Vaccines, hypersensitivies/deficiencies, lab tests Flashcards
Who do you vaccine? (4)
- Those at risk
- Family/close contacts
- Health professionals
- Location specific travelers
Symptoms of Leukocyte adhesion deficiency (LAD-1)? (5)
- Delayed umbilical separation
- Omphalitis
- Persistent leukocytosis
- Severe gingivitis
- Recurrent infections of the skin, respiratory tract, GI tract with no inflammation
What is the hallmark of Multiple drug hypersensitivity?
Massive and permanent T-cell activation
How to assess the complement system:
- No CH50: indicative of what?
Deficiency of complement classical pathway
What is Type IV hypersensitivity: Delayed type? Give two examples
o T-cell mediated (often seen with the PPD tuberculin skin test to determine previous exposure) and you seen redness/swelling at site of exposure. MHC class I Peptides of the test activates the T-cells o Examples: contact dermatitis with poison ivy (and other contact dermatitis like Nickel and Latex), PPD tuberculin skin test
Clinical features of Chronic granulomatous disease (CGD)? (5)
- Infection of one of the following rare bacteria: o Burkholderia cepacian o Aspergillus species o Serratia marcesens o Staphylococcus o Nocardia species - No fever and no leukocytosis - Liver abcesses - Osteomyelitis - Persistent inflammation with (ineffective) granulomas obstructing the GI tract or urinary tract
Relative distribution of Inborn Errors of Immunity: three most common cause?
- Antibody disorders (most common)
- T-cell disorders (second most common)
- Phagocyte disorders (third most common)
What is the lectin pathway of the complement system?
Mannose binding lectin pathway: Mannose complex binds lectin and protease, which lead to the formation of C3 convertase
Dx tests for Chronic granulomatous disease (CGD)? (2)
Test: incubation of patient macrophages and we test them as following
- Positive on Flow Dihidrorhodamine (DHR)
- Blue result on Nitro Blue Tetrazolium (NBT)
Recurrent Neisseria infections is a hallmark of what?
Recurrent Neisseria infections is a hallmark of complement component deficiencies
What is the classical pathway of the complement system?
Activated by antigen-antibody -> C1 complex binds to Ab’s bound to an antigen on the surface of a bacterial wall (C1, C2, C4)
What is Type B classification for drug adverse reactions?
- Unpredictable (type B): 20-20% o Dose independent o Genetics related o Possible activation of immune system Type B reactions and examples: o Intolerance o Hypersensitivity: penicillin anaphylaxis o Pseudoallergic reaction o Idiosyncratic: dapsone hemolytic anemia
What is IgE-mediated adverse reaction to food?
When crossed bringing with mast cells, mast cells will degranulate and release histamine and cause Anaphylaxis
When to suspect a T-cell defect/cellular immunity defect? (4)
- Opportunistic infections: Candida, Pneumocystis jiroveci
- Fungal, viral, intra-cellular infections
- Diarrhea/Malabsorption
- Poor growth
What is the difference between drug hypersensitivity and drug allergy?
- Drug allergy: specific immune response to drug acting as allergen (presence of hapten). This is the p-i concept
- Drug hypersensitivity: immune stimulations and drugs bind directly to immune receptors or inflammatory cells are stimulated by drug receptor or drug enzyme (pseudoallergy)
Diseases that are prevented by vaccination? (11)
- Polio
- Diphtheria
- Tetanus
- Pertussis (with measles, it is the only by vaccine preventable disease with a death toll growing due to antivax mvmt)
- Measles
- Rubella
- Mumps
- Chicken pox
- Haemophilus
- Pneumococcus
- Meningococcus
Subtype of Type IV hypersensitivity: E. What is it? Symptoms?
- Type IV E: More CD8 than CD4 causing the release of histamine via mast cell degranulation, but this time it causes urticaria
Cause of Meningococcal disease or SLE?
Properdin deficiency
What are the four types of hypersensitivies?
