Immune Compromised, Immunization And Diagnostic Testing Flashcards
What are classic features of inflammation
Rubor (redness)
Calor (heat)
Tumor (swelling)
Dolor (pain)
Describe innate immunity
Primitive and broad Immediate onset No memory Unspecific Lasts a few days
Describe Adaptive Inmunity
Highly specific 3 day lag High potency Memory & amplification Lasts months to years
What are some components of innate immunity
Barriers ex. skin Secretions ex. Sweat, vaginal, vomiting Macrophages NK cells Complement pathway
Describe macrophage’s
Component of innate immunity
Form of cellular defence
Eat foreign materials and dead cells dissolve in enzymes
Describe NK cells
Component of innate immunity also known as natural killer cells
Kills strange looking cells and important in cancer surveillance
Delivers signals to abnormal cells to kill them
What are the two types of adaptive immunity
Antibody mediated immunity
Cell mediated immunity
What are components of antibody mediated immunity
B- cells
Plasma cells
Antibodies
What are components of cell mediated immunity
T helper and T killer cells
What are the two immunodeficiency states
Primary and secondary
Describe primary immunodeficiency
Genetic
Describe secondary immunodeficiency
Acquired such as infection, splenectomy,malignancy etc
What are some examples of genetic immunodeficiencies
Complement deficiencies Defects in phagocytic cell function Lymphocyte function (SCID) B-cell deficiency T cell deficiency
Describe complement deficiencies
Loss of early components as result in increased staph and strep
Loss of late components results in increased neisseria (meningitis)
Describe phagocytic defects
Predispose to bacterial infections
Inability to kill organisms that have been ingested is typical of chronic granulotamous disease
Describe subacute combined immune deficiency (SCID)
Lymphocyte deficiency
Genetic defects may result in failure of development of B cells, T cells, or NK lymphocytes
Patients present with fungal and viral infections as maternal immunity weans
Live vaccine can cause severe disease
What happens if you have a B cell deficiency
Patients tend to get encapsulated bacterial infections
What happens if you have T cell deficiencies
Tend to get infections with viruses especially herpes; intracellular bacteria and fungi
What are primary immunodeficiency diseases
Chronic granulomatous (ineffective phagocytes = uncontrolled infections)
SCID (lack of T/B-cells = no resistance to infection leading to rapid death)
What are some examples of secondary/acquired deficiencies
Chemo Corticosteroids Post transplant Splenectomy HIV/AIDS
Describe chemotherapy
Inhibit regeneration of cells that have a rapid turn over (neutrophils)
These PMN drop and remain depressed for 1-4 weeks in which case there is increased risk of death and infection due to neutropenia
Describe corticosteroids
Steroids
PMN unable to migrate to infection
Reduced macrophage migration
Reduction in T lymphocytes
This can result in increased viral, bacterial and fungal infection
Describe post transplant
Commonly used agents inhibit cytokine (messengers for immune system) production and T lymphocyte function
Describe the spleen
Kind of our biggest lymph node
The main site of opsonizing antibody which is very important for destroying capsulated bacteria
W/o spleen capsulated bacteria can take over
Describe a splenectomy
Removal of spleen can result in increase of life threatening disease including strep, staph and neisseria
Infections progress rapidly
Immunization strongly recommended for these patients to combat s.pneumoniae, H.influenzae and N.meningitidis
Describe HIV/AIDS
AIDS is primarily a disease of poor T cell function and production
Opportunistic infections affecting people with AIDS reflect the lack of CD4 + T cells
How can bacteria invade the immune response
Destroying complement (strep) Destroying immunoglobulin (neisseria producing IgA protease) Preventing phagocytosis (encapsulated organisms) Preventing intracellular killing
How else can bacteria invade the immune system
Bacteria growing inside the cytoplasms if cells are protected from antibody or detection
Bacteria may change their surface antigens rapidly (borrelia)
What is immunization
The use of a specific immune response to prevent or lessen the severity of disease
Immune system learns adaptive immunity
What are the objectives of immunization
Individual protection from infection
Herd immunity
Elimination of infecting organism
Describe the action of antibodies in immunization
- Bind to antigen and block biological activity (neutralizing)
- Coat bacterium and make it more easily phagocytosed (opsonization)
- Bind to organism to activate complement and cause lysis, recruit immune cells to area
What is opsonization
Macrophage cells eat bacteria, happens mainly in the spleen
Improves clearance if organisms
Describe B cells
Antibodies produced by B lymphocytes are activated to become plasma cells
