Immunology Flashcards
What are the main 5 causes of secondary immune deficiency?
Physiological immune deficiency
Infection
Treatment interventions
Malignancy
Behavioural and nutritional disorders
Physiological causes of immune deficiency?
Extremes of life - aging, prematurity
Infectious causes of immune deficiency?
HIV, measles
Treatment intervention causes of immune deficiency?
Immunosuppressive therapy
Anti-cancer agents
Corticosteroids
Malignant causes of immune deficiency?
Cancer of the immune system - lymphoma, leukaemia, myeloma.
Metastatic tumour
Biochemical and nutritional disorder causes of immune deficiency?
Malnutrition
Renal insufficiency/dialysis
T1DM and T2DM
Specific mineral deficiencies e.g. iron, zinc
What is a granuloma?
An organised collection of activated macrophages and lymphocytes
Underlying process for the formation of a granuloma?
Non-specific inflammatory response triggered by diverse antigenic agents or by inert foreign materials
Results in activation of T lymphocytes and macrophages
Failure of removal of the stimulus results in persistent production of activated cytokines
End result is organised collection of persistently activated cells
What are the various conditions that could cause granulomas to be present in the lungs?
Sarcoidosis
Mycobacterial disease, e.g. Tuberculosis, leprosy
Leprosy (some forms)
Berylliosis, silicosis and other dust diseases
Chronic stage of hypersensitivity pneumonitis
Foreign bodies
Examples of antibody mediated autoimmune diseases?
Idiopathic thrombocytopaenia
Autoimmune haemolytic anaemia
Features of common variable immune deficiency?
Low IgG, IgA and IgM (causes mostly unknown)
Recurrent bacterial infections, esp. respiratory
Often associated with autoimmune disease
What is hypogammaglobinaemia?
A disorder caused by low serum immunoglobulin or antibody levels.
What are primary causes of recurrent bacterial infections and hypogammaglobulinaemia?
Antibody deficiency
Common variable immune deficiency
Specific antibody deficiency
Other conditions, rare in adults, f.i.:
Bruton’s agammaglobunemia (no B-cells)
What are secondary of recurrent bacterial infections and hypogammaglobulinaemia?
- Protein loss
Protein losing enteropathy
Nephrotic syndrome - Failure of protein synthesis
Lymphoproliferative disease
- Chronic lymphocytic leukaemia
- Myeloma
- Non Hodgkins Lymphoma
What is the complement?
a system of plasma proteins that interacts with pathogens to mark them for destruction by phagocytes.
What are the 2 main groups of white blood cells?
Granulocytes
Agranulocytes
What are granulocytes?
Granulocytes: White blood cells with granules in their cytoplasm. Includes neutrophils, eosinophils, and basophils.
What are agranulocytes?
White blood cells without granules. Includes lymphocytes and monocytes.
Examples of granulocytes?
Neutrophils: Phagocytic cells that engulf and destroy pathogens.
Eosinophils: Involved in allergic responses and defense against parasites.
Basophils: Release histamine and other inflammatory mediators.
Examples of agranulocytes?
Lymphocytes: Key cells of the adaptive immune system.
- B Cells: Produce antibodies to neutralize pathogens.
- T Cells: Regulate immune responses and directly kill infected cells.
- Natural Killer (NK) Cells: Attack infected or abnormal cells.
Monocytes: Precursors to macrophages and dendritic cells.
- Macrophages: Phagocytic cells that engulf pathogens and debris.
- Dendritic Cells: Antigen-presenting cells that initiate adaptive immune responses.
What are natural killer cells?
Natural killer (NK) cells are a type of lymphocyte that plays a crucial role in the innate immune response.
Functions of NK cells?
Innate immune response
Cytotoxic Activity
Recognition of Target Cells
Indirect Antigen Presentation
Regulation of Immune Responses
Role in Viral Defense
What is cytotoxic activity in NK cells?
NK cells have the ability to directly kill infected or cancerous cells by releasing cytotoxic molecules such as perforin and granzymes.
What is MHC in NK cells?
MHC (Major Histocompatibility Complex) complexes play a crucial role in the function of natural killer (NK) cells.
How does MHC affect the role of NK cells?
MHC complexes, specifically MHC class I molecules, play a role in regulating the activity of NK cells by providing inhibitory signals through inhibitory receptors.
Loss or downregulation of MHC-I expression on infected or abnormal cells can lead to NK cell activation and targeted destruction of these cells.
What are cytokines?
Cytokines are small proteins that act as messengers between cells in the immune system.
Function of cytokines?
They regulate immune responses by promoting communication and coordination among immune cells.
What are examples of cytokines?
Cytokines can be pro-inflammatory, promoting inflammation and immune activation, or anti-inflammatory, dampening immune responses and promoting resolution of inflammation.
Examples of cytokines include tumor necrosis factor-alpha (TNF-α), interleukins (IL), interferons (IFN), and chemokines.
What are TNF inhibitors?
Medications that block the action of tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine.
TNF-α plays a key role in the immune response by promoting inflammation and activating immune cells.
By blocking TNF-α, TNF inhibitors reduce inflammation and modulate immune responses, making them effective in treating various autoimmune and inflammatory conditions.
Conditions treated by TNF inhibitors?
rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, and ulcerative colitis.
Common examples of TNF inhibitors?
adalimumab, infliximab, etanercept, certolizumab, and golimumab.
Features of Adalimumab?