- Type I: Allergic Anaphylaxis and Atopy/Immediate hypersensitivity (IgE)
- Type II: Antibody-dependent cell mediated cytotoxicity (ADCC) (IgG, IgM)
- Type III: Immune complex mediated (IgG, IgM)
- Type IV: Delayed type (T cell mediated)
Genetics of Chronic granulomatous disease (CGD)
Autosomal recessive x-linked
Subtype of Type IV hypersensitivity: B. What is it? Symptoms?
- Type IV B: CD4 Th2 (IL4, IL5) leading to emission of eotaxin with eosinophil infiltration
Symptoms:
o Maculopapular rash
o Bullous exanthemas
What is included in secondary immunodeficiency? (6)
HIV Neoplasia (or radiotherapy, or anti-metabolic/chemotherapy) Transplantation Immunosuppressor Severe malnutrition Uremia, diabetes
When to suspect a phagocytic defect? (3)
- Infections of the skin, liver, GI tract with abscesses
- Delayed separation of the umbilical cord and wound healing
- Gingivitis/Periodontitis
What autoimmune diseases is included in Type II: Antibody-dependent cell mediated cytotoxicity (ADCC)? (4)
- Idiopathic Thrombocytopenic Purpura
- Myasthenia gravis
- Goodpasture’s disease
- Grave’s disease
Most common food allergies for adults? (2)
Shellfish, tree nut
Who should be investigated in immunology (general population case)? (5 sufficient criteria)
- Infections with very mild inflammatory signs
- Recurrent autoimmune phenomena
- Dysmorphic features
- Patients that develop vaccine pathogen after vaccination
- Chronic diarrhea
When to suspect a complement defect:When to suspect a complement defect? (2)
- Pyrogenic infections, rheumatic disorders: C1-C4 deficiency
- Susceptibility to encapsulated organisms (pneumococcus, meningococcus, H. flu): C5-C9 complement deficiency
What are the four arms of the immune system?
- Humoral arm: B lymphocytes
- Cellular immunity: T lymphocytes
- Phagocytic arm
- Complement system
- Humoral arm: B lymphocytes
- Cellular immunity: T lymphocytes
- Phagocytic arm
- Complement system
Most common food allergies for children? (3)
Peanut, tree nut, egg
Type I hypersensitivity (allergy) includes what? (5)
Asthma Anaphylaxis Rhino-conjunctivitis Urticaria Dermatitis
Undetectable AH50 is indicative of what?
If AH50 is undetectable: alternative pathway is impaired, preventing hemolytic activity
Infectious agents associated with B-cell antibody deficiency? (8)
o Encapsulated bacteria: Pneumococcus Haemophilus Meningococcus Pseudomonas o Sinusitis, otitis, pneumonia o Bacteremia, meningitis, arthritis o Enterovirus (CNS) o Giardia
What is Type A classification for drug adverse reactions?
- Predictable (type A): 80-90% Characteristics: o Dose dependent o No activation of immune system Type A reactions and examples: o Overdosage: acetaminophen hepatic necrosis o Side effect: salbutamol tremor o Secondary effect: Clindamycin C difficile colitis
What is Type II: Antibody-dependent cell mediated cytotoxicity (ADCC) ?
o IgG or IgM are made against the Ag. However, the self cells surface molecule cross reacted with the Ag (or looks very much like the Ag), and the IgG or IgM attacks the host cells. Possible scenarios:
Opsonization/Complement activation: seen in penicillin after there’s activation of classical complement pathway (MAC lysis of the host cells)
Following activation of NK cells, the lysed cells die, and the Ag receptors float around and bind to the surface of other cells
What is Type III: Immune complex mediated? This causes what? (4)
o When circulating antigen is in excess for the number of antibodies, you have the formation of many Antigen-Antibody complexes form. They can deposit in capillaries of tissues like skin, joints, kidneys, etc. This can activate the classical complement pathway and cause: Influx of neutrophils MAC lysis Aggregation of platelets Massive inflammation
Examples of type III hypersensitivity? (3)
Serum sickness: occur when patient is injected with someone else’s antibodies, but also not-self proteins
Immune complex glomerulonephritis
Extrinsic allergic alveolitis (‘Farmer’s lung’)
Undetectable CH50 is indicative of what?
