Immunological Disorderand Infectious disease

Chia-Chun Tang, PhD, RNNational Taiwan University

School of Nursing12/13/2021

Table of Content

Aim, function, involved cells

Function, definition, and concepts

Immune system01

Aim, function, involved cells

Inflammation02

Aim, function, involved cells

Antibody Mediated Immunity03

Cell Mediated Immunity04

05 Immunodeficiency and infectious disease

Allergy, autoimmune disorders, infectious disease, GVHD, Healthcare-acquired infections

Immune System-1

• Function: defense mechanism against invasion and response to foreign substances in a specific manner

• Related to: CNS, GI, integrity, endocrine, emotional status, disease, age, drug, environment…

• Immunocompetent:

✓ Inflammation

✓Antibody Mediated Immunity (AMI)

✓Cell Mediated Immunity (CMI)

Immune System-2

• Mechanism:

✓Recognition of self vs. non-self (self tolerance): Human leukocyte antigens (HLAs)

✓Destruction

✓Production: antibodies and cytokines

✓Complement activation

Inflammation – overview

• Innate-native immunity

• Immediate but short-term response

• Non-specific: same reaction at each location, differ in the extent

• 3 stages, 5 manifestations

• Involved cells:

✓Neutrophils, macrophages, eosinophils, basophils, mast cell

✓P. 278, table 17-1

Inflammation – stages & manifestation

• Stages:

✓ I-Vascular reaction: small veins constrict, arterioles dilate, blood flow increase and stay at site; phagocytosis by macrophage (24-72 hours)

✓ II- Cellular exudate: Neutrophilia to destruct and remove

✓ III- Repair and replacement: scar

• Manifestation: redness, swelling, warmth, pain, function decreased

Vascular leak syndrome

What is a “left shift”?

How to calculate ANC and its meaning?

Inflammation = infection??

Absolute Neutrophil Count (ANC)

• The percentage of neutrophils (Polys)

• White blood count (WBC) x total neutrophils (segmented neutrophils% + segmented bands%) x 109

• A normal ANC is typically over 1,000

Inflammation = infection??

• Inflammation can’t provide immunity, which is

✓ Long-term protection

✓ Learned (needs prior exposure)

✓Completed by lymphocytes

✓Can be active or passive

Antibody-mediated immunity (AMI)

• Humoral immunity

• Functional part: B cell with the help from T and macrophage

• Antigen-antibody interactions: steps by steps (p.283, 17-8)✓Active immunity

✓Artificial immunity

✓Passive immunity

✓The Y shape of antibodies (Fc fragment)

• Antibody classification: Large proteins, immunoglobins

Exposure

Recognition

Sensitization: plasma and memory cell

AgglutinationActivate complement system

Lysis, complement activation, Precipitation, Inactivation (neutralization)

• size, location, amount, and timing

• In breast milk

• Crosses the placenta

Cell-mediated immunity (CMI)

• Primary function:✓Eliminated non-self and infected cells

✓Prevent hypersensitivity

✓Present/ recognize non-self cell

✓Regulates immune system: cytokines

• Functional part: T cells & Natural killer cells (NK)✓Helper/ inducer: T4/CD4+, many subtypes

✓Suppressor/ cytotoxic: T8/CD8+, attack cells infected by parasites

✓Memory: can be CD4+ or CD8+

✓CD4+:CD8+ ratio is about 2:1

Complement system

• Complement cascade: enhance (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells; promote inflammation

• Small proteins made in Liver, activated through 3 major pathways:✓classical (CP): permanently active at low level

✓ alternative (AP): dominant active complement pathway; tick-over

✓lectin (LP)

• Three major functions: ✓Defending against bacteria

✓Bridging natural and acquired immunity

✓Disposing of immune complexes/ inflammation byproducts

What cause immunological disorder and infectious disease?

