Overview of Adaptive Immunity Flashcards
Name the 5 routes of infection
Recall the 4 stages of an immune response
- Recognition
- Recruitment
- Elimination
- Resolution and repair
Briefly outline how the innate and adpative immune system are linked
INNATE (Day 1-3)
- Pathogen infects cells
- Cells release alarmins
- Alarmins recognised by PRRs
- Release of cytokines and chemokines
- Innate effector cells kill infected cells
DENDRITIC CELLS (Day 4-7)
- Antigens are released from cells and APCs recognise them
- APC presents to CD4+ cells
ACQUIRED (Day 7-9)
- Activate CD8+ and B cells
- Clear infected cells
- Antibody production
Which cells are involved in the adaptive immune system
Dendritic Cells
T cells
B cells
Innate cells kill infected cells, Adaptive cells highly specific and target signel strains of bacteria
Define adaptive immunity
Immune response:
- Mediated by T and B cells
- Highly specific and focused
- Has memory
- Needs time
Which genes code for MHC and how many of these genes are there?
HLA genes
6 genes
What are the principles of adaptive immune defence (3)
- Recognition of self vs non-self
- Licensing of immune response
- Communication between cells
Clonal Selection, Cell migration
How does the immune system recognise self vs non-self
- Use of PRRs (to recognise PAMPs/DAMPs)
- MHC
MHC - Major Histocompatibility Complex
Define tolerance and describe it’s subtypes
Tolerance: State of unresponsiveness (to substances that can induce immune response)
- Central: destroy self-reactive T/B cells before they enter circulation
- Peripheral: destroy self-reactive T/B cells in the circulation
Explain the process of clonal selection (4)
- Lymphocytes have a single unique receptor
- Clonal deletion to remove self-reactive lymphocytes
- Antigen activates receptor
- Proliferation and differentiation of activated lymphocyte
An immune response needs to be licensed and this is done through 3 signals in T cells
- Antigen recognition (TCR-MHCII)
- Co-ctimulation (CD28-CD80)
- Cytokine stimulation
Explain how cells move from blood to tissue with receptors invovled (5 steps)
- Tethering
- Rolling (selectin)
- Adhesion triggering (integrin)
- Extravasation
- Chemotaxis
Outline receptors and ligands involved in cell comomunication between APC and T cell
Define an antigen and the epitope
Antigen: Proteins or molecules that can induce an adaptive immune response
Epitope: the region where receptors/antibodies bind on an antigen
Outline the function of a dendritic cell
Dendritic cells activated by PRRs (innate)
Capture antigens
Travel to lymhpoid tissue via lymphatic system where they mature
Present antigen to lymphocytes (T cell)
Specialised APC which patrol tissues - main function is surveillance
Complete the table on MHC/TCR interaction
Where do T and B cells mature?
Differentiate between the two T cell subtypes
T cell: thymus
B cell: bone marrow
Th (helper) = CD4+, recognises MHCII
CTL (killer) = CD8+, recognises MHCI
TCR=CD3
Explain how cytotoxic T cells induce apoptosis of target cells (2)
Apoptosis = programmed cell death, characterised by fragmentation of DNA and no inflammation
CTL induce apoptosis in two ways:
Granule Exocytosis
- Granule containing perforin and granzyme
- Perforin creates pores on target cell membrane
- Granzymes enter and induce apoptosis via caspase cascade
Fas Pathway
- T cell Fas Ligand binds to target cell Fas
- FADD and initiator caspase activate caspase cascade
- Apoptosis
How do T and B cell receptors recognise pathogens/non-host protein structures
T cells: primary structure (linear aa)
B cells: tertiary structure (epitopes)
Describe the effect of HLA-B57+ in a patient with HIV and describe what happens when the same virus is transmitted to a patient with HLA-B57-
HLA-B57+ presents epitope of ?reverse transciptase
Virus degrades RT and therefore decreases its fitness (i.e. HLA-B57 protective against HIV)
Transmission to HLA-B57- reverts the virus back to its fitter self -> increase virus activity
Name the 5 T helper cell subsets
- Th1
- Th2
- T17
- Treg
- Tfh
What cytokines do Th1 cells produce and what is its function
IFN-γ
Intracellular immune response
What cytokines do Th2 cells produce and what is its function
IL-4. IL-5, IL-13
anti-multicellular organism (involved in allergy)
What cytokines do Th17 cells produce and what is its function
IL-17, IL-22
Autoimmune (arthritis IL-17)
Bacterial control
What cytokines do Treg cells produce and what is its function
IL-10, TGF-β, IL-35
Immunosuppressive (regulates T cell activity)
What cytokines do Tfh cells produce and what is its function
IL-21
Reside in B cell follicles - generation of isotype-switched antibodies
B-cells make antibodies which are found on their surface (BCR). We need a large pool of antibody diversity to be able to respond to pathogens. We can make 1010 antibodies but don’t have 25,000 genes to code for all of these. How is diversity generated?
Diversity generated through Immunoglobulin Gene Rearrangment
There is rearrangment of vairable (V), joining (J) and sometimes diversity (D) segments to form the diverse antibody pool.
Describe the 3 steps that occur in B cells after antigen exposure
- Antibody production
- Affinity Maturation
- Memory
Explain what affinity maturation i in B cell fuction
The process where B cells produce antibodies with higher affinity to antigen after many antigen presentation. Regulated by Tfh cells with IL-21
Explain the T/B cell interaction in B cell activation
- Ag presented to B cell by T cell or internalised and processed MHCII -> SIGNAL 1
- CD4+ T cell recognise Ag with co-stimulation from CD28-B7
- Leads to increased CD40L expression which binds to CD40 on B cell -> SIGNAL 2
- T cell cytokines bind to B cell receptors -> SIGNAL 3
- B cells proliferate and differentiate
Describe the structure of an antibody
Variable region
Constant region
4 chains (2 heavy, 2 light)
Describe the 3 main functions of antibodies
- Neutralisation
- Opsonisation
- Coomplement activation
Define memory T/B cells and their effect in pathogen exposure
Cells that become quiescent instead of effector cells
Re-infection causes larger response at a faster rate and requires less stringent activation
Which lymphocyte goes through isotype switching and affinity maturation - T or B cells
B cells
T cells do NOT isotype switch or have affinity maturation
Briefly outline the typical life of a memory t cell from naivity
Naive T cell
Expansion of effector cell
Contraction of memory cell
Secondary expansion from memory cell is massive and faster
Explain T cell exhaustion
Chronic inflammation leads to decreased function of effector cells.
They stop releaseing IFN-γ and IL-2
Start expressing anti-proliferative receptors such as PD-1 (binds to PDL in cancer cells)
Describe how the immune response (memory) can go wrong
Immunopathology (excess activity)
Autoimmunity
Allergy
