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2420 Pathology > Module 5 Immunocellular Alterations > Flashcards

Module 5 Immunocellular Alterations Flashcards

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1
Q

Innate Immunity

A
  • Physical protective barrier of skin & mucosal surfaces
  • Automated response to physical/infectious injury
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2
Q

Processes

A
  • Phagocytosis
  • Inflammation
  • Complement activation
  • Coagulation
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3
Q

Stratum Corneum

A
  • Physical impermeable barrier
  • Works with granular & spinous cell layer
  • Corneocytes embedded in lipid matrix
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4
Q

Sebaceous Gland

A
  • Secrete sebum
  • Coats skin in antimicrobial lipid
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5
Q

Physical Barrier

A
  • Acidic pH
  • Antimicrobial lipids & peptides
  • Disrupt bacterial membranes
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6
Q

Mucosal Surface Barrier

A
  • Bacteria trapped in mucus
  • Mucus contains antimicrobial peptides & secretory IgA
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7
Q

Goblet Cells

A
  • Attract bacteria
  • Intestinal
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8
Q

Skin Infection Barrier

A
  • Keratin
  • Mucous
  • Tight junctions between epithelial cells
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9
Q

Microbe Death via Antibiotics

A
  • Defensins
  • Dermcidin
  • Acidic pH
  • Sebum
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10
Q

Epithelial Functions

A
  • Portals of entry of microbes
  • Provide physical barriers
  • Produce antimicrobial substances
  • Harbor lymphocytes
  • Kill microbes & infected cells
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11
Q

Granulocytes

A
  • Multi-lobed nucleus
  • Spotted surface (protein, peptides)
  • Cytoplasm packed with granules
  • Granules loaded with antimicrobial enzymes
  • All contribute to innate immunity
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12
Q

Polymorphonuclear Cell (PMN) /Neutrophils

A
  • Recognized by multi-lobed nucleus
  • 60% of bone marrow
  • Develop within bone marrow
  • 10hr lifespan
  • 10^11 enter & leave circulation daily
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13
Q

Neutrophil Granules Function

A
  • Kills bacteria by iron restriction
  • Destruction of cell wall & membrane
  • Oxidation
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14
Q

Phagocytosis

A
  • Optimised by antibody
  • Compliment protein binds to bacteria receptor
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15
Q

NADPH Oxidase System

A
  1. Electrons pumped into vacuole
  2. Convert oxygen into super oxygen animes
  3. Interact with protons to form hydrogen peroxide
  4. MPO reacts with hydrogen peroxide & halide (Cl, Br, I)
  5. Form toxic oxidizing agents (HOCl, OH,)
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16
Q

Chronic Granulomatous Disease

A
  • Genetic defect X-linked & autosomal recessive
  • Failure to produce cytochrome b558
  • Unable to generate superoxide (NADPH Oxidase)
  • Can’t kill bacteria, form granulomatous lump
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17
Q

Basophils

A
  • Fight parasitic & allergic reactions
  • Produce heparin (anticoagulant)
  • Produce histamine (vasodilator)
  • Initiate chronic allergy & anaphylaxis
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18
Q

Eosinophils

A
  • Fight parasitic infection
  • Pathology of asthma
  • Produce reactive oxygen species
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19
Q

Macrophage Lifespan

A
  • Emerge from bone marrow as stem cell
  • Circulate as monocytes
  • Migrate into tissue (differentiation) take up properties
  • Activated macrophage
  • Inject microbe
  • Life span several months
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20
Q

Macrophage Function

A
  • Efflux of iron & manganese (nutrition)
  • Influx of copper & zinc (support oxidate killing)
  • Produce nitric oxide synthase
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21
Q

Pattern Recognition Receptors

A
  • Recruitment of adapter proteins
  • Recruitment & activation of protein kinases
  • Activation of transcription factors
  • Gene transcription
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22
Q

TLR 1, 2, 6

A
  • Peptidoglycan
  • Lipoproteins
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23
Q

TLR 4

A
  • Bacterial LPS
  • Fungal mannans
  • Viral envelope proteins
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24
Q