Immune dysfunction -1

• Immunodeficiencies✓Phagocytic dysfunction: innate immune system

✓B-cell deficiencies: Immunoglobins are low in the blood, infection soon start after birth (5-6 m/o)

✓T-cell deficiencies: Opportunistic infections

✓Combined B-cell and T-cell deficiencies: ataxia-telangiectasia (A-T), Severe combined immunodeficienctdisease (SCID)

✓Non-Hodgkin lymphomas, childhood cancers

• Fail to regulate immune activities due to secondary causes✓GVHD, cancers/ drugs

Immune dysfunction -2

• Autoimmunity problem: Rheumatoid disease✓Connective tissue disease (CTD): Rheumatoid arthritis,

SLE, Sjoren’s syndrome, vasculitis

✓Spondylitis: Ankylosing spondylitis

✓Thyroid disease

✓Allergy

✓Autoimmune disease associated symptoms

• Infectious disease✓ Infective arthritis and more…

Beyond infectious disease

• HIV infection/ AIDS

• Drug-resistant microorganisms

• Healthcare-acquired infections (HAIs)

• Sepsis

• Flu, 2019 COVID…pandemic

Rheumatoid arthritis

• Immune system attacks the synovium→ joint inflammation

• Symptoms and signs: pain, joint swelling, limited movement, stiffness, weakness, and fatigue

• Interventions: aggressive and early treatment ✓Pharmacologic therapy (NSAIDs, antirheumatic drugs)✓ Individualized exercise program ✓Follow up with sleep quality✓Nutrition therapy: high in vitamins, protein, and iron ✓Patient education: self-care, heart disease

Rheumatoid arthritis-treatment

Rheumatoid arthritis-inflammatory vs. mechanical

Inflammatory mechanical

Morning stiffness >1h <30’

Fatigue Profound Minimal

Physical activity Improves Worsens

Rest Worsens Improve

Systemic involvement

+

Corticosteroid response

+ -

NSAIDs responses + +

Systemic Lupus Erythematosus (SLE)

• Immune system attacks its own tissues, causing widespread inflammation and tissue damage in the affected organs: skin rashes/ flares, fatigue, pain and swelling in the joints, organ problems

• Chronic disease: no cure but can control• Range from mild to life-threatening • Unknown causes but may relate to

environmental, genetic, and hormonal factors; 15-44 years women

Systemic Lupus Erythematosus (SLE)-symptoms and signs

• Malar rash• Discoid rash• Photosensitivity• Oral ulcers• Neurological disorder• Serositis• Renal disorder• Arthritis• Hematology disorder• ANA (+)

• Diagnosis: symptoms, PE, Lab test✓ Antinuclear antibody (ANA) test

• Treatment goals:✓ Reduce swelling✓ Calm down immune system to prevent it

from attacking the organs and tissues Reduce or prevent damage to the joints

✓ Reduce or prevent organ damage and pain• Drugs: NSAIDS, corticosteroids,

immunosuppressive agents/ chemotherapy

Systemic Lupus Erythematosus (SLE)- diagnosis & treatment

Autoimmune Thyroid disease

• immune system attacks thyroid ✓ Hypothyroidism (Hashimoto's disease)✓ s/s: Low T3, T4L, high cholesterol, atherosclerosis✓ Risk factor: Type 1 DM, family history, treatment

side effects✓ Treatment: Levothyroxine

• Hyperthyroidism (Graves’ disease)✓ More common on Women, age<40✓ s/s: anxiety, fine tremor, heat sensitivity and

warm/moist skin, weight loss, goiter, cycle changes, bowel movement↑, bulging eyes, fatigue, palpitation, sleep disturbance, graves’ dermopathy, thyroid storm, brittle bones

✓ Radioactive iodine therapy, anti-thyroid drugs, beta blockers

Allergic disorders

• Interaction between antigen and antibody →tissue damage→ allergic reaction (4 types)

• Inappropriate response triggered by normally harmless substance (allergens)

• Diagnosis test: CBC/DC, IgE level, skin test

• Drugs: antihistamine (e.g., Benadryl), adrenergic agents, mast cell stabilizers, corticosteroids

• Management

Management of allergic disorders

• Sings and symptoms of anaphylaxis: airways, v/s, edema

• Emergency: O2 or intubation, medications, IV lines, fluid administration

• Blood transfusion reaction

• Patient education about future exposure

Autoimmune disease associated pulmonary hypertension (PAH)

• Chronic obstruction of small pulmonary arteries due to endothelial cell, vascular smooth muscle cell and fibroblast dysfunction and proliferation→Result in high pressure in lungs

• 8-12 % systemic sclerosis pts developed PAH

• Symptoms: common lung symptoms (asthma, COPD, SOB, fatigue, edema, chest pain, palpitation)

Immunodeficiencies due to secondary causes

• Medication-induced immunosuppression:✓Recurrent, severe, unusual, opportunistic

✓Steroids, Azathioprine (SLE), Ciclosporin (inflammatory illness), Cytotoxic drugs, Biological agents

