Infectious Diseases Flashcards
What is an infectious disease?
a disease aka. abnormal funciton of body caused by pathogen invading the body, which can be transmitted from one organism to another uninfected person
What is meant by a non-self antigen?
Foreign molecule that stimulates an immune response
Describe the non-specific/innate immune system: barriers
Anatomical barriers: intact skin & mucous membrane→ prevent pathogens from entering organism
Chemical barriers:
- secretions w antimicrobial substances e.g. lysozyme (cleave glycosidic bonds of bac’s peptidoglycan cell wall)
- acidic pH (denature proteins in pathogens)
Describe the non-specific/innate immune system: cellular component
Role: phagocytosis; induce inflammation; APC
- Phagocytes engulf pathogens by phagocytosis
- Macrophages and dendritic cells are APCs
- Macrophages
> Secrete chemokines to recruit neutrophils to site of infection→ inflammatory response
> Secrete cytokines that increase permeability of blood vessels→ neutrophils can migrate into tissue from blood
Compare the innate and adaptive immune system
Non-specific vs specific
Rapid vs takes time to develop
No memory vs shows memory
Compare T cells and B cells
- Differentiate in thymus vs bone marrow
- Naive cell’s TCR/BCR recognises and bind to specific, complementary processed peptide of peptide MHC complex on APC/unprocessed antigen of pathogen
- Naive T/B cells–> activation by APC/helper T cell–> clonal expansion and differentiation–> effector T/B cells (helper, cytotoxic, plasma) & memory cells
- S: has a specific T/B CR on its surface
- S: memory T/B cells confer long term immunity
What is in the cell-mediated and humoral response of adaptive immunity?
Cell-mediated: cytotoxic T cells
Humoral response: antibodies target extracellular pathogens
Compare active immunity and passive immunity
Immune response antibody production duration E.g. natural E.g. artificial
What happens during a secondary immune response:
Re-exposure to the same sf antigen→ specific memory T/B cells quickly recognise it→ memory B/T cell faster clonal expansion and differentiation into effector T/B cells→ faster & stronger secondary immune response; plasma cells produce high conc of antibody which prevent further infection by neutralisation, agglutination & opsonisation
Compare primary and secondary immune response
Slower response and lag period VS faster response
Weaker/Stronger response: [antibody] rises gradually/sharply and peaks at a lower/much higher level–> fewer/more antibodies produced, produced for a shorter/longer time
No memory VS has memory hence confers LT immunity to same pathogen
Describe phagocytosis and antigen-presentation
- Phagocytes/APC engulf pathogen via phagocytosis
> Pseudopodia extends outwards to engulf bac→ ends of pseudopodia fuse→ vesicle pinched off→ phagosome - Phagosome fuse w lysosome→ phagolysosome
- Bac antigen broken down by hydrolytic enzymes in lysosome into short peptides
> Nuclease hydrolyses phosphodiester bonds in bac nucleic acids
> Bac also killed by hydrogen peroxide/free radicals; - , which bind to MHC protein (major histocompatibility complex)→ peptide:MHC complex→ ready for presentation to naïve T cells
Why must antigen be processed before being presented?
epitopes of antigen recognised by TCR are buried. Antigen must be processed into short peptides, so that epitope can bind to MHC for presentation
Very briefly outline the adaptive portion of the immune response
- clonal selection
- activation of T cells–> memory cells & effector cells: cytotoxic and helper T cells
- activation of B cells–> plasma cells and memory cells
- action of antibodies
- immunological memory
Describe clonal selection and the activation of T cells (w/o details of roles of each effector cell)
- Clonal selection: specific naive T cells w specific TCR binds to complementary peptide-MHC complex on APC→ APC secretes cytokines that activates naive T cell
- T cell undergoes clonal expansion & differentiation into effector T cells (cytotoxic, helper) and memory T cells
What is the role of the cytotoxic T cells?
kill cells infected w intracellular pathogens like viruses→ prevent reproduction of intracellular pathogens
- Infected host cells display same peptide-MHC complex presented earlier→ cytotoxic T cells recognise it, TCR complementary in shape and binds to peptide-MHC complex on target cells→ produce perforins (make pores in infected cell’s cell membrane; may lyse) and granzymes (diffuses in via pores & activate enzymes→ apoptosis)
- Also kills tumour cells
Describe the activation of B cells and the role of helper T cells (w/o role of plasma cells)
- Clonal selection & receptor-mediated endocytosis: Specific naive B cell has a BCR w antigen binding site that’s complementary in shape and binds to antigen of pathogen→ cell sf membrane invaginates, pinches off, endocytic vesicle
- Pathogen processed, peptide of antigen binds to MHC protein→ peptide-MHC complex, transported to sf membrane for presentation
- Specific TCR on specific T helper cell binds to complementary peptide-MHC complex on specific naive B cell→ helper T cell secretes cytokines→ activates B cell→ clonal expansion and differentiation into effector B cells/plasma cells and memory B cells
Describe the role of plasma cells and antibodies
Plasma cells secretes antibodies, which destroy extracellular pathogens and toxins
Antigen-binding site of antibodies bind to antigens of pathogen/bac toxin→
- Neutralisation: prevents antigen from binding to host cell sf receptor & prevents receptor-mediated endocytosis→ prevent entry
- Agglutination: each antibody has 2 antigen binding site→ 2 pathogen binds to 1 antibody simultaneously→ aggregation of pathogens→ promote phagocytosis
- Opsonisation: Fc portion of antibody binds to Fc receptors on phagocyte→ recruits macrophages/ phagocytes→ increase feq of phagocytosis (tag it for uptake by phagocytosis)
Link the structure of IgG to its function
- Globular protein→ Soluble, transported in blood
- Folding of VH and VL chains→ unique 3D conf→ antigen binding site complementary in shape to specific epitope of antigen
> Can carry out neutralisation by binding to specific epitope of antigen→ prevent pathogen from binding to host cell receptor and infecting host cell - IgG has 2 antigen binding sites per antibody mlc
> Each IgG can bind to 2 antigens simultaneously→ pathogens aggregate→ allows agglutination - Fc region of antibody is complementary in shape to Fc receptors on phagocytes
> Fc bind to Fc receptors on phagocytes→ tag/promote phagocytosis→ opsonisation - Constant region of H chain determines class of antibody and hence their different functions
- Disulfide bridges between H and L chain/2 H chains hold them tgt
> Stability to quaternary struc - Hinge region–> flexibility when binding to antigens that are variable distances apart
Where and when does somatic recombination, HC and LC combinatorial pairing, somatic hypermutation and class switching occur?
In bone marrow, during B cell maturation: somatic recombination and HC and LC combinatorial pairing
In lymph nodes after activation of B cells: somatic hypermutation and class switching
Describe somatic recombination in both H and L chains
V(D)J recombination: DNA rearrangement, where various gene segments joined tgt randomly, some intervening segments are enzymatically removed, followed by rejoining of remaining seq
- HC gene: 1 V gene segment, 1 D segment, and 1 J segment randomly joined→ 1 VDJ exon, coding for VH
- D & J rearrangement: 1 D and 1 J segment joined (intervening seq enzymatically removed)
- V & DJ rearrangement: 1 V segment and DJ segment joined (intervening seq enzymatically removed)
- LC gene: 1 V gene segment and 1 J segment randomly joined→ 1 VJ exon, coding for VL
- V & J rearrangement: 1 V segment and 1 J segment joined (intervening seq enzymatically removed)
- Then, transcription→ pre-mRNA→ RNA splicing: V(D)J exon and C exon joined→ mature mRNA→ translation→ specific H/L chain protein with specific VH/L and C domains
Describe somatic hypermutation
Somatic hypermutation: random point mutations in the rearranged VDJ/VJ region (V region) of H/L chain gene locus in activated B cells, during clonal expansion→ further diversifies variable regions (aim: ‘fine-tuned’ to have higher affinity)
→ B cells expressing low affinity Ig chains on plasma membrane→ apoptosis
→ B cells expressing higher affinity Ig chains in plasma membrane→ selected for clonal expansion and differentiation a.k.a. affinity maturation→ plasma cells & memory B cells have BCRs with higher affinity antigen binding sites; antibodies secreted with higher affinity binding affinities for specific antigen
Describe class switching
DNA rearrangement at constant gene segment of H chain gene locus→ allows production of antibodies with same antigen binding site, but diff function - VH linked to Cμ (IgM)→ class switching: VH linked to another constant gene segment, C𝛾 (IgG)
Compare somatic recombination and meiosis
Alters H and L chain gene loci VS Alters any gene locus
Involves removing and joining of gene segments VS Crossing over involves exchange of equivalent segments
Occurs on a single chromosome VS Involves non-sister chromatids on a pair of homologous chromosomes
Define vaccination
administration of a harmless form of a pathogen to induce a specific adaptive immune response→ production of memory cells→ protects indiv against later exposure to same pathogen; an artificial active immunity
Explain how vaccine can provide long-term immunity against disease/protect from actual pathogen
- Live attenuated/heat killed inactivated form of pathogen in vaccine cannot cause disease but still can elicit an immune response as specific sf antigens of pathogen are retained and recognised by APCs
- APCs e.g. macrophages engulf virus by phagocytosis, process antigen and present it as a peptide:MHC complex;
- Naïve T cell has a specific TCR that binds to complementary peptide:MHC complex on APC. APC secretes cytokines→ activates naïve T cell→ clonal expansion and differentiation
- T helper cells secrete cytokines to activate specific naïve B cells to undergo clonal expansion and differentiation and form antibody-secreting plasma cells and memory B cells
- *Memory B and T cells when re-exposed to same measles virus→ faster and stronger secondary immune response, where more antibodies are prooduced for a longer period of time
- *Booster shot given to further stimulate memory cell formation
What are the advantages and disadvantages of live, attenuated vaccine
A: Closest thing to natural infection: wide range of antigens that will elicit a strong immune response w small dosage→ LT protection (i.e. effective)
DA:
- Possibility of reversion to virulent form by mutation→ disease
- Need to be refrigerated to stay viable and potent
What is herd immunity?
(Larger % of ppl vaccinated & immune = did not contribute to transmission of the disease)
Herd immunity: w sufficiently large proportion of immunised indivs who cannot spread the disease→ transmission is prevented→ entire community including the unvaccinated are protected
What are the benefits of vaccination?
- protect indivs against disease
- herd immunity
- eradicate diseases e.g. smallpox
What circumstances contributed to the eradication of diseases like smallpox?
- Compulsory vaccination in many countries–> herd immunity
- live attenuated vaccine to elicit a strong response
- heat stable vaccine–> deliver to rural areas–> effectiveness
- one dose enough of life long immunity, no booster required
- virus did not mutate–> vaccine effective for long period of time
- human the only host–> limit transmission
- no symptomless carrier state–> easy to identify and isolate to prevent spread
What are the disadvantages of vaccination?
- Live, attenuated→ risk of reversion to virulence→ disease
- Immunity from vaccination may not be as effective as natural immunity
- Pathogens mutate quickly→ new vaccines needed
- Some allergic to vaccine components
- Excessive vaccination→ reduce effectiveness of immune system to respond to new infections
What is bacteriostatic and bactericidal?
Bacteriostatic: prevent replication via binary fission (graph: amt of bac stays the same)
Bactericidal: kills bac during cell division by binary fission (graph: amt of bac decreases)
What are the ways in which antibiotics can disrupt metabolic pathways?
- disrupt cell wall synthesis e.g. penicillin
- disrupt protein synthesis (translation)
- disrupt nucleic acid synthesis/transcription
Describe the action of penicillin on bacteria
- Bac cell wall made from peptidoglycan→ penicillin only effective when bac is growing/making new cell wall (bactericidal)
- Penicillin inhibits bac cell wall synthesis/disrupts peptidoglycan synthesis: act as a competitive inhibitor & binds to AS of transpeptidase→ inhibits formation of cross-links between adj chains of peptidoglycans
- Cell wall weakened
- High osmotic pressure inside bac when it takes in water by osmosis→ increased turgor pressure→ swell & lyse
Why is it necessary to complete the course of antibiotics?
So that all susceptible strains killed; immune system can focus on tackling resistant strains.
