Lymphocytes Flashcards
What is Adaptive Immunity?
An immune response which is tailored to a specific pathogen - involves the expansion of antigen -specific lymphocytes which target the pathogen specifically and involve the formation of memory cells which provide longer lasting immunity
What are the innate immune cells?
macrophages, neutrophils
What are the adaptive immune cells?
lymphocytes
T cells (orchestrates immune response/ kills infected cells), B cells (makes antibodies)
Why do we need adaptive immunity?
Only evolved relatively recently
Absence of adaptive immunity results in inability to clear infections e.g., “SCID babies”
Protect us from repeat infections with the same pathogens
Not without costs- can lead to autoimmunity
What are the characteristics of adaptive immunity?
Improves the efficacy of the innate immune response
Focuses on the site of infection and the organism responsible
Has memory
Needs time to develop
What are the characteristics of immunological memory?
Once the immune system has recognised and responded to an antigen, it exhibits “memory”
Memory responses are characterised by a more rapid and heightened immune reaction that serves to eliminate pathogens fast and prevent diseases
Reduction in severity on re-exposure
Antigen specific lymphocytes (B&T) are the cellular basis
Basis for vaccines
What are the 2 types of adaptive immune responses?
T cells
B cells
What is the role of the T cell adaptive immune response?
The ‘cell-mediated’ response
Produces cytokines to help shape immune response (CD4)
Kill infected cells (CD8)
What is the role of B cell adaptive immune response?
Humoral response
Produces antibodies
When is an adaptive immune response generated?
Once the pathogen overwhelms innate defense mechanisms
What major event occurs in the peripheral lymphoid organs/tissues to initiate the adaptive immune response
B or T lymphocytes encounter antigens for which their receptors have specific reactivity to
What is an antigen?
molecules that act induce an adaptive immune response
What is an epitope?
the region of an antigen which the receptor binds to
What are the two hallmarks of the adaptive immune response?
Highly specific and provide lasting immunity
How is diversity generated in the adaptive immune response?
Immunoglobulin gene rearrangement - each BCR chain is encoded by separate multi gene clusters on different chromosome, and during B cell maturation, these gene segments are rearranged and brought together
What type of epitopes do T and B cells recognise?
T cells recognise linear epitopes, B cells recognise structural epitopes
What are the chains of the BCR receptor?
Kappa, lambda and heavy chain
Where does B cell Maturation occur?
In the bone marrow
What is another word for gene reassortment?
recombination
How does recombination occur and what is it?
○ Functional genes for antigen receptors do not exist until they are generated during lymphocyte development
○ Each BCR receptor chain (kappa, lambda, and heavy chain genes) is encoded by separate multigene families on different chromosomes
○ During B cell maturation these gene segments are rearranged and brought together
○ This process is called immunoglobulin gene rearrangement
○ Immunoglobulin gene rearrangement generates the diversity of the lymphocyte repertoire
What are some problems with the random process of gene reassortment to generate the high number of BCRs we need.
Autoimmunity - producing BCRs and TCRs that complement your own self antigens
What is immunological memory?
Where memory lymphocytes exist in the blood that are able to recognize and bind to the same antigen upon subsequent infections and therefore induce an immune response
What are characteristics of a a secondary immune response?
Faster and must larger response
What are the two primary cells involved in the adaptive immune response and which response are they involved in?
T cells = Cell Mediated Response
B cells = Humoral / Antibody Reponse
What are the differences between B cells and T cells?
T cells mature in thymus, B cells in bone marrow
T cells have CD4 and CD8 receptors, B cells have different one
T cells do not produce antibodies, B cells do
B cells need to be activated by T cells to function
B cells tend to stay outside of lymph nodes eg in Peyers Patches, T cells inside lymph nodes
What are characteristics of the T cell receptor (TCR)?
The T cell receptor part of a complex proteins on the cell surface
The variable region made by gene reassortment (10^15-10^20)
Recognise antigen fragments presented by other cells in the context of MHC
What is MHC?
Major histocompatibility complex
Group of genes that code for proteins found on the surfaces of cells that help the immune system recognize foreign substances
- plays a central role in defining self and nto self
- presents antigens to T cells
- Critical in surgery and donor matching
What is MHCI?
MHC class 1:
all nucleated cells, although at various levels
Has a single variable alpha chain plus a common beta-microglobulin
What is MHCII?
MHC class 2:
normally only on ‘professional’ antigen presenting cells
- Has 2 chains, alpha and beta
Describe MHC gene expression.
Encoded by HLA genes in humans
The MHC is polygenic: 3 class I and class II loci
Expression is co-dominant (maternal and paternal; genes both expressed)
- Therefore each person can have up to 6 of each gene if completely heterozygous
More than 17000 MHC variants
What are the regions on a TCR?
variable region
constant region
transmembrane aspect (not a part of it but it crosses this)
cytoplasmic tail
alpha and beta sides
Describe MHC/ TCR interaction.
(Type, processed in…, presented on…, presented to…)
What are the three kinds of T cells?
Regulatory, helper (CD4) (Th), killer (CD8) (CTL)
What happens when an antigen binds to a TCR?
The cell proliferates and differentiates into one of three functional types of effector T cells: Cytotoxic (killer), helper or regulatory
What do CD4 and CD8 bind to?
cell surface molecules of CD4= MHCII
cell surface molecules of CD8= MHCI
What are cytotoxic T cells?
The kill other cells that are infected with viruses or intracellular pathogens that bear the specific antigen
What do helper T cells do?
They provide signals, normally in the forms of cytokines which activate the functions of other cells, like B cells to produce antibodies
What do regulatory T cells do?
They suppress the activity of other Lymphocytes and help to limit the possible damage due to immune response
How would a virus/ intracellular bacteria pathogen be killed?
1) pathogen with MHCI encounters tissue-resident myeloid cells/ barrier tissue cells with PPR and macrophages
2) The myeloid cells trigger ILC1/ NK cells/ TH1/ neutrophils
3) -The ILC1 triggers neutrophils
- Th1 triggers NK cells/ neutrophils/ CD8+ T cells
- NK cells kill the pathogen
4) Neutrophils/ macrophages/ NK cells/ CD8+ T cells kill the pathogen
5) This leads to a lysed cell
ILC1, neutrophils, macrophages= innate immune cells
NK, Th1, CD8+= adaptive
How would a helminth parasite be killed?
1) pathogen encounters tissue-resident myeloid cells/ barrier tissue cells with PPR
2) The myeloid cells trigger Th2/ basophils/ ILC2
3) - ILC2 triggers basophils
- Th2 triggers eosinophils/ B cells
4) B cells (via antibodies)/ eosinophils kill the parasite
5) leads to parasite expulsion
ILC2, basophils, macrophages, eosinophils= innate immune cells
Th2, B cells= adaptive immune cells
How would an extracellular yeast/ bacteria be killed?
1) pathogen encounters macrophages and tissue=-resident myeloid cells/ barrier tissue cells with PPR
2) the myeloid cells trigger ILC3 and Th17
3) - ILC3 trigger macrophages
- Th17 triggers macrophages/ neutrophils
4) macrophages and neutrophils kill pathogen
5) leads to lysed pathogen
What do T helper cells fo?
T helper cells produce cytokines (family of inflammatory mediators)
Cytokines have diverse actions on a wide range of cells
Cytokines influence the outcome of the immune response
what are the types CD4 cells?
tfh, Th1, Th17, Th2, Treg (Th0)
What are T Helper Cell 1 (Th1)?
Pro-inflammatory
Boost Cellular immune response
Interferon gamma
Tumour necrosis factor
IL-12
What are T Help Cell 2 (Th2)?
Pro-allergic
Boost multicellular response
IL-4, IL-5, IL-13
What do Th2 do?
are involved in the B cell class switching to produce IgE for allergic reactions and parasitic infections (ALLERGY AND WORMS)
What are Th17 involved in?
Neutrophil responses which help to clear bacteria and fungi
What are Th17?
Pro inflammatory
Control bacteria and fungal infection
IL-17, IL-23, IL-6
What do TfH do? t follicular helper cell
Pro-antibody
IL-21
B cell support
What do Tregs produce?
IL-10, TGF-beta
What are Tregs for?
Anti-inflammatory to limit the immune Reponse
In what way do T helper cells help B cells?
They have surface proteins and secrete cytokines which help the B cells proliferate into antibody- secreting plasma cells and memory B cells
Help finetune the antibody response to increase the affinity of the antibody to the antigen through immunoglobulin class switching
How does a cell present non-self MHC?
1) In uninfected cells, MHCI molecules show self peptides
2) The CD8 cell scans cells, looking for non-self MHC (not finding it does nothing)
3) A virus infects the cell and releases its contents
4) The cell now starts making viral proteins
5) It displays these as non-self MHC
6) The CD8 cells detects the non-self MHC and attacks
7) The CD8 cell kills virally infected cell
What do cytotoxic cells store?
stores perforin, granzymes, granulysin in cytotoxic granules
- they are released after target recognition
Why is how cytotoxic cells kill infected cells counted as apoptosis?
because apoptosis is characterized by fragmentation of nuclear DNA
How do CD 8 cytotoxic T cells kill pathogens / cells infected with pathogens?
