T3: Immunopathology Flashcards
What are the two divisions of the immune system?
The innate and adaptive immune system.
The innate system can be mobilized immediately – it includes neutrophils, complement and PRRs and dendritic cells. It has no memory but research has found trained immunity may exists.
The adaptive immune system is made up of B cells. T cells and high affinity antibodies. It is highly tailored to infection and can form immunological memory. It however takes time to come in action. It typically takes 4-6 weeks to develop memory. There is extensive communication between them and cells that resemble both features so the lines have blurred.
What are the cells of the innate system?
The cells of the innate system have many roles:
- Recognize threat – have professional antigen presenting cells – dendritic cells, macrophages and monocytes
- Have phagocytes such as macrophytes and neutrophils
- Granulocytes for destruction – neutrophils, eosinophils, mast cells and basophils.
What are the proteins of the innate system?
Proteins of the innate system
- Cytokines - Chemical signals which modulate cell activity or attract cells (chemokines)
- Acute phase proteins - Opsonize or present pathogens to the immune system
- Complement - Cascade of proteins triggered which has multiple functions such as opsonization, killing, activation, chemoattraction
What is a Toll-like Receptor an example of?
Danger-Associated Molecular Patterns (DAMPs).
Pattern recognition receptors are recently discovered components of the innate immune system. They have diversity in type but each immune cell carries identical receptors of a given type. They can recognize fragments of pathogens such as bacterial cell wall, pathogens with nucleotides or RNA. The common them is recognition of pathogen-associated molecular patters (PAMPs) but also Danger Associated Molecular Patterns (DAMPs). DAMPs are patterns associated with host cell damage.
What is the NLRP3-inflammasome?
An example of a DAMP.
IL1-beta is produced initially in its inactive form. An NLRP3 inflammasome can catalyze the activation of the cytokine. It can sense additional danger symptoms to suggest the cell in under attack e.g. potassium flux and ATP release. It is only then the mature cytokine is released. This two stage release is important as if IL6-beta is released in large quantities it can induce a sepsis like state.
What is the functions of the different types of lymphocytes?
The adaptive immune system has a high degree of specificity. Each lymphocyte has its own unique antigen receptor, in response to infection this can undergo massive clonal expansion.
- B lymphocytes can develop into antigen producing cells
- Killer T cells – kill directly infected cells or pathogens
- T helper cells – secrete growth factors which control the immune response and help other B and T lymphocytes
- Suppressor T lymphocytes which may dampen down the immune response
What are the causative associations of autoimmunity?
Autoimmunity is caused by, for the majority, by genes, environmental factors and failure of immune regulation. Women tend to get more autoimmune disease than men, this is thought to do with hormonal changes. Autoimmunity is more common in the elderly (due to gradual changes in immune regulation). There are also environmental riggers:
- Infection
- Trauma-tissue damage
- Smoking
What are the general clinical features of autoimmune diseases?
- More than 100 different diseases
- Can affect any organ of body
- Onset in middle age, old age
- More common common in the elderly and women
- Leads to loss of organ function
- Lifelong-chronic condition
- Characteristic exacerbation and remission
- Traditionally divided into organ specific or systemic
- Common for diseases to overlap
In what autoimmune disease is there destruction of thyroid follicles by autoimmune processes?.
Hashimoto’s thyroiditis - This is destruction of the thyroid follicles by autoimmune processes. Associated with autoantibodies to thyroglobulin and to thyroid peroxidase, leading to hypothyroidism.
It presents with weight gain, feeling cold, hypertension, constipation.
What are the features of hyperthyroidism?
- Weight loss
- Diarrhoea
- Palpitation
- Feeling warm
- Graves’ like presentation
Give examples of systemic autoimmune diseases.
Other systemic autoimmune disease include:
- Scleroderma
- Polymyositis
- Sjogren’s syndrome
- Vasculitis
Define autoinflammation.
Defined as clinical disorders caused by defect(s) or dysregulation of the innate immune system, characterized by recurrent or continuous inflammation, elevated acute phase reactants and the lack of a primary pathogenic role for the adaptive immune system (autoreactive T-cells or autoantibody production).
Give an examples of an auto-inflammatory diseases and it’s treatment.
Muckle-Wells Syndrome - treated with IL-1 inhibition (anti-inflammatory).
Give differences between autoinflammatory and autoimmune diseases.
Autoimmunity:
- Disruption of adaptive immunity
- Involvement of B and C cells
- Autoantibodies are present
- There is continuous progression
- It is due to the breakdown of self-tolerance
- Therapy is Anti-B and T cell
Autoinflammatory:
- Disruption in innate immunity
- Due to issues with neutrophils and macrophages
- Has few or no antibodies present
- Shows recurrent, and often unprovoked attacks
- Due to tissue-specific factors/danger signals
- Therapy is anti-cytokine (IL-1, TNF, IL-6)
Define immunodeficiency.
Immunodeficiency: the lack of an efficient immune system-susceptibility to infections
Uses:
- Transplant rejection
- Autoimmune diseases
- Lymphoproliferative diseases