TLR 5

A
  • Bacterial flagellin
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25
TLR 3, 7, 8, 9
- Microbial & viral nucleic acids
26
Innate Immunity Specificity
- Structures shared by classes of microbes/damaged cells
27
Innate Immunity Receptors
- Tool-like - N-formyl peptide - Mannose - Scavenger - Identical on each cell
28
Adaptive Immunity Specificity
- Structural detail of microbial molecules - May recognize nonmicrobial antigens - Distinct antibody molecules
29
Adaptive Immunity Receptors
- Encoded by genes - Produced by recombination of gene segments - Greater diversity - Clonal distribution
30
Cytokine Production
- Complement - Microbe engagement of toll receptors
31
Cytokine Function
- Modify functionality of immune cells & vascular endothelium
32
TLR Engagement
- Immune cells produce cytokines & chemokines
33
Tumour Necrosis Factor (TNF)
- Macrophages & t cells - Endothelial & neutrophils activation - Hypothalamus fever - Upregulate expression of adhesion proteins
34
Interleukin -1 (IL-1)
- Macrophages & endothelial cells - Endothelial activation (inflammation/coagulation) - Hypothalamus fever
35
Chemokines (IL8)
- Macrophages, dendric cells - Activated endothelial cells - Attract neutrophils
36
Chemokines Function (IL8)
- Upregulate oxidative capacity - Change in shape - Promote adhesion to endothelium - Promotes granulation (protein to surface)
37
Interleukin -12 (IL12)
- Dendritic cells & macrophages - Act on t & NK cells - IFN production - Activate macrophage killing capacity
38
Interleukin-10 (IL-10)
- Macrophages, endothelial cells, T cells - Inhibit IL-12 production - Anti-inflammatory
39
Cytokines Process
1. Phagocytosis, macrophage/dendritic cell produces IL-12, IL-1, TNF 2. IL12 instructs NK-cells to produce IFN-y 3. Macrophages produces more inflammatory mediators 4. TNF & IL-1 pro-inflammatory mediators acting on other immune cells 5. Promotes adhesion & extravasation of neutrophils
40
Complement Cascade Activation
- Alternative pathway (C3) - Classical pathway - Lectin pathway
41
Membrane Attack Complex (MAC)
- Cascade pathway - 9 protein complex on bacteria surface - Bacteria opsonized for phagocytosis by deposition of C3b - C3a & C5a (proinflammatory) chemo attractants - Poke hole in bacteria
42
Alternative Complement Pathway
- Deposition of C3b on bacterial surface - No specific antibody required
43
Classical Pathway
- Antibody binds to antigen on bacteria - C1 engages antibody - Initiate complement activation - Production of C3a&b
44
Lymphocyte Functionality
- Recognize pathogens - Antigen specific receptors - Like antibodies on cell surface
45
B cells
- Produce antibodies - Develop within bone marrow
46
Antibodies of B cells
- Circulate in blood - Bind to specific bacteria/viruses to neutralize - Assist other immune cells in killing
47
Clonal Expansion of B cells
- Aided by T-helper - Produce cytokines - Promote b-cell development
48
T cells
- Develop in thymus - Regulatory & immune effector functions
49
Th1
- Facilitate macrophage & cytotoxic t-cell responses - Produce cytokines IFN-y & IL-2
50
Th2
- Stimulate antibody production by B-cells - Produce cytokines IL-4, IL-6, IL-10
51
Th17
- Promote inflammation - Produce cytokines IL-17
52
Treg
- Suppress inflammation - Produce cytokines TGF-b & IL-10
53
CD8 T-cells
- Receptor recognizes viral antigen present in infected cell - T-cell receptor & CD8 engage MHC - T-cell releases perforin & granzyme
54
Perforin & Granzyme
- Proteins that damage membrane & nucleus of target cell
55
Major Histocompatibility Complex 1 (MHC)
- Expressed by all nucleated cells - Self-antigen - Any infected cell can also present an antigen to CD8 T-cells - Presents antigens from virus infected cells
56
MHC 2
- Only present on professional antigen presenting cells (CD4 helper T-cells) - Present antigens from extracellular pathogens
57
Professional Antigen Presenting Cells
- B-cells - Macrophage - Dendritic cells - Langerhan cells - Activated T-cells
58
Immune Disorders Linked to Variant MHC
- Psoriasis - Ankylosing spondylitis - Type 1 diabetes - Multiple sclerosis - Rheumatoid & reactive arthritis
59
Natural Killer (NK) Cells
- Recognize activating ligands expressed on nucleated cells - If inhibitory receptor not engaged NK degranulates - Release perforin & granzyme to kill target cells
60
Type 1 Hypersensitivity
- IgE-mediated allergic reaction - Immediate (occurs within minutes) - 2 phases (sensitization & re-exposure)
61
Sensitization Phase (Type 1)
- Allergens detected by dendritic cells - CD4+ T cells develop into Th2 cells - Cytokines mediate production of IgE antibodies - IgE binds to surface receptors - Tissue mast cells & blood basophils are sensitized
62
Re-Exposure Phase (Type 1)
- Allergen binds to IgE on surface receptors - 2 IgE receptors are cross-linked by allergen - Signal transduction through y chains of receptor - Influx of calcium - Degranulation & release of mediators
63
Systemic Anaphylaxis
