Immunopathology Flashcards
What can the immune system be divided into?
Innate and adaptive
What cells does the innate immune system involve?
- Neutrophils
- Complement and PRRs (pattern recognition receptor)
- Dendritic cells
What cells are involved in the adaptive immune system?
- B cells (memory)
- T cells High affinity antibody
What are the 2 important roles of the innate immune system?
- Recognise threat
- Engulf and destroy threat
Which cells of the innate immune system recognise threat?
Professional Antigen presenting cells (APCs):
- Dendritic cells
- Macrophages / monocytes
How do Antigen Presenting Cells work?
When a pathogen is detected, these APCs will phagocytose the pathogen to form many different fragments of the antigen –> these fragments are then presented
How do cells of the innate immune system engluf and destroy threat?
Via phagocytosis
Phagocytes:
- Macrophages
- Neutrophils
Granulocytes:
- Neutrophils
- Eosinophils
- Mast cells
- Basophils
How do granulocytes and phagocytes differ?
Granulocytes are phagocytes, that is they are able to ingest foreign cells such as bacteria, viruses and other parasites. Granulocytes are so called because these cells have granules of enzymes which help to digest the invading microbes.
What are the proteins of the innate immune system?
- Cytokines
- Acute phase proteins
- Complement
What are cytokines?
Chemical signals which modulate cell activity or attract cells (chemokines)
What are acute phase proteins?
Defined as proteins that change their serum concentration by >25% in response to inflammatory cytokines –> Opsonise or present pathogens to the immune system
What are complement proteins?
A cascade of proteins with multiple functions; opsonisation, killing, activation, chemoattraction
What are PRRs?
Pattern Recognition Receptors:
- Each immune cell carries identical receptor of a given type
- These receptors recognise conserved molecular structures known as pathogen- or damage-associated molecular patterns (PAMPs and DAMPs)
What are 2 examples of PRRs?
- Toll-like receptor (TLR)
- Inflammasomes (NLRP3)
What are PAMPs?
Derived from pathogens –> Fragments of pathogen such as bacterial cell wall
E.g. LPS
What are DAMPs?
Derived from host cells –> including tumor cells, dead or dying cells, or products released from cells in response to signals such as hypoxia
What are inflammasomes?
The inflammasomes are innate immune system receptors and sensors that induce inflammation in response to infectious microbes and molecules derived from host proteins (PAMPs and DAMPs)
What is a central feature to the adaptive immune response?
- UNIQUE antigen receptor found on each lymphocyte
- In response to infection this lymphocyte undergoes CLONAL expansion
- High degree of specificity
What is the function of B lymphocytes?
Develop the potential to secrete antibodies: humoral immunity
What is humoral immunity?
The aspect of immunity that is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides
What are the different types of T lymphocytes?
- Killer/cytotoxic
- Helper
- Suppressor
Function of killer/cytotoxic T lymphocytes?
Able to kill –> cellular immunity
Function of helper T lymphocytes?
- Secrete growth factors (cytokines) which control the immune response
- Help B lymphocytes and T lymphocytes
Function of suppressor T lymphocytes?
May dampen down immune response
Overview of physiological immune response
What is immunodeficiency?
Inappropriately decreased response to danger signals –> increased susceptibility to infection
What is autoimmuniy and autoinflammation?
Inappropriately increased response to danger signals –> can cause damage
Pathogenesis of autoimmune disease?
Combination of:
- Genes
- Immune regulation
- Environment
How does sex affect autoimmunity?
Women tend to be more prone to autoimmunity than men
How does age affect autoimmunity?
Autoimmunity more common in elderly
What are the environmental triggers for autoimmunity?
- Infection
- Trauma-tissue damage
- Smoking
What is ‘pathophysiology’?
the disordered physiological processes associated with disease or injury
Pathophysiology of autoimmunity?
- Autoreactive B cells and autoantibodies
- Autoreactive T cells
- General inflammation and end-organ damage
How do autoreactive B cells and autoantibodies cause damage?
- Directly cytotoxic
- Activation of complement
- Interfere with normal physiological function
How do autoreactive T cells cause damage?
- Directly cytotoxic
- Inflammatory cytokine production
What are organ specific autoimmune diseases?
- Affects a single organ
- Autoimmunity restricted to autoantigens of that organ
- May overlap with other organ specific diseases
E.g. autoimmune thyroid disease is typical
What are systemic autoimmune diseases?
- Affect several organs simultaneously
- Autoimmunity associated with autoantigens found in most cells of body
- Overlap with other non-organ specific diseases
E.g. connective tissue diseases are typical
What is Hashimoto’s thyroiditis?
- An autoimmune disease that damages the thyroid gland
- Destruction of thyroid follicles by autoimmune process
- Leads to hypothyroidism (most common cause)
What is the destruction of the thyroid in Hashimoto’s thyroiditis caused by?
Autoantibodies to thyroglobulin and to thyroid peroxidase
What are classic features of Hashimoto’s thyroiditis?
