Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Pathology - Mechanisms of Disease > L10-12: Microbiome and Immunopathologies > Flashcards

L10-12: Microbiome and Immunopathologies Flashcards

1
Q

Define: Microbiome

A

Collection of all genomes of microbes in an ecosystem

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define: Microbiota

A

Microbes that collectively inhabit a given ecosystem (symbiotic - commensals, NOT parasites)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Define: Pathobionts

A

Typically benign endogenous microbes with the capacity, under altered conditions to elicit pathogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Prebiotics

A

Nutritional substrates that promote the growth of microbes that confer health benefits in the host

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Probiotics

A

Live microbes that confer health benefits when administered in adequate amounts in the host

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Synbiotics

A

Formulations consisting of a combination of probiotics and prebiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

T or F:

In utero environment is sterile in healthy conditions.

A

False, DNA-based microbiota studies have detected bacterial species in the placentas of healthy mothers, in amniotic fluid of preterm infants and in meconium.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Key cells involved in Innate immunity

A

Monocytes, macrophages, NK cells, dendritic cells,

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Role of dendritic cells in innate immunity

A

Recognition of microbial patterns (PRRs/TLRs)

Co-stimulation for T lymphocytes - instructing naive T cell to differentiate into different subsets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Cells/molecules involved in adaptive immunity

A

T lymphocytes - secretion of cytokines/chemokines

B lymphocytes - secretion of antibodies

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

T lymphocytes

A 
Helper T (Th)
Cytotoxic T (Tc)
Regulatory T cells (Treg)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

B lymphocytes

A

Produce Ab
B1/B2
Marginal zone B cells (MZB)
Follicular B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Immunoglobulin class types: primary vs. secondary response

A

Primary response predominantly IgM

Secondary response predominantly IgG, IgA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Most abundant Ig class type

A

IgG

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

GC/Follicular pathway

A

Typically associated with protein antigens
FDC presents Ag to B cell via the BCR which receives further help from a helper T cell via MHCII/TCR and CD40/CD40L interactions. This causes B cell to differentiate into plasma cells which produce Ab and memory B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Non-GC or extrafollicular pathway

A

T-independent antigens include large polysaccharides (pneumococcal PS) that can cross-link BCRs
No or few somatic hypermutations
Short-living plasma cells
No memory B cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Regulatory T cells

A

Control inflammation, allergy and autoimmunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Two types of Treg cells

A
  1. Naturally-occurring: CD4+CD25+FoxP3+ emerge from the thymus during development
  2. Inducible (can be induced in the periphery): CD4+CD25-FoxP3- (Tr1; IL-10) and CD4+CD25+/-
    FoxP3+ (Th3; TGF-β)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Primary immunodeficiency

A

Genetic (inherited/present) at birth, approximately 150 different conditions, most rare
Symptoms may not appear until adulthood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Secondary immunodeficiency

A

Due to factors other than genetics e.g. HIV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Majority of primary immunodeficiencies are ___ related

A

antibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Types of PID

A

• Antibody deficiencies (B-cell related):
– Common Variable Immune Deficiency (CVID)
– Specific (selective) antibody deficiency (SAD)
• T-lymphocyte disorders:
– Severe Combined Immune Deficiency (SCID)
– Immunodysregulation polyendocrinopathy enteropathy X-linked syndrome (IPEX) (Treg)
• Innate deficiencies:
– IRAK-4 deficiency, CGD

23
Q

Common Variable Immunodeficiency (CVID)

A

One of the most common PIDs - 1:50,000 affected. Characterized by low levels of serum Igs (hypogammaglobulinemia). Increased susceptibility to infections, predominantly lung. Enlarged spleen and lymph nodes, polyarthritis. Genetic causes unknown (10-25% inherited) - TACI (Transmembrane activator and calcium modulator and cyclophilin ligand interactor).
B cell function, not numbers, are affected. B cells fail to differentiate into plasma cells, and therefore lack of Ab production. Deficient memory B cells, and poor response to vaccines.