Infected cell will present viral antigen on MHC1
CD 8 t killer cell detects these non self MHC1 molecules and attacks
Release chemicals like perforin and granzymes
These polymerase the cell membrane, creating pores which allows molecules in and out the cell, disturbing the osmolarity and therefore killing the cell
What does granzymes cause and how to they enter cells following Cytotoxic T cell recognizing an MHC1
Granzymes causes apoptosis and enter into the infected cell through pore / channels created by perforin
What makes up the epitope which the T cell receptors recognize?
The MHC
Are MHC molecules glycoproteins?
Yes, they are glycoproteins which display peptide fragments of the pathogens proteins (antigens) on their surface
What are the “professional” antigen presenting cells which have MHC 2?
Dendritic cells, B lymphocytes and macrophages
Which MHC will interact with TCR?
MHC 2
How is MHC expressed?
Co-dominant
What is meant by the fact that MHC is polygenic?
Contains several different MHC Class 1 and MHC class 2 genes so that every individual possesses a set of MHC molecules with different ranges of peptide binding specificities
What is meant by the fact that MHC is highly polymorphic?
There are multiple variants or alleles of each gene within the population
What is a BCR?
A surface bound Antibody
What does the BCR do?
It encodes the antibody which the B cell will eventually make
What do B cell produce?
Antibodies
What is the antibody structure?
2 light and 2 heavy chains
Variable region and constant region
What are the roles of antibodies?
Neutralisation
Opsonization
Complement activation
What is meant by neutralisation?
antibody prevents bacterial adherence
What is meant by opsonisation?
antibody promotes phagocytosis
What is meant by complement activation?
antibody activates complement, which enhances opsonization and lyses some bacteria
What are the types of antibodies?
IgE, IgM, IgG, IgA, IgD
What is the function of IgG antibodies?
highest opsonization and neutralisation activities
Classified into four subclasses (IgG1,2,3,4)
What is the function of IgM antibodies?
Produces first upon antigen invasion. Increases transiently.
What is the function of IgA antibodies?
Expressed in mucosal tissues. Forms dimers after secretion.
What is the function of IgD antibodies?
Unknown function
What is the function of IgE antibodies?
Involved in allergy
What is a general rule about naive antigen-specific lymphocytes (B or T)?
they cannot be activated by antigen alone
What are the accessory signals naive B cells need?
Directly from microbial constituents
From a T helper cell
What two pathways activate B cells?
Thymus dependent (T cells) and thymus independent (microbial constituents)
Explain the thymus dependent pathway of B cell activation?
BCR recognizes antigen
The antigen is then internalized and degraded
Peptides bind to MHC 2 which are expressed at the cell surface
This complex is recognized by CD4 T helper cells
B cells are activated
involves all Ig-classes
Memory
What can an activated B cell go and do?
Mature into a plasma cell which secretes antibodies, or class switch
Describe the activation of B cells via the thymus independent pathway?
Some microbial constituents can induce antibody production without T helper cells
Only IgM
No memory
What are the thymus-independent antigens like?
Directly activate B cells without the help of T cells
Often polysaccharide, needs to have a repetitive structure e.g. bacterial surface sugars
The second signal required is provided by a microbial PAMP e.g. LPS
What happens after B cells are activated?
Clonal expansion and clonal selection
What is clonal expansion of lymphocytes?
Once a B cell has been activated, it is triggered to divide, giving rise to a clone of identical progeny (also has same MHC). This allows antigen specificity to be maintained as the progeny differentiate into effector cells
Which antibody type has the highest affinity?
IgG
Which antibody type is produced first?
IgM
Which antibody type is produced in allergic disease?
IgE
Describe the structure of IgG antibodies?
Made up of two heavy chains and two light chains
The V part at the top is the Fab region, the bottom part is the Fc region
The heavy chains are linked together by disulfide bridges
Has two identical antigen-binding sites
What part of the antibody determines its antigen-binding specificity?
The variable domains of the heavy and light chains
How do antibody opsonised bacterium bind to phagocytic cells?
Fc receptors on phagocytic cell binds to Fc region of antibody
Increasing the numbers of what T helper cell will help with an autoimmune disorder?
Treg cells
What is VDJ rearrangement ?
When the many copies of the V D AND J genes are randomly rearranged so that a variety of TCRs and BCRs can be generated - allows for a large immune cell repertoire
Describe B cell activation by T cells.
- the membrane bound BCR recognises antigen
- the receptor-bound antigen is internalised and degraded into peptides
- peptides associate with “self” molecules (MHCII) and is expressed at the cell surface
- This complex is recognised by matched CD4 T helper cells
- B cell activated