- When stimulated by infection B cell clone multiplies
- Some become B memory and long lived to provide rapid response to subsequent exposure
Describe T cells
Specific T lymphocytes also survive as memory T cells which regulate the immune response
On reexposure they multiply and shorten time to a response
What is passive immunization
Host receives antibody produced by another host
Protection is short lived (2-3 months) and no long term protection generated
What are examples of passive immunization
IVIG, HBIG, VZIG, RSV and Rabies Ig
How does passive immunization take place
Naturally occurring: transplacentally or in colostrum
Therapeutic: immunoglobulin or IG given; provides rapid protection,lessen severity
What is active immunization
Generation of immunity by administering an antigen to elicit an immune response in the host
What was the first type of active immunization
Jenner administered cowpox virus in order to prevent small pox
What are types of active immunization
Live attenuated (MMRV) Virus vectors Inactivated whole cell , subunit, virus like particles DNA/RNA Toxoid
Describe live attenuated vaccines
- Use organisms which are limited in their ability to cause disease
- Attenuated organisms are repeatedly cultured until they lost their virulence
- Administration may mimic natural route of infection
- Give stronger long term immunity
What are disadvantages of live attenuated vaccines
Virulent for immunosuppressed
May revert to the virulent form
Must be handled properly (refrigerated) to maintain viability
What are some examples of live attenuated
BCG (TB)
MMRV
Sabin Polio vaccine
Describe Replicating virus vectors
Viruses that don’t cause human disease are engineered to express target virus protein
Allows immune response to the target virus without infection by it
What are non replicating viral vectors
- A carrier virus (ex. Adenovirus) is treated so that it can not replicate if cause disease
- A gene from the target virus is added to the carrier virus so that it expressed the target virus protein
- easily transported and stored than replicating virus
What are those of inactivated vaccines
Whole cell, subunit and virus like particles
Describe inactivated vaccines
- Often given with a substance that increases immunogenicity
- conjugation of polysaccharide to protein improves response
- boosters required to maintain effectiveness
Describe the nuts and bolts of inactivated vaccines
Given by injection
Require multiple doses at specific intervals
Give immunity that wanes over time
Give antibody response but not cell mediated immunity
What are examples of inactivated vaccines
Influenza, Hep A
What are subunit vaccines
Vaccines made with purified antigens derived from pathogen
Less prone to side effects
Ex.
Hep B,
haemophilis influenza, pneumococcal and meningococcal (meningitis causing bacterias)
Pertussis
Describe virus like particles
Prepared from viral proteins that self assemble to form particles
No nucleic acid; look like disease without causing disease
Ex. HPV and Hep B
Describe RNA vaccines
Made of mRNA that instructs cells to produce a viral protein from the target virus
RNA is unstable so needs to be kept in lipid envelope and stored in low temp
Describe DNA Vaccines
Similar to RNA but more stable
Plasmid injected which includes gene for a target virus protein
Potential for oncogenicity
Describe Toxoids
Inactivated toxins protects from action of the toxin
Multiple doses given
Very effective
Ex. Tetanus and diphtheria
Who makes recommendations for vaccinations
National advisory committee on immunizations (NACI)
Why do vaccine programs fail?
Missed opportunities to immunize by health care workers
Improper vaccine storage
Vaccine hesitancy
What are the current vaccine targets
Diphtheria/ tetanus/ pertussis
Often combined with poliovirus and haemophilis influenza type B
Diphtheria toxoid and tetanus toxoid booster (14-16yrs) less diphtheria toxoid for adverse reactions
Describe the polio vaccine
Salk = injection (inactivated)
Sabin = oral (live)
Shedding in GI tract offered opportunity for vaccine associates infections
Immunized at 2,4,6 months boosters at 18 mo and 4-6 years
Why is the oral polio vaccine no longer used
Vaccine associated paralytic polio
Describe haemophilus B vaccine
Used to be most common meningitis cause
Vaccine consists of polysaccharide conjugated to a protein
Conjugation activates T-cell dependent immunity
Describe measles mumps and rubella (MMR) vaccine
Live attenuated vaccine
Given 12-15 months
Contraindications: severe acute illness or immunosupression
Describe the influenza vaccine
Inactivated whole or split virus vaccine
Contains TWO influenza A strains and TWO influenza B strains
What does split virus vaccine mean
Multiple types in it
Who typically receives the influenza vaccine
High risk groups
Health care workers
>65 years
Chronic Conditions
Describe Hepatitis B vaccine