24
Q

Treatment of CVID

A

Effective treatment allows patients to lead a normal life

  • immunoglobulin replacement therapy (IVIg)
  • antibiotics for chronic infections
25
Q

Specific Antibody Deficiency (SAD)

A

Patients have normal Ig levels and normal Ig subclasses, however deficient in IgG2 important in responses to encapsulated bacteria (fails to produce protective Ab levels in response to polysaccharide antigens e.g. Streptococcus pneumoniae). Responses to protein Ag/vaccines normal.

26
Q

Pneumococcal disease and SAD

A

Encapsulated bacteria – the capsule is a T-independent antigen (no T cell help). Significant pathogen causing pneumonia, otitis media and sinusitis. Also more serious invasive diseases such as meningitis and sepsis.

27
Q

SAD – Laboratory Diagnosis

A
  • Evaluate response to pneumococcal polysaccharide vaccine – 23 serotypes, response to at least half of serotypes (4-fold rise in IgG or >1.3μg/mL)
  • Memory B cell numbers indicative of SAD
  • Treated with IVIg and/or antibiotics
28
Q

Severe Combined Immunodeficiency (SCID)

A

Rare, potentially fatal (‘bubble boy’), affects 1 in 58,000 (US data)
Lack of T-lymphocyte differentiation
– Lack of various T cell subsets
– Also B cells (through lack of T cell help)
Clinical presentation <6 months - diarrhoea, failure to thrive, pneumonia, persistent infections

29
Q

Genetic defects identified associated with SCID

A

Most common is X-linked (45%) - common IL-2 receptor gamma chain mutation.
Also IL-7a, Jak3, CD3, CD45

30
Q

Typical vs. Leaky SCID

A

Typical SCID - <300 autologous T cells/uL, lymphocyte function <10% of lower limit of normal range, deleterious SCID gene mutations
Leaky SCID - 300-1,499 autologous T cells, lymphocyte function 10-25%, hypomorphic SCID gene mutation

31
Q

IPEX syndrome

A

Very rare condition caused by mutation in Foxp3
Lack of functional Treg cells
Multiple autoimmune disorders - diabetes, thyroiditis, haemolytic anaemia

32
Q

IPEX pathology

A
  • Absence of small bowel mucosa
  • Inflammatory infiltrate in many organs
  • Liver: fatty change
  • Kidney: nephritis
  • Skin: eczematous
  • Duodenal villous atrophy
  • No goblet cells
33
Q

Chronic Granulomatous Disease

A

X-linked disorder, incidence 1:500,000
• Defect in intracellular bacterial killing by neutrophils and monocytes due to mutations in NADPH oxidase (> 400 known)
• Increased susceptibility to infections by ‘catalase’ organisms

34
Q

IRAK-4 deficiency

A

Interleukin-1 receptor-associated kinase-4
• Extremely rare condition (48 worldwide as at 2010)
• Essential role in TLR and IL-1 receptor signalling
– Innate immune receptors for pathogen binding
– Affects NFκB signalling
– Inability to activate T cells
• Susceptible to pyogenic bacteria, not viruses, fungi
– predominately S. pneumoniae
• Vaccination can be beneficial

35
Q

T cell tolerance mechanisms

A

Central tolerance occurs as T cell matures:

  • Occurs in the thymus
  • Positive selection - T cell has to recognise Ag in context of MHC
  • Negative selection - affinity too high
Peripheral tolerance:
– Occurs in peripheral tissues
– ‘Regulatory’ responses involving mature T cells
– Clonal anergy (lack of costimulation)
– Ignorance (do not encounter Ag)
– Suppression by cytokines (e.g. TGF-β)
– Specific regulation (Treg induction)
– Negative regulation (engagement of CTLA4)
36
Q

B cell tolerance

A 
Occurs in the bone marrow
• Needs T cell tolerance to be intact
• Self-reactive B cells can be:
– Deleted when high affinity for antigen
– Made anergic when antigen is soluble and at high
concentration
– Ignorance when lack of T cell help or low antigen
concentration
37
Q

