Lecture 9 Flashcards
Complement Cascade
2x activation pathways:
1. Alternative pathway: recognising structures on pathogen surfaces.
2. Classical Pathway: Antigen-antibody complexes. T –>Y shape, change in CH2 shape configuration, so complements can be activated by binding to that
Antibodies have 2x activating sites, so can enhance phagocytosis via crosslinking things. bringing molecules together and glutinate things. Forms a lattice. Phagocytic cell ingest alot of bacteria at one time instead of having to do them individually
Activation, leads to early components forming enzyme (C3 convertase)
Enzyme cleaves C3 into 2x components (C3a and C3b) via enzymatic cleavage
C3a affects BV permeability + attracts neutrophils (vasodilation and chemotaxis)
C3b is chemically reactive, which covalently links to anything close by (bacterial surface and others) opsinises them, enhancing phagocytosis. Also focuses on late components of complements, assembling into membrane pores/ attaches and punctures holes in membrane. Leading to membrane lysis
Lymphadenopathy and Splenomegaly
“Lymphadenopathy”= lymph nodes and adenoid tissue being swollen
“splenomegaly”= spleen being larger than normal - protrodes down past rib cage
can feel spleen protruding
Lymphocytosis= more than normal number of lymphocytes
-not many granulocytes or monocytes, some lymphocytes but also some larger than normal lymphocytes, and strange smear cells (not losing cells. is containing abnormal cells)
Lucapenia = fewer than normal number of lymphocytes
smear cells= something is occurring in generation of blood cells.
Smear cells are cells which break when smeared on glass slides as are more fragile (kinda an artfact but highlights abnormality)
Hints at problem with development of lymphoid lineage in bone marrow, resulting in overloading of immature (potentially tumorous) leukemic lymphocytes,
-likely to be lymphocyte leukemia
a) variety of ways to see changes in development of blood and immune system, by monitoring what is in our circulation
b) swollen lymph nodes and splenomegaly, not because having lots of immune responses. more that has alot of immature cells infiltrating secondary lymphoid organs causing them to swell as now packed with largely non-functional tumorous cells derived from bone marrow
Indications of having swollen nodes
could indicate infection
could indicate something wrong with immune system development/leukemic state (blood cell production problem in bone marrow(spilling over in circulation))
Why do we need more than antibodies to deal with infectious agents?
- Viruses grow inside cells.
- Inaccessible to antibodies
viruses infect and grow within cells. Antibodies may be able to neutralise prior to entering host cells. but once in cell, the antibodies cannot get through the membrane and reach them
e.g. Hepatitis B infection, likes to infect hepatocytes (liver cells) due to object on surface which they bind to and enter from.
Humoral Immunity
Product of B cells
Involve antibodies
Effective against antigens Outside viruses (in fluids, on surface, in Extra cellular spaces between cells)
-viruses and toxins (stop attachment)
-extracellular bacteria (enhance phagocytosis, activate complement)
Cell-mediated Immunity
“T-cell mediated immunity”
Product of T cells
No antibodies
Effective against Intracellular antigens (displayed on cell surfaces) - recognise cell surface changes which indicate changes inside the cell
-virus infected cells
-tumour cells (changes gene expression to become unrestricted growth- can sometimes be shown on surface (not always))
-transplanted organs (surface on transplanted tissue HLA antigens which T cells are really good at recognising)
Classes of T Lymphocytes
- cytotoxic (killer) T cells (have CD8 on surface, works with t cell receptor to stabilise binding of what t cell receptor is recognising)
- helper T cells (have CD4 on surface works with t cell receptor to stabilise binding of what t cell receptor is recognising)
- dont use Antibodies
- dont use Immunoglobulins
- comprable set of genes forming T cell receptors-AB (have variable and constant regions) anchored into membrane. How t cells recognise things. Alpha and Beta as have 2x chains. variable regions are the same on all receptors of a t cell
- CD3 marker/complex of proteins on surface. Transmembrane proteins. Link to T cell receptor. when binds, changes telling inside of cell that binding has occurred. Transduction mechanism.
