Immune system Flashcards
What is the name of the group of proteins on the plasma membrane of all somatic cells which identifies the cell as being part of that particular individual?
Major Histocompatibility Complex (MHC)
in humans this is called the HLA (human leucocyte antigen) system
What is the name of the component which sets off an immune response?
antigen
What happens in the first stage of the innate immune response (immediate: 0-4 hours)?
infection
recognition by non-specific molecules in body fluids
removal of infectious agent
What happens in the second stage of the innate immune response (early induced: 4-96 hours)?
infection
innate immune cells activated
Pathogen-Associated Molecular Patterns (PAMPs) recognised and immune cells activate inflammation
removal of infectious agent
What happens in the adaptive immune response (late response: >96 hours)?
infection antigen transported to lymphoid organs naive B and T cells recognise antigen immune cells multiply and become active removal of infectious agent
What are cytokines?
small proteins which act to pass signals between cells
cells involved in both immune responses secrete and respond to cytokines released throughout the body and act both locally and at a distance
How does the increased cytokine level, primarily from the macrophages, influence the liver?
stimulated to produce acute-phase proteins which raises the viscosity of the plasma
an increase in C-reactive protein (CRP) indicates infection:
normal CRP level is <10 mg/L
10-40 mg/L found in mild inflammation and viral infections
40-200 mg/L found in active inflammation and bacterial infections
>200 mg/L found in burns and severe