Infection and Immunity Flashcards
1
Q
Describe the structure of a gram negative bacteria cell wall
A
Cell membrane
thin layer peptidoglycan
outer membrane
lipopolysaccharides
2
Q
Describe the structure of a gram positive bavteria cell wall
A
Cell membrane
thick layer of peptidoglycan
3
Q
Four components of gram staining in order
A
- Crystal Violet
- Iodine to trap dye
- Acetone to decolourise
- Safranin to counter stain
4
Q
5 features of inflammation
A
Rubor
tumour
calor
dolor
functio laesa
5
Q
describe monocytes
A
White blood cells that originate in bone marrow and spleen. Mature in BM then circulate blood. Once in tissues they differentiate into macrophages (phagocytes)
6
Q
Describe neutrophils
A
Identified by multi-lobed nucelus. They are chemotactic and phagocytic. First cells to respond to infection. They contain granules. They make up 65% of white blood cells and have a lifespan of 7 hours.
7
Q
What are Toll-Like receptors
A
They recognise different PAMPS to initiate the immune response. Found on macrophages.
8
Q
What is Lymph
A
Interstitial fluid that collects within tissue and is taken up by lymphatic vessels.
9
Q
Describe structure of lymphatic capillaries
A
Surrounded by LVs. They are lined by endothelial cells and their basement membrane is incomplete or absent allowing fluid to enter
10
Q
What are lacteals
A
Lymphatic vessels within the villi of the small intestine that absorb dietary fats in the interstitial fluid that cant enter blood stream.
11
Q
Fucntion of Lymphatic vessels
A
Carry and rturn lymph from lymphatic capillaries to the circulatory system. Pulsation from close-by arteries and muscle contraction can help to move lymph. Valves prevent backflow.
12
Q
Describe lymphatic trunks
A
LVs come together to form LTs. They drain lymph. From the right thorax, upper limb, upper abdominal walla nd side of head/neck drains to RIGHT SUBCLAVIAN VEIN
from all other regions drain into LEFT SUBCLAVIAN VEIN via the THORACIC DUCT
13
Q
What are the primary lymphoid organs
A
Bone marrow and thymus. Mature lymphocyte production.
14
Q
What are the secondary lymphoid organs
A
lymph nodes
tonsils
spleen and mucosa-associated lymphoid tissue
are filters where antigen-driven proliferation and differentiation occurs.
15
Q
What are lymph nodes
A
Small structures that interrupt lymphoid vessels. They are dense areas of lymphoid tissue that are surrounded by a dense fibrous capsule. Afferent LVs enter the node and efferent LVS exit. They filter lymph to detect for any foreignantigens and mount an immune response
16
Q
What does swollen nodes indicate
A
An active immune system. Underlying infection or cancer - cells that break away from tumour can often lodge in lymph nodes and grow as secondary tumours.
17
Q
Function of lymphatic system
A
removal of IF from tissues
absorbs and transports fats from digestive system
involed in immune sytem - producing mature lymphocytes and detecting foreign antigens.
18
Q
What are the seven main nodes
A
Axillary
cervical
inguinal
mediastinal
pelvic
retroperitoneal
supercalvicular
RACIMPS
19
Q
How does IF enter the lymphatic capillaries
A
Higher blood pressure at arteriole end of capillary bed causes water to leak.
Reduced water content in blood causes osmosis and water is reabsorbed into capillaries at venule end.
Excess fluid must be reabsorbed and transported to blood circulation.
20
Q
How do T helper cells mature
A
Antigen presenting cells (dendritic cells) ingest pathogens and present them to immature CD4 T cells at the nearest lymph node
21
Q
How do T helper 1 cells activate macrophages
A
By secreting interferon-y
22
Q
What is Tumour necrosis factor-a
A
TNF-alpha is an inflammatory cytokine produced by macrophages/monocytes.