Hep B has higher risk if cirrhosis and carcinoma
Purified HBsAg
3 doses at 0,1 and 6 months
Booster not recommended
What are the 2 types of pneumococcal vaccines
Polysaccharide
Conjugate
Describe pneumococcal polysaccharide vaccine
23- valent; 90% of pneumonia strains covered
80% effective
> 65 yrs or those without spleen, sickle cell disease or CSF leaks
Describe pneumococcal conjugate vaccine
13 valent (conjugated to diphtheria toxoid)
Provides better immunity in small children
Improved memory via cell mediated immunity
May decrease carriage
May result in fewer infections in elderly
Describe varicella vaccine
Live attenuated Virus vaccine
12 months
Recombinant VZV used in 60+ to reduce shingles
<5% of children develop lesions as a side effect
Describe the HPV vaccine
Subunit vaccine containing protein of up to 9 types of HPV
Given in 3 doses 0,2,6 months @ age 9-13
hopes to decrease incidence of warts and cervical cancers
Less effective after sexually active
Describe the Covid 19 vaccine
RNA
Non replicating viral vector
Highly effective
How can immunity be conferred
Natural infection
Passively via administration of antibody
Active immunization
True or false: current vaccine schedule has greatly increased childhood morbidity and mortality
FALSE it has greatly REDUCED morbidity and mortality
What does the immunogenicity of a vaccine depend Kim
Multiple factors and can be enhanced by adjuvants and happen conjugates
What are polyclonal antibodies
Used in diagnostic purposes
Animals repeatedly immunized to develop high antibody levels (organism or interest, protein or human antibodies)
What are monoclonal antibodies
Used for diagnostic purposes
Antibodies developed when animal spleen cells are fused with malignant myeloma cells
Cells are selected that produce only one kind of antibody in a very pure and high amount
What are IgM antibodies
Used to detect infection
Usually a reflection of a recent infection
Ex. Measles, Hep A
What do rising levels of IgG antibodies indicate
Often indicate recent infection
Ex. Respiratory viruses
What is used to determine immunity
Any IgG antibody
Ex. Rubella, hepatitis A
How is IgG better than IgM
Take longer to make (IgM rapidly present at initial infection)
Part of memory immune system
More effective
Can determine immunity
IgM wanes over time IgG better longer lasting protection
How does the enzyme immune assay work?
Coat well with antigens from organism of interest
Add patient serum
Wash well to remove antibodies not bound to antigen
Add store bought antibody to patients anti body
Wash well to remove any unbound antibodies
In EIA how do you develop a reaction
If patient had antibody it will also have secondary antibody bound to it also with the enzyme
Add substrate for the enzyme
Measure amount of colour
More colour = more enzyme = more antibody
No colour = no antibody
Describe fluorescence microscopy
Put specimen on slide
Dry and fix specimen
Add antibody to antigen you are looking for
Antibody labelled with fluorescent tag
Wash it off
Unattached antibody is washed away
Look under a special microscope to see if the cells are fluorescent
How might fluorescence microscopy be used
To detect influenza or RSV
To detect herpes from unroofed ulcers
To detect varicella zoster from base of chicken pox lesion
To detect pneumocystis
Describe mini EIA kits
Throat swab
Treat to extract the strep antigens
Put drop in device
Let diffuse along filter, it will bind here
Add enzyme tagged antibody to sandwich antigen
Add drop of substrate and observe colour change
Describe mini ELISA kits
Detect pregnancy using urine sample
Let diffuse along filter until It comes up to the antibody, if positive it will stop here and bind to HCG antigen
Add substrate and observe colour change
What does the c mean on a rapid test
Control
Shows the test worked and can be read
What does the T mean on a rapid test
The test
Gives test result
What can particle agglutination tests be used for
Patient specimens ex CSF
Identification of bacteria in lab
Describe particle Agglutination tests
Specimen mixed with tiny beads which are coated with specific antigen
If specimen contains the right antigen particles clump together making substance go from milky to granular
How can particle agglutination be used to detect antibodies
Instead of costing beads with antibody coat them with antigen
Add patient serum and if patient has antibodies the particles clump together
Ex, mono, syphilis
What does skin testing use
Cellular immune response
Describe TB skin test
Tb ANTIGENS injected into skin
Over 48 hours cells migrate towards antigen if TB antigens recognized
Produces swelling (induration)
Individuals WITHOUT past TB exposure have no induration
What should asplenic patients be vaccinated against?
H. Influenza
N. Meningitidis
S. Pneumoniae
What does iatrogenic mean
Secondary immunodeficiency caused by a healthcare professional
Ex. Removal of spleen
