Autoimmune Diseases Flashcards
What are the cells involved in innate immunity?
- Macrophages
- Dendritic cells
- Mast cells
- Neutrophils
- Complement
What are the cells involved in adaptive immunity?
B cells and T cells
What cells are involved in both innate and adaptive immunity?
T cells and natural killer T cells
What is innate immunity responsible for?
Inflammation in target tissues
it has pattern recognition against broad classes of antigen
What are the characteristics of the innate immune response?
What is the duration and response time like?
- No memory
- No amplification
- Little regulation
Fast response (hours to days) and short duration
What is adaptive immunity responsible for?
Learned responses in immune organs
it is highly specific and involves T and B cell receptors
What are the characteristics of the adaptive immune response?
What is the duration and response time like?
- Strong memory and amplification component (e.g. vaccines, previous infection)
- Many regulatory mechanisms
Slow response (days to weeks for initial exposure)
Responses may last from months to years
What is the first stage involved in the interaction between innate and adaptive immune systems?
Innate immune cells directly detect and attack antigenic targets
this occurs at sites of infection e.g. barrier organs
it involves phagocytosis, cytotoxicity, inflammatory mediators and chemokines to attract other cells
What is the second stage in the interaction between the innate and adaptive immune systems?
Dendritic cells present antigens to T cells
What is the third stage in the interaction between the innate and adaptive immune systems?
Crosstalk between dendritic cells, T cells and B cells
This occurs in lymphoid tissues
Immune memory determines specific learned responses
What is the fourth and final stage in the interaction between the innate and adaptive immune systems?
Adaptive immune cells activate innate immune cells, directing tissue inflammation to specific targets
T cell cytokines activate monocytes and macrophages
B cell antibodies activate complement
What are the 5 main components of the innate immune system inflammation?
- Phagocytic cells
- Histamine-producing cells
- Complement
- Cytokines
- Chemokines
What are the 3 phagocytic cells involved in innate immune system inflammation?
What are their other roles?
Neutrophils:
- eat and destroy pathogens
Macrophages:
- also produce chemokines to attract other immune cells
Dendritic cells:
- also present antigens to the adaptive immune system
What are the histamine producing cells involved in innate immune system inflammation?
What is their role?
Mast cells, basophils and eosinophils
they produce histamine and other chemokines and cytokines
this attracts other immune cells and causes vasodilatation
histamine also is involved in defence against parasites and wound healing
It is also involved in allergy and anaphylaxis
What is the role of complement in innate immune system inflammation?
How may they be activated?
Directly attacks pathogens via alternative and lectin pathways
may be activated by adaptive immune system via antibodies
What is the role of cytokines and chemokines in innate immune system inflammation?
Cytokines:
- signal between different immune cells (e.g. innate to adaptive, adaptive to innate)
Chemokines:
- attract other immune cells to sites of inflammation
How do T cells cause inflammation?
By inflammatory cytokines or by helping B cells make autoantibodies
Label the diagram showing how T cells cause inflammation
What are the problems with autoantibodies produced by plasma cells during T cells causing inflammation?
Some autoantibodies directly interfere with normal physiological function rather than causing inflammation and tissue damage
What is the definition of autoimmunity and its defining characteristic?
The adaptive immune system recognises and targets the body’s own molecules, cells and tissues
(instead of infectious agents and malignant cells)
What are the 3 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 actions of T cells, B cells and autoantibodies
What are the 4 main characteristics of autoinflammation?
- Seemingly spontaneous attacks of systemic inflammation
- No demonstratable source of infection as precipitating cause
- Absence of high-titre autoantibodies and antigen-specific autoreactive T cells
- No evidence of auto-antigenic exposure
Complete the table comparing autoinflammation and autoimmunity
What is meant by autoimmunity?
What characteristics is it defined by?
A theoretical concept involving breakdown of self-tolerance
many cells of the immune system have capacity for autoimmune functions
there is overlap with normal immune functions such as anti-tumour immunity
some people have autoantibodies without any symptoms
What is meant by autoimmune disease?
How is it related to autoimmunity?
Distinct clinical entities
environmental factors acting on favourable genetic background
wide variety of pathogenic mechanisms between diseases
autoimmunity, leading to inflammation, organ dysfunction and damage
What are the 3 key mechanisms of autoimmunity?
- Failure of central tolerance
- Genetic predisposition
- Antigenic factors
How can failure of central tolerance occur?
During…
- T cell selection in the thymus
- B cell selection in the bone marrow
How can someone have a genetic predisposition to autoimmunity?
Certain HLA (MHC) types select for certain self-antigens
there may be involvement of other genes that regulate immune functions
What are examples of antigenic factors that are involved in autoimmunity?
- Infections that trigger autoimmune responses
- Environmental triggers - UV light and smoking
- Alterations in self-proteins that increase their immunogenicity
How can autoimmune disease be summarised?
- There is usually some genetic predisposition
- But no one is born with autoimmunity - there must be environmental triggers
- The immune system has regulatory functions to shut down immune functions - tolerance of self is a dynamic state
What is meant by central tolerance in the thymus?
T cells are randomly generated in the thymus so must be tested against self-antigens
this occurs through:
- Deletion
- Effector CD4 and CD8 T cells
- Regulatory T cells
What is the role of MHC class I molecules?
What genes are they encoded by?
- Encoded by genes in HLA-A, HLA-B, HLA-C
- present on all nucleated cells
- presents antigens to CD8+ T cells
What is the role of MHC class II molecules?
