TOPIC Q: Infectious Diseases Flashcards
(40 cards)
What is the structure and function of a granulocyte?
Structure: Contains granules in the cytoplasm
Also known as polymorphonuclear leukocytes due to irregularly shaped nuclei.
Function: Circulates in the bloodstream, involved in cellular innate defences during innate immunity. Engulf pathogens via phagocytosis, pathogen is digested by hydrolytic enzymes upon fusion of phagocytic vesicle.
Neutrophils are one of the most important phagocyte in innate immunity, they are the most numerous WBC in blood, and are able to release antibacterial proteins stored in their cytoplasmic granules that kill surrounding microorganisms.
What is the structure and function of antigen-presenting cells?
S: Carry the major histocompability complex molecule which is a membrane glycoprotein on the cell surface.
F:
APCs engulf pathogens through phagocytosis duringh innate immunity.
Main role is not pathogen clearance but to activate the adaptive immune response.
APCs digest the pathogenic proteins into peptides.
APCs present peptides on MHC complexes to T lymphocytes to activate adaptive immunity.
Antigen is any substance recognised by the B or T lymphocytes to activate adaptive immunity.
An antigen is any substance that is recognised by the B ot T lymphocyte of the adaptive immune system.
What are the two types of APCs?
Macrophages reside in tissues and are the mature form of monocytes. Monocytes leave the bone marrow and circulate in the blood, continually migrating into tissues where they differentiated into macrophages.
Dendritic cells mostly reside in tissues and they are the most efficient at antigen presentations.
What are the structure and function of lymphocytes?
S: Contains a large nucleus with a little amount of cytoplasm.
F: Non-antigen specific lymphocytes- Natural Killer Cells
NK cells recognise and kill abnormal cells such as tumour cells
They are not specific for a particular antigen and are involved in innate immunity.
What are the different kinds of B and T lymphocytes?
B lymphocytes are produced in the bone marrow and they also mature there.
T lymphocytes are produced in the bone marrow but mature in the thymus.
Upon maturation, both B and T lymphocytes enter the bloodstream as naive lymphocytes where they circulate between the blood and the lymph.
CD4+ T lymphocytes which cell surface CD4 protein marker.
CD8+ T lymphocytes which have CD8 protein marker.
Each naive B and T lymphocytes have antigen receptor on their cell surface, which are specific for a particular anitgen.
Naive lymphocytes are lymphocytes that have not yet been activated by antigens.
Once naive lymphocytes have met their antigen, they become activated and further differentiated into fully functional lymphocytes aka effector lymphocytes.
What is innate immunity?
Innate immunity is a set of non-specific that is active immediately upon infection and is the same regardless of whether the pathogen has been encountered before. Innate immunity comprises two forms: barrier defences and cellular innate defences.
What is barrier defences in innate immunity?
Physical Barriers
- Protective covering
epithelial tissues forming the skin and mucus membranes lining the digestive respitory, urinary and reproductive tracts are held together by tight junctions, therefore blocking the entry of pathogens.
Mucus-covered epithelial tissues
Certain cells of mucous membrane produce mucus which enhances defences by trapping pathogens, allowing them to be removed effectively.
- Chemical barriers
Antibacterial enzymes in body secretions. Lysozyme in tears, saliva and mucus and secretions destroys cells walls of susceptible.
Hydrochloric Acid in the stomach Low pH enzymes of pathogens to be denatured and therefore kill the organisms.
What are cellular innate defences?
If the first line of defense is unsuccessful and the pathogen enters the body, there is a second line of defense.
This line of defense involves WBCs, particularly phagocytes which are non-specific and will respond to any invading pathogen,
Phagoctyes that are involved in innate immunity include macrophages, neutrophils and dendritic cells.
What happens when a pathogen breaches the epithelial barrier?
Phagocytes residing in the tissues such as macrophages, dendritic cells engulf the pathogen via phagocytosis.
Macrophages then release cytokines and chemokines which act to increase permeability of blood vessels and recruit cells such as neutrophils from the blood to the infected tissues.
Cytokines are proteins secreted by immune cells which acts as signalling molecules to enhance immune responses.