• Cancers ✓Immune system cant’ recognize or is turned off

✓Lymphomas and leukemias and other types of cancers

✓Immunotherapy, stem-cell transplant

• Transplant

Care for patients with cancer-manage infections-1

• Notice the risk factors: ✓Types of cancer: tumor burden

✓Treatment: surgery, chemotherapy, radiation, target therapy, immunotherapy, stem cell transplant

✓Poor nutrition

✓Other comorbidities

Care for patients with cancer-manage infections-2

• Nursing care and patient education• Timeline- critical time points and treatment

procedure (nadir, chemotherapy cycles)

• Infection control (neutropenia) and avoid injuries

• Food safety

• Monitor infection signs, get vaccines

• Preventive drugs: prophylactic antibiotics, growth factor drugs (colony-stimulating factors)

Care for patients with cancer-manage infections-3

• Signs of infection: ✓Fever

✓Redness, tenderness, swelling

✓Pus or yellowish discharges

✓New cough or SOB

✓New abdominal pain

✓Chillness/ sweating

✓Burning or pain during urination

✓Sore throat

Graft-versus-host disease (GVHD)

• Hyper-acute: immediately occur, antigen-antibody reaction

• Acute: 1 week to 3 months, humoral & cellular reaction (NK & cytotoxic T)

• Chronic: inflammation and scaring

• Maintenance and rescue therapy

Infectious disease

• diseases are caused by pathogenic microorganisms, such as bacteria, viruses, parasites or fungi; the diseases can be spread, directly or indirectly, from one person to another. Zoonotic diseases are infectious diseases of animals that can cause disease when transmitted to humans.” (WHO)

Drug-resistant microorganisms

• Methicillin-resistant Staphylococcus aureus (MRSA)

• Vancomycin-resistant Enterococcus (VRE)

• multi-drug-resistant Mycobacterium tuberculosis (MDR-TB)

• Carbapenem-resistant Enterobacteriaceae (CRE) gut bacteria.

Healthcare-acquired infections (HAIs)

• 32 percent of all healthcare acquired infection are urinary tract infections: Catheter-related urinary tract infections (CAUTI)

• 22 percent are surgical site infections: SSI

• 15 percent are pneumonia (lung infections)

• 14 percent are bloodstream infections: Catheter-related bloodstream infection (CLABSI)

Sepsis-background

• Life threatening organ dysfunction due to dysregulated host responses to infection [medical emergency!]

• May proceed to septic shock, multiple organ failure, and death

• Antimicrobial resistance is a major factor determining clinical unresponsiveness to treatment and rapid evolution to sepsis and septic shock

• Risk population: vulnerable groups

Flu vs. coldWhat is flu-like?

What are the different types of flu?

TOCC

Flu monitor in Taiwan

What is the flu season?

三價VS.四價?

孕婦?

今年三價疫苗猜錯病株?白打了?

克流感?

COVID-19 background

• Nidovirales, coronavirus✓α-CoV

✓β-CoV: SARS-CoV, MERS-CoV, SARS-CoV-2（2019-nCoV）

• Origin: directly from bat to human

• Entry: spike protein, protease, binds to virus receptor (such as ACE2 at intestine and lung)

• Affinity and severity: 65-73% of SARS

• Route of transmission: direct, fomite, aerosol (droplet), vertical (?)

• R0= 3.6-6.1

• Ct value?

普篩之必要?隔離14天後仍意外篩檢出病毒?

COVID-19 clinical manifestation

COVID-19 clinical manifestation

COVID-19 Lab data

• Abnormal liver function

• Lymphopenia (35%)

• Thrombocytopenia (12%)

• Anemia (51%)

• Unilateral pneumonia (25%)

• Bilateral pneumonia (75%)

• LDH increases (76%)

• A lot of times, CXR has no findings…

Chen N, et al.，The Lancet

COVID-19-cormorbidity

• Risk population• Chronic disease, cancer

• Can cause sever illness in relatively healthy population!

• Mortality rate: 5-10%?

COVID-19- identification and treatment

• Rule of thumb: TOCC and symptom

• Medication:

• Supportive care

COVID-19 Critical Care

• MuLBSTA: cut point 12

• Early recognition: possible infections, pneumonia, ARDS

Take-home points

• Anatomy and Physiology: Immune “network”, left shift, type of immunity

• Signs and Care for immunodeficiencies and autoimmune disease

• Recognize and Management of common infectious diseases: HAIs and pandemic

• When there is a new disease, new treatment, new evidence…how do you quickly react to the ever-changing health care?