- acts on endothelium to induce leakiness
- act on other WBCs resulting in their activation and proliferation and further recruitment to site of infection
23
Q
Function of IL-17
A
Stimulates the differntiation and chemotaxis of neutrophils
24
Q
Function of interleukins 4, 5, 10 and 13
A
Secreted by T-helper 2 cells. defends against extracellular pathogens by stimulating B cells to make antibodies
25
Th1 or Th 2 differtniation decision
Determined in part by cytokines produced by dendritic cells. Microbes at a site of infection stimulate dendritic cells to produce different cytokines.
26
What cell primarily fights bacteria
Neutrophils
27
What cell primarily fights parasites
Eosinophils
28
Describe prokaryotes
No membrane bound nucleus
circular chromosomal DNA found loose in cytoplasm some species have plasmids. BACTERIA
29
Describe eukaryotes
DNA carried on chromomes in membrane-bound nucleus cytoplasm is rick in membrane-bound organelles. Cellular organisms OTHER than bacteria
30
Describe bacteria
Single celled prokaryotes complex cell wall and often a thick capsule
may be motile due to flagellum
31
Example of gram neg
Rods: E-coli and salmonella
Cocci: Neisseria meningiditis
32
Examples of gram pos
Rods: Listeria monocytogenes
corynebacterium diptheriae
Cocci: Staphylococcus aureus
streptococcus pneumoniae
33
What is colonisation
The commensal and mutualistic symbiotic relationship between two species. Many body sites are natrurally colonised by bacteria. Normal bacteria is beneficial to us as they stimulate our immune system produce beneficial substances and compete with other pathogens.
34
List some sterile body sites
Blood, tissues and organ systems
CNS
Lower respiratory tract
Sinuses
inner and middle ear
Renal system down to posterior urethra
Female reproductive tract down to the cervix
Eye
35
List some non-sterile body sites
Vagina
Urethra
Mouth and teeth
Nose and airways
Skin
Stomach and intestines
36
List some virulence factors
Antigenic mimicry
masking and shift
Encapsulation
Evasion of host immune response
Infectious doses
Colonisation factors
toxigenicity
37
What is the chain of infection
1. Infectious agent
2. Reservoirs
3. Portal of exit
4. Means of transmission
5. Portal of entry
6. Susceptible host
7. REPEAT
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38
What is a parasite
Organism that requires another to survive
39
What is an opportunistic infection
Bacteria of low pathogenic potential that colonise organisms causing infections in immunocompromised host
40
What is a nosocomial infection
A hospital acquired infection
41
What are endotoxins
Lipopolysaccharides found in outer cell wall of gram negative bacteria. When the bacteria cell is killed/dies these endotoxins are released into the circulation. They activate complement and bring about toxic effects such as fever, multi-organ failure, septic shock and sepsis
42
What are exotoxins
Toxins released by living bacterial cells. They damage cells and disrupt regular cellular metabolism.
43
Two main steps of specimen journey
1. Sample is processed in appropriate area of the lab. Eg culture sensitivity testing or PCR.
2. Samples that are contaminated with commensal flora require decontamination steps.
44
What is sepsis
Physiological response to severe infection involving cytokine cascades free radical production and vasoactive mediators.
45
Describe Viruses
Simoke acellular infectious pathogens that are incapable or self-replication and metabolic activity. They are obligate intracellular parasites.
46
List viral components
Genome and Capsid (together = nucelocapsid). May also contain essential or accessory enzymes to facilitate initial replication. Naked or enveloped both contain viral attachment proteins
47
What is a capsid
Protein coat composed of capsomeres (several different polypeptides grouped together). Capsids have distinctive symmetry either helical or icosahedral.
48
What are viral attachment proteins
They express glycoproteins which facilitate host cell entry. Either alongside capsid proteins in naked viruses or anchored in the phospholipid bilayer of enveloped viruses. Different viruses express different glycoproteins which attach to specific host cell receptors. Thes 'spike' glycoproteins confer virus antigenicity.
49
Describe the structure of the HIV virus
It is a single stranded +ve sense RNA retrovirus. It is enveloped. It's genomes encodes 9 genes. HIV expresses 72 transmmebrane glycoprotein antigens (gp41 and gp20). Also expresses a matrix and capsid protein. Enzymes found inside nucleocapsid include reverse transcriptase integrase and protease.
