Give examples of cell migration?
- to sites of infection and inflammation
- from blood to lymph and vice versa
- primary to secondary lymphoid organs
- between secondary lymphoid organs
Chemotaxis
the directional migration of cells up a conc gradient (0.1%) of chemotactic molecules
e.g. cytokine/chemokine (IL-8)
-> produced by macrophages and attracts NFs to site of infection
Chemokines
- family of secreted chemoattractant cytokines
- play a vital role in the cell migration between immune organs and sites of infection and inflammation
Number of chemokines and receptors
47 known chemokines
19 chemokine receptors
2 main groups of chemokines
alpha (CXC)
beta (CC)
Example of chemokine
- IL-8 (CXCL7)
- cells expressing CCR7 migrate to lymph nodes in response to secretion of their ligands CCL19 and CCL21
What are the 3 components of an inflammatory response?
- Blood supply - increased in area
- Capillary permeability - increased allowing exudation of serum proteins around surrounding tissue (Abs, complement)
- Leukocyte migration to site - phased
Explain the phasing of leukocyte migration as part of an inflammatory response?
- NFs - peaks 1 to 2 days (x10 increase in production in bone marrow)
- APCs - present at start, migrate to lymph nodes/spleen to act as APCs
- CTLs and Th2 - days later - must be activated by APCs in lymph nodes/spleen
- B lymphocytes - small numbers - secretes Abs
Where do chemokines bind?
- secreted chemokines bind to both the proteoglycan on surface of endo cell and to the chemokine receptors on leukocytes
Specific Immunity
aka. Adaptive
Identifies each specific pathogen
e.g. H1N1 vs H5N1 influenza A virus
-> produce unique T cell responses to each antigen individually
Antigens
What the specific immune system sees
- enormous diversity of BCRs and TCRs
How are antigens recognised
Abs on B cells
TCRs on T cells
What does antigenicity depend on
Size
Hydrophobicity
Complexity
Epitopes
Antigenic determinants
- portion of a macromolecule of infection that is detected by Ab
*more complex pathogens (fungi, bacteria) will have many antigens that can be detected by different Abs
Examples of epitopes
- AAs - their side chains (most antigenic)
- Polysaccharides/sugars
- Lipids/nucleic acids (least antigenic)
Types of epitopes
- Linear
- formed by several adjacent AA residues (~6 AAs)
- accessible (external surface) or inaccessible (buried in protein)
- may only be accessible when denatured - Conformational
- formed by AAs not in a linear sequence
- spatially juxtaposed
What is the primary function of an antibody?
Binds to its antigen
Direct and Secondary effector function of Abs
Direct
- neutralization of bacterial toxins & viruses -> prevents binding
Secondary
- complement activation -> lysis
- opsonisation -> pathogen gets covered in Abs -> phagocytosis
Examples of viruses that neutralise Abs
- Rhinovirus - block attachment to cells
- Poliovirus - block virus from uncoating capsid
- Influenza A - Abs enter cell and prevent replication
How are most bacteria killed?
Phagocytosis
Ab-mediated opsonisation
Why do we need T cell Immunity?
Viruses are intracellular pathogens
(bacteria, fungi, viruses in bodily fluids are eliminated by phagocytes (innate) and B Cells/Abs (humoural))
Types of viruses
- Naked - Norovirus, Poliovirus (cause lysis)
- Enveloped - Influenza, HIV (viral envelope proteins insert into the cell membrane of infected cell)
How does immune system see viruses within infected cells
(also cancer cells)
- proteolysis of proteins in the proteasome (cytoplasm)
- short peptides loaded onto MHC
- shipped through ER via TAP to external surface of cell
- T cells only recognise peptides when bound to MHCs on APCs or infected cells
*self reactive T cells already eliminated during thymic education
How are virus peptides on surface of infected cells seen?
CD8 (CTLs) w/ TCRs recognise peptide bound to MHC
NKs recognise infected cells w/ no MHC
-> apoptosis