Molecular mimicry

A
  • Similar/identical epitopes between microbe and host

* Important when host Ag has important biological function eg. Streptococcal protein and bacterial endocarditis

38
Q

Treg function and mechanism

A

Downregulation of receptors on APC or T cell directly in cell-cell contact inhibition
Secretion of immunosuppressive cytokines (IL-4, IL-10, TGF-β)

39
Q

Milgrom and Witebsky’s criteria for

autoimmune diseases

A
  • Lymphocytic infiltration of the target organ
  • Presence of circulating autoantibodies and/or cellular immunity against the target organ
  • Identification of the specific antigen(s)
  • Production of humoral and/or cellular autoimmune response in animals sensitized by autologous antigen
  • Close association with other autoimmune disorders
40
Q

Diabetes

A

Group of diseases affecting insulin production and/or function
• Organ-specific autoimmune disease (Type 1)
• Targets the islets of Langerhans cells of the pancreas – important for insulin secretion
• Secondary damage to kidneys, eyes, nerves, blood vessels
• Onset from first year of life to older adulthood

41
Q

Type 1 diabetes

A

5-10% of cases
• pancreatic β cell destruction
• Insulin deficiency

42
Q

Type 2 diabetes

A

90-95% of cases
• ‘relative insulin deficiency’
• Inadequate production or peripheral resistance to insulin action
• Defect in signaling to Glut-4 from insulin receptors

43
Q

Latent Autoimmune Diabetes in Adults (LADA)

A

A form of autoimmune diabetes which is diagnosed in
individuals who are older than the usual age of onset of type 1 diabetes.
• Also known as “Late-onset Autoimmune Diabetes of
Adulthood”, “Slow Onset Type 1” diabetes, and sometimes also “Type 1.5”
• LADA patients often thought to have Type 2 diabetes due to their age at diagnosis

44
Q

Immunological events in diabetes

A

Failure of T cell tolerance:
– Defective clonal deletion (central)
– Regulatory response altered (peripheral)

Prior to clinical symptoms:
– Autoreactive T cells become activated
– Autoantibodies are produced
– Destroy islets of Langerhans in pancreas
– Occur over many years until nearly all beta cells affected

45
Q

Autoantibodies in diabetes

A

Major autoantibodies are reactive to 4 islet autoantigens
(termed islet cell autoantibodies, ICA):
– Insulinoma-associated antigen-2 (ICA512)
– Insulin (micro-insulin autoantibodies, IAA)
– Glutamic acid decarboxylase 65 (GAD65)
– Zinc transporter 8 (ZnT8)

46
Q

Genetics of type I diabetes

A

Major linkage to MHC class I and II genes (HLA), also linked to polymorphisms in CTLA4

47
Q

Pathogenesis of type Idiabetes

A

Dysfunction in Tregs leading to breakdown in self-tolerance to islet-autoantigens

48
Q

Pathology of type I diabetes

A

Insulitis (inflammatory infiltrate of T cells and macrophages)
β-cell depletion and islet atrophy

49
Q

Systemic Lupus Erythematosus

A
  • Multi-system chronic autoimmune disease - remitting and relapsing
  • Type III hypersensitivity (immune complex) - anti-DNA complexes
  • Acute or insidious in onset
  • Many organs affected but main affected sites are kidneys and small blood vessels - Glomerulonephritis and skin involvement
50
Q

Diagnostic feature of SLE

A

Antinuclear antibodies to Sm antigen and dsDNA
Malar rush
Photosensitivity

51
Q

Pathogenesis of SLE

A

Genetics: HLA-DQ, complement components

52
Q

Type III hypersensitivity reactions

A
  • Immune complexes formed mainly in organs where blood is filtered e.g. kidneys, joints
  • acute inflammatory response
  • IgG and IgM (Complement fixing)
  • phagocytosis
53
Q

Treatment for SLE

A

Corticosteroids, immunosuppressants

54
Q

Most common cause of death in SLE

A

renal failure

Pathology - Mechanisms of Disease (13 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions