W11 Intro to immune system Flashcards
Immunology
is the study of our body’s systems for preventing disease
Organisation of the Immune System
Innate Immunity – front line defence
then
Adaptive immunity – specific and memory responses
then
Humoral – B cells and antibodies
Humoral – B cells and antibodies
The innate immune system
is your ever-present defense against infection. It is made up of barriers that keep viruses, bacteria, parasites, and other foreign particles out of your body or limit their ability to spread and move throughout the body
The importance of innate immunity
is demonstrated by the fact that you are normally healthy despite the barrage of potential infectious challenges you face every minute.
The innate immune system includes:
Epithelial barriers to the environment (eg skin, gastro-intestinal tract, respiratory tract) that prevent microbe entry.
Secretions at mucosal surfaces – flushing action and antimicrobial properties.
Cells that are resident in tissues (eg mast cells) or circulating in the body (eg neutrophils).
Circulating proteins in the blood (eg complement proteins).
Cytokines (eg interferons) that are locally produced by infected cells.
Non-specific activity.
No “memory”, the response is the same to repeated challenge.
PAMPs
are small molecular motifs conserved within a class of microbes. A vast array include glycans, lipopolysaccharides, bacterial flagellin, lipoteichoic acid, peptidoglycan and nucleic acid variants normally associated with viruses, such as double-stranded RNA
DAMPs
are molecules released by stressed cells undergoing necrosis. Some are proteins - heat-shock proteins and cytokines. Non-protein DAMPs include ATP, heparin sulfate, and DNA
PAMPS and DAMPS are recognized by
by Pattern Recognition Receptors (PRRs) on immune cells
Phagocytosis
is a processby which cells internalise solid matter, including microbial pathogens
a mechanism by which microorganisms can be contained, killed and processed for antigen presentation
Inflammation
is the process whereby immune cells (which are normally distributed throughout the body) can be recruited and concentrated to a site of infection or damage
Following PAMP or DAMP recognition
PRRs trigger proinflammatory and antimicrobial responses by inducing the release of a broad range of cytokines
The main events in inflammation are:
Increased blood supply to the affected area;
Increased permeability of the vasculature ;
Migration of WBCs out of the blood capillaries into the affected tissue
Dendritic cells
capture, process and present antigens
T lymphocytes
control the immune response by providing “help” to B cells and macrophages (helper T cells); direct killing of infected or tumour cells (cytotoxic T cells).
1-4x10^9/l in blood
Cytokines
soluble proteins secreted mainly by T cells that control activities of other cells
B lymphocytes
produce and secrete antibodies, proteins that specifically bind target molecules (antigens) on microbes or cells
1-4x10^9/l in blood
The Lymphoid System
Immunological cells are largely organised into tissues and organs for best efficiency.
Collectively, these structures are known as the lymphoid system.
Primary lymphoid organs
are the sites of maturation of white blood cells – they differentiate from stem cells, multiply, are programmed and mature into functional cells.
Secondary lymphoid organs
provide the site for interaction between antigens and WBCs. They also allow spread of the immune response.
Secondary lymphoid organs are associated with systemic and mucosal immune compartments (blue).
TheLymphatic System
The lymphatic system is part of thecirculatory systemand an important part of theimmune system. It comprises a network oflymphatic vesselsthat carry lymph fluid and cells from the tissues back into the blood stream
Lymph Nodes
At regular intervals along the lymph vessels are organised structures – lymph nodes
Lymp entrance/exit
Lymph arrives at the node by an afferent lymphatic vessel, it filters through multiple layers of antigen presenting cells, T cells and B cells, and exits via the efferent lymphatic vessel
dense concentration of immune cells provides..
an ideal environment for initiating immune responses and communication between immune cells. Lymph nodes are common battleground sites for the immune system and infections.
Immunoglobulins (Igs)
Immunoglobulins (antibodies), are glycoproteins produced by plasma cells.
They specifically recognise and bind strongly to particular antigens on pathogens, and prevent disease or aid in the destruction of the pathogen.
There are different classes and subclasses of immunoglobulins, which differ in their structure, biological features and distribution.
Immunoglobulins are produced by B cells – humoral immunity
T-cell antigen receptors (TCRs)
T-cell receptors are found on the surface ofT cells. They are responsible for recognizing processed fragments ofantigen (peptides)which are “presented” by host cells.
The binding between TCR and antigen peptides is relatively weak compared to antibodies.
When the TCR engages with antigenic peptide, the T lymphocyte is activated through a series of biochemical events (signal transduction), leading to cell proliferation and biological activity (eg cytokine production).
TCRs are produced by T cells – cellular immunity
B cells
B cells are lymphocytes, which when activated, become plasma cells and then produce antibodies. This is often known as humoral immunity.
Antibodies
Antibodies are glycoproteins that are made by B cells and plasma cells.
They bind specifically and with high affinity to “non-self” antigens.
Antigens are usually proteins or carbohydrates attached to, or secreted by, microbes and infected cells.
Antibodies can neutralise targets, or recruit other components of the immune system to kill targets
Potential antibody repertoire
~10^15
T cells – cell mediated (cellular) immunity
T cells control the immune response and combat microbes that are inside cells (intracellular)
Different T cells have different functions and are distinguished by the array of proteins on the cell surface (Cluster of Differentiation – CD – markers).
Two major groups are CD4 (helper T cells), and CD8 (cytotoxic T cells)
foreign antigen fragments (peptides) are displayed at …
displayed at the cell surface by molecules of the major histocompatibility complex (MHC)
T cells recognise antigens via
via cell-surface receptors (TCRs) proteins, that are related to antibodies.
But unlike antibodies, T cells do not recognise foreign molecules in their “native” state
Mature cytotoxic T cells kill by
Mature cytotoxic T cells kill target cells using cytokines, cytotoxic granules and the caspase cascade.
Mature helper T cells secrete…
Mature helper T cells secrete cytokines to “help” (activate) macrophages, B cells and other T cells
Immunological techniques in diagnostics and research
Two key features of antibodies – antigen specificity and high affinity binding are extremely valuable in laboratory assays.
They allow rapid and highly sensitive identification of specific molecules.
Immunological techniques in diagnostics and research
- examples
ELISA
Western blotting
Lateral flow assay
Fluorescence-activated cells sorting (FACS)