- T cells recognise changes on surface of cells which resemble changes on the inside of the cell
How do you count the number of t cells within a blood sample?
All T cells have a CD3 marker
therefore you stain for the CD3 to count all the CD3 positive cells/t cells
How do you count the number of cytotoxic (killer) t cells?
All Killer T cells contain a CD8 marker.
stain for CD8 to count for all the CD8 positive cells/cytotoxic t cells
How do you count the number of helper t cells?
Alh Helper T cells contain a CD4 marker.
stain for CD4 to count for all the CD4 positive cells/helper t cells
T cell antigen recognition
- Only recognise Peptide antigens (fragments of proteins/10-20 aa)
- Only recognise peptides when presented on the surface of cells with specific antigen presenting molecules (class I/II HLA molecule, associated with Killer and helper t cell recognition respectively)- Human Leukocyte Antigen as found in high concentrations on blood cells
When virus is replicating, it is producing new proteins, some of those proteins will be broken down during cellular metabolic processes, and some peptide fragments will appear on the cells surface associated with HLA molecules
-Both fundamentally Peptide presenting molecules on the surface of cells, which show peptide antigens to T cells
Classes of HLA
HLA = Human Leukocyte Antigen
found in high concentration on blood cells (and many other cells)
Both fundamentally Peptide presenting molecules on the surface of cells, which show peptide antigens to T cells
2x classes:
Class 1: presents peptides to cells with CD8 (cytotoxic/killer T cells)
Class 2: presents peptides to cells with CD4 (helper T cells)
-derived from HLA genes
HLA genes and their products
Major Histocompatibility Complex/Genes (HLA in humans)
“histo”=tissue
-discovered during tissue transplants
-some people’s immune system’s resisted tissue transplants more than others
-HLA is what was recognised in the rejection
-very strongly recognised HLA’s were called “major”
HLA are derived from HLA genes, which are made up of 3 classes
-Class I (3x genes. HLA-B, -C, -A. code for Class I HLA. each codes for single polypeptide molecule. Associated with B2-microglobulin)
-Class II (3x genes. HLA-DP, -DQ, -DR. each codes for two polypeptides. Alpha and Beta molecules)
_Class I and II code for structures which present peptides to T cells (HLA) transmembrane surface molecules. Cell surface antigen presentation structures
-Class III in between. Antigen Processing
Properties of HLA
cell surface antigen(small peptide fragments form inside of cells) presentation structures
Class I (HLA-B, -C, -A):
1. Found on virtually al nucleated cells (varying conc.) (not RBC)
2. co-dominant (both transcribed and translated from mum and dad)
3. Polymorphic (many allelles within human population)
4. Present peptides to CD8 T Cells (cytotoxic T cells)
Class II (HLA-DP, -DQ, -DR)
- Found on B cells and specialised APCs(antigen presenting cells: dendritic cells, monocytes, macrophages)
- Co-dominant (express both maternal and paternal haplotypes)
- Polymorphic
- Present peptides to CD4 cells (helper T cells)
Antigens and Class I MHC
Class I MHC (HLA-A, -B, -C)
Always have peptide fragment associated with it from the metabolic processes associated with the cell (as proteins are broken down and recycled) - showing a sample of the peptides that cell is making/breaking down at any one time
Virus infection, takes over some ribosomes, and starts making some of its own proteins. some will get broken down in cells metabolic processes and appear on surface
-therefore during a virus infection there will be a slightly different distribution of peptides on surface
-potentially recognisable by CD8 bearing cells
Cell could also change the genes that is it transcribing and translating as is becoming tumorogenic- immune system can recognise this change by what is being mirrored on outer surface of the cell
Endogenous Pathway:Pathway of processing peptides and cell surface presentation of what is occurring Inside the cell