50
What is Tropism
The ability of a given virus to productively infect a particular cell tissue host species
51
Two methods by which a virus enters a cell
Micropinocytosis - once the virus attaches to the host cell it can become engulfed by the host cell membrane
Membrane fusion - where the virus inserts itself into the host cell
52
What are the 6 steps of the viral replication and infection cycle
1. Attatchment/absorbtion via a cellular receptor
2. Penetration. Virus is engulfed by the membrane or fusion with the membrane.
3. Uncoating. Viral componenets are opened and contents are released into the cell.
4. Replication/synthesis. Virus uses host ribsome to synthesise new proteins.
5. Assembly. Viral proteins assemble into new virions.
6. Release via cell lysis (naked) or using portions of host cell membrane to form envelope and then released (enveloped). Viruses can also move through neighbour cells by fusing with the membrane.
53
How does HIV infect T lymphocytes and monocytes/macrophages
Through the interaction of gp120 and the CD4 receptor. In T cells facilitated by coreceptor CXCR4. In Monocytes coreceptor CCR5.
54
What is antigenic drift caused by
Small mutations with antigenic genes allow viruses to evade host immune systems
55
What is antigenic shift caused by
Gene recombination and re-assortment
Recombination; Exchange of entire genes between two strains
Reassortment; Exchange of entire segments of genomes between strains
56
Describe Influenza
Exhibits both antigenic shift and antigenic drift.
It has 8 segments of -ve sense ss RNA.
Susceptible to all 3 types of mutation.
Also able to infect and co-infect multiple species.
Antigenic shift pf entire segments of influenza genome can occur in co-infection
Antigenic drift of the HA and NA glycoproteins causes the repeat outbreaks of the seasonal flu
57
Describe PID / IEI
Primary immunodeficiency / inborn errors of immunity are congenital (present at birth). They can be inherited or as a result of a novel infection. They are hard to diagnose. Can be due to monogenic mutation or polygenic mutation.
58
Describe x-linked agammaglobulinemia
Defect in IL2RG gene which encodes a receptor that many cytokines use. Some of these cytokines are required for T and B cell development. This puts patients at higher risk of bacterial infections.
59
What is retrovirus gene therapy a tratement for?
ADA-SCID: patients are able to make T and B cells but they dont live very long due to intracellular S-adenyosylhomocysteine buildup
60
What is hyper IgM syndrome
Hyper IgM syndrome (HIGM) is a rare primary immunodeficiency characterized by low or absent levels of IgG, IgA, and IgE antibodies, with normal or elevated IgM levels, resulting from a mutation in the CD40L gene which normally allows B cells to undergo class switching.
61
What is chronic granulamotous disease
Patients are unable to create superoxide burst that is used by phagocytes to kill the pathogens that they have phagocytosed. This us due to defects in NAPDH enxymes. Multiple granulopmas form as a result of a defective elimination
ie granulomas in the lungs that hinder breathing.
62
Describe acquired immunodeficiency
It is a secondary immunodeficiency that isnt present at birth. Due to malnutrition, infection, age or certain drugs. Treatment with antiretroviral therapy can limit/prevent the development of AIDS.
63
What is an aberrant immune response
When a functioning immune system causes harm.
64
What are the products of a mast cell
Histmaine - vasodilation, shock, swelling, wheezing
Leukotriene - wheezing, airways narrowing, snot secretion, prostaglandin Paf
Cytokines - inflammation, wheezing, airways narrowing, snot secretion, proteases
65
What are the difficulties with anti-viral drugs
Most anti-viral drugs attack enzymes and viruses dont have many enzymes and so there arent many targets.
Viruses are very mutagenic when the drug attacks the virus can escape by mutating and changing its protein structure.
Drugs for acute infections arent always effective as by the time the patient recieves medication
the virus has already infected everything and the infection is over.
66
What are the two strategies to target viral infection
Vaccination and immunotherapy
Antiviral therapy
67
Describe how rabies infects an individual
Spread through bite injuries from infected animals
muscle pentration - rabies infects muscle cells first. It then enters the nervous system travelling trhough nerves to the central nervous system. Once in the brain, confusion and saliva overproduction.