- IV or oral absorption - Edema (laryngeal) - Increased vascular permeability - Circulatory collapse - Death
64
Acute Urticaria
- Skin entry - Local increase in blood flow & vascular permeability - Edema
65
Seasonal Rhinoconjunctivitis
- Eye/nasal mucosa contact - Edema of eye/nasal mucosa - Sneezing
66
Asthma
- Contact with mucosa lining of airway - Bronchial constriction - Increased mucous production - Airway inflammation
67
Food Allergy
- Oral entry - Vomit/diarrhea - Itching/hives - Anaphylaxis
68
Type 2 Hypersensitivity
- IgG & IgM mediated - Antibodies directed against antigen (slef/non-self) - Cells of particular tissues only - 3 mechanisms
69
Antibody Mechanisms of Type 2
- Activate normal cell function (hyperactive) - Activate complement cascade causing target cell destruction - ADCC exhibited by NK/phagocytic cells
70
Graves Disease
- Antibodies bind to TSH receptor - Activation of receptor - Cells produce hormone - No natural shut off mechanism - Overproduction of thyroid hormone
71
Rheumatic Fever
- Following throat infection by bacterium streptococcus pyogenes - Production on antibodies against tissues - IgG-mediated cytotoxic hypersensitivity
72
Rheumatic Fever Process
1. Bacterium infects susceptible host 2. T-cells & antibodies against M protein of streptococcus 3. T cells & antibodies may attack look-alike proteins of body 4. Bacterial infection clears 5. Development of rheumatic heart disease
73
Type 3 Hypersensitivity
- IgG bind to free antigens forming immune complexes - Complexes circulate in free state
74
Increased Vascular Permeability
- Complexes deposit within tissues - Blood vessel walls (vasculitis) - Synovial joints (arthritis) - Glomerular basement membrane
75
Deposition of Immune Complexes
- Activation of complement system - Chemotaxis of neutrophils to sites of complex deposition - Local tissue damage & inflammation
76
Vasculitis
- Immune complexes in blood vessels
77
Type 4 Hypersensitivity
- Reaction occurs within 24-48hrs (delayed type) - Mediated by T-cells - Antibody independent - Sensitization & effector phase
78
Sensitization Phase (Type 4)
- Primary exposure CD4+ T cells develop into Th1 cells - Sensitizing agents (metals, chemicals, natural)
79
Effector Phase
- Re-exposure activates Th1 cells & cytotoxic T cells - Release pro-inflammatory cytokines & chemokine - Attract & activate macrophages & T-cells - Causing inflammation & tissue damage
80
Poison Ivy
- Biological agent inducing type 4 - Delayed response (24-48) - Skin reaction - Red, itchy, blisters
81
Nickle Exposure
- Type 4 sensitizer
82
Patch Test
- Number of different compounds onto skin - 3-5 days (allow delayed response)
83
Hypofunction Consequences
- Disorders in defense - Disorders in surveillance
84
Disorders in Defence
- Increased susceptibility to infections - Infection type dependent on form of immunity affected
85
Disorders of Surveillance
- Increased frequency of malignant disease - Immunodeficiency syndromes & immunosuppressive meds increase cancer risk
86
Clinical Features with Immunodeficiency
- Chronic infection - Recurrent infection - Unusual infecting agents - Poor response to antibiotic treatment
87
Primary Immunodeficiency Disorders
- Pure B cell dysfunction - Cell-mediated immune deficiencies - Both T & B cell deficiency can occur in same patient
88
Pure B cell Dysfunction
- T cells unaffected - Detected at 5-6 months old - Protection by maternal IgG antibodies - Bruton's syndrome
89
Cell Mediated Immune Deficiencies
- T-cell dysfunction - Presents early in neonatal period - DiGeorge syndrome
90
Chronic Granulomatous Disease
- Phagocytic dysfunction - Absence of lysosomal enzymes in monocytes & granulocytes
91
Secondary Immunodeficiency Disease Causes
- Infections - Immunosuppressive therapy - Malignancy (lymphoma especially) - Chronic illness - Malnutrition - Aging
92
Infections
- Rubella, measles, mycoplasma (temporary) - HIV, AIDS cell-mediated & humoral immunity
93
Immunosuppressive Therapy
- Cytotoxic drugs (cancer chemo) - Irradiation - Anti-lymphocyte serum globulin (ALG)
94
Autoimmune Disease (Hyper)
- Breakdown of normal processes to maintain self-antigen tolerance - Discrimination of antigens by reactive T-cells - Suppression of immune responses to self-antigen by T-cells
95
Genetic Factors
- Inheritance of susceptibility genes that disrupt different tolerance - Autoimmunity runs in families - Common to have 1+ autoimmune diseases - Particular HLA alleles are linked to autoimmune diseases - Genetic polymorphisms are linked to autoimmune diseases
96
Environmental Factors
- Infections & tissue injury expose self antigens - Activate antigen presenting cells & lymphocytes in tissues - Microbes including viruses & bacteria may trigger autoimmune - UV radiation & smoking cause tissue damage
97
Clinical Presentation Factors
- Target (antigen) - Immune reaction type (cell-mediated, humoral, both) - Changes secondary to destruction of target organ/immune reaction

2420 Pathology (13 decks)

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