Immunology Flashcards
What is innate immunity?
instinctive, non-specific immunity independent of lymphocytes and present from birth, 1st line of defence and no memory
What is adaptive immunity?
specific ‘acquired/learned’ immunity, requires lymphocytes and antibodies, faster response and has memory of specific antigens.
What do innate and adaptive immunity have in common?
They are both humoral defences, made up of cells and soluble factors
What are the components of blood?
Upper layer - Plasma (50%) = 90% water + electrolytes, proteins, lipids, sugars etc.
Middle layer - buffy coat (~1%) = leukocytes (WBCs)
Lower layer - haematocrit (45%) = erthyrocytes, platelets
What is serum?
Blood plasma minus clotting factors (e.g. fibrinogen)
What are leukocytes and where are they produced?
Leukocytes is the over-arching term for white blood cells and they are produced in the bone marrow by haematopoiesis.
What are polymorphonuclear leukocytes?
Leukocytes with multi-lobed nuclei which also contain granules that release enzymes during infections, allergic reactions and asthma. (Neutrophils, eosinophils and basophils)
What are mononuclear leukocytes?
Leukocytes with round, single-lobed nuclei that are agranular. (Monocytes, T and B lymphocytes)
What are the soluble factors in the blood involved in immune response?
Complement factors, antibodies and cytokines/chemokines.
What are complement factors?
A group of ~20 proteins secreted by the liver which help immune cells to fight infection and maintain homeostasis.
What are the 3 modes of action of complement factors?
- Direct lysis
- Attract more leukocytes to the site of infection (chemotaxis)
- Coat invading organism
What are antibodies?
Also known as immunoglobulins, antibodies are soluble blood proteins produced by B-lymphocytes (plasma cells) in response to and counteracting a specific antigen.
What are the 5 classes of antibodies and their functions?
IgG - the most common antibody (70-75% of antibodies in humans), found mainly in blood and tissue fluids, help protect your body from viral and bacterial infections.
IgA - found in saliva, tears, mucus, breast milk and intestinal fluid, protect against ingested and inhaled pathogens.
IgM - found in the blood and lymph system, first line of defence against infections, also important in immune regulation.
IgD - found on the surface of your B cells, exact function unknown but thought to support B cell maturation and activation.
IgE - found mainly in the skin, lungs and mucus membranes, cause mast cells to release histamine and other chemicals into your bloodstream in allergic responses
What is the function of IgG antibodies?
- Enhance phagocytosis of bacteria and viruses
- Fixes complement and passes to the fetal circulation
- Most abundant isotype in blood serum
What is the function of IgA antibodies?
- found in breast milk, saliva, tears, mucus and intestinal fluid
- provides localised protection on mucous membranes against inhaled and ingested pathogens
What is the function of IgM antibodies?
- first immunoglobulins secreted in immune response
- fixes complement but does not pass onto foetal circulation
- Anti-A, B blood antibodies
What is the function of IgD antibodies?
- role largely unknown
- found on surface of B cells
- thought to be involved in B cell activation
What is the function of IgE antibodies?
- mediate type 1 hypersensitivity reactions
- synthesised by plasma cells
- binds to Fc receptors found on the surface of mast cells and basophils
- provides immunity to parasites like helminths
What is the structure of antibodies?
Y-shape made up of 2 variable (Fab) regions which bind specific antigens and 1 constant (Fc) region which binds to complementary Fc receptors on phagocytes, natural killer cells etc.
What are cytokines?
The “hormones” of the immune response. Proteins secreted by immune and non-immune cells which communicate between them.
What are 5 types of cytokines and their functions?
Interferons (IFNs) - induce antiviral resistance in uninfected cells (IFNa & b - produced by virus infected cells, IFNg - released by activated T cells)
Interleukins (e.g. IL-1) - produced by many cells and over 30 types, regulate inflammatory response and can cause cells to divide, differentiate and secrete factors.
Colony Stimulating Factors (CSFs) - involved in directing the division and differentiation of bone marrow stem cells (leukocyte precursors)
Tumour Necrosis Factors - mediate inflammation and cytotoxic reactions (TNFa & b)
Chemokines (IL-8) - leukocyte chemoattractants
What are the components of innate immunity?
- Physical and chemical barriers
- Phagocytic cells (neutrophils and macrophages)
- Blood proteins (complement, acute phase)
Why do we need adaptive immunity?
- microbes evade innate immunity
- intracellular viruses and bacteria ‘hide’ from innate immunity
- need memory to specific antigen for a faster response
What is cell-mediated immunity?
An adaptive immune response requiring intimate cell-cell contact and involving antigen presenting cells and T-cells.
How do T-lymphocytes recognise self or non-self?
T cell receptors (TCR) on the cell surface recognises foreign antigens in association with major histocompatibility complex (site on cells which presents antigens).