- Failure to complete→ some bac survive→ spontaneous mutation→ antibiotic-resistant strains
- When antibiotic given, it acts as a selection pressure→ those with antibiotic resistance gene survive, reproduce… → increased freq of antibiotic-resistant allele in population
- Higher chances to develop resistance→ potentially serious, difficult to treat, requires longer course
What is the target cell of the influenza virus?
epithelial cells of respiratory tract
How is influenza transmitted?
droplets of moisture from lungs of infected person
Describe the pathogenicity of influenza
- Virus settles on mucous membrane lining the nose, pharynx, trachea, bronchi–> Neuraminidase helps virus penetrate mucoproteins in mucus layer
- Haemagglutinin binds to sialic acid receptors on cell membrane of epithelial cells lining respiratory tract→ virus penetrates into host cells & replicates within them
- Incubation period: 24-48h, after which infected epithelial cells are destroyed leads to inflammation & build-up of dead epithelial cells in airways
- Symptoms: runny nose, scratchy throat
- Viral replication weakening of epithelial layer → respiratory passage more susceptible to secondary bacterial infections, leading to fatal diseases like pneumonia
How do viral infections lead to death?
- Immune system recognises infected cells→ lysed
- Budding off causes progressive loss of host plasma membrane
- Host cell transcription and translation mechanism has been taken over by virus producing viral proteins, compromising vital functions of the cell
What is the treatment for influenza?
- No treatment for most: bed rest; aspirin/paracetamol
- antiviral drugs
- antibiotics
How is influenza prevented?
Vaccination: purified inactivated material from 3 common influenza viral strains
What is the target cell of HIV?
T helper cells or macrophages of immune system
What are the modes of transmission of HIV?
- Unprotected sexual contact
- Exposure to infected blood & blood products
- From mother to child via the placenta, during childbirth / breastfeeding
Describe the pathogenicity of HIV
- Virus in bloodstream infects T helper cells & macrophages: very strong affinity for & binds to CD4 receptors
- *infected T helper cells destroyed → T helper cell levels fall
> *impaired immune responses
> *increasingly susceptible to opportunistic diseases - macrophages not lysed by virus→ survive→ act as reservoirs
- HIV can pass from cell to cell in an individual, or to other individuals while remaining undetected
- High rate of mutation of virus during replication→ altered proteins on sf of virus → escapes recognition & elimination by immune system → evolves rapidly within body
- Secondary infections e.g. tuberculosis→ death
- *Integration of viral dsDNA into host genome is random → possible activation of a proto-oncogene into oncogene/ inactivation of a tumour suppressor gene→ cancer e.g. Karposi sarcoma is a rare skin cancer that’s more prevalent in AIDS patients
What are the treatments for HIV/AIDS?
- 3 agents administered tgt (due to high rates of production & mutation)
- Retroviral drugs that inhibit revers transcriptase, protease, integrase and entry
- sustained treatment
What is mycobacterium tuberculosis?
Bac causing tuberculosis
- Obligate aerobe: need O2 for aerobic respiration, survival, growth
What is the target cell of tuberculosis ?
lungs (primary infection)
Describe how a person may become infected with TB
Bac, Mycobacterium tuberculosis, are transmitted when an infected (w active TB disease) sneezes or coughs, and uninfected inhales fine, aerosol droplets which contains the bac
Describe the pathogenicity of tuberculosis
- *Macrophages phagocytose bac (in lungs)
- *In phagosome, bacteria inhibits fusion of phagosome with lysosome→ no phagolysosome, no lysosomal enzymes to kill bac
- Bac survives, multiply inside macrophage + more macrophages are brought to infected alveolus
- Tubercle formed→ cell death by necrosis in centre of tubercle→ rupturing of macrophage cell membrane & releasing of cell contents (i.e. bac) into tubercle cavity
- Disease may be arrested at this stage & remain *latent for years
- TB disease: tubercle ruptures, bac spills into a bronchiole & spreads throughout the lungs→ productive cough that facilitates aerosol spread of bac
- Rupturing of tubercles→ cavities in lungs → lungs progressively destroyed
- *TB often first opportunistic infection to strike immunocompromised HIV-positive people
Suggest why TB is more fatal in ppl with HIV/AIDS
- HIV/AIDS leads to weak immune system due to reduced no. of helper T cells
- Bac can multiply faster/not destroyed by immune system
- More likely to reactivate dormant TB bac
- Treating both conditions simultaneous challenging due to side-effects
What are the treatments for tuberculosis?
6 months of daily treatment with a combination of at least 2 antibiotics: combination minimises risk of developing resistance & achieve an additive effect against bacteria
How is tuberculosis prevented?
Vaccination: BCG vaccine prepared from live, attenuated Mycobacterium bovis (bovine TB); often used to prevent spread of TB among children