68
What is oseltamivir
Neuraminidase inhibitor. It reduces the rate at which influenza is able to replicate within a host.
(Active neuraminidase cleaves the virion from the receptor)
Often given to patients with low immune systems before they are infected.
69
What is the humoral aspect of the immune system
The system involving molecules not cells
70
Describe antibodies
They are produced by B cells and secreted by plasma cells and they costitute a mjaor protein component of plasma. They recognise foreign antigens (extracellular) and bind to and remove them.
71
What are the 5 types of antibodies
IgM: first antibody made, strong bidning to antigen, Pentamer
IgG: Most abundant antibody, crosses the plasma for immunoprotection for developing foetus. Monomer.
IgA: Secreted, found in tears, saliva, mucus membranes of resp and GI systems, also found in breast milk. Dimer
IgE: Allergic response (type 1 hypersensitivity); parasitic immune response. Monomer
IgD: Less well understood, present on the surface of B cells. Monomer
72
Structure of an antibody
Y shaped macromolecule consisting of four polypeptide chains. Ends of Y shape is where antigen/foreign pathogen binds.
4 polypeptide chains: immunoglobulins
- 2 short chains called 'light'
- 2 long chains are called 'heavy'
joined together by disulphide bonds
each chain has a variable (V) region and a constant (C) region
Antibody can be divided into Fab domain which binds to the antigen and the Fc domain which binds to complement.
73
How does an antibody eliminate a pathogen
1. Neutralisation: Coats a virus/toxin and neutralises its activity
2. Opsonisation: Pathogen coated in antibodies making it more recognisable for macrophages.
3. Complement activation: Antibodies activate complement which results in destruction of extracellular pathogens.
74
What is complement
A Cleavage cascade to amplify small responses into large responses that stimulate multi-protein complexes that attack bacteria. It is activated by an antibody or molecules from pathogens. can directly kill pathogens or attract immune cells.
75
What components are involved in innate immunity
Soluble mediators in plamsa (complement)
Phagocytes: neutrophils and macrophages
76
Why ar macrophages better phagocytes than neutrophils
They re-organise their actin cytoskeleton to engulf bacteria that are digested inside the cell. they can also engulf apoptotoc cells. The finger-like extensions that encapsulate the apoptotic cells are called pseudopodiathey develop in tissues from precursors.
77
What ate the four stages of innate cell migration to infection sites
Adhesion
bindind
diapedesis
migration
78
Describe CD4 cells
T helper cells that recognise antigen presenting in MHC 2 on the surface of antigen presenting cells and 'help' them.
79
Describe CD8 cells
Cytotoxic cells that recognise antigens presented in MHC 1 on many cell types and can be induced to kill.
80
What do T helper cells do
Help the antigen-driven maturation of B and T cells. Facilitate and magnify the interaction between antigen-presenting cells and immunocompetent lymphocytes.
81
List the 3 activation signals
1. Antigen presented in the context of MHC and recognised
2. Surface molecules ' costimulation' (safety catch to ensure T cell is killing the correct cell)
3. Cytokine-mediated differentiation
82
what are the four type of allergy
IgE antibody
IgG and IgM cytotoxic antibody
Immune complex
cell mediated (T cell)
83
What are the origins of auto-immune disease
Infection - thyroid or Pancreas
Damage - Of which reveals privelaged tissues (Eye and Testis)
Genetic factors - Predisposing to autoimmunity
84
describe Graves disease
(auto-immune thyroid) Thyroid hormones regulated by thyroid stimulating hormone. -ve feedback then switches off TSH producition.
Graves disease results in 'activating' auto-antibodies that bidn to the TSH receptorleading to overstimulation and production of thyroid horomes - hyperthyroidism.
