HOST DEFENCE 2 Flashcards
What’s the role of TH / CD4+ cells?
Recognise antigens presented on Class II MHC (Major Hisrocompatibilty Complex)
What are the three antigen presenting cells?
- Dendritic cells
- B cells
- Macrophages
What are the different types of TH/ CD4+ T cells and what are their functions?
- TH1 - stimulates cell mediated immunity (CDI)
- TH2 - stimulate the growth of specific plasma cell and antibody secretion
What’s the role of Tc or CD8+ T cells?
- Recognise Antigen presented on class I MHC.
- Trigger cytotoxicity (Cell Mediated Immunity)
All nucleated cells in the body produce MHC Class I molecules. True or false?
True
What’s the function of B lymphocyes?
Differentiate to plasma cells which produce antibodies (stimulated by cytokines)
Describe the structure of antibodies/ immunoglobulins? (6)
- Tetramer of two light chains and two heavy chains
- Light chains are two types - the lambda and kappa families
- Heavy chains form a single family
- Each chain has an N-terminal variable region (V) and a C-terminal constant region (C)
- The V domain recognizes antigen
- The C domain binds to specific receptors present in cells of the immune system such as macrophages
What’s the function of antibodies? (4)
- Opsonisation - antibodies bind to the pathogen, this attracts phagocytes
- N terminal binds to the antigen
- Fc portion of the antibody binds to an Fc receptor on the phagocyte, facilitating phagocytosis
- Neutralisation - ability of the antibody to prevent the interaction between the pathogen and the cell
- Complement Activation
- Antibody dependent Cytotoxicity - antibody bound to pathogen interacts with Fc receptors on the NK cell = leads to release of cytoplasmic granules containing perforin and granzymes.
Where are dendritic cells found?
Found in thymus, lymph nodes and spleen (lymphoid organs)
What’s the function of dendritic cells?
Present the antigen or bring it to the lymphoid organs where an immune response is initiated = informing T cells that there is an infected cells
What are the different types of specific acquired immunity and what microbes do eliminate?
- Humoral immunity - extracellular microbe
- Cell-mediated immunity - intracellular microbe (phagocytosed microbes or microbes replicating within infected cells)
What lymphocytes are involved in humoral immunity?
B lymphocyte
What lymphocytes are involved in cell-mediated immunity? (2)
- Helper T lymphocytes - phagocytosed microbes
- Cyotoxic lymphocytes - microbes replicating within infected cell
How are infected cells killed by Tc lymphocytes?
- CTL precursors are activated
- TCR-MHC mediated recognition of target cells and re-orientation of the killing machinery on target cell through polarisation (lytic granules are orientated where MHC class I engages with TCR)
- lytic granules within T cell fuse with cell membrane releasing contents into small gap between T cell and target cell = cytotoxins + pores created on the cell membrane
- CTL then dissociates from the target = not affected
- the release of perforin pokes holes in cell = allows entry of Granzyme B = pathogen is killed by apoptosis
What are the three characteristics of vaccinations?
- Vaccine immunogenicity
- Vaccine efficacy
- Vaccine effectiveness
What is meant by vaccine immunogenicity?
The ability to induce antibodies
What is meant by vaccine efficacy?
Reduction in incidence between those who have been vaccinated and those who haven’t
What is meant by vaccine effectiveness?
The ability of a vaccine to protect a community
Describe the 5 different types of vaccines
- Killed Virulent Organism: Pathogen killed but antigen intact
- e.g. Whooping cough
- Live Attenuated: Strain doesn’t cause disease but still elicits an immune response
- e.g. Rubella
- Modified Toxins: Toxin treated with heat/chemicals, no symptoms experienced but immune response is triggered
- Diphtheria
- Isolated Antigens: Antigen injected to elicit immune response
- Influenza
- Genetically Engineered Antigens: Antigen is isolated and genetically engineered
- Hepatitis B
What affects the response to a vaccine? (7)
- Antigen content (e.g. live vaccines have higher content)
- Protein content (results in increased antibody content)
- Adjuvants present
- Type of antigen
- Dosage intervals - Longer intervals = more MHC interaction
- Genetics
- Age
How do viruses replicate? (8)
- Adsorption: the attachment of the extracellular virus particle to the surface of the host cell
- Penetration: virus fuse their envelope with the plasma membrane of the host cell and move into the cystol (endocytosis)
- Uncoating: is broken down and viral genome is released into the cytoplasm.
- Transcription: the production of viral mRNA (enzymes that are required are in the nucleocapsid)
- Translation: the production of viral polypeptides from viral mRNA
- Replication
- Assembly: the newly replicated viral genes are encapsidated.
- Egress: the release of virus from the infected cell
How does the immune system identify virally infected cells?
- The proteases of the host cell break down the viral products
- These bind to MHC class 1 (if epithelial cell) in the endoplasmic reticulum
- They are transferred onto the surface of the epithelial cell and the viral antigen is displayed on the surface.
What is the first response against the viral infection?
Non-specific.
Cytokines produced include IFN-alpha, IFN-beta, TNF-alpha and IL-12 (act on target cells to inhibit viral replication, not the virus)
What is the second response against a viral infection? (After cytokines)
- NK mediated killing of infected cells
What is the third response against a viral infection?
- Specific
- T-cell mediated killing of infected cell
What type of virus is Influenza?
Single stranded RNA virus
Which types of influenza virus can infect humans?
- Type A
- Type B
- Type C
(so, all types of influenza virus can infect humans)
Which types of influenza virus cannot infect birds/animals?
Type B
Type C
Which antigenic surface proteins does the influenza virus have?
Haemagglutinin
Neuraminidase
How many types of haemagglutinin are there?
15 types
How many types of neuraminidase are there?
9 types
What caused the 1918 “Spanish influenza”?
Bird-to-human transmission of H1N1 virus
What type of haemagglutinin/ neuraminidase caused the 1957 “Asian Influenza”?
H2N2
What type of haemagglutinin/ neuraminidase caused the 1968 “Hong Kong Influenza”?
H3N2
What is the function of haemagglutinin?
- Binds to sialic acid-containing receptors expressed on the host cells (this allows the endocytosis of the virion)
What is the function of neuraminidase?
- Cleaves the bond between the host cell and the newly produced viruses (this allows the viruses release into the body and spread the infection)
What protein does the virus use to produce a new capsid?
M1 protein
What is the function of M2 proteins?
- Proton pump (buffers the pH of the environment where the virus is = more virions produced)
What is the problem with trying to target haemagglutinin receptors by making antibodies against them?
Every year, a different type of haemagglutinin is in circulation = new vaccine needed because the antibodies are different
What are the 2 types of epidemics that can occur?
Antigenic drift and Antigenic shift
What is antigenic drift?
- minor changes to the surface of the influenza virus (small changes in haemagglutinin)
What is a antigenic shift?
- two or more different strains of a virus combine to form a new subtype = different type of neuraminidase and haemaggluttin
(RNA exchanged) - The virus is not recognized
How can viruses evade the B and T cell immune response?
- Inhibition of the function of cytokines
- Inhibition of antigen presentation
- Reduction of the MHC class I expression
- Reduce the levels of class II MHC molecules (HIV and measles do this)
- Evade complement mediated destruction
- Constantly changing their antigens (influenza virus) = cannot be recognised