Molecular target: Anti-TNF
Main action: Anti-inflammatory
Used in: Many rheumatic and inflammatory diseases
Features of Pembrolizumab?
Molecular target: Anti-PD1
Main action: Activates T-cells
Used in: Cancer
Features of Secukinumab?
Molecular target: Anti – Interleukin 17
Main action: Blocks ONE inflammation pathway
Used in: Psoriasis, arthritis, (MS)
Types of transplant rejection?
Hyperacute rejection
Acute cellular rejection
Acute vascular rejection
Chronic allograft failure
Hyperacute transplant rejection features?
Time: min to hrs
Pathology: thrombosis and necrosis. Type 2 hypersensitivity.
Mechanism: preformed antibody and complement fixation.
Acute cellular transplant rejection features?
Time: 5-30 days
Pathology: Cellular infiltration. Type 4 hypersensitivity.
Mechanism: CD4 and CD8 T cells
Treatment: immunosuppression
Acute vascular transplant rejection features?
Time: 5-30 days
Pathology: Vasculitis. Type 2 hypersensitivity.
Mechanism: De novo antibody and complement fixation.
Treatment: immunosuppression +++ (high amounts)
Chronic allograft failure features?
Time: > 30 days
Pathology: Fibrosis, scarring
Mechanism: Immune and non-immune mechanisms
Treatment: minimise drug toxicity, hypertension and hyperlipidaemia.
What do vaccinations do?
Produces memory in both B and T cells (B and T lymphocytes).
How are memory B cells generated?
Long-lived Memory B cells are generated during primary immune responses that can survive for many years even after the antigen has been eliminated
When do memory B cells re-activate?
Memory B cells rapidly re-activate in response to a second encounter with that specific antigen
Clonal expansion, differentiation into plasma cells, antibody production
What does the vaccination do to T cells?
Vaccination simulates rare naive T cells
Induces a strong T-cell response in 14–21 days
What can occur with T cells after the vaccination is administered?
Some become effector T cells, which:
- Mostly die by apoptosis in the absence of persisting antigen
- Smaller number become memory T cells and are maintained at low frequency
What are the 5 main vaccine types?
Inactivated
Live attenuated
RNA vaccines
DNA vaccines
Virus – like particles
Each of these have their own strengths and limitations.
Advantages of inactivated vaccines?
Can be made quickly (prevent epidemics)
Elicit good antibody responses
Easy to store; No refrigeration required
Usually safe
Disadvantages of inactivated vaccines?
Overall not very potent
many killed organisms don’t stimulate good immune response because they don’t replicate or disseminate
Doesn’t stimulate clonal expansion of B and T cells, thereby requiring multiple injections
Antibody titres diminish over time, requiring booster-shots
What are the two main groups of inactivated vaccines?
Whole cell vaccines i.e. whole organism used
Fractional vaccines - Only part of the organism used in the vaccine
Examples of whole cell inactivated vaccines?
Polio (Salk, inactivated)
Hepatitis A
Rabies
Cholera
Plague
Pertussis (now superceded)
Examples of fractional inactivated vaccines?
Subunit vaccines
- Hepatitis B
- Influenza
- Acellular pertussis
- HPV
- Anthrax
Toxoid
- Diphtheria
- Tetanus
Pure polysaccharide vaccines
- Haemophilus influenza type B
What is vaccinated against with the UK’s “5in1” vaccination?
Polio
Pertussis
Diphtheria
Tetanus
Haemophilus influenza type B
Advantages of live attenuated vaccines?
All relevant effector mechanisms elicited (antibody, AND activated T cells)
Localised, strong response
Usually only one single dose required
Disadvantages of live attenuated vaccines?
Safety
May revert to virulence (eg vaccine associated poliomyelitis)
May cause infection in immune-compromised host
Fragile – must be stored and handled carefully i.e. depends on cold chain
Viral examples of live attenuated vaccines?
Measles
Mumps
Rubella
Chickenpox
Yellow fever
Rotavirus
Smallpox (vaccinia)
Polio (Sabin, “sugar lump”)
Bacterial examples of live attenuated vaccines?
BCG
oral typhoid
What does the MMR jab vaccinate against?
Measles
Mumps
Rubella
What are DNA/RNA vaccines?
DNA or RNA which directs the assembly of the antigenic protein inside the host cell
Can be given as “naked” DNA/RNA or packaged into a virus which then infects the host cells, instructing the cells to assemble the antigenic protein
Advantages of DNA/RNA vaccines?
Can be very potent
Easier to make than protein vaccines
One production platform adaptable to other vaccines
Can be applied to target mutated proteins found in cancer (so-called “neo antigens”)
Disadvantages of DNA/RNA vaccines?
May require complex cold-chain
So far no long-term experience
Examples of DNA/RNA vaccines?
Against Covid 19:
- Johnson&Johnson vaccine (adenovirus)
- Oxford vaccine (adenovirus)
- Moderna vaccine (RNA)
- Biontech vaccine (RNA)
What are virus like particles (VLP) vaccinations?
Empty shells (“capsids”) made from viruses that look like the real virus but have no DNA/RNA
Advantages of VLP vaccines?
Non-infectious
Very potent, usually only one single dose required
Activates both T- and B-cell responses
Disadvantages of VLP vaccines?
Complex manufacture
Fragile – must be stored and handled carefully i.e. depends on cold chain
Examples of VLP vaccines?
Against Papillomavirus associated cancer:
Cervarix
Gardasil
Gardasil-9
Against Hepatitis B:
Engerix
