Infectology exam 2/3

Specifics of the immune response against viruses.

Specifics of the Immune Response against Viruses:

Innate Immune Response: The first line of defense. 

1) Physical Barriers: Skin and mucous membranes. 

2) Phagocytic Cells: Macrophages and neutrophils attempt to engulf virus-infected cells. 

3) Natural Killer (NK) Cells: Recognize and kill virus-infected cells (especially those with reduced MHC class I expression). 

4) Pattern Recognition Receptors (PRRs):

5) Inflammation: Cytokines and chemokines

*Adaptive Immune Response: A highly specific, slower response that generates immunological memory. 

1) Humoral Response (B cells):

2) Cellular Response (T cells): 

Specifics of the immune response against intracellular bacteria, fungi.

phagocytes
Kcells
Th1cells → IFN-γ → macrophages
T cells
neutrophils

Specifics of the immune response against extracellular bacteria.

• Antibodies (IgG, IgM) → neutralization, opsonization

• Complement activation → opsonization (C3b), lysis (MAC)

• Neutrophils → main effector cells (phagocytosis, killing)

• Macrophages → phagocytosis, antigen presentation

• Th17 cells → recruit neutrophils (IL-17)

• IL-8 → neutrophil chemotaxis

• Inflammation → edema, pus formation

Cytokine storm, its pathogenesis. Clinical and laboratory signs.

excessive and uncontrolled release of pro-inflammatory cytokines! Triggerd by infections, → release por inflammoty cytokins IIL-6, IL-1β, TNF-α, and IFN-γ. . → possitive feedback loop releaseing even more,

Clinical signs:

• High fever

• Hypotension / shock

• Tachycardia

• Dyspnea / ARDS

• Confusion / encephalopathy

• Organ failure

Laboratory signs:

• ↑ CRP, ↑ ferritin

• ↑ IL-6 (key marker)

• Leukocytosis or leukopenia

• ↑ D-dimer, coagulopathy

• ↑ liver enzymes

• ↑ lactate

• Thrombocytopenia

Dynamics of antibody production in case of first and repeated contact with the pathogen. Infections as triggers for autoimmune processes.

First:
Lag phase: no atnibody detection for 5-7 days
IGM, IgG, Low affinity antibodies
Short lived responce

Second+
Rapid responce 1-3 days
IgG
High affinity antibodies
Long lasting response

Autoimmune processes
Moleculat mimicry: Pathogen antigens resemble self-antigens.
Bystander activation: intense inflammatory environment created by infection acitve autoreactive lymphocytes
Epitope spreading: tissue damage from an infection can release self-antigens
Exposure of hidden antigens: Tissue damage exposes self antigens to the immune system

Features of immunological memory depending on the type of antigen.

T cell dependent anigen:
Need T cell help to activeate B cell
Memory cells - Rapid responce on second expoture, IgG

T cell independent antigen:
Activeate B cell witout help
Memory cells: weaker short lived, IgM

Latent and chronic infections (pathogens and disorders of the immune response, examples).

Latent Infections: The pathogen persists in the host in a dormant or inactive form, witout symptoms
hERPES, TUBERCULOSIS, Toxoplasma gondi

Chronic Infections: The pathogen persists in the host and actively replicates, causing ongoing or progressive disease.
Hepatitis B/C, HIV

Immune Disorders: Chronic infections often involve viral evasion strategies

Post-COVID syndrome.

Persistent/new symptoms > 3 months after covid 19

More common in those with severe initial illness,

no single test. Diagnosis is clinical, based on history of COVID-19

supportive and symptom-based,

Laboratory diagnosis of SARS-CoV-2 infection.

PCR
Serology IgM, IgG
Rapid antigen test

lymphopenia, crp, ferritin

Differential diagnosis of a patient with sore throat.

