flashcards AI
1
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Q: What is inflammation?
A
A: A local response to cellular injury marked by capillary dilation, leukocytic infiltration, redness, heat, and pain, aimed at eliminating noxious agents and damaged tissue.
2
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Q: What are the two main goals of inflammation?
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A: Eliminate the initial cause of injury (e.g., microorganisms, toxins) and clear necrotic cells and tissue.
3
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Q: How is inflammation linked to tissue repair?
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A: Inflammatory responses activate tissue repair and healing processes.
4
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Q: Is inflammation the same as infection?
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A: No. Infection can cause inflammation, but they are different processes.
5
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Q: Can inflammation be harmful?
A
A: Yes, although usually protective, inflammation can cause tissue damage if uncontrolled.
6
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Q: What is acute inflammation?
A
A: The immediate and early response to tissue injury, aiming to deliver leukocytes to the site of injury.
7
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Q: What are the 5 signs of acute inflammation?
A
Rubor (redness)
Tumor (swelling)
Calor (heat)
Dolor (pain)
Functio laesa (loss of function
8
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Q: What is the first line of defence of the body?
A
Physical barriers and secretions
Normal microbiota
Chemical actions (e.g., stomach HCl, acidic urine)
9
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Q: What is included in the second line of defence?
A
Inflammation
Complement enzyme series
Toll-like receptors (TLR)
NOD proteins
Fever
Cytokines (e.g., interferons, interleukins, TNF)
Phagocytosis
10
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Q: What do Toll-like receptors (TLRs) do?
A
A: Recognize molecular patterns of microbes and activate gene expression changes in cells.
11
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Q: Where are NOD proteins found, and what do they do?
A
A: Found inside cells; they recognize microbial molecules and trigger immune responses, similar to TLRs.
12
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Q: What is the third line of defence?
A
Specific immune responses:
Cell-mediated immunity
Antibody-mediated immunity
13
Q
Q: Which leukocytes are involved in inflammation?
A
Neutrophils
Lymphocytes
Eosinophils
Basophils
Monocytes
14
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Q: Which leukocyte is most associated with bacterial infections?
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A: Neutrophils.
15
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Q: Which leukocyte is most associated with viral infections?
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A: Lymphocytes.
16
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Q: Which leukocyte is most associated with parasitic infections?
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A: Eosinophils.
17
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Q: What is leucocytosis?
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A: An increase in white blood cell count, typically seen in infections (often up to 20.0 x 10⁹ cells/L or more).
18
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Q: What is leukopenia?
A
A: A severe drop in white blood cell count, sometimes occurring in serious infections.
19
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Explain why inflammation can be considered both beneficial and detrimental to the body.
A
Beneficial: important apart of immune defence to allow leukocytes to fight and eliminate the pathogen and the debris as consequence of inflammation
Detrimental: in some circumstanced such as prolong and chronic inflammation or autoimmune disease, the inflame and their mediators can damage the tissue
20
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Q: What happens to blood vessels during the earliest phase of inflammation?
A
A: Vasodilation occurs, increasing blood flow (hyperaemia) to the tissue.
21
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Q: What facilitates vasodilation and increased blood flow in inflammation?
A
A: Various chemical mediators.
22
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Q: What does increased intravascular hydrostatic pressure cause?
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A: Movement of fluid from capillaries into tissues.
23
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Q: What is the fluid called that first moves out of capillaries during inflammation?
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A: Transudate.
24
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Q: What is transudate?
A
A: An ultrafiltrate of blood plasma containing little protein.
24
Q: What follows transudation during the vascular response?
A: Increased vascular permeability and the formation of exudate.
25
Q: What is exudate?
A: A protein-rich fluid containing inflammatory cells that escapes from vessels during inflammation.
26
Q: What mechanisms cause increased vascular permeability?
Endothelial cell contraction via chemical mediators
Loosening of intercellular junctions
Direct endothelial injury
Leukocyte-endothelial injury via enzymes and free radicals
27
Q: How does protein-rich exudate affect osmotic pressures?
Reduces intravascular osmotic pressure
Increases interstitial osmotic pressure
28
Q: What is a simple way to understand osmotic pressure?
A: More protein in a compartment = higher osmotic pressure.
29
Q: What is the result of altered osmotic pressures in inflammation?
A: Outflow of water and ions into extravascular tissues, causing oedema (swelling).
30
Q: What causes pain and impaired function during inflammation?
A: Tissue swelling and the release of chemical mediators.
31
Q: What happens to red blood cells due to vascular leakage?
A: They become more concentrated, increasing blood viscosity and slowing circulation (stasis).
32
Q: What is stasis?
A: Slowing of blood circulation due to increased viscosity from concentrated red blood cells.
33
Q: What are the three main haemodynamic changes during inflammation?
Exudation of fluid to dilute toxic agents
Aid in controlling the effects of injurious agents
Blood clotting in small capillaries to localize the injury
34
Describe the advantages of the vascular stage of acute inflammation.
Increased permeability – fluid moves out of b.v – tissue oedema – dilutes toxic and irritating agents. Then leukocytes will move to site n injury via chemotaxis to fight the pathogens. Then clothing factors which then limit the injury and then blood in b.v more concentrated which equal slower flow = stasis
Vasodilation – widening of blood vessels = more blood flow = increased blood hydrostatic pressure = fluid moves out of b.v – and then neutralises the pathogen
35
Q: What is the cellular response in inflammation?
A: The movement of leukocytes from blood vessels toward the site of tissue invasion or injury, mainly occurring in venules and partly in capillaries.
36
Q: What are the four main stages of the cellular response?
Margination & rolling
Emigration & adhesion
Chemotaxis
Phagocytosis
37
Q: What is margination (pavementing) and rolling?