Classical pathway is impaired, preventing hemolytic activity
Subtype of Type IV hypersensitivity: A. What is it? Symptoms?
- Type IV A: CD4 Th1 (IFN-gamma) causing macrophage activation
Symptoms: Maculopapular rash
What are the symptoms of Severe combined Immunodeficiency (SCID)? (4)
- Lymphopenia
- No growth
- Protracted diarrhea
- Infection susceptibility
What is a blockbuster drug?
> 1 billion sell/year
What are the symptoms of X-linked Agammaglobulinemia? (4)
- Infections begin after 4-6month of birth
- No circulating B cells
- No antibody responses to antigen
- Chronic infections with enteroviruses
Stats of vaccine market expansion? (3)
Vaccine market expanding at 12-16% per year: vaccines are more lucrative for pharma
- Estimated total value of vaccine market (2016): 52 billion
- Value of Cancer vaccine market (2019): 4.3 billion
3 main mechanisms of HDR classification for drug hypersensitivity?
- Allergic/Immune stimulation: hapten and prohapten concept
- Pharmacological stimulation of immune receptors: p-i concept
- Pseudo-allergy (non-immune-mediated DH)
What are the clinical features of immune system disease indicating phagocytic defects? (4)
o Minimal or no pus
o Tendency for granulomas
o Gingivitis
o Delayed separation of umbilical cord
What is the alternative pathway of the complement system?
Low grade cleavage of C3 in the plasma and the binding of our natural (small amount) C3b to hydroxyl group on cell surface with factors B, D, properdins will create C3bB which can also act as C3 convertase
What is Chronic granulomatous disease (CGD)?
Immunodeficiency where the patient is vulnerable to bacterial/fungal infections that we usually granulate with macrophages (mycobacterium, TB) due to malfunction of NADPH subunits
What are the three receptors of NK cells?
They have cytotoxicity receptors NKp46 and NKp44, plus specific receptor for MCHI, the Killer Ig-like receptors
What is the Hygiene Hypothesis?
Hygiene hypothesis: there’s more TH2-cells in neonates, but less hygienic environment increases TH¬1-cell response. This decreases TH2-cells and its (allergic) response later in life.
Other possibilities: climate change, obesity, western diet, housing, etc.
Genetics of Classical NK deficiency?
Autosomal dominant
Treatment for Neisserial infection/Neisseria meningitis? (2)
- Prophylactic antibodies
- Frequent immunization
Diagnostic test for Neisserial infection/Neisseria meningitis?
Low CH50, classical pathway is impaired, preventing hemolytic activity (Neisseria live intracellularly)
What is Inborn errors of immunity? What does it include? (4)
Inborn Errors of Immunity: predisposes the person to infection susceptibility by arming the immune system
Includes:
- Immunodeficiency diseases: Primary immunodeficiency: single-gene disorders and Secondary (acquired) immunodeficiency
- Immune dysregulation syndromes
- Auto-inflammatory syndromes
Diagnostic test for Meningococcal disease or SLE?
No AH50, alternative pathway is impaired, preventing hemolytic activity and C3 and C5 convertase stabilization
What is X-linked Agammaglobulinemia
X-linked recessive mutation in btk gene, causing an arrest of B-cell development at pre-B cell stage
What is Leukocyte adhesion deficiency (LAD-1)?
Ch21 integrins are unable to adhere to endothel
Infectious agents associated with T-cell deficiency? (5)
o Viruses o Fungi o Mycobacteria o Protozoa: Toxoplasma, Intestinal protozoans o Strongyloides
Immune mediated adverse reactions include what?