How does the variable (Fab) site of antibodies work to protect against infection?
- neutralize e.g. toxins (IgG, IgA)
- immobilise motile microbes (IgM)
- prevent binding to and infection of host cells
- form complexes
How does the constant (Fc) region of antibodies prevent infection?
- activate complement (IgG, IgM)
- bind Fc receptors (IgG, IgA enhance phagocytosis, IgE cause mast cells to release inflammatory mediators, IgG cause natural killer cells to enhance killing of infected cells)
What is the action of T helper cells (CD4 +ve)?
- help B cells make antibodies
- activate macrophages and natural killer cells
- help development of cytotoxic T cells
What is the action of T cytotoxic cells (CD8+ve)?
To recognise and kill infected host cells.
What is the action of T regulatory cells (CD4+ve)?
To suppress immune responses.
What is the major histocompatibility complex?
Also known as human leukocyte molecules (HLA) it is a group of genes that code for proteins found on the surface of cells that help the immune system recognise foreign substances.
Which cells express MHC1?
All nucleated cells express MHC1. (e.g. a virus-infected or cancer cell would express MHC1). MHC1 displays antigens to CD8+ve (cytotoxic) T cells
What is the function of CD8+ T cells (cytotoxic T cells)
cytotoxic killing
- perforin secretion (mediated by granzyme B)
- express Fas L –> activated caspases
Which cells express MHC2?
Antigen presenting cells ONLY e.g. macrophages, B cells, dendritic cells. MHC2 displays antigens to CD4+ve (helper) T cells.
What is the function of CD4+ T cells (T helper)?
Th1 produce interferon gamma and activate NK cells and macrophages (↑innate response)
Th2 produce IL4 which activates B cells to differentiate into plasma cells
What are the steps of antigen presentation and T-cell antigen recognition? (MHC1)
- Virus infected cell makes virus proteins which are broken down in cytosol.
- Viral peptides are transported to host cell ER where they bind to MHC1 and are presented on CSM.
- Cytotoxic T cells recognise peptide bound to MHC1.
- Activated cytotoxic T cells kill the infected cell by inducing apoptosis.
What are the steps of antigen presentation and T-cell antigen recognition? (MHC2)
- Macrophage/dendritic cell/B cell internalises and breaks down foreign material.
- Peptides bind to MHC2 in endosomes and are presented on CSM.
- Helper T cells recognise peptide bound to MHC2.
- Activated T helper cells help B cells make antibody and produce cytokines which which activate/regulate other leukocytes.
What is the function and source of IL-1?
Induces inflammation, fever, activation of leukocytes and is produced by macrophages, endothelial and epithelial cells.
What is the function and source of IL-2?
To stimulate T, B and NK cell growth, produced by T cells.
What is the function and source of IL-8?
To induce neutrophil chemotaxis. Produced by macrophages, endothelium, fibroblasts, keratinocytes.
What is the function and source of IL-10?
To down-regulate TH1 cytokines, MHC2 expression. Produced by monocytes, TH2 cells.
What is the function and source of Interferon gamma?
To activate macrophages and NK cells, increases MHC2 expression, produced by TH1 cells, NK cells
What is the function and source of tumour necrosis factor-a?
Activates neutrophils, endothelial cells and induces cachexia (loss of muscle & body fat). Produced by T cells, macrophages and NK cells.
What is the function of TH1 cells?
Important in intracellular infections
- Produce IL-2, y-interferon and TNF-b.
- Activate macrophages –> inflammation.
- Promote production of cytotoxic T cells
- Induce B cells to make IgG antibodies
What is the function of TH2 cells?
Important in parasitic worm (helminth) infections and allergy.
- Produce IL-4, -5, -6, -10 and -13
- activate eosinophils and mast cells
- induce B cells to make IgE - promotes release of inflammatory mediators (e.g. histamine from mast cells)
Which cytokines do regulatory T cells (TREG) produce?
IL-10, TGF-b.
What kind of immunity are PRR’s (pattern recognition receptors) and PAMP’s (pathogen-associated molecular patterns) associated with?
Innate immunity
Name 3 receptors that make up the PRR family.
- Toll-like receptors (TLR)
- Nod-like receptors (NLR)
- Rig-like receptors (RLR)
What is the main function of TLRs?
They send signals to the nucleus to secrete cytokines and interferons which initiate tissue repair. Enhanced TLR signalling = improved immune response
What are some important types of TLRs and their functions?
2 - detects gram +ve bacteria + TB
4 - detect lipoploysaccharide on -ve bacteria (most important)
5 - detect flagellin on bacteria
7 - single stranded RNA (intracellular TLR)
9 - non-methylated DNA (intracellular TLR)
Which types of TLRs are intracellular?
3, 7, 8, 9
What is the action of TLR-4?