Pharygitis viral/streptococcal
allergic rhinitits
GERD
Tonsilitis
Epiglottis

Viral hepatitis A: epidemiology, clinical presentation, diagnosis, treatment and prophylaxis

Epidemiology,
Fecal--oral
Developing countries
1moth incuation

Clinical Presentation,
Fever, malaise, anorexia, nausease, abdominal pain,
Jaundice, pale stool
acute, self limitinng

Diagnosis,
Anti-HAV-IgM antibodies
liver markers ALT AST

Treatment
Supportive: rest, hydration, Avoid alcohol

Prophylaxis:
Vaccinnation (pre & post expoture)

Viral hepatitis B: epidemiology, clinical presentation, diagnosis and treatment.

epidemiology,
blood, sex transmission
2-3 monts incubation

clinical presentation,
Fever, malaise, anorexia, nausease, abdominal pain,
acute or chronic
Jaundice, liver failure, carcinoma

diagnosis
HBsAg
Anti-HBs
Anti-HBc Igm
HBV DNA
liver markers ALT AST

treatment.
Supportive: rest, hydration, Avoid alcohol
antivirals Tenofovir, transplant
Pegylated interferon-α

Viral hepatitis B:  specific and non-specific prophylaxis.

specific and non-specific prophylaxis.
Vaccination (pre & post), (risk, newborn, child)
Education, safe practives in hospital, safe sex, no sharing needels, screening for donors and risk people

Acute viral hepatitis C: epidemiology, clinical presentation, diagnosis, treatment and possible outcomes.

Epidemiology,
Blood borne
1-2 monts incubation

Clinical presentation,
Asymptomatic
Fever, malaise, anorexia, nausease, abdominal pain,
Jaundice, liver failure, carcinoma

Diagnosis,
HCV RNA (PCR)
Anti-HCV antibodies
liver markers ALT AST

Treatment
Antivirals (Sofosbuvir)

Possible Outcomes.
chronic infection
Spontaneous recovery
Cirrhosis, carcinoma, liver failure

Chronic viral hepatitis C: diagnosis and treatment.

Diagnosis,
HCV RNA (PCR)
Anti-HCV antibodies
assessment of liver fibrosis
liver markers ALT AST

Treatment
Antivirals (Sofosbuvir)

Viral hepatitis E: epidemiology, clinical presentation, diagnosis, treatment and prophylaxis

Epidemiology,
Fecal oral, undercooked meat
Acia/afrika
2-4 mons incubation

Clinical presentation,
Asymptomatic
Fever, malaise, anorexia, nausease, abdominal pain,
Jaundice, liver failure, carcinoma

Diagnosis,
Anti-HEV IgM
Anti-HEV IgG
HEV RNA (PCR)
liver markers ALT AST

Treatment
self limiting
Supportive: Rest,Hydraion, Avoid alcohol

Prophylaxis
safe drinking/food
sanitation
hygine
Vaccine

Viral hepatitis D: epidemiology, clinical presentation, diagnosis, treatment and prophylaxis

epidemiology,
Blood, sex
Caused by hepatitis B

clinical presentation,
Fever, malaise, anorexia, nausease, abdominal pain,
Jaundice, liver failure, carcinoma
With hepatitis B

diagnosis,
Anti-HDV IgM
Anti-HDV IgG
HDV RNA (PCR)
liver markers ALT AST

treatment
Pegylated interferon-α
Reduce HBV: Tenofovir

prophylaxis
Prevent HBV: Vaccine
Safe sex, blood screening

Hemorrhagic fevers – etiology, pathogenetic principles

Etiology,
RNA viruses: Ebola, yellow fever, dengue

Pathogenetic Principles
Viral entry and replication
Viremia: spread though bloodstream
Endothelial injury: increase vascular permeability
immune activation with cytokines
Coagulation disorders
organ damage

Ebola virus infection – epidemiology, clinical symptoms and diagnostic principles

Epidemiology,
In bats, intermediate host human
Blood, body fluids, sex, needles

Clinical symptoms
incubation 2-21 days
Fever, weakenss, headache, myalgia, sore throat
Vomiting, diarrhea, abdominal pain, dehydraiton
Liver/renal/organ failure
Bleeding/coagulation disorder

Diagnostic principles:
symptoms + traveling
Thrombocytopenia, high AST/ALT, coagulation abnormalities
PCR ELISA, Serology

Ebola virus infection – principles of treatment and prevention

Treatment
Supportive: fluids, electrolytes, oxygen, blood pressure, organ support
Antiviral therapy: Inmazeb

