Immunology Flashcards
What is innate immunity?
An instinctive non-specific immune response present from birth, which does not rely on lymphocytes
What is adaptive immunity?
A specific learned immunity present in higher organisms, which requires lymphocytes and antibodies
What does the top layer of a centrifuged blood sample contain?
Plasma - mostly water, but also contains electrolytes, proteins, lipids, sugars etc.
Where would you find the white blood cells in a centrifuged blood sample?
The white fluffy layer in the middle
What does the bottom layer of a centrifuged blood sample contain?
Haematocrit (erythrocytes and platelets)
Where are leukocytes made?
In the bone marrow
What are the 3 types of polymorphonuclear leukocytes?
- Neutrophils
- Eosinophils
- Basophils
What do monocytes differentiate into on leaving the bloodstream?
Tissue macrophages
Which type of cells differentiate into plasma cells, which secrete antibodies?
B cells
What is Complement?
A group of about 20 different serum proteins secreted by the liver that when activated, cleave specific proteins to release cytokines, initiating a cascade of further protein cleavages.
What are the 3 modes of action of Complement?
- Direct lysis by activation of the MAC (membrane attack complex)
- Attracting more leukocytes to the site of action by secretion of chemotaxin factors (C3a and C5b)
- Opsonisation (C3b), which coats the surface of the microbes and makes them more tasty for phagocytes
What do antibodies bind to?
Specific antigens
Which immunoglobulin is the most abundant in the blood and can get into all tissues?
IgG
Which immunoglobulin is the first to be produced as part of an immune response?
IgM
Which immunoglobulin is overproduced during an allergic reaction?
IgE
How do antibodies help phagocytes to engulf microbes?
By acting as an adapter, binding the phagocyte to the antigen on the surface of the microbe
Name 5 types of cytokines
- Interferons
- Interleukins
- Colony stimulating factors
- Tumour necrosis factors
- Chemokines
What do interferons do?
Induce a state of antiviral resistance in uninfected cells
Interleukins are produced by many cells, what effects can they have on cells?
Can cause cells to divide, to differentiate and to secrete factors
What are colony stimulating factors involved in?
Directing the division and differentiation of bone marrow stem cells to form leukocytes
What do tumour necrosis factors do?
Mediate inflammation and cytotoxic reactions
What do chemokines do?
Leukocyte chemoattractants - they direct immune cells to particular parts of the body, e.g. if an infection is in a certain body part, chemokines are released in that area
What 3 things make up the innate immune system?
- Physical and chemical barriers
- Phagocytic cells
- Blood proteins (complement)
What are the 6 things that need to happen in response to tissue damage?
- Stop bleeding (coagulation)
- Acute inflammation (immune cells to the area)
- Recognise and kill pathogens, neutralise toxins, limit pathogen spread
- Clear pathogens/dead cells
- Proliferation of cells to repair tissue damage
- Re-establish normal structure and function of tissue
By which process do immune cells get from the blood vessels to the tissues?
Extravasation
Briefly describe extravasation of a neutrophil
TNFa secreted, which acts on the endothelium. The endothelial wall becomes sticky rather than smooth, Integrin on neutrophil surface binds to adhesion molecule (CAM-1) on endothelial surface, stops moving through the vessel and squeezes out between endothelial cells
What are PAMPs?
Pathogen-associated molecular patterns
What are PAMPs recognised by?
PRRs (pattern recognition receptors)
How do macrophages present antigen?
When a microbe is engulfed, some of its proteins are chopped up into little bits and presented on the macrophage cell surface
What determines donor compatibility for organ transplant?
Major histocompatibility complex
How does a T cell recognise an antigen?
An infected cell presents an antigen peptide bound to an MHC molecule on its surface, which is recognised by the T cell receptor
Why do we only have T cells that recognise non-self?
Any T cells that recognise self are killed in the fetal thymus as they mature (T cell selection)
What happens when a T cell is activated?
IL-2 is secreted by the T cell and binds to the IL-2R receptors (autocrine function); this then leads to diffusion, differentiation, effector functions and memory.
What are CD8 cells?
When activated, become cytotoxic T cells, which can kill intracellular pathogens directly
What are CD4 cells?
Helper T cells, which differentiate into Th1 and Th2
What do Th1 cells do?
Secrete IL-2 and IFN-gamma, which helps kill intracellular pathogens
What do Th2 cells secrete?
IL-4,5, 10 and 13
How do cytotoxic T cells kill infected host cells?
By forming proteolytic granules, releasing perforins and granulysin into the cell and inducing apoptosis
What happens when an APC presents antigen with MHC2 to a naive CD4 cell?
Stimulation with high levels of IL-12 activates the naive CD4 cells to become Th1 cells, which travel to secondary lymphoid tissue (spleen lymph nodes) and proliferate. The Th1 cells recognise the antigen on infected cells via CD4 receptor and secrete INF-gamma, which activates macrophages.
Why are humans born with more than 10^9 immature B cells?
Because each B cell can only make one antibody that will bind one epitope on one antigen; humans therefore have enough to cover all combinations and to detect every single possible epitope on all antigens ever.
What happens to B cells that recognise self?
They are killed in the bone marrow
What happens when a primed Th2 cell binds a B cell presenting antigen via MHC II?
The Th2 cell secretes cytokines IL-4,5,10 and 13, which cause B cells to divide (clonal expansion) and then differentiate into plasma cells and memory B cells.
What 3 things can a specific secreted antibody do?
- Neutralise a toxin by binding to it
- Increase opsonisation via phagocytosis
- Activate complement
What risks might come with mutations in TLRs?
Increased risk of infections, some variants associated with increased risk of chronic inflammatory diseases
What do TLRs do?
They recognise structurally conserved molecules derived from microbes and trigger an immune response by recruiting adaptor proteins to propagate the antigen-induced signal pathway, which eventually leads to the upregulation/suppression of genes that regulate inflammation/transcription
At what point would a TLR recognise a microbe?
When physical barriers have been breached
Why is TLR4 important?
It recognises lipopolysaccharide, which is present in many gram negative bacteria and some gram positive bacteria. It also recognises several viral proteins.
Besides TLRs, name 3 other PRRs
- C-type lectin receptors
- Mannose receptor on macrophages
- Dectin-1 and Dectin-2 (widespread on phagocytes, help recognise beta glucans in fungal walls)
What do Nod-like receptors recognise?
PAMPs and DAMPs (damage-associated molecular patterns)
What happens when a Nod-like receptor recognises a PAMP or a DAMP?
It cooperates with TLRs to regulate inflammatory and apoptotic responses
What specific peptide does NOD2 recognise?
Muramyl dipeptide (MDP), which is a breakdown product of peptidoglycan (forms cell wall of most bacteria)