Chemokines are a specialised group of cytokines that act as chemoattractants to attract cells out of the bloodstream and into infected tissues.
This is known as inflammation which helps to remove the pathogen.
What is an antigen?
An antigen is any substance that is recognised by the B or T lymhpocytes of the adaptive immune system. It is usually foreign to the host.
They are typically large molecules like proteins,peptides glycoproteins or polysaccharides from invading pathogens like viruses and bacteria.
How are T lymphocytes activated?
Upon digestion of pathogenic proteins in antigen presenting cells during innate immune response, the peptides bind to MHC molecules to form a peptide MHC complex.
T-cell receptors bind to peptide MHC complex on cell surface of APCs, resulting in the activation of T lymphocytes.
How are B lymphocytes activated?
The B-cell receptors can bind directly to intact antigens circulating in body fluids. Upon activation, antibodies produced are also able to bind directly to antigens found on pathogens.
Binding of T cell receptor to peptide MHC complex on the cell surface receptor of the B lymphocytes.
The portion of an antigen that binds to the antigen receptor or antibody is the epitope.
What is antigen recognition and clonal selection and expansion in the innate immune response?
Naive T lymphocytes circulate the blood and lymph. They possess a repetoire of antigen receptor, each cell having receptors that are specific for a particular antigen.
The T-cell receptor of a naive T lymphocyte binds to the peptide MHC complex on a macrophage or dendritic cell.
CS+E: The naive T lymphocyte is activated to proliferate and produce many identical progenies, a process known as clonal expansion.
What is differentiation in the innate immune response?
(After Clonal Expansion)
The progeny of clonal expansion then differentiates into one of the different types of effector T lymphocytes which carry out different functions when these cells subsequently detect the antigen.
These differentiated effector T lymphocytes inherit the same antigen receptor specificity.
Naive CD4+ T lymphocytes differentiate into memory helper T cells.
Naive CD8+ lymphocytes differentiate into cytotoxic T cells.
Helper T cells release cytokines which help in the activation of Naive CD8+ T lymphocytes to differentiate into cytotoxic T cells. Some CD8+ lymphocyte progeny differentiate into memory cyotoxic T cells.
How are antigens eliminated in innate immunity?
Cytotoxic T cells carry out cell-mediated immune responses by killing infected cells.
T cells receptor of cytotoxic T cells recognises peptide MHC complex of infected cells.
Cytot T cells releases perforin which forms pores in the infected cell.
Cytot T cell releases cytotoxic proteins (granzymes) which enter the infected target cell by endocytosis, inducing apoptosis.
Releases cytokines which inhibits viral replication and induces expression of MHC molecules.
After destroying an infected cell, the cytotoxic T cell moves on and kill other cells infected with the same pathogen.
What is the memory in innate immunity?
Most effector T lymphoyctes generated from clonal expansion in an immune response eventually die. After the antigen is eliminated, a significant number of activated antigen-specific T lymphocytes persist.
These are memory cells and form the basis of immunological memory.
They can be reactivated much more quickly than naive lymphocytes and are generated upon primary responses to antigen.
Memory cells provide lasting protective immunity and mediate a more rapid and effective secondary response to subsequent encounters with the antigen.
What are the antigen recognition and presentation in humoral immune response?
Activation of B lymphocytes to carry out humoral (antibody) mediated immune response requires two distinct signals:
Antigen recognition and binding by the B-cell receptors.
Interaction with helper T cells
- Naive B lymphocytes circulate the blood and lymph.
- They possess a repertoire of antigen receptors, each cell having receptors that are specific for a particular antigen.
- The B-cell receptor of a naive B lymphocyte binds to an intact antigen in the blood or lymph.
- Antigen is taken up via endocytosis and digested into short peptides. The peptide is then presented on the MHC moleq forming a peptide-MHC complex.
- T-cell receptor of the helper T cell binds to the peptide MHC complex on the B lymphocytes.
- Secretion of cytokines by helper T cells
What is differentiation in the humoral immune response?
The progeny differentiate into plasma cells and Mem B lymphocytes.
Plasma cells are the effector form of B lymphocytes.