- Weight gain
- Cold
- Constipation
- Decline in memory
- Tiredness
- Difficult concentrating
- Brittle hair and nails
- Delayed deep tendon reflexes
How are the deep tendon reflexes affected in hypothyroidism?
Delayed relaxation of deep tendon reflexes seen in about 92% of hypothyroid patients
What is Grave’s disease?
- Inappropriate stimulation of thyroid gland by anti-TSH-autoantibody
- Leads to hyperthyroidism
Mechanism of Grave’s disease?
The body produces antibodies to the receptor for TSH. (Antibodies to thyroglobulin and to the thyroid hormones T3 and T4 may also be produced.) These antibodies cause hyperthyroidism because they bind to the TSHr and chronically stimulate it.
Mechanism of Hashimoto’s thyroiditis?
Various autoantibodies may be present against thyroid peroxidase, thyroglobulin and TSH receptors –> destruction of thyroid follicles
What is Systemic lupus erythematosus (SLE)?
- Connective tissue autoimmune disorder
- The most common form of lupus
- Characterised by a global loss of self-tolerance with activation of autoreactive T and B cells
- Leading to production of pathogenic autoantibodies and tissue injury
Symptoms of SLE?
- Tiredness
- Fever
- Joint and muscle aches
- Headaches
- Butterfly rash across the cheeks and bridge of the nose
What are autoinflammatory diseases?
Autoinflammatory diseases are clinical disorders caused by defect(s) or dysregulation of the innate immune system, characterised 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)
What is Muckle-wells syndrome?
- Autoinflammatory disease
- Autosomal dominant
- Urticarial rash
- Sensorineural deafness
- AA Amyloidosis (25%)
What is familial cold urticaria?
- Autoinflammatory disease
- Autosomal dominant
- Cold induced rash
- Arthralgia
- Conjunctivitis
What is NOMID/CINCA?
- The most severe and rarest form of cryopyrin-associated periodic syndrome (CAPS)
- Sporadic
- Progressive chronic meningitis - deafness, visual and intellectual damage
- Destructive arthritis
What are Cryopyrin-associated periodic syndrome (CAPS)?
A group of rare, heterogeneous autoinflammatory disease characterised by interleukin 1β-mediated systemic inflammation and clinical symptoms involving skin, joints, central nervous system, and eyes.
What part of the immune system is disrupted in autoinflammation vs autoimmunity?
Autoinflammation –> innate immunity
Autoimmunity –> adaptive immunity
Main cellular involvement in autoinflammation vs autoimmunity??
Autoinflammation - neutrophils, macrophages
Autoimmunity - B and T cells
Antibody involvement in autoinflammation vs autoimmunity?
Autoinflammation - few or no autoantibodies
Autoimmunity - autoantibodies present
Clinical features of autoinflammation vs autoimmunity?
Autoinflammation - recurrent, often seemingly unprovoked attack
Autoimmunity - continuous progression
Root cause of autoinflammation vs autoimmunity?
Autoinflammation - tissue-specific factors, danger signals
Autoimmunity - breaking of self-tolerance
Main genetic susceptibility in autoinflammation vs autoimmunity?
Autoinflammation - cytokine and bacterial sensing pathways
Autoimmunity - MHC class II associations and adaptive response genes
Therapy for autoinflammation vs autoimmunity?
Autoinflammation - Anti-cytokine (IL-1, TNF, IL-6)
Autoimmunity - Anti-B and T cell
Is Crohn’s disease an example of autoinflammation or autoimmunity?
Autoinflammation
Is SLE an example of autoinflammation or autoimmunity?
Autoimmunity
What is immunosuppresion? What can it lead to?
A natural or artificial process which turns off the immune response, partially or fully, accidentally or on purpose –> can lead to immunodeficiency
When would immunosuppression be used clinically?
- Transplants
- Autoimmune diseases
- Lymphoproliferative diseases
What are the causes of immunodeficiency?
- Often 2ary to effects of external factors
- Can be 1ary caused by genetic defects in individual components of immune system
What are the causes of 2ary immunodeficiencies?
Many causes; transient or long-lasting; minor or major.
- Stress
- Surgery/burns
- Malnutrition
- Cancer – especially lymphoproliferative disease
- Immunosuppressive effect of drugs inc. cancer therapy
- Irradiation (clinical or other)
- AIDS
- Other infections e.g. measles, TB.
Why are defects in T cells more severe than in B cells?
B cells also need T cell help
What are the symptoms for defects in T cells?
- Recurrent infection with opportunistic infections
- Bacteria
- Viruses
What is severe combined immunodeficiency (SCID) syndrome?
Combined immunodeficiency syndromes –> defect in both T and B cells
Bone marrow transplant is curative
What are opportunistic infections?
Infections that occur more frequently and are more severe in people with weakened immune systems, including people with HIV.
What do PRRs recognise?
Molecules frequently found in pathogens (PAMPs), or molecules released by damaged cells (DAMPs)
