Theme 2 Lecture 7: Autoimmune diseases Flashcards
What is innate immunity and what cells does it involve?
- inflammation in target tissues
- pattern recognition against broad classes of antigen
- fast response but short lasting
- involves macrophage, dendritic cells, mast cells, neutrophils and complement
What is adaptive immunity and what cells does it involve?
- learned responses in immune organs
- highly specific
- slow response but long lasting
- T and B cells
Is there memory, amplification or regulation involved in innate immunity?
no memory, no amplification, little regulation
Is there any memory, amplification or regulation involved in adaptive immunity?
strong memory, amplification component, many regulatory mechanisms
How do the innate and adaptive immune systems interact?
- innate immune cells directly detect and attack antigenic targets - occurs at sites of infection, phagocytosis, cytotoxicity, inflammatory mediators and chemokines to attract other cells
- dendritic cells present antigen to T cells
- Cross talk between DCs, T cells and B cells
- immune memory to determine specific learned responses
- occurs in lymphoid tissues - adaptive immune cells activate innate immune cells, directing tissue inflammation to specific targets
- T cell cytokines activate monocytes, macrophages
- B cell antibodies activate complement
What are 3 types of phagocytic cells and what do they do?
- Neutrophils: eat and destroy pathogens
- Macrophages: eat and destroy pathogens and also produce chemokines to attract other immune cells
- Dendritic cells: eat and destroy pathogens and also present antigen to adaptive immune system
Name the histamine producing cells and their action
- mast cells, basophils and eosinophils:
- produce histamine, other chemokines and cytokines
- vasodilatations - attract other immune cells
- defence against parasites
- wound healing
- allergy and anaphylaxis
What do complement do?
- directly attacks pathogens via alternative and lectin pathways
- may be activated by adaptive immune system via antibodies
What do cytokines do?
send signals between different immune cells
What do chemokines do?
Attract other immune cells to sites of inflammation
What are the two main actions of Th cells?
- could turn into a Th1 cell which produces inflammatory cytokines
- could turn into a Th2 cell which cross-talks with a B cell to produce plasma and memory cells
What is autoimmunity?
the adaptive immune system recognises and targets the body’s own molecules, cells and tissues (instead of infectious agents and malignant cells)
Describe the main characteristics of autoimmunity
- T cells that recognise self antigens
- B cells and plasma cells that make autoantibodies
- inflammation in target cells, tissues and organs is secondary to action of T cells, B cells and autoantibodies
What are the 4 main autoinflammatory conditions?
FMF, TRAPS, CAPS and HIDS
What are the main characteristics of autoinflammation?
- seemingly spontaneous attacks on systemic inflammation
- no demonstrable source of infection as precipitating cause
- absence of high titre autoantibodies and antigen specific autoreactive T cells
- no evidence of auto-antigenic exposure
Compare autoinflammation and autoimmunity in terms of the following:
- Immune system involved
- Main cellular involvement
- Antibody involvement
- Clinical features
- Therapy
- autoinflammation - innate
autoimmunity - adaptive - autoinflammation - neutrophils, macrophages
autoimmunity - B and T cells - autoinflammation - few or no antibodies
autoimmunity - autoantibodies present - autoinflammation - recurrent, often seemingly unprovoked attacks
autoimmunity - continuous progression - autoinflammation - anti-cytokine (IL-1, TNF, IL-6)
autoimmunity - anti-B and T cell
What are some examples of autoinflammatory conditions?
monogenic hereditary periodic fevers, polygenic chrohn’s disease, spondylarthropathies
What is autoimmunity?
breakdown of self tolerance
What are the 3 mechanisms of autoimmunity?
- Failure of central tolerance (T cell selection in thymus and B cell selection in bone marrow)
- Genetic predisposition
- central HLA (MHC) types select for certain self-antigens
- other genes that regulate immune functions - antigenic factors/ environment
What are examples of antigenic factors that can cause autoimmunity?