Prevention
isolation
Contact tracing
Vaccination
Educaiton

Yellow fever – epidemiology, clinical picture and principles of prevention

epidemiology,
Monkeys and human, spread by mosquitos
Afrika, south america

clinical picture
3-6 days incubation
fever, chills, headache, myalgia, nausea,
bradycardia
Jaundice, hemorrhages, pain, vomiting
organ damage

principles of prevention
Vaccination
Mosquito control/avoidance
education

Dengue fever – clinical forms, their symptoms and principles of therapy

forms:

Classical: Mild/moderate
Fever, headache, pain, weakness, nauausea, rash

Hemorrhagic fever: Severe
Hemorrhagic, GI bleeding

shock syndrome:Critical
hypotension, tachycardia, low pulse pressure, organ failure, severe bleeding

Treatment:
Rehydration
Crystaloids
Paracetamol
blood transfusion, platelets

Hanta virus infection – renal syndrome, stages and typical symptoms, diagnostic principles

stages and typical symptoms,
Febrile stage: fever, headace, pain, myalgia, thrombocytopenia
Hypotensive stage: shock, capillary leakage, proteinuria
Oliguric stage: Acute kidney injury, oliguria, proteinuria, hematuria, fluid overload
Diuretic stage: Polyuria, kidney function recovers
Convalescent stage: recovery of renal function

diagnostic principles
Serology
PCR

Urinanalysis
Blood test

Hanta virus infection – cardiopulmonary syndrome, stages and typical symptoms, diagnostic principles

Stages and typical Symptoms,
Prodromal stage: Flue symptoms, nausea, vomiting
Cardiopulmonary stage: Severe respiratory distress, pulmonary edema, cough, tachypnea, dyspnea,hypoxemia,
Convalescent stage: impoved resporatory and cardiac function

Diagnostic Principles.
Serology
PCR
Xray, CT
blood test

Clinical manifestations and diagnosis of pulmonary TB.

Symptoms:
Fever, weight loss, malaise, sweats
pulmonary symptoms: cough, chest pain, dyspnea, wheezing, hoarsness

Diagnosis:
Sputum smear, NAAT,
X ray: upper love infiltrate, cavitations

Peripheral lymph node tuberculosis: clinical manifestation and diagnosis.

Symptoms
Fever, weight loss, malaise, sweats
Lymphadenopathy: painless lymph node swelling → matted

Diagnostics:
Fine needle aspiration cytology
Biopsy
Sputum smear, NAAT,
X ray:

Pleural tuberculosis: clinical manifestation and diagnosis.

Symptoms
Fever, weight loss, malaise, sweats
Sharp local pain, non productive cough, shortness of breath

Diagnostics:
pleural fluid analysis
Biopsy
Sputum smear, NAAT,
X ray

Miliary tuberculosis: characteristics of pathogenesis, clinical and radiological manifestation, principles of diagnosis.

Pathogenesis
Spread of Mycobacterium tuberculosis into bloodstream, causing deposits in multiple organs → “millet seed” appearance

Symptoms:
Fever, weight loss, malaise, sweats
pulmonary symptoms: cough, chest pain, dyspnea, wheezing, hoarseness
Organ specific

Radiological manifisations
Miliary pattern X-ray, ‘‘millet seed like’’

Diagnostics:
Biopsy
Sputum smear, NAAT,
X ray: Millary patten

Microbiological diagnosis of tuberculosis.

ADD MORE??

Specimen collection: from site of disease (Sputum, alveolar, pleural fluid, uring, biopsy)

Microscopy:Smear, staining. Visualize acid fast bacilli

NAAT: PCR,

Culture: gold standard: solid/liquid media

Drug susceptilibility testing: gruide treatment

Diagnostic algorithm of tuberculosis.

Clinical sympoms:
Fever, weight loss, malaise, sweats, cough
Chest X ray
Collect sputum sample, PCR, biopsy, NAAT, culture

Criteria for determining infectiousness of TB patient.

Pulmonary and laryngeal TB produces droplets and are infectious

Positive sputum smear → high bacterial load

Positive culture → active TB

Cavitary lesions on X ray → high bacillary load

cough → Spreads droplets

On or off treatment