Immunology Flashcards
What is tolerance
Tolerance = Acquired inability to respond to an antigenic stimulus
What is central tolerance?
Deletion of auto-reactive cells in central immune organs
T-cells mature in thymus and B-cells mature in the bone marrow
T-cells recognise peptides presented on MHC in thymus in thymic epithelial cells and dendritic cells and undergo thymic selection (only useful T-cells receive survival signal - those that can recognise MHC but do not respond strongly to self)
B-cells have 4 fates:
No reaction to self = good => to periphery
Multivalent self-molecules cause reaction => apoptosis or receptor editing
Reaction to soluble self antigens => to periphery and becomes anergic
Some reaction to self-antigens –> ignorance (they won’t get deleted)
○ These have the potential to cause AI disease since they have not encountered their antigen and hence couldn’t be identified to be deleted
What is peripheral tolerance?
Prevention of mature lymphocytes becoming auto-reactive to antigens that may not be expressed in the thymus or bone marrow, and may be expressed only after the immune system has matured.
Anergy – lack co-stimulation leading to no cell proliferation or factor production. If re-exposed to stimulus, enter refractory state
Ignorance – If antigen concentration too low to stimulate or antigen presenting molecules are absent or antigen presented at immunologically privileged sites (sites where immune cells cannot normally penetrate therefore cells never produce tolerance against auto-antigens
Suppression/regulation – autoreactive T-cells are present but do not respond to autoantigen due to regulatory T-cells
Difference between central tolerance and peripheral tolerance?
Central tolerance is where T-cells and B-cells are being exposed to self-antigens and deletion of autoreactive cells occurs, during development, whereas peripheral tolerance when the cells are already developed and prevention of activation by the autoantigen occurs (e.g. by anergy, ignorance, suppression).
Central tolerance occurs in the central immune organs (thymus for T-cells and bone marrow for B-cells) but peripheral tolerance occurs in the periphery.
Mechanisms by which failures in tolerance can lead to autoimmune disease
- Mutation in the transcription factor AIRE which is required for expression of tissue-specific antigens in the thymus and involved in the selection of T-cells => APECED = Rare AI condition which affects all the endocrine glands
- Mutation in FOX p3 gene – a transcription factor required for T-reg cells development and T-reg cells are crucial for tolerance and adequate immune response => IPEX
Define hypersensitivity
Increased reactivity or increased sensitivity by the animal body to an antigen to which it has been previously exposed
What are the four types of hypersensitivity?
Type 1 – Immediate hypersensitivity
Type 2 – Antibody dependant hypersensitivity
Type 3 – Immune complex mediated hypersensitivity
Type 4 – Delayed hypersensitivity
Describe Type 1 hypersensitivity and give an example
Immediate hypersensitivity - Upon primary exposure to the antigen, sensitisation occurs rather than tolerance and therefore IgE antibodies are formed, which bind to mast and basophil cells. Upon secondary exposure, more IgE antibodies form causing cross-linking of the IgE receptor, leading to mast cell and basophil degranulation.
E.g. Food allergy - anaphylaxis
Describe Type 2 hypersensitivity and give an example
Antibody dependant hypersensitivity– Antibody form against specific antigens.
E.g. myasthenia gravis (Antibody against acetylcholine receptor)
Describe Type 3 hypersensitivity and give an example
Immune complex mediated hypersensitivity – form Antibody-Antigen complexes in blood which then deposit in blood vessels and tissue causing compliment and cell activation as well as activating other cascades.
E.g. Systemic Lupus Erythematosus
Describe Type 4 hypersensitivity and give an example
Type 4 – Delayed hypersensitivity – 3 subtypes:
- T-helper 1 cell mediated – cause release of Ifn-γ leading to macrophage activation and release of chemokines, cytokines and cytotoxins
- T-helper 2 cell mediated - release eotaxins, IL-4 and IL-5 which causes eosinophil activation
- Cytotoxic T-lymphocytes - causes cytotoxicity
E.g. Rhinitis
What is the main difference between type 2 and type 3 and type 4 in autoimmune disease
Type 2 is where antibodies bind to specific antigens in cells or the ECM and cause localised tissue injury
Type 3 is when antibody-antigen complexes form which then deposit in blood vessels or tissues to cause compliment activation and cell activation as well as activating other cascades to cause inflammation
Type 4 involves T-cells not antibodies and it’s the T-cells causing destruction of cells.
