infant transfer (placenta or breast milk) or injection of antibody.

Humoral immunity

Involves B lymphocytes and antibodies secreted from plasma cells (IgA, IgD, IgE, IgG, IgM).

Memory cells

Cells that are activated with first recognition of a specific antigen, leading to primary adaptive immune response.

Secondary adaptive immune response

Reactivation with later recognition of the same antigen.

Cell-mediated immunity

Involves cytotoxic T lymphocytes (CD8) and helper T lymphocytes (TH1, TH2: CD4).

Major histocompatibility complex (MHC)

Includes MHC class 1 molecules (CD8) and MHC class 2 molecules (CD4), also known as human leukocyte antigen (HLA).

Hypersensitivity

Includes Type 1 (immediate), Type II antibody-mediated, Type III immune complex-mediated, and Type IV cytotoxic T lymphocyte-mediated hypersensitivity reactions.

Autoimmunity

Failure to distinguish self from nonself, causing damage to specific organs or to the entire system.

Alloimmunity

Includes graft rejection and graft versus host disease.

Acquired immunodeficiency syndrome (AIDS)

A condition characterized by altered host defense resulting from secondary immunodeficiency due to HIV infection.

AIDS Pathophysiology

Infection of CD4 helper T lymphocytes with human immunodeficiency virus (HIV) results in loss of cell-mediated and humoral immunity.

AIDS Clinical Manifestations

Includes immunosuppression and opportunistic infections such as fungal infections and pneumocystis jirovecii pneumonia.

AIDS Diagnostic Criteria

Includes history and physical examination, risk factors, signs and symptoms of infection, laboratory analysis, detection of antibodies to HIV, HIV viral load, and CD4 T helper lymphocyte cell counts.

AIDS Treatment

Involves antiretroviral therapy (ART) to suppress viral load, restore or preserve immune function, and reduce morbidity and mortality.

Anaphylactic Reaction

An exaggerated systemic immune response due to a type 1 hypersensitivity reaction triggered by insect stings, food allergies, or drug allergies.

Anaphylactic Reaction Pathophysiology

Antigen exposure stimulates an IgE-mediated response in a previously sensitized individual.

Degranulation of mast cells and basophils

Causes local and systemic responses.

Dilation of vascular smooth muscle

A response caused by degranulation.

Constriction of bronchial smooth muscle

A response caused by degranulation.

Increase in vascular permeability

A response caused by degranulation.

Anaphylactic Reaction Clinical Manifestations Phase 1

Difficulty breathing, skin flushing and itching, angioedema.

Anaphylactic Reaction Clinical Manifestations Phase 2

Difficulty breathing, severe hypotension, severe edema.

Anaphylactic Reaction Diagnostic Criteria

History and physical examination, allergy testing.

Anaphylactic Reaction Treatment

Symptomatic drugs to relax bronchial smooth muscle, drugs to constrict vascular smooth muscle, limit inflammation, and preventative desensitization to allergen.

Systemic Lupus Erythematosus (SLE)

An autoimmune disease with various clinical manifestations.

SLE Pathophysiology

Type III hypersensitivity reaction, autoimmune response involving innate and adaptive immune systems.

Chronic disease in SLE

Due to persistent antigen, activation of B cells producing antibodies, activation of T cells promoting inflammation.

SLE Clinical Manifestations

Specific to organs injured by inflammation and complex deposition, affecting local and systemic organs.

SLE Diagnostic Criteria

History and physical examination, laboratory analysis, antibodies against cell components and DNA, inflammatory markers: complement (C3 and C4).

SLE Treatment

Pharmacologic options including anti-inflammatories, DMARD, antimalarial, and immunosuppressants.

Rh Isoimmunization Pathophysiology

Type II cytotoxic antibody-mediated reaction involving the Rho(D) antigen on red blood cells.

Rh Isoimmunization Clinical Manifestations

Fetal effects include anemia, hydrops (edema), death; infants may experience kernicterus, lethargy, hearing loss, cerebral palsy, and learning problems.

Rh Isoimmunization Diagnostic Criteria

History and physical examination, screening tests, identification of D antigen and anti-D antibodies, amniocentesis to measure bilirubin, fetal blood sampling to determine anemia.

Rh Isoimmunization Treatment

Risk reduction through prevention, administration of Rh immunoglobulin to prevent maternal sensitization to fetal D antigen, and exchange transfusion to replace damaged red blood cells.