A: The process where leukocytes move toward and tumble along the vessel periphery due to slowed blood flow, transiently adhering to the endothelium.
38
Q: What mediates rolling during margination?
A: Special selectin molecules expressed on endothelial cells and leukocytes.
39
Q: What happens during adhesion and emigration?
A: Leukocytes firmly adhere to endothelial cells and then crawl through the endothelial basement membrane into the extravascular space (diapedesis).
40
Q: How does Diabetes Mellitus affect adhesion?
A: It reduces the number of adhesion molecules, impairing leukocyte movement and bacterial clearance.
41
Q: Which leukocytes predominate early in acute inflammation?
A: Neutrophils for the first 24 hours, followed by monocytes.
42
Q: Why do neutrophils arrive first in acute inflammation?
A: They have greater mobility and respond to chemotactic signals more quickly.
43
Q: What is chemotaxis?
A: The directed movement of leukocytes toward the site of injury along a chemical gradient.
44
Q: What substances act as chemotactic agents for leukocytes?
Soluble bacterial products
Leukotrienes and interleukins from activated leukocytes/macrophages
Activated complement components
45
Q: How do leukocytes move during chemotaxis?
A: By extending pseudopods to anchor to the extracellular matrix and pulling the rest of the cell along the chemical gradient.
46
Q: What is the first step of phagocytosis?
A: Recognition and attachment of particles to leukocytes, often enhanced by opsonins like IgG and C-reactive protein.
47
Q: What are opsonins?
A: Serum proteins that coat particles, making them easier for leukocytes to recognize and engulf.
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Q: What is the second step of phagocytosis?
A: Engulfment: Pseudopods surround the particle, forming a phagocytic vacuole that fuses with a lysosome.
49
Q: What is the third step of phagocytosis?
A: Killing and degradation of ingested microbes using reactive oxygen metabolites and hydrolytic enzymes.
50
Q: What happens if leukocytes can't engulf large or tightly bound foreign material?
A: They release toxic metabolites and proteases outside the cell, potentially causing tissue damage.
51
Q: How can inflammation cause tissue damage?
A: Activated leukocytes may damage surrounding normal tissue if phagocytosis fails or if inflammation is misdirected (e.g., autoimmune diseases).
52
Q: Give two examples of autoimmune diseases where inappropriate inflammation damages normal tissues.
Rheumatoid arthritis
Systemic lupus erythematosus (SLE)
53
Which of the following contribute to the redness and warmth associated with acute inflammation?
a. Hyperaemia
b. Exudation
c. Increased vascular permeability
A
54
Which of the following contribute to the swelling which is associated with acute inflammation?
a. Hyperaemia
b. Exudation
c. Increased vascular permeability
B
55
Q: What are inflammatory mediators?
A: Chemical substances that facilitate the acute inflammatory process, essential for both vascular and cellular responses.
56
Q: What are the three sources of inflammatory mediators?
Degranulation of mast cells
Activation of plasma systems
Release of cellular components
57
Q: What substances are released during mast cell degranulation?
Histamine
Serotonin
Chemotactic factors
Prostaglandins
Leukotrienes
58
Q: What are the three plasma systems involved in inflammation?
The kinin system
The complement system
The clotting system
59
Q: What is the role of the kinin system in inflammation?
Releases bradykinin, which:
Produces pain
Increases vascular permeability
Contracts smooth muscle
60
Q: What does the complement system do during inflammation?
A: Enhances the inflammatory response and leads to the destruction of the antigen (foreign agent).
61
Q: What is the function of the clotting system in inflammation?
Stops bleeding
Localizes microbes
Provides a stroma (supporting tissue) for repair processes
62
Q: What cellular components may be released during inflammation?
Platelets
Neutrophils
Lymphocytes
Monocytes
63
Q: What does IL stand for?
Interleukins
64
Q: What does IFN stand for?
Interferon
65
Q: What does IgG stand for?
A: Immunoglobulin G.
66
Q: What does PAF stand for?
A: Platelet Activating Factor.
67
Q: What does TNF stand for?
A: Tumour Necrosis Factor.
68
Q: What are C5a and C3b?
A: Complement enzymes involved in enhancing the inflammatory response.
69
Histamine has a role in mediating which of the following events relating to acute inflammation?
a. Pain
b. Vasodilation
c. Increasing vascular permeability
d. Fever
e. Phagocytosis
B, C
70
Prostaglandins have a role in mediating which of the following events relating to acute inflammation?
a. Pain
b. Vasodilation
c. Increasing vascular permeability
d. Fever
e. Phagocytosis
A, B, C,D
71
Leukotrienes have a role in mediating which of the following events relating to acute inflammation?
a. Pain
b. Vasodilation
c. Increasing vascular permeability
d. Fever
e. Phagocytosis
B, C, E
72
Bradykinin has a role in mediating which of the following events relating to acute inflammation?
a. Pain
b. Vasodilation
c. Increasing vascular permeability
d. Fever
e. Phagocytosis
A, C
73
Q: What are inflammatory exudates?
A: Fluids produced during acute inflammation that vary based on the type of injury and tissue response.
74
Q: What is serous exudate?
A: A watery, low-protein fluid, largely composed of plasma.
75
Q: What is fibrinous exudate?
A: Exudate that contains large amounts of plasma proteins, including fibrinogen and fibrin; must be removed for proper healing.
76
Q: What is membranous exudate?
A: Exudate that develops on mucous membranes and consists of necrotic cells within a fibro-purulent base.
77
Q: What is purulent (suppurative) exudate?
A: Exudate containing pus, rich in proteins, leukocytes, and cell debris from necrotic leukocytes.
78
Q: What is haemorrhagic exudate?
A: Exudate that contains blood, typically occurring with severe tissue injury.
79
Q: What is the typical outcome if an acute inflammation is limited or short-lived?
A: Resolution, with restoration to normal histological and functional state.
80
Q: What processes are involved in the resolution of acute inflammation?
Neutralisation/removal of the invading agents and chemical mediators
Normalisation of vascular permeability
Inhibition of leukocyte emigration
Clearance of oedema fluid, inflammatory cells, and necrotic debris
81
Q: When does scarring (fibrosis) occur after acute inflammation?
When tissue cannot regenerate
After substantial tissue destruction
When the stromal framework is destroyed
When fibrinous or purulent exudates cannot be completely absorbed
82
Q: What is the process behind connective tissue adhesion formation in pleuritis or pericarditis?
A: Organisation of fibrinous or purulent exudates by ingrowth of connective tissue.
83
Q: What is an abscess?
A: A localised collection of pus, sometimes enclosed in a connective tissue capsule.
84
Q: What organisms are considered pyogenic?
Staphylococci
Klebsiella
Pseudomonas
85
Q: What is pus composed of?
Tissue debris
Exudate
Bacterial cells
Alive and dead leukocytes
Thick whitish-yellowish fluid
86
Q: What are the possible outcomes if acute inflammation is not resolved?
Progression to chronic inflammation
Formation of abscesses
Scarring/fibrosis
Death in severe cases
87
Q: How can acute inflammation lead to death?
A: Life-threatening inflammatory reactions (like anaphylaxis) can cause massive tissue swelling in the airways, leading to asphyxiation.
88
Q: What is chronic inflammation?
A: Chronic inflammation is slow, long-term inflammation that can last for several months to years, with variable effects depending on the cause and the body's ability to repair damage.
89
Q: What are some key characteristics of chronic inflammation?
Long-lasting (months to years)
Variable extent and effects
Dependent on injury cause and repair capability
90
Q: What are the main causes (aetiology) of chronic inflammation?
Inability to resolve acute inflammation
Persistent low-grade infections
Recurrent episodes of acute inflammation
Prolonged exposure to toxic agents
Autoimmune diseases
91
Q: What factors cause the inability to resolve acute inflammation?
Compromised host immunity (impaired immune system)
Extensive tissue destruction interrupting healing
Delayed healing factors (e.g., underlying diseases, poor nutrition)
Persistence of injury (e.g., retained foreign material
92
Q: Which infectious agents are known for resisting body defenses and persisting?
Mycobacterium tuberculosis (causes tuberculosis)
Treponema pallidum (causes syphilis)
Certain fungi and protozoa
93
Q: How does persistent low-grade infection contribute to chronic inflammation?
A: Some microorganisms, such as Mycobacteria species, cause ongoing low-grade infections that stimulate chronic inflammatory responses.
94
Q: How do recurrent episodes of acute inflammation lead to chronic inflammation?
A: Repeated acute inflammatory attacks prevent complete healing, leading to ongoing tissue injury and chronic inflammation.
95
Q: What exogenous agents can cause chronic inflammation due to prolonged exposure?
Silica particles
Asbestos fibers
Coal dust
(These materials are resistant to enzymatic breakdown or phagocytosis.)
96
Q: Why does prolonged exposure to inhaled particles like silica, asbestos, or coal cause chronic inflammation?
A: Because these substances are non-degradable and resist enzymatic breakdown, they persist in tissues and continuously stimulate an inflammatory response.
97
Q: How do autoimmune diseases cause chronic inflammation?
A: The body mounts an immune response against self-antigens, causing continuous inflammation and tissue damage (e.g., rheumatoid arthritis, systemic lupus erythematosus).
98
Name 4 reasons why an acute inflammatory event may not resolve.
Compromised host immunity (impaired immune system)
Interruption to the healing process (due to extensive tissue destruction)
Persistence of injury (e.g., retained foreign material or infective agents that resist body defenses like Mycobacterium tuberculosis or Treponema pallidum)
Factors that delay healing (e.g., underlying diseases, poor nutritional status)
99
Q: What are the typical histological features of chronic inflammation?
Infiltration of tissue by mononuclear cells (lymphocytes, plasma cells, macrophages)
Tissue damage from inflammatory cytokines, enzymes, growth factors
Ingrowth of granulation tissue, leading to fibrosis and possible granuloma formation
100
Q: What types of cells typically infiltrate tissue during chronic inflammation?
Lymphocytes
Plasma cells
Macrophages (may become epithelioid cells or giant cells
101
Q: What is the role of lymphocytes in chronic inflammation?
Involved in specific and non-specific immunity
Activated by antigen-presenting cells (mainly macrophages)
Release cytokines that stimulate monocytes and macrophages
Help form the wall of granulomas
102
Q: What do plasma cells do in chronic inflammation?
Derived from B lymphocytes
Produce antibodies against persistent antigens or altered cellular components
103
Q: What are the key roles of macrophages in chronic inflammation?
Main cells in chronic inflammation
Arise from monocytes after entering tissues
After activation:
Increase in size and lysosomal enzymes
Release cytokines, proteases, reactive oxygen metabolites
Contribute to tissue destruction, immune response, angiogenesis, fibrosis
May form giant cells or differentiate into specialized cells (e.g., microglia, Kupffer cells, alveolar macrophages, osteoclasts)
104
Q: What is the function of epithelioid cells?
Specialized macrophages
Take up debris and small particles
Contribute to the centre of granuloma formation
105
Q: What is the function of giant cells in chronic inflammation?
Formed by the fusion of macrophages
Capable of engulfing very large particles
Contribute to the centre of granuloma formation
106
Q: What is the role of eosinophils in chronic inflammation?
Common in parasitic infections and IgE-mediated allergic responses (e.g., asthma)
Release enzymes (e.g., histaminase) to counter histamine
Phagocytose antigen-antibody complexes
Potent killers of parasites
107
May produce antibodies?
Plasma cell
108
b. Forms when a monocyte leaves blood and enters tissue
➔ 7. Macrophages
109
c. Numbers increase in allergic or parasitic infections
Eosinophils
110
d. Forms when a number of macrophages join together
➔ 5. Giant cell
111
e. Are formed from the differentiation of macrophages, take up debris and small particles
➔ 4. Epithelioid cell
112
f. Examples are microglia and Kupffer cells
➔ 7. Macrophages
113
g. May be found in the centre of a granuloma (name 3)
➔ 4. Epithelioid cell, 5. Giant cell, 7. Macrophages
114
h. Found in the wall of a granuloma
➔ 1. Lymphocyte
115
i. Derived from B lymphocytes
➔ 2. Plasma cell
116
Q: What are the two main forms of chronic inflammation?
Non-specific proliferative chronic inflammation
Granulomatous inflammation
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Q: What characterizes non-specific proliferative chronic inflammation?
Presence of granulation tissue
Infiltration by mononuclear cells (lymphocytes, macrophages, plasma cells)
Fibroblasts laying down fibrin
Formation of new blood vessels
118
Q: What characterizes granulomatous inflammation?
Formation of distinct nodules called granulomas
Central area of macrophages, epithelioid cells, and giant cells
Surrounded by lymphocytes, fibroblasts, and plasma cell
119
Q: What are the different types of granulomas?
Foreign body granuloma
Immune granuloma
Suppurating granuloma
Granulomas of unknown aetiology
120
Q: What is a foreign body granuloma?
Caused by inert material (e.g., glass, silica, suture material)
No inflammatory or immune reaction
Material too large to be phagocytosed by a single macrophage
121
Q: What is an immune granuloma?
Caused by insoluble or poorly soluble particles that induce a cell-mediated immune response
May be caseating (e.g., tuberculosis) or non-caseating (e.g., sarcoidosis)
122
Q: What is a suppurating granuloma?
Contains necrotic material and produces pus
Example: Cat scratch disease
123
Q: What are granulomas of unknown aetiology?
Granulomas where the cause is unknown
Example: Crohn’s disease
124
Q: What are the risk factors for chronic inflammation?
Increasing age
Obesity
Diet rich in saturated fats, trans-fats, or refined sugar
Cigarette smoking
Low levels of sex hormones
Stress
Sleep disorders
124
Q: What are possible outcomes of localized chronic inflammation?
Significant scarring
Ulcers
Strictures and obstructions
Fistulas
Deformations
Pain
Impaired function of affected structures (e.g., joints
125
Q: What can happen if chronic inflammation remains unchecked?
White blood cells may attack nearby healthy tissues and organs, leading to diseases such as:
Rheumatoid arthritis
Cancer
Heart disease
Diabetes
Asthma
Alzheimer’s disease
126
Q: What is healing?
A: Healing is the process by which a damaged object is made whole, sound, or well again.
127
Q: What is regeneration?
A: Regeneration is the replacement of damaged tissue with healthy tissue, restoring normal structure and function.
128
Q: What is repair?
A: Repair occurs when damaged tissue is replaced by scar tissue, restoring strength but not function.
129
Q: What is scar tissue made of?
A: Predominantly collagen fibers, providing strength but lacking functional capability.
130
Q: What is wound healing?
A: A series of processes aimed to fill in, seal, and shrink a wound.
131
Q: How does regeneration occur?
A: Through mitotic division of remaining viable cells, restoring structure and function.
132
Q: Which tissues can undergo regeneration?
A: Tissues with labile and stable cells, provided the stromal framework is preserved.
133
Q: What regulates regeneration?
A: A complex interplay of polypeptide growth factors, gene transcription, protein synthesis, and DNA replication.
134
Q: When does tissue repair dominate over regeneration?
A: When there is severe or persistent injury damaging both parenchymal cells and the stromal framework.
135
Q: What are the three overlapping stages of wound healing?
Inflammatory phase
Proliferative phase
Maturation (or Remodeling) phase
136
Q: What happens during the inflammatory phase?
Immediate hemostasis
Formation of platelet plug and fibrin clot
Scab formation
Cellular debris clearance
Increased cell division and fibroblast migration
137
Q: What occurs during the proliferative phase?
Angiogenesis (new blood vessel formation)
Formation of granulation tissue
Epithelialization (migration of epithelial cells)
Contact inhibition when cells meet
138
Q: What happens during the maturation/remodeling phase?
Collagen realignment along stress lines
Increased tensile strength
Scar maturation into pale, avascular tissue
Scar contraction (cicatrization)
139
Q: What is healing by first intention?
A: Healing of clean, closely approximated wounds (e.g., surgical incisions), resulting in minimal scarring.
140
Q: What is healing by second intention?
A: Healing of larger, gaping, or infected wounds involving more inflammation, granulation tissue, scarring, and wound contraction.
141
Q: What cells are responsible for wound contraction during second intention healing?
A: Myofibroblasts.
142
Q: What local factors influence wound healing?
Wound type, size, and location
Infection
Mechanical stress
Presence of foreign bodies
Ionizing radiation
Blood flow
Type of tissue affected
143
Q: What systemic factors affect wound healing?
Circulatory issues (arteriosclerosis, varicose veins)
Nutritional deficiencies (Vitamin C, zinc)
Metabolic disorders (e.g., diabetes mellitus)
Hormonal/medication effects (corticosteroids, immunosuppressants)
Age
Haematological disorders
Immune status
Underlying diseases (malignancies, Cushing’s)
144
Q: What are common complications of wound healing?
Infection
Excess granulation tissue (hypertrophic scar or 'proud flesh')
Keloid scarring (extends beyond wound margins)
Contractures (permanent tissue shortening)
Adhesions (fibrous bands connecting normally unconnected surfaces)
Dehiscence (wound separation)
Ulceration (loss of tissue surface)
145
Q: How does hypertrophic scar differ from a keloid?
Hypertrophic scar remains within wound margins
Keloid extends beyond wound margins
146
Q: What is Genetics?
A branch of biology dealing with heredity and variation of organisms.
It refers to the genetic makeup and phenomena of an organism, type, group, or condition.
147
Q: What is Genomics?
A: The study of genes, their functions, and related techniques.
148
Q: What is Epigenetics?
A: The study of heritable changes in gene function without altering the DNA sequence; focuses on gene expression changes.
149
Q: What is DNA (Deoxyribonucleic Acid)?
A: DNA contains instructions for growth and development, organized into chromosomes, and made of a double helix structure with base pairs (A-T, G-C).
150
Q: What is RNA (Ribonucleic Acid)?
A: A single-stranded nucleic acid that replaces thymine with uracil; various types include mRNA, tRNA, miRNA, siRNA, and lncRNA.
151
Q: What are Chromosomes?
A: Thread-like structures in cells made of DNA and proteins (histones) that carry genetic information.
152
Q: What are Genes?
A: The basic physical and functional units of heredity made up of DNA; may or may not code for proteins.
153
Q: Describe the structure of DNA.
A: - Double helix shape.
Bases: Adenine (A) pairs with Thymine (T), Guanine (G) pairs with Cytosine (C).
Backbone made of sugar and phosphate molecules.
154
Q: What are Nucleotides?
A: Units made up of a base, a sugar molecule, and a phosphate molecule.
155
Q: What is a Codon?
A: A specific sequence of three consecutive nucleotides that codes for an amino acid or signals the start/stop of protein synthesis.
156
Q: How are DNA and RNA connected?
A: DNA is transcribed into mRNA, processed, and exported to the cytoplasm, where it undergoes translation to synthesize proteins.
157
Q: Types of RNA and their roles?
A: - mRNA: Carries genetic info from DNA to ribosomes.
tRNA: Matches amino acids to codons during protein synthesis.
Others: miRNA, siRNA, lncRNA regulate gene expression.
158
Q: How many chromosomes do humans have?
A: 46 chromosomes (23 pairs): 22 pairs of autosomes and 1 pair of sex chromosomes.
159
Q: What is a Locus?
A: The specific location of a gene on a chromosome.
160
Q: What is a Genotype?
A: The genetic makeup (allele combination) of an organism at a specific locus.
161
Q: What is a Phenotype?
A: The observable traits resulting from the expression of the genotype (e.g., hair color).
162
Q: Define Dominant and Recessive Alleles.
Dominant allele masks the effect of the recessive allele.
Recessive allele is only expressed when paired with another recessive allele.
163
Q: Define Homozygous and Heterozygous.
Homozygous: Two identical alleles (BB or bb).
Heterozygous: Two different alleles (Bb)
164
Q: Example of dominance in eye color?
BB = Homozygous brown eyes
Bb = Heterozygous brown eyes
bb = Homozygous blue eyes
165
Q: What is a Mutation?
A: A change in the DNA sequence, either hereditary (inherited) or acquired (environmental factors).
166
Q: Possible effects of mutations?
No effect
Formation of abnormal proteins
Death of embryo/foetus
Development of diseases
Beneficial adaptations (rare)
167
Q: Types of gene mutations?
See Types of Gene Mutations; can involve insertion, deletion, duplication, point mutation, etc
168
Consider chromosomal abnormalities.
a. Name some of the types which may occur.
Trisomy – down syndrome
monosomy – turners syndrome
Abnormal numbers: polyploidy, aneuploidy
abnormal structures: deletion, repetition
169
b. Is Down syndrome an example of polyploidy or aneuploidy
aneuploidy
170
c. What is the chromosomal abnormality in Turner’s syndrome and Kleinfelter’s syndrome
Turners syndrome (X0) – missing one X chromosomes
Kleinfelters’s syndrome (XXY) – extra X chromosomes
171
Explain in simple words what is meant by each of the following:
a. Autosomal dominant disorder
An autosomal dominate disorder occurs when a person inherits just one faulty gene from one parent. If person has the gene, they will show symptoms of the disorder
172
Autosomal recessive disorder
when a person inherits two copies of a faulty gene (one from each parent). If only inherit one, they carry the gene does not have the disorder
173
. X-linked recessive disorder
caused by a faulty gene on the X chromosomes. Since males have only one X chromosomes (XY), they are more likely to be affected. Females (XX) can be carriers if that have one faulty gene
174
d. Multifactorial inheritance disorder
A multifactorial inheritance disorder is caused by a combination of genetic and environmental factors
175
1. What is autoimmunity?
Autoimmunity is when the body's immune system attacks its own cells and tissues. The target can be specific (a type of cell or tissue, an organ) or widespread. The resulting disease is called autoimmune disease.
176
2. Why does autoimmunity occur?
Autoimmunity occurs when the immune system fails to recognize the body’s own tissues as "self" due to a breakdown of self-tolerance, leading to immune attack against body tissues.
177
3. What is tolerance in immunology?
Tolerance is the immune system's ability to avoid forming immune responses (antibodies or sensitized lymphocytes) against the body’s own antigens, established in the primary (central) and secondary (peripheral) lymphoid organs.
178
4. How is self-tolerance maintained normally?
Self-reactive immune cells are eliminated in lymphoid organs (central tolerance) or suppressed by regulatory T cells (peripheral tolerance).
179
5. What leads to the failure of tolerance?
Factors include genetic predisposition (MHC/HLA genes), environmental stressors (infection, trauma), and mechanisms like cross-reacting antigens or altered immune regulation.
180
6. What is the role of genetics in autoimmunity?
Autoimmune diseases often have a familial pattern and are associated with specific HLA alleles. Example: HLA-B27 is strongly associated with Ankylosing Spondylitis.