- infections that trigger autoimmune responses
- environmental triggers: UV light, smoking
- alterations in self proteins that increase their immunogenicity
Explain central tolerance in the thymus
as T cells are randomly generated in the thymus they are tested against self antigens
What genes are MHC Class I molecules encoded by?
HLA-A, HLA-B, HLA-C
Where are MHC Class I molecules found and where do they present ?
- on all nucleated cells
- present antigen to CD8+ T cells
What genes are MHC Class II encoded by?
HLA-DP, HLA-DQ, HLA-DR
Where are MHC Class II molecules found and where do they present ?
- found on dedicated APCs
- present antigens to CD4+ T cells
What are other causative associations with autoimmunity?
- sex (hormonal influence) - women»_space; men
- age (autoimmune more common in elderly)
- sequestered antigens - may be recognised as foreign by the immune system e.g cell nucleus
- environmental triggers - infection, trauma-tissue damage, smoking
How can changes in the amount or nature of autoantigens cause immunity?
- citrullination (made from amino acids - citrullinate switches places with alanine and antigen can look more foreign e.g RA)
- tissue transglutamase alters gluten to help it bind to HLA-DQ (–> coeliac disease)
- failure to clear apoptotic debris increases availability of sequestered antigens inside the cell e.g SLE
Explain the features of organ-specific autoimmunity
- affect a single organ
- autoimmunity restricted to autoantigens of that organ
- overlap with other organ specific diseases
- autoimmune thyroid disease is typical
Explain the features of systemic autoimmunity
- affect several organs simultaneously
- autoimmunity associated with autoantigens found in most cells of body
- overlap with other non-organ specific diseases
- connective tissue diseases are typical
What is the pathogenesis of hashimotos thyroiditis?
- destruction of thyroid follicles by autoimmune process
- associated with autoantibodies to thyroglobuin and thyroid peroxidase
- leads to hypothyroidism
What is the pathogenesis of graves disease?
- inappropriate stimulation of thyroid gland by anti-TSH autoantibody
- leads to hyperthyroidism
What is the pathogenesis of myasthenia gravis?
autoantibodies block the ACh receptor on the post synaptic receptor so nerve impulses can’t travel
What are the symptoms of myasthenia gravis?
- weakness of the eye muscles (ocular myasthenia)
- drooping of eyelids (ptosis)
- blurred or double vision (diplopia)
- a change in facial expression
- difficulty swallowing
- shortness of breath
- impaired speech (dysarthria)
- weakness in arms, hands, fingers, legs and neck
What is pernicious anaemia?
a condition where the body can’t make enough healthy red blood cells because it dosen’t have enough vitamin B12
It is easily treated- you can just inject B12
What are 5 charachteristic symptoms of systemic lupus erythematosus?
- photosensitive malar rash
- multiple mouth ulcers
- arthralgia
- alopecia
- left pleural effusion
What are sequestered antigens?
antigens that are shielded from the immune system
Why might there be failure of clearance of nuclear antigens?
- UV light causes DNA damage and cell death
- in cell death by necrosis, nuclear antigens may not be cleared and may then act as antigens to the immune system
- some people have genetic defects in mechanisms to clear cell debris
How are immune complexes formed in the circulation?
- antibodies against antigens in the nucleus combine with their target to form immune complexes
- immune complexes deposit in any organ - activate complement and cause inflammation
How does lupus nephritis develop?
- immune complex deposition
- inflammation
- leaky glomerulus
- loss of renal function
- scarring
- irreversible renal failure
What is a immune complex?
antibodies bounded to antigens
What are examples of connective tissue diseases?
- SLE
- Scleroderma
- Polymyositis - muscle weakness
- siogrens syndrome - autoimmune disease of exocrine glands
- ubiquitous antigens
Scleroderma is an autoimmune disease where the body makes too much of which protein?
collagen