What genes are they encoded by?
- Encoded by genes in HLA-DP, HLA-DQ, HLA-DR
- present on all dedicated APCs
- presents antigen to CD4+ T cells
What is the involvement of class II MHC genes in autoimmunity?
There are a limited range of MHC class II types, some of which predispose to activation of autoreactive T cells
class II MHC genes may shape the T cell repetoire and predispose to autoimmunity
What happens if someone has a mutation of FOXP3 gene?
This causes failure to develop regulatory T cells
this causes severe autoimmunity from birth
What can mutations in PTPN22 cause?
T cells are activated more easily
This leads to a stronger immune response in general
What are the 4 other causative associations with autoimmune disease?
Sex:
- more common in women than men due to hormonal influence
Age:
- autoimmunity more common in elderly
Sequestered antigents:
- may be recognised as foreign by the immune system
- e.g. Cell nucleus, eyes, testis
Environmental triggers:
- infection
- trauma-tissue damage
- smoking
How can infections influence autoimmunity?
Infections activate the immune system generally
infections may cause autoimmunity as well as a normal immune response
What is meant by molecular mimicry in rheumatic fever?
Antibodies against M protein of Streptococcus also react against the glycoproteins of the heart
This is an example of an infection causing autoimmunity
How can changes in autoantigens affect autoimmunity?
Changes in the amount or nature of autoantigens may cause autoimmunity
What change in autoantigens may make them more immunogenic?
What condition is this seen in?
Citrullination of proteins may make them more immunogenic
e.g. Rheumatoid arthritis
What change in autoantigens is present in coeliac disease?
Tissue transglutamase alters gluten to help it bind to HLA-DQ
What change in autoantigens is present in systemic lupus erythamatosus?
Failure to clear apoptotic debris increases availability of sequestered antigens inside the cell
What is meant by an organ specific disease?
What is a typical example?
A disease that affects a single organ
autoimmunity is restricted to the autoantigens of that organ
a typical example is autoimmune thyroid disease
What is meant by a systemic disease?
What is a typical example?
A disease that affects several organs simultaenously
autoimmunity associated with autoantigens found in most cells of the body
typical examples involve connective tissue diseases
What are the general clinical features of autoimmune diseases?
- Can affect any organ in the body
- Onset in middle age and old age
- More common in the elderly and women
- Leads to loss of organ function and lifelong chronic conditions
- Characteristic exacerbation and remission
- Common for diseases to overlap
What is the background behind Hashimotos thyroiditis?
What does it lead to?
Destruction of thyroid follicles by autoimmune process
it is associated with autoantibodies to thyroglobulin and to thyroid peroxidase
Leads to hypothyroidism
What is the background behind Grave’s disease?
What does this lead to?
Inappropriate stimulation of the thyroid gland by anti-TSH autoantibody
This leads to hyperthyroidism
What is the main underlying difference between the 2 types of autoimmune thyroid disease?
Hashimoto’s thyroiditis:
- antibodies DESTROY the thyroid
- leads to hypothyroidism
Graves’ disease:
- antibodies STIMULATE the thyroid
- leads to hyperthyroidism
What symptoms would a patient present with in myasthenia gravis?
- Difficulty keeping their eyes open
- difficulty speaking and swallowing
- difficulty smiling
- problems become worse as the day progresses
What is the mechanism behind myasthenia gravis?
Autoantibodies block the acetylcholine receptor
this prevents transmission of nerve impulses
What types of symptoms would a patient with pernicious anaemia present with?
- Increasing fatigue over time
- Tingling in the feet
What is the mechanism behind pernicious anaemia?
Autoantibodies from plasma cells block IF, preventing vitamin B12 absorption in pernicious anaemia
What are the 4 characteristic symptoms associated with systemic lupus erythematosus?
What else may it be associated with?
- Photosensitive malar rash
- Multiple mouth ulcers
- Arthralgia
- Alopecia
May also be associated with pleural effusion
What are antinuclear antibodies?
Autoantibodies form against many different molecules in the cell nucleus
ddDNA, dsDNA, ribosomes, histones
What type of antinuclear antibody distribution is seen in SLE?
Antibody deposition and inflammation are seen in the skin
What is an alternative name for nuclear antigens?
Why do they have this name?
Sequestered antigens
nuclear self-antigens are normally always intracellular and shielded from the immune system
What happens to nuclear material in cell death by apoptosis?
How is this different in necrosis and what can this lead to?
Apoptosis:
- nuclear material is digested and cleared
necrosis:
- nuclear antigens may not be cleared
- they may then act as antigens to the immune system
What other factors can lead to failed clearance of nuclear antigens?
- UV light causing DNA damage and cell death
- genetic defects in mechanisms to clear cell debris
Complete the diagram showing cell death and failed clearance of nuclear antigens
What happens when antibodies against the antigens in the nucleus combine with their targets?
What is the result of this?
They form immune complexes in the circulation
immune complexes deposit in any organ
they activate complement and cause inflammation
What causes lupus nephritis?
What are the symptoms of this and what does it lead to?
- Caused by immune complex deposition leading to inflammation
- leads to leaky glomerulus, loss of renal function and scarring
- end result is irreversible renal failure
What are examples of connective tissue diseases?
What are they caused by?
- Systemic lupus erythrematosus
- Scleroderma
- Polymyositis
- Sjögren’s syndrome
caused by ubiquitous antigens (components of the cell nucleus) that cause multisystem inflammation