Activated by LPS of gram -ve bacteria (endotoxin).
Lectins in the bloodstream bind the pathogen
Then trigger immune response –> activated complement , stimulate cytokine release (TNFa, IL1, IL6)
Results in increased phagocytosis
What is the main function of NLR’s?
They detect intracellular microbial pathogens. They release cytokines and can cause apoptosis if the cell is infected.
What is the main function of RLR’s?
To detect intracellular double stranded RNA. This triggers interferon production and so an antiviral response.
Steps of Phagocytosis
- Pathogen binds to neutrophil/macrophage
- Engulfment of pathogen
- Phagosome formation
- Lysosome fusion - phagolysosome.
- Pathogen is destroyed
Which MHC would an intracellular antigen (endogenous) lead to the expression of?
MHC1
Which MHC would an extracellular antigen (exogenous) lead to the expression of?
MHC2
What do B cells differentiate into?
Plasma cells. The plasma cells then produce antibodies.
How many antibodies can each B cell make?
Each B cell can only make 1 antibody. This 1 antibody can only bind to 1 epitope.
Define allergy
Abnormal response to harmless foreign material (allergens).
Define atopy
Tendency to develop allergies.
What are the common clinical indications of an allergic reaction?
- skin - swelling, itching, reddening
- airways - excessive mucus production, bronchoconstriction
- GI - abdominal bloating, vomiting, diarrhoea
- anaphalaxis - airway, breathing, circulation…
Define hypersensitivity
Exaggerated or inappropriate immunologic responses occurring in response to an antigen or allergen.
What are 4 allergic diseases?
allergic asthma, anaphylaxis, atopic dermatitis (exzema), allergic rhinitis (hay fever)
What does a type 1 hypersensitivity reaction involve?
Immediate hypersensitivity, or ‘allergy’, due to activation of IgE antibody on mast cells or basophils
What does a type 2 hypersensitivity reaction involve?
antibody to cell-bound antigen (IgG antibody mostly but also IgM)
What does a type 3 hypersensitivity reaction involve?
immune complex reactions, IgG antibodies and T cells involved
What does a type IV hypersensitivity reaction involve?
Delayed hypersensitivity mediated by T cells
Which cell types express FcεRI (high affinity IgE receptor)?
Eosinophils, mast cells, basophils
What are macrophages and what is their function?
White blood cells with single round nuclei derived from monocytes.
- Involved in phagocytosis of cellular debris and pathogens
- antigen-presenting cells
- secrete cytokines (TNF-a, IL-1, IL-12)
Describe neutrophils and their function
Principle cell of acute inflammation, polymorphonuclear, phagocytic and bactericidal. Most common wbc and have multi-lobed nucleus.
- granules contain myeloperoxidase and lysozyme
- rapidly egress into tissues during acute infection.
Describe basophils and their function
Circulating mast cells with bi-lobed nuclei.
- Release histamine during allergic response upon IgE cross-linking Fcε receptors.
- Granules contain histamine and heparin
Describe eosinophils and their function.
Bi-lobed WBCs important in parasitic infections (protozoa and helminths)
- Release cationic granules and reactive oxygen species.
Describe mast cells and their function.
Similar in function to basophils.
- release histamine in allergic response
- granules contain histamine and heparin
- express IgE receptors on CSM
Describe NK cells and their function.
Non-phagocytic white blood cells that release lytic granules that induce apoptosis in virus-infected cells. They recognise self and non-self by the presence of MHC-1 on cell surfaces.
Which cells are the most potent antigen presenting cells?
Dendritic cells
Differentiate active and passive immunity
Active immunity involves exposure to the pathogen and the body producing its on antibodies in response which takes time but is long-lasting.
In passive immunity the body receives antibodies from another immune individual and this protection is immediate but temporary.
What are examples of passive immunity?
- cross-placental transfer of antibodies from mother to child
- transfusion of blood or blood products including immunoglobulins
What kind of immunity does vaccination result in?
Active immunity as the body produces its own antibodies in response to a specific antigen/infection.
What is the function of cytotoxic T cells?
- involved in cell-mediated immune response
- recognises antigens presented by MHC I molecules
- Induce apoptosis in virally infected and tumour cells
- Express CD8, CD3, TCR
- Mediates acute and chronic organ rejection
Which cells are antigen-presenting?
Dendritic (main ones), macrophages, B cells
Which cells are antigen-presenting?
Dendritic (main ones), macrophages, B cells
What are the 3 main functions of the complement system?
- activation of inflammation
- opsonisation (labelling) of pathogens and cells for clearance/destruction
- direct killing of target cells/microbes by lysis
What are the immunological changes seen in progressive HIV?
reduction in CD4 count
increased B2-macroglobulin
decreased IL-2 production
polyclonal B-cell activation
decreased NK cell function
reduced delayed hypersensitivity responses