181
7. List diseases associated with specific HLA alleles.
Ankylosing spondylitis: B27
Type 1 Diabetes: DR3, DR4
Rheumatoid arthritis: DR4
SLE (Systemic Lupus Erythematosus): DR3
Reactive arthritis: B27
Coeliac disease: DR3
Graves disease: DR3
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8. Theories explaining the breakdown of tolerance.
Cross-reacting antigens: Immune response against foreign antigen mistakenly targets self-antigens (e.g., rheumatic fever).
Altered T cell balance: Reduced regulatory T cells lead to increased immune activity.
Modified self-antigens: Injury or infection changes self-antigens, making them seem foreign.
Sequestered antigens: Hidden tissues (brain, eye) become exposed to the immune system.
Survival of forbidden clones: Self-reactive lymphocytes survive and later cause damage.
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9. What is alloimmunity?
Alloimmunity is when the immune system reacts against cells or tissues from another individual of the same species, seen in transfusion reactions and transplant rejections.
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10. Examples of autoimmune diseases.
Rheumatoid arthritis, Systemic lupus erythematosus, Scleroderma, Graves disease, Hashimoto’s thyroiditis, Type 1 Diabetes, Crohn’s disease, Ulcerative colitis, Psoriasis, Ankylosing spondylitis, Sjögren’s syndrome, Coeliac disease, Multiple sclerosis, etc.
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11. Rheumatoid Arthritis (RA): Definition.
RA is a progressive, systemic autoimmune disease causing chronic inflammation of synovial membranes and connective tissues.
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12. RA: Aetiology.
Unknown; likely triggered by an external factor (infection, trauma) in genetically susceptible individuals.
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13. RA: Pathophysiology.
Chronic inflammation of synovial membranes
Articular cartilage and subchondral bone erosion
Synovitis of tendons
Inflammatory nodules in soft tissue
Joint deformities and ligament damage (e.g., atlantoaxial subluxation in the cervical spine)
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14. RA: Epidemiology.
Women affected 3× more than men
Peak onset: 35-50 years
2-3× risk in first-degree relatives
Can occur in children
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15. RA: Clinical features.
Gradual or acute onset
Symmetrical joint pain and swelling (esp. fingers, toes)
Warm, tender joints
Muscle atrophy and deformities (e.g., ulnar deviation)
Rheumatoid nodules on olecranon, occiput, etc.
Non-articular symptoms: fever, tachycardia, pleuritis, pericarditis, eye changes
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16. What is a major spinal complication in RA?
Atlantoaxial subluxation due to destruction of the transverse ligament – contraindication to cervical spine manipulation.
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17. Systemic Lupus Erythematosus (SLE): Definition.
SLE is a chronic, multisystem autoimmune disease affecting connective tissues, exacerbated by UV light, infection, and stress.
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18. SLE: Aetiology.
Unknown; likely involves genetic and environmental factors.
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19. SLE: Epidemiology.
9:1 female to male ratio
Peak age 12-40 years (commonly 20-30 years)
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20. SLE: Pathology.
Vasculitis and fibrinoid necrosis in small vessels; deposition of immune complexes in tissues causing inflammation (e.g., vasculitis, synovitis, pleuritis).
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21. SLE: Clinical features.
Fever, rash (malar or discoid), joint pain
Multisystem involvement: musculoskeletal, renal, neuropsychiatric, respiratory, digestive, cardiovascular, haematological
Laboratory findings: anaemia, leukopoenia, thrombocytopoenia, antinuclear antibodies, proteinuria
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22. Triggers for SLE exacerbations.
Hormones, infections, dietary changes, UV exposure, certain medications and chemicals, stress, pregnancy.
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23. What is the ABO blood group system?
Classification based on presence or absence of A and B antigens on red blood cells and corresponding antibodies in plasma.
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24. Explain transfusion reactions.
Occur when antibodies in the recipient's plasma attack antigens on donor red blood cells, leading to haemolysis.
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25. Who is a universal blood donor and why?
Type O individuals – they have no A or B antigens on red cells, so their red cells are not destroyed by recipients' antibodies.
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26. Plasma transfusions and compatibility.
In plasma transfusions, donor antibodies matter. Example: Plasma from Type A donor has anti-B antibodies that can attack Type B or AB recipients.
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27. What is RhD antigen?
An antigen found on red blood cells; individuals are either Rh positive (have antigen) or Rh negative (lack antigen).
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28. What is haemolytic disease of the newborn?
Condition where an Rh-negative mother forms antibodies against Rh-positive fetal red blood cells, causing fetal haemolysis unless prevented with anti-D immunoglobulin.
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What is meant by self-tolerance? How do we develop it?
Self-tolerance is the immune system's ability to recognize the body's own cells and tissues and not mount an immune response against them. It is developed in two stages:
Central tolerance occurs in the embryo within primary lymphoid organs (bone marrow and thymus), where self-reactive immune cells are eliminated.
Peripheral tolerance continues after birth in secondary lymphoid organs, involving the suppression of any remaining self-reactive lymphocytes by regulatory T cells
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Explain how our genetic make-up can contribute to the development of autoimmune diseases.
Genetic factors influence autoimmunity. Certain genes, especially those related to the MHC (Major Histocompatibility Complex) set of alleles, make individuals more susceptible. Specific HLA (Human Leukocyte Antigen) types are strongly associated with particular autoimmune diseases, e.g., HLA-B27 with ankylosing spondylitis. Inherited variations can impair the immune system’s ability to maintain self-tolerance.
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What is the relationship between MHCs and HLAs?
MHC (Major Histocompatibility Complex) molecules are proteins found on the surface of cells that help the immune system recognize foreign substances. HLAs (Human Leukocyte Antigens) are simply the human version of MHC molecules. The terms are often used interchangeably in human medicine.
