Yr 2 - EMS > Immunopathology > Flashcards

Immunopathology Flashcards

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1
Q

What can the immune system be divided into?

A

Innate and adaptive

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2
Q

What cells does the innate immune system involve?

A
  • Neutrophils
  • Complement and PRRs (pattern recognition receptor)
  • Dendritic cells
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3
Q

What cells are involved in the adaptive immune system?

A
  • B cells (memory)
  • T cells High affinity antibody
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4
Q

What are the 2 important roles of the innate immune system?

A
  1. Recognise threat
  2. Engulf and destroy threat
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5
Q

Which cells of the innate immune system recognise threat?

A

Professional Antigen presenting cells (APCs):

  • Dendritic cells
  • Macrophages / monocytes
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6
Q

How do Antigen Presenting Cells work?

A

When a pathogen is detected, these APCs will phagocytose the pathogen to form many different fragments of the antigen –> these fragments are then presented

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7
Q

How do cells of the innate immune system engluf and destroy threat?

A

Via phagocytosis

Phagocytes:

  • Macrophages
  • Neutrophils

Granulocytes:

  • Neutrophils
  • Eosinophils
  • Mast cells
  • Basophils
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8
Q

How do granulocytes and phagocytes differ?

A

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.

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9
Q

What are the proteins of the innate immune system?

A
  • Cytokines
  • Acute phase proteins
  • Complement
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10
Q

What are cytokines?

A

Chemical signals which modulate cell activity or attract cells (chemokines)

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11
Q

What are acute phase proteins?

A

Defined as proteins that change their serum concentration by >25% in response to inflammatory cytokines –> Opsonise or present pathogens to the immune system

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12
Q

What are complement proteins?

A

A cascade of proteins with multiple functions; opsonisation, killing, activation, chemoattraction

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13
Q

What are PRRs?

A

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)
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14
Q

What are 2 examples of PRRs?

A
  • Toll-like receptor (TLR)
  • Inflammasomes (NLRP3)
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15
Q

What are PAMPs?

A

Derived from pathogens –> Fragments of pathogen such as bacterial cell wall

E.g. LPS

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16
Q

What are DAMPs?

A

Derived from host cells –> including tumor cells, dead or dying cells, or products released from cells in response to signals such as hypoxia

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17
Q

What are inflammasomes?

A

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)

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18
Q

What is a central feature to the adaptive immune response?

A
  • UNIQUE antigen receptor found on each lymphocyte
  • In response to infection this lymphocyte undergoes CLONAL expansion
  • High degree of specificity
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19
Q

What is the function of B lymphocytes?

A

Develop the potential to secrete antibodies: humoral immunity

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20
Q

What is humoral immunity?

A

The aspect of immunity that is mediated by macromolecules found in extracellular fluids such as secreted antibodies, complement proteins, and certain antimicrobial peptides

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21
Q

What are the different types of T lymphocytes?

A
  • Killer/cytotoxic
  • Helper
  • Suppressor
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22
Q

Function of killer/cytotoxic T lymphocytes?

A

Able to kill –> cellular immunity

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23
Q

Function of helper T lymphocytes?

A
  • Secrete growth factors (cytokines) which control the immune response
  • Help B lymphocytes and T lymphocytes
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24
Q

Function of suppressor T lymphocytes?

