Immunology Flashcards
Describe the structure of the thymus
Bi-lobed
Packed with proliferating lymphocytes
Medulla and cortex
What happens to the thymus during infection
No obvious change
What are Hassall’s corpuscles and where are they found
Fibroblasts for regulatory T cell development found in the thymus
What happens to the thymus with age
Decrease in output of new lymph (but total does not decrease)
Describe the bone marrow
Site of B cell and RBC production
Yellow fat surrounded by red marrow
What happens in the bone marrow during infection
Increase in white blood cell production
Describe the lymphatic system
Drainage system to collect antigens and filter through the nodes and return fluid to the blood
Antigen is likely to enter the lymphatic system
Draw/describe a lymph node
Kidney shape
Medullary sinus is surrounded by the T cell area with many germinal centres surrounding this
Lymphoid follicle surrounds this
What is a germinal centre
Area where B cell proliferate
What happens to the lymph nodes during infection
Lymph nodes become enlarged/swollen
What is the purpose of high endothelial venues and where can they be found
causes cells to move from the blood to lymph
Found in the lymph nodes
Which secondary lymphoid organ does not have many HEV
Spleen
What is the function of the spleen
Filters for antigens in the blood
Describe the structure of the spleen
White pulp (WBC) Red pulp (RBC) Germinal centres
What happens to the spleen during infection
Larger follicles
Describe how epithelium is a secondary lymphoid organ
Mucosal and skin as a physical barrier
Mucosae-associated lymphoid tissue (MALT)
Lymph drains in villi
What are Peyer’s patches and where are they found
Large aggregates of B cells that contain germinal centres important for immune response found in the gut epithelium
What are microfold cells and where are they found
Cells that sample antigens to pass them to the Peyer’s patch in the gut
Which immune response cells are found in the skin
Epidermal langerhans cells
T lymphocytes
Macrophages
Dermal dendritic cell
Describe the process of extravasion
- Naive T cells rolls along the endothelium
- They bind to proteins and carbs along the epithelium
- HEV has chemokine bound to the cell surface
- Lymphocytes have receptors for this and binds to the receptor
- Lymphocytes deliver a signal to the T cell, changing the structure of integrin
- Integrin becomes high affinity binding and binds to the epithelium to stop movement
- Transport through epithelium
Describe a neutrophil
Phagocytosis 40-75% of leukocytes short-lived circulates the blood First cells recruited
What are NETs
neutrophil extracellular traps
Release of granules and chromatin to form extracellular fibres
Describe eosinophils
phagocytosis and granule release
Defence against parasites
Helps B cells in GALT (IgA production)
Describe basophils
Granule release
Acts as an APC for type 2 immunity
Describe monocytes
phagocytosis , killing, cytokine release, APC
less abundant
dispersed in tissue
Signal infection to soluble mediators
Become macrophages when the leave the blood
Describe mast cells
Phagocytosis, granule release (pro-inflammation), histamine and leukotrienes
Mucosal in the lung or connective tissue in the skin
Activation by complement products (anaphylatoxins)
vasodilation (red skin) and increased vascular permeability (inflammation)
Describe dendritic cells
APC and cytokine secretion
migration to lymph node
network site of infection
adaptive
Describe natural killer cells
10% of blood
Infected cell lysis, secretion of interferon gamma, activating and inhibitory receptors (NO antigen receptor), binds to opsonised cells
Large granulated lymphocytes (cytotoxic)
Bind to opsonised cells
Cancer and viral infections
What are soluble mediators
Small secreted proteins important in cell-cell communication that are generally local acting
Effective even in low concentration
What are the types of soluble mediators and what are their functions