85
What is guided therapy
Depends on identifying cause of infection and selecting agent based on sensitivity testing
86
What is empirical therapy
best (educated) guess therapy based on clinical/epidemiological acumen
Used when therapy cannot wait for culture
87
What is prophylactic therapy
Preventing infection before it begins
88
What requires guided therapy
Mild infections that can be waited a few days to be treated
- Cystitis
- Mild wound infections
rationalising therapy in patients already on treatment
89
What requires empirical therapy
Patients with more severe infection
-Sepsis
-Meningitis
Delay in therapy would result in worsening of condition
Need to cover all likely causes
90
What requires prophylactic therapy
Healthy people exposed to
- Surgery
- Injury
- Infected material
Immunocompormised individuals
- HIV
- Transplantation
- Splenectomy
91
Target effects of antibiotics
Highly toxic to bacteria causing infection
penetrate the body area affected by infection
Limit release of toxins from bacteria
Convenient administration
92
Ideal limits of co-lateral damage of antibiotics
Non-toxic to patient
Limited effect on colonising bacteria which reduces:
- Mucosal canida
- Clostridium difficile infection
- Selection of resistant bacteria
Low potential for bacteria to escape treatment through developing resistance
93
What are narrow spectrum antibiotics
Small but effective action
Chosen for guided therapy
94
What are broad spectrum antibiotics
Antibiotics with an effect on many different bacterium
Often used for empirical therapy
95
action of bactericidal antibiotics
achieves sterilisation of the infected site by directly killing bacteria
lysis of bacteria can lead to release of toxins and inflammatory material
96
action of bacteriostatic antibiotics
inhibits growth but does not directly sterilise infected site
requires additional factors to clear bacteria - immune mediated killing
97
4 antibiotic targets
cell wall peptidoglycan
Bacterial metabolism
DNA
Ribosomes
98
Describe Penicllin
First members of beta-lactam group of antibiotics
Rapid bacterial killing and low toxicity
Chemically produced derivatives
Vary widely in antibiotic spectrum
99
Mechanism of penicillin action
"They bind to beta-actin ring active sites on ""penicllin binding proteins""
Normallythese proteins bind peptidoglycan together
When penicillin binds to these they can no longer bind peptidoglycan together which in turn breaks up the cell wall and results in death."
100
Beta-lactam class includes?
Penicillin
Cephalosporins
Carbapenems
101
Describe Vancomycin class
Large molecules and so cannot penetrate gram -ve cell wall
useful against penicillin resistant bacteria
102
Describe ciprofloxacin class
Broad spectrum
Damage to DNA leads to bacterial cell death
103
Describe clarithromycin and doxycycline classes
Highly concentrated within cells - useful against intra cellular pathogens
Against both gram +ve and -ve
Act on ribosomes
104
Describe trimethoprim class
Used for non-severe UTIs
105
3 principle mechanisms of antibitotic resistance
Mutation/modification of target site
Inactivating enzymes
Limit access: reduced permeability or increased efflux
106
Action of beta-lactamase
Targets B-lactam ring in penicillin and breaks it open
107
2 ways to overcome beta-lactamases
Beta-lactamase inhibitors
beta-lactamase stable drugs
108
What is antimicrobial/antibiotic stewardship
Systemic approach to safe and effective use of antibiotics.
109
How can AMS be achieved
Monitoring/Surveillance
Guidelines/protocols
Education
Specific restrictions
Specific interventions
MDT
110
Antibiotic prescribing steps
1. Is an antibiotic required?
2. Which antibiotic
3. IV or Oral
4. Dose/Interval
5. Adjunctive measures
6. Duration and ivost
7. Review
111
Describe instances where antibiotics shouldn't be prescribed
Viral + Self-limiting bacterial RTIs
Asymptomatic bacteriuria
In-growing toenails
Leg ulcers without cellulitis
Varicose eczema
112
Define Sepsis
Life-threatening organ dysfucntion which occurs as a result of a dysregulated host reposne to an infection
113
what are the four types of hypersensitivity
Hypersensitivity reactions: ACID
type 1 --Anaphylactic (IgE)
type 2 --Cytotoxic (IgG or IgM)
type 3 --Immune complex (IgG and IgA combine)
type 4 --Delayed hypersensitivity (t cell mediated)