Non-IgE
IgE-mediated: when crossed bringing with mast cells, mast cells will degranulate and release histamine and cause Anaphylaxis
What is the treatment for Type I: Allergic Anaphylaxis and Atopy/Immediate hypersensitivity?
NO Benadryl, that shit kills. Go for epinephrine (alpha-1, beta-1 and beta-2 stimulation)
Subtype of Type IV hypersensitivity: C. What is it? Symptoms?
- Type IV C: Cytotoxic T lymphocytes (CD4 and CD8) involved where the keratinocytes are killed Symptoms: o Maculopapular o Pustular o Bullous
Subtype of Type IV hypersensitivity: D. What is it? Symptoms?
- Type IV D: T cell (IL8) with PMN recruitment
Symptoms: pustular exanthema
Distinction between passive and active immunity?
Passive immunity: give the patient the antibodies formed in other patients (provide protection for some months at best)
Active immunity: the patient develops its own antibodies after being exposed to the pathogen
How to assess the complement system:
- No AH50: indicative of what?
Deficiency of complement alternative pathway
What is Type I: Allergic Anaphylaxis and Atopy/Immediate hypersensitivity?
o Most common type, allergic reaction provoked by re-exposure to the same antigen and mediated by specific IgE antibodies
IgE (produced by plasma cells) are bound to FceRI at the surface of tissue mast cells and basophils and the inflammatory mediators causing the symptoms are released upon the binding of IgE to allergen
What is Severe combined Immunodeficiency (SCID)?
Severe defect in T cell development (no T cells). Requires transplant
When to suspect a B-cell defect/humoral defect? (2 conditions)
When to suspect a B-cell defect/humoral defect: usually after 6 months when maternal antibodies are lost
- Multiple/Severe Bacterial infections
- Respiratory tract bacterial infections: streptococcus, haemophilus
Diagnosis of inborn errors of immunity is often too much delayed. Who should be investigated (children case)? (10 sufficient criteria)
- 8 or more new ear infections within 1yr
- 2 or more serious sinus infection within 1yr
- 2 or more months on antibiotics with little effects
- 2 of more pneumonias within 1yr
- Failure of an infant to gain weight or grow normally
- Recurrent deep skin or organ abscesses
- Persistent thrush in mouth, or elsewhere on skin after age 1
- Need for intravenous antibiotics to clear infections
- 2 of more deep-seated infections
- Family history of primary immunodeficiency
What is the cause of Neisserial infection/Neisseria meningitis?
Deficiency of proteins of the membrane attack complex (C5-8)
Gross timeline of vaccines development?
The basis of our method to make vaccines came after WW2, but the first molecular vaccine (for Hepatitis B) came in the late 1980’s
Treatment for Leukocyte adhesion deficiency (LAD-1)?
- Hematopoietic stem cell transplant
Two contact interface of vaccines?
- Encapsulated organisms (usually in lipid/fats and polysaccharides/sugar): haemophilus SP, pneumococcus, meningococcus induce poor immunity if pathogen is killed or given in particles
- Particulate vaccines: whole pertussis vaccine comes with high fevers and/or convulsions. Acellular/particulate diminish this side effect
Impaired T cell development can be caused by deficiencies in what molecules/proteins? (8)
- ADAyc chain/ADA
- JAK3
- IL-7alpha
- RAG1
- RAG2
- Artemis mutation
- ZPA-70
- MHC II
What is Classical NK deficiency?
Deficiency of the transcription factor GATA2, which is required for NK survival
What is the role of hapten in drug hypersensitivity?
o Hapten will bind to protein or MHC molecule/peptide. The antigen recognized as the major antigenic determinant is either the hapten or the hapten-modified peptide
What are the diagnostic tests for Leukocyte adhesion deficiency (LAD-1)? (2)
- High WBC
- Negative test for CD18/CD11