Plasma cells then secrete antibodies that have the same antigen specificity as the B-cell receptor found on the Naive B lymphocyte previously.
Antigen that activated the Naive B lymphocyte now become the target of the antibodies produced by the differentiated plasma.
What is antigen elimination in the humoral immune response?
Antibodies provide humoral immunity by protecting against pathogens or their products.
Neutralisation of bacterial toxin and virus particles.
- Antibodies bind to the toxins and virus particles to prevent them from interacting with host cells.
- Antigen-antibody complex is then phagocytosed and degraded by macrophages.
Opsonisation and phagocytosis of bacterial cells
- Antibody binds to antigens on the bacterial cell.
- The antibody then binds to receptors expressed on macrophages and other phagocytes, facilitating phagocytosis.
Agglutination of bacterial cells
- As each antibody has 2 antigen binding sites, one antibody can bind to two bacterial cells and cause clumping.
What is the memory of the humoral immune response?
Most plasma cells generated from clonal expansion in an immune response will eventually die.
After the antigen is eliminated, a significant number of activated antigen specific B lymphocytes persist.
These cells known as memory cells and form the basis of immunological memory.
They can be reactivated much more quickly than naive lymphocytes and are generated upon primary response to antigen.
They provide lasting protective immunity and mediate a more rapid and effective secondary response to subsequent encounters with the antigen.
What is the structure and function of lgG?
- Large quartenary protein composed of 4 polypeptide chains.
It consists of two identical heavy chains and two identical light chains.
The two chains are linked by disulfide bonds and each heavy chain is linked to a light chain by a disulfide bond. - Heavy and light chains have variable and constant regions. Variable regions of heavy and light chains at the amino terminus form the antigen binding site. Hypervariable loops in both Vh and Vl are brought together to form a single hypervariable site at the tip of each arm. This forms the antigen-binding site which determines the antigen specificity of the antibody. There are two identical antigen-binding sites, allowing antibody to bind to two identical antigens simultaneously, increasing total strength of the interxn.
- The two arms of the antibody molecule that contain the antigen binding site are known as the Fab fragments and the trunk is known as Fc fragment.
- The flexible stretch of polypeptide chain joining the Fab and Fc fragments is known as the hinge region. Allows flexibility in the movement of the two Fab arms to bind to antigens.
What is somatic recombination?
The variable regions of the immunoglobin are coded by gene segments which are rearranged by the process of somatic recombination during the development of each naive B lymphocyte.
Dvlpment of B lymphocyte begins with rearrangment of the heavy-chain gene locus followed by the rearrangement of the light chain gene locus.
It is encoded in 3 gene segments, Vh, Dh and Jh.
A complete immunoglobin heavy chain mature mRNA is formed when the variable region exon is joined to the constant region sequenced by RNA splicing after transcription.
The variable region of light chain is encoded in only 2 gene segments, Vl and Jl. Joining of a Vl and Jl gene segment forms and exon that codes for Vl region. A complete immunoglobin light chain mature mRNA is formed when the variable region exon is joined to the Cl sequence by RNA splicing after transcription.
There are multiple different copies of the V,D,J gene segments in germline DNA at the ig heavy and light chain gene loci.
Somatic recombination is the random selection of 1 gene segment of each type produces different combinations of gene segments of the variable region.
What is somatic hypermutation?
Somatic hypermutation occurs in activated B lymphocytes during clonal expansion.
It introduces point mutations into the rearranged variable region genes.
Resulting in a change of one to a few amino acids in the Ig, producing closely related B lymphocytes progeny with B cell receptors that differ slightly in specificity and antigen affinity. Mutations that improve the affinity of a B cell receptor for antigen will allow these B lymphocytes to be selected via a process called affinity maturation.
What is class switching?
Upon encountering its specific antigen, activated B lymphocyte undergoes class switching to produce Ig of several different classes, depending on constant regions of heavy chain. Regulated by signals from T helper cells.
Class switching is the process where the same rearranged VDJh gene segment is linked to different heavy chain constant regions at the DNA level, resulting in Igs with the same antigen specificity but different effector functions.