A

May dampen down immune response

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25
Overview of physiological immune response
26
What is immunodeficiency?
Inappropriately **decreased** response to danger signals --\> increased susceptibility to infection
27
What is autoimmuniy and autoinflammation?
Inappropriately **increased** response to danger signals --\> can cause damage
28
Pathogenesis of autoimmune disease?
Combination of: * Genes * Immune regulation * Environment
29
How does sex affect autoimmunity?
Women tend to be more prone to autoimmunity than men
30
How does age affect autoimmunity?
Autoimmunity more common in elderly
31
What are the environmental triggers for autoimmunity?
* Infection * Trauma-tissue damage * Smoking
32
What is 'pathophysiology'?
the disordered physiological processes associated with disease or injury
33
Pathophysiology of autoimmunity?
* Autoreactive B cells and autoantibodies * Autoreactive T cells * General inflammation and end-organ damage
34
How do autoreactive B cells and autoantibodies cause damage?
* Directly cytotoxic * Activation of complement * Interfere with normal physiological function
35
How do autoreactive T cells cause damage?
* Directly cytotoxic * Inflammatory cytokine production
36
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
37
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
38
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)
39
What is the destruction of the thyroid in Hashimoto's thyroiditis caused by?
Autoantibodies to thyroglobulin and to thyroid peroxidase
40
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**
41
How are the deep tendon reflexes affected in hypothyroidism?
Delayed relaxation of deep tendon reflexes seen in about 92% of hypothyroid patients
42
What is Grave's disease?
* Inappropriate stimulation of thyroid gland by **anti-TSH-autoantibody** * Leads to **hyperthyroidism**
43
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.
44
Mechanism of Hashimoto's thyroiditis?
Various autoantibodies may be present against thyroid peroxidase, thyroglobulin and TSH receptors --\> destruction of thyroid follicles
45
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 autoantibodie**s and **tissue injury**
46
Symptoms of SLE?
* Tiredness * Fever * Joint and muscle aches * Headaches * Butterfly rash across the cheeks and bridge of the nose
47
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)
48
What is Muckle-wells syndrome?
* Autoinflammatory disease * Autosomal dominant * Urticarial rash * Sensorineural deafness * AA Amyloidosis (25%)
49
What is familial cold urticaria?
* Autoinflammatory disease * Autosomal dominant * Cold induced rash * Arthralgia * Conjunctivitis
50
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
51
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.
52
What part of the immune system is disrupted in autoinflammation vs autoimmunity?
Autoinflammation --\> innate immunity Autoimmunity --\> adaptive immunity
53
Main cellular involvement in autoinflammation vs autoimmunity??
Autoinflammation - neutrophils, macrophages Autoimmunity - B and T cells
54
Antibody involvement in autoinflammation vs autoimmunity?
Autoinflammation - few or no autoantibodies Autoimmunity - autoantibodies present
55
Clinical features of autoinflammation vs autoimmunity?
Autoinflammation - recurrent, often seemingly unprovoked attack Autoimmunity - continuous progression
56
Root cause of autoinflammation vs autoimmunity?
Autoinflammation - tissue-specific factors, danger signals Autoimmunity - breaking of self-tolerance
57
Main genetic susceptibility in autoinflammation vs autoimmunity?
Autoinflammation - cytokine and bacterial sensing pathways Autoimmunity - MHC class II associations and adaptive response genes
58
Therapy for autoinflammation vs autoimmunity?
Autoinflammation - Anti-cytokine (IL-1, TNF, IL-6) Autoimmunity - Anti-B and T cell
59
Is Crohn's disease an example of autoinflammation or autoimmunity?
Autoinflammation
60
Is SLE an example of autoinflammation or autoimmunity?
Autoimmunity
61
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**
62
When would immunosuppression be used clinically?
* Transplants * Autoimmune diseases * Lymphoproliferative diseases
63
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
64
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.
65
Why are defects in T cells more severe than in B cells?
B cells also need T cell help
66
What are the symptoms for defects in T cells?
* Recurrent infection with opportunistic infections * Bacteria * Viruses
67
What is severe combined immunodeficiency (SCID) syndrome?
Combined immunodeficiency syndromes --\> defect in both T and B cells Bone marrow transplant is curative
68
What are opportunistic infections?
Infections that occur more frequently and are more severe in people with weakened immune systems, including people with HIV.
69
What do PRRs recognise?
Molecules frequently found in pathogens (PAMPs), or molecules released by damaged cells (DAMPs)
Yr 2 - EMS
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