What are 4 ways in which pathogenic infections can contribute to the onset of autoimmune disease
- Molecular mimicry of self-molecules
- Induce changes in expression and recognition of self-proteins
- Induce co-stimulatory molecules or inappropriate MHC class II expression
- Failure in regulation thus effect on regulatory T-cells
- Immune deviation between T-helper and T-helper 2 cells causing different responses
- Tissue damage at immunologically privileged sites
Name some autoimmune diseases and state the organ they affect
Grave’s – Thyroid gland (type 2)
Type 1 diabetes mellitus – Pancreas (type 4)
Pernicious anaemia – Stomach (type 2)
Systemic Lupus Erythematosus (Type 3) (multiple targets so not really in this question)
Name four ways in which pathogenic infections can predispose a person to hypersensitivity reactions/allergy (basically same as autoimmune disease)
- Cause an immune deviation (shift between T-helper 1 and T-helper 2 cells causing different responses)
- Induction of co-stimulatory molecules causing the hypersensitivity reaction
- Induce changes in expression and recognition of harmless antigens
- Molecular mimicry of harmless antigens
- Failure in regulation thus effect on regulatory T-cells
Outline the classification of the types of rejection in renal transplantation and briefly explain their time scale and underlying mechanisms by filling in the table below.
- Hyper acute – due to preformed antibody. Quickest
- Acute - anywhere between first week and 3 months after transplant
- Chronic – slow, subclinical degradation of quality of organ function - many years
Cellular classification:
- T-cell mediated – due to CD4+ve T-cells infiltrating the graft, cytotoxic T-cells releasing toxins to kill the target or macrophages causing phagocytosis therefore releasing proteolytic enzymes thus producing cytokines, oxygen and nitrogen radicals
- Antibody mediated – Antibody against graft HLA and ABO antigens – either there pretransplant or formed post-transplant
Explain/describe the immunological occurrences in asthma
Has 2 phases:
1st phase – due to immediate hypersensitivity, caused by IgE antibody production which causes cross linking of basophils and mast cells, leading to histamine releas
2nd phase – due to delayed hypersensitivity – involves T-helper 2 cells, which release eotaxins, IL-4 and IL-5 which causes further eosinophil activation – EDIT THIS
Give the 3 main clinical features of asthma
Reversible generalised airway obstruction with chronic episodic wheezing
Bronchial hyper-responsiveness causing bronchial irritability
Coughing
Breathlessness and chest tightness
Give 4 treatments in managing asthma in order of severity
From least severe to most severe:
- Short acting B2 adrenoceptor agonist
- Inhaled steroid of low to moderate dose
- Long acting bronchodilator
- Further oral steroids, sublingual immunotherapy of azithromycin
Explain what happens during an anaphylaxis. You may use diagrams
Anaphylaxis = severe generalised allergic reaction. Essentially a systemic type 1 (immediate hypersensitivity) reaction -- symptoms: ○ Itchiness around lips ○ Swelling of the lips ○ Wheeze, chest tightness, SOB ○ Fitness and collapse ○ Vomiting & Diarrhoea ○ Death if untreated
What is atopy?
A syndrome characterized by a tendency to be “hyperallergic”. A person with atopy typically presents with one or more of the following: eczema (atopic dermatitis), allergic rhinitis (hay fever), or allergic asthma
Name three diseases associated with Type 1 hypersensitivity, and for each disease list two important features.
- Anaphylaxis – caused by generalised degranulation of IgE sensitised mast cells. Can be potentially fatal. Symptoms include itchiness around the mouth, pharynx and lips, swelling of lips, wheeze, chest tightness and dyspnoea, faintness, diarrhoea and vomiting
- Asthma – Due to acute inflammation of the airways causing mast cell activation and degranulation leading to acute airway narrowing therefore causing vascular leakage and smooth airway contraction. Has 2 phases – type 1 and type 4 phase. It is characterised by reversible generalised airway obstruction with chronic episodic wheezing, bronchial hyper-responsiveness, coughing, mucus production, breathlessness, chest tightness and decreased peak flow
- Rhinitis – Either seasonal or perennial. Features include sneezing, rhinorrhoea, itchy nose and eyes, nasal blockage, sinusitis and loss of smell and taste
Name the different types of transplantation
Autograft - same person
Isograft - genetically identical (twins)
Allograft - different people same species
Xenograft - From an animal
Prosthetic graft - material e.g. metal or plastic