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Under what circumstances could an individual be predisposed to an autoimmune disease?
Predisposing factors include:
Having specific HLA alleles (e.g., HLA-DR3 or DR4).
Genetic susceptibility inherited from family.
Exposure to environmental stressors like infections, UV light, or trauma.
Gender (females are more commonly affected).
Hormonal factors and stress.
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Explain the relationship between infection and autoimmune diseases.
Infections can trigger autoimmune diseases through several mechanisms:
Cross-reacting antigens: Pathogens may have antigens that mimic self-antigens (molecular mimicry), leading to an immune response against the body’s own tissues (e.g., rheumatic fever after streptococcal infection).
Modified self-antigens: Tissue injury by infections can alter self-antigens, making them appear foreign to the immune system.
Release of sequestered antigens: Infections can damage barriers (like the blood-brain barrier), exposing hidden self-antigens to the immune system.
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What is meant by alloimmunity?
Alloimmunity is an immune response against antigens from another individual of the same species. Examples include blood transfusion reactions and organ transplant rejections due to incompatibility between donor and recipient tissues.
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Explain the basic pathological processes that are present in:
a. Rheumatoid Arthritis (RA):
Chronic inflammation of synovial membranes.
Thickening of synovial membranes.
Erosion of cartilage and bone at joint margins due to lytic enzymes.
Formation of rheumatoid nodules in soft tissues.
Damage to ligaments and tendons, leading to deformities.
b. Systemic Lupus Erythematosus (SLE):
Vasculitis involving small blood vessels (arterioles, capillaries, venules).
Deposition of immune complexes and fibrinoid necrosis.
Chronic inflammation leading to damage in various tissues (joints, kidneys, skin, heart, brain).
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What gender is most commonly affected by RA and SLE? What age group do they commonly commence?
Rheumatoid Arthritis (RA):
Women are affected about 3 times more than men.
Peak onset: 35–50 years.
Systemic Lupus Erythematosus (SLE):
Females affected 9 times more than males.
Most common in the 20–30 year age group, with a peak between 12–40 years.
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When would you suspect that a patient may be suffering from:
Rheumatoid Arthritis?
Symmetrical joint pain and swelling (especially fingers and toes).
Morning stiffness lasting more than 30 minutes.
'Boggy' joint swellings, reduced range of motion, and deformities like ulnar deviation.
Possible systemic signs like fever, rheumatoid nodules, or pleural involvement.
b. SLE?
Non-specific symptoms like fever, rash (especially malar "butterfly" rash), joint pain.
Oral ulcers, pleuritis, pericarditis.
Neurological symptoms (seizures, psychosis).
Laboratory findings like antinuclear antibodies, anemia, proteinuria.
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State whether the following transfusions are compatible, and give your reasons:
Q: Donor Type O, Whole blood → Recipient Type A blood. Compatible? Why?
A: ❌ Not compatible.
Reason: Type O plasma has anti-A antibodies, which will attack A recipient’s red blood cells.
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Q: Donor Type A, Red blood cells → Recipient Type B blood. Compatible? Why?
A: ❌ Not compatible.
Reason: Type B blood has anti-A antibodies, which will destroy A donor red blood cells.
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Q: Donor Type B, Plasma → Recipient Type AB blood. Compatible? Why?
A: ✅ Compatible.
Reason: Type AB blood has no anti-A or anti-B antibodies, so B plasma is safe.
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Q: Donor Type AB, Whole blood → Recipient Type O blood. Compatible? Why?
A: ❌ Not compatible.
Reason: Type O has both anti-A and anti-B antibodies, which will attack AB donor red blood cells.
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Donor Type O, Red blood cells → Recipient Type AB blood. Compatible? Why?
A: ✅ Compatible.
Reason: Type O red blood cells have no A or B antigens, so they won't trigger an immune reaction in AB recipient
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Donor Type AB, Whole blood → Recipient Type B blood. Compatible? Why?
A: ❌ Not compatible.
Reason: Type B recipient has anti-A antibodies, which will attack the A antigens on AB donor cells
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Donor Type B, Whole blood → Recipient Type A blood. Compatible? Why?
A: ❌ Not compatible.
Reason: Type A blood has anti-B antibodies, which will destroy B donor red blood cells.
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Donor Type A, Plasma → Recipient Type O blood. Compatible? Why?
A: ❌ Not compatible.
Reason: Plasma from Type A contains anti-B antibodies, and Type O has both anti-A and anti-B plasma antibodies already.
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Q: What are hypersensitivity reactions?
A: Hypersensitivity reactions are exaggerated or unwanted immune responses that can cause serious cell and tissue injury. The immune system, rather than the antigen, causes the damage.
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Q: How are hypersensitivity diseases classified?
A: They are classified based on the immunologic mechanism mediating the disease into four types:
Type I: Anaphylactic
Type II: Tissue-specific
Type III: Immune complex
Type IV: Delayed (cell-mediated)
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Q: Are all hypersensitivity reactions allergic reactions?
A: No. Only those triggered by environmental antigens (allergens) are termed allergic reactions. Most Type I and many Type IV reactions are allergic in nature.
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Q: What are Type I hypersensitivity (Anaphylactic) reactions?
A: These involve IgE antibodies, mast cell degranulation, and are typically allergic in nature. Reactions can be local (e.g., hay fever, eczema) or systemic (e.g., anaphylaxis to bee venom or penicillin).
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Q: What is the sequence of events in a Type I hypersensitivity reaction?
Initial allergen exposure activates CD4+ T cells and B cells → IgE production
IgE binds to mast cells and basophils
Upon re-exposure, allergen cross-links IgE → mast cell degranulation
Release of primary (e.g., histamine) and secondary mediators (e.g., prostaglandins, cytokines)
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Q: What is atopy in the context of Type I hypersensitivity?