Interleukins - leukocyte communication Interferons - anti-viral Chemokines - chemotaxis Growth factors - proliferation and differentiation Cytotoxic - tumour necrosis factor
What is complement
Complex series of 30 proteins and glycoproteins
Major role in complimenting the activity of specific antibodies in lysing bacteria
Triggers enzyme cascade systems to give a rapid and highly amplified response
What are the secondary effector functions of immunoglobulins after binding
Complement activation
Opsonisation (promotion of phagocytosis)
Cell activation via antibody-binding receptors (Fc receptors)
What are hyper variable regions
there are 3 in antibodies: CDR 1,2,3)
CDS = complement determining regions that acts as binding sites for antigens
Define antibody affinity
The strength of the total noncovalent interactions between a single antigen binding site and a single epitope on the antigen
Define antibody avidity
The overall strength of multiple interactions between n antibody with multiple binding site and a complex antigen with multiple epitopes
Better measure of binding capacity
Give examples of antibody-cross reactivity
Vaccination with cowpox induces antibodies which are able to recognise smallpox
ABO blood group antigens
Antibodies made against Microbial antigens on common intestinal bacteria may cross-react with carbs on RBC
Describe IgG
gamma heavy Most abundant Has 4 subclasses Actively transported across the placenta Major activator of the classical complement pathway (1&3) Blood and extracellular fluid
Describe IgA
alpha heavy 2nd most abundant 2 subclasses Occurs as a monomer or dimer secretory Protects mucosal surfaces from pathogens Across epithelia
Describe IgM
Micro heavy First Ig synthesised after exposure Multiple low affinity binding sites Large pentamer Agglutination and complement activation Blood
Describe IgE
E heavy Allergic reactions Parasitic infections Binds to mast cell receptors and basophils to release histamine Very low levels
Describe IgD
Delta heavy
Expressed in B cell development and activation
very low levels
Give the actions of antibody-antigen
Neutralisation Agglutination Opsonisation Complement activation Bound by cells expressing Fc receptors (innate immunity: phagocytes, NK cells)
Describe the process of T cell dependent B cell activation
- Phagocytosis of the pathogen
- Pathogen broken down and displayed on the B cell and the dendritic cell via MHC II
- T helper recognises the presented antigen on the dendritic cell then finds the B cell with the same antigen
- Co-stimulatory molecules (CD28) provides more signalling
- T cells produce cytokines
- Lymphokine secretion
- B cell enters the cell cycle and produces clones with identical BCR
What does class switching involve
IgM and IgD are "weak" When signals (lymphokines) are given from T helper there is a class switch
Where does affinity maturation occur
Germinal centres
Describe the process of affinity maturation
AID enzyme causes a mutation in the antibody coding genes of the B cells (somatic hypermutation)
Cells can become worse -> apoptosis
Cells can become better -> stronger antibodies -> plasma or memory cell
Explain clonal selection
From a large population, 1 cell is activated via antigen binding to BCR which leads to proliferation (clonal selection). Division and differentiation is clonal expansion
Describe the T cell independent activation pathway
A repetitive bacterial polysaccharide acts as the first signal
Microbial constituent or accessory cell provides second signal e.g. LPS
What causes differences in Ig for T cell independent and dependent
No lymphokines released in T cell independent
Describe the TCR
The Fab region of an antibody, top is variable, bottom is constant. One alpha and one beta and a cytoplasmic tail.
What is the difference between the alpha and beta chains of the TCR
alpha = V and D and 1 recombination Beta = V, D and J and 2 recombinations
What are CD4 and CD8 and where are they found
Co-receptors that bind to MHC.
