Adaptive Immunity 2 Flashcards
Bacteria
Breach of skin - staph aureus gets into the skin
On site of invasion are macrophages that capture the bacteria
If microbe gets into the blood stream, they are taken up by myeloidm plasmacytoid and dendritic cells
The spleen is largest lymphoid tissue has everything with regards to APC to mount an immune response
Langerhans cells present in the skin act as APC and TLR (2/4/9) present in the skin to sense the microbe
Microbes are caught via phagocytosis with these cells and use exogenous pathway to enter cells
They then enter lymph tissue, where the antigen is presented by dendritic cells via the MHC class2 and present it to the naive CD4 T cells
T cells then activate B cells and this is directed to the adapted immune response
Patients are susceptible if they have a HLA (human leukocyte polymorphism) polymorphism as T cell and B cells dont function properly, therefore have a compromised immune system
Viruses
E.g. Adenovirus in the lung
Virus breaches mucosal memebrane - if escapes to blood, it will be taken to spleen
APC present in lungs are dendritic cells
Sensors in the cell are TLR9
Antigen processed via the endogenous pathway - as you want to express the peptide on a different class of MHC molecule becusae you want to activate different class of T cell
In the lung the APC takes the microbe to the bronchial associated lymphoid tissue
Presented to naive CD8 T cells via the MHC class 1 viral peptide as these bind to MCH class 1
This leads to cell mediated immune response
B and T lymphocytes
Produced by the bone marrow
T cells mature in the thymus
B cells mature in tissues following contact with Antigen
Present in the blood
5-15% B cells,
Antigen recognition by T lymphocytes
1) T cell receptor (TCR) - made up of alpha and beta chains, combined to a CD3 complex - can also have accessory molecules (either a CD4 or a CD8)
2) There is diversity of antigen receptors (>10 to the 16 differnt types)
3) forms of antigen recognised - peptides displayed by MHC molecules
4) different subtypes - Helper T cells (CD4+) recognise peptide presented by APCs containing MHC class 2 molecules - Cytotoxic T cells (CD8+) recognise peptide presented by APCs containing MHC class 1 molecules
Activation of CD4+ Helper T cells
APC stimulates T cells via 2 signals - both are needed for activation of naive T cell
Cytokines are produced by the APC which dictate which T cells come and bind to the APC
If APC binds to a naive CD4+ T cell then it leads to -
Cell mediated immunity - defences against IC and EC pathogens - like bacteria, viruses and fungi
- IL-12 is released by APC, CD4+ complex which recruits Th1, which leads to the recruitment of macrophages and B cells, and the differentiation into CD8+ T cells
Humeral immunity - defence against EC pathogens (parasites and worms)
- if IL-4 is released then Th2 cells are recruited, which leads to the recruitment of B cells (IgE production), eosinophils (kills pathogens) and mast cells (to deal with allergies) - If IL-1/6 is released then Th17 is recruited which means neutrophils are recruited and activated - if Il-10/TGFß is released Treg are recruited and this goes into immune suppression
Effector functions of CD8+ T cells
APCs that activate CD8+ T cells can either actiavte memory or effector CD8+ T cells
Effector CD8+ T cells then go on to form Cytoxic T cells, which go to the peripheries and kill all of the infected cells that are presenting with MHC class 1 peptides
Antigen recognition by B lymphocytes
Antigen recognition receptor
B Cell Receptor or BCR: - are Membrane bound antibodies
They have Unique specificity for each cell
Diversity of antigen receptors
Combinatorial diversity (>10to the 11)
Different forms of antigen recognized
Macromolecules (proteins, polysaccharides, lipids, nucleic acids)
Small chemicals
Activation of B lymphocytes - requires multiple signals
Outcomes of B lymphocyte activation
1st signal is a BCR engagement allowing for signal transduction
2nd signal is the T helper cell’s receptor engagement - when T helper cells have been activated by APCs, they go and bind to B cells to help with proliferation a and differ action of antibody production
3rd signal is cytokines binding
Outcomes of B lymphocyte activation
Antibody production
IgM production is T helper independent - is the initial B cell response to every infection
After a couple of days other antibodies such as IgG etc are made by B cells that are specific for this infection
IgG, IgA, IgE production is T helper dependent (isotype switch) - these then circulate in the blood and are present to provide immunity and resistance when this infection occurs again
Affinity maturation in antibody response
Prolonged or repeated exposure
Memory B cells
Upon re-challenge can give a faster, stronger and longer antibody response
Characteristics of the antibody response
1st time we get an infection - i..e new pathogen - our IgM slowly rises
IgG will rise but only 20 days later
2nds time we get infected out IgG rockets up - we have a faster and stronger response that lasts longer with higher affinity - this only occurs if the antigens that we have been infected with are the same
If they kinda different then response will be slightly stronger
If they are not similar at all then being infected with a “new virus”
Effector functions of antibodies
IgG - Fc -dependent phagocytosis Complement activation Neonatal Immunity Toxin / virus neutralization IgA - mucosal immunity IgE - Immunity against helminths Mast cell degranulation (allergies) IgM - complement activation
Medical achievements derived from the study of the adaptive immune response -
Disease prevention - Vaccination (or active immunization)
Immunoglobulin therapies - Immune deficiencies
Immediate protection - Passive immunization (antibody transfer)
Diagnostic tests (antibody-based) can check for -
Infectious diseases
Autoimmune diseases
Blood type and HLA types