A: A genetic predisposition to develop localized allergic reactions such as asthma or eczema, often associated with elevated IgE levels.
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Q: What is the role of histamine in Type I hypersensitivity?
A: It causes vasodilation, increased vascular permeability, bronchospasm, mucus secretion, and GI motility.
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Q: What are Type II hypersensitivity reactions?
A: These are antibody-mediated reactions against tissue-specific antigens, leading to tissue destruction or altered cell function.
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Q: What are the five mechanisms of Type II hypersensitivity?
Complement-mediated cell lysis (e.g., transfusion reaction)
Opsonization → phagocytosis
Neutrophil-mediated damage via reactive enzymes
NK cell-mediated cytotoxicity
Antibody alters cell function without killing (e.g., Graves' disease)
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Q: What is Graves’ disease in the context of Type II hypersensitivity?
A: An antibody (LATS) mimics TSH, overstimulating the thyroid gland without feedback regulation, leading to hyperthyroidism.
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Q: What are Type III hypersensitivity reactions?
A: These involve immune complexes (Ag-Ab) that deposit in tissues, activate complement, attract neutrophils, and cause tissue damage.
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Q: What are examples of Type III hypersensitivity diseases?
Extrinsic allergic alveolitis (e.g., farmer’s lung)
Poststreptococcal glomerulonephritis
Rheumatoid arthritis
Systemic lupus erythematosus
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Q: What tissues are commonly affected in Type III hypersensitivity?
A: Kidneys, joints, skin, heart, and small blood vessels.
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Q: What is Type IV hypersensitivity?
A: A delayed, T cell–mediated response that does not involve antibodies. Involves Tc, Th1, and Th17 cells.
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Q: How do Tc and Th1/Th17 cells cause tissue damage in Type IV hypersensitivity?
A: Tc cells release toxins like perforin. Th1/Th17 cells recruit macrophages, which release lysosomal enzymes and ROS.
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Q: What is a classic example of a Type IV hypersensitivity reaction?
A: The Mantoux (tuberculin) test, which shows a delayed skin reaction in people previously sensitized to Mycobacterium tuberculosis.
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Q: What are some other examples of Type IV hypersensitivity?
Allergic contact dermatitis (e.g., poison ivy, latex)
Milk intolerance
Coeliac disease
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Q: What are the primary immunogenic molecules responsible for graft rejection?
A: Major histocompatibility complex (MHC) antigens, also known as human leukocyte antigens (HLA), are the main immunogenic molecules that stimulate rejection of transplanted organs.
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Q: Why is HLA matching important in transplantation?
A: Closer HLA matching between donor and recipient improves graft survival by reducing the risk of immune rejection.
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Q: What triggers graft rejection in the host?
A: Graft rejection is triggered when the host’s immune system recognizes the transplanted tissue as foreign and initiates an immune response against it.
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Q: What immune mechanisms are involved in graft rejection?
Type IV hypersensitivity: Cell-mediated immune reaction
Type II hypersensitivity: Antibody-dependent cellular cytotoxicity (ADCC)
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Q: What are the three types of graft rejection?
Hyperacute rejection
Acute rejection
Chronic rejection
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Q: What characterizes hyperacute rejection?
Occurs within minutes to hours of transplantation
Can be recognized intraoperatively
Caused by pre-existing antibodies in the recipient that react with donor antigens
It is a Type II hypersensitivity reaction involving vascular injury
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Q: What is the immunological mechanism behind hyperacute rejection?
A: It is primarily an antigen-antibody reaction at the vascular level, consistent with Type II hypersensitivity.
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Q: What characterizes acute rejection?
Occurs within days to weeks post-transplant or suddenly after stopping immunosuppressive therapy
Involves both cell-mediated and humoral immune responses
Leads to acute cellular rejection, vasculitis, and extensive tissue necrosis
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Q: What hypersensitivity types are involved in acute rejection?
Type IV hypersensitivity: T cell–mediated attack on graft
Type II hypersensitivity: Antibody-mediated mechanisms may also be involved
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Q: What characterizes chronic rejection?
Occurs months to years after transplantation
Marked by vascular changes, interstitial fibrosis, and loss of parenchyma
Primarily driven by Type IV hypersensitivity (chronic T-cell mediated injury)
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Q: Which hypersensitivity type predominates in chronic rejection?
A: Type IV hypersensitivity, involving chronic T cell–mediated damage.
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What is the relationship between MHC antigens and HLA?
MHC (Major Histocompatibility Complex) antigens are the immunogenic molecules that stimulate graft rejection. In humans, MHC antigens are specifically referred to as HLA (Human Leukocyte Antigens). Therefore, HLA is the human version of MHC, and matching HLA between a donor and recipient is crucial for the optimal survival of a graft to minimize immune rejection.
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
a. Examples include allergic contact dermatitis and the Mantoux test reaction.
Type IV hypersensitivity
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
b. IgE antibodies are most important
Type I hypersensitivity
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
(Examples include acute poststreptococcal glomerulonephritis, rheumatoid arthritis, and systemic lupus erythematosus (SLE).
Type III hypersensitivity
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
(Involves Th1, Th17, and Tc cells.)
Type IV hypersensitivity
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
(Involves antibodies attaching to a cell-specific antigen, then causing tissue damage via complement activation, phagocytosis, neutrophil activation.)
Type II hypersensitivity
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
(Mast cells and basophils involved.)
Type I hypersensitivity
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
(An example is Graves disease – antibody binding alters cell function without destroying the tissue.)
Type II hypersensitivity
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Name the type of hypersensitivity reaction that fits each of the following characteristics:
(Examples include asthma, hay fever, reactions to some foods or drugs, reaction to a bee sting, etc.)
Type I hypersensitivity