CD4 is found one T helper cells while CD8 is found on T cytotoxic cells
What is HLA and where is it found
Human leukocyte antigen - genes found in all vertebrates that code for MHC. polygenic
Chromosome 6
co-dominant expression
Relationship between HLA and MHC
MHC class I = A,B,C MHC class II = DP, DQ, DR
What is haplotype
Group of MHC alleles on 1 chromosome
Describe the endogenous MHC pathway
MHC I. Synthesised in the cytoplasm
- TAP transports protein to RER
- calnexin and calreticulin and tapasin fold and stabilise the MHC
- molecules transport to the golgi
Describe the exogenous MHC pathway
MHC II. Antigens from external environment
- invariant chain stabilised the MHC complex
- transport to the golgi
- invariant chain is digested to leave a CLIP
- Antigen is endocytose and broken down
- Peptide presented on MHC
- MHC exocytosed
Why may antibodies be inefficient
Pathogens: Can hide within cells Can change antigen shape Can coat the antigen with antibodies Can produce fake antigens
What are T cells defined by
inputs (STAT) and outputs (cytokines)
How do killer T cells induce apoptosis
Granule release - Perforin, granzyme, granulising
Fas ligand - binds to Fas receptor on the cell
Release of caspases to drive apoptosis
What are the activation steps of a naive T cell
- TCR/CD8 - MHC I Binding
- CD28 co-receptor activation
- cytokines from infected cell
What is Th1 involved in
Macrophage activation
Delayed type hypersensitivity
B cell activation
Regulation
What occurs when the macrophage cannot kill the pathogen e.g. tuberculosis
- Cytokine release
- endothelial cells express proteins
- Monocyte and Th1 migration
- Th1 activates monocyte and macrophage
What is the process of Th1 amplification
- Activated Th1 binds to MHC II and CD40 on the B cell
- Secretion of IFN gamma
- Upregulation of MHC II, CD40 and tumour necrosis factor alpha
- Increase in TNF alpha secretion (autocrine) from macrophages
- amplification
Give features of Tfh
Activation by dendritic cells
Stimulates B cells
Generation of isotope-switched antibodies
Describe tuberculosis
Ingested by macrophages
TB inhibits phagosome -lysosome fusion and lives in macrophages
Granuloma formation contains the infection
What is the role of Th2
Targets and stimulates eosinophils
Trigger in tracheal epithelia
Travels from dendritic to naive
What CD marker is expressed on naive memory T cells
CDC45RA+
What CD is expressed on central memory cells
CCR7
What is the function of Treg
Regulation of T cells and tolerant of self-antigens
secretes immune-suppressive cytokines and inactivates dendritic cells
What is the function of Th17
Interleukin 17, bacterial control and neutrophil recruitment
Describe the process of T cell development
Produced in the bone marrow (CD4-CD8-TCR-)
In the cortex = CD4+CD8+TCR+
In the medulla = CD4+CD8-TCR+ vice versa
Describe selection in the thymus of T cells
Thymocyte can’t bind = apoptosis
Weak binding = survival (+ve selection)
Strong binding = apoptosis (-ve election)
Prevents autoimmunity risks
What is the purpose of Interferon type 1
Activation of NK
What is the purpose of interferon type 2
Produced by T cells pre-inflamamtion
Define cytokine storm
Over production of cytokines and accumulation of cells
What are the main modes of pathogen transmission
Respiratory - large SA
GI tract - large SA
Zoonosis
Sexually transmitted
Define pathologic
Immune response against a self antigen, often classified under immune mediated inflammatory diseases
Define pathogenesis
susceptibility genes and environmental triggers
Describe hypercytokinaemia
Too much immune response
positive feedback loop
pathogens enter the wrong compartment e.g. the blood (Sepsis) or failure to regulate response to the correct level
What is the 3 signal model
Licensing a response
- Antigen recognition
- Co-stimulation
- Cytokine release
How is immune response controlled
Responses against pathogens decline as the infection is eliminated
Compare central to peripheral tolerance
central - destroys self-reactive T or B cells
peripheral - destroy or control self-reactive cells that do enter circulation
What is AIRE
AutoImmune Regulator
A gene for a specialised transcription factor that allows expression of genes in peripheral tissues for self tolerance
What is the function of IL-10
Master regulator Shuts down dendritic cells Pleitropic (multifunctional) Blocks pro-inflammatory cytokine synthesis Downregulates macrophages
What are the main mechanisms of peripheral tolerance
Anergy - APC presents the antigen but the T cell is shut down
Deletion - apoptosis of the T cell
Ignorance - less APCs
Regulation - regulation of the response by cytokines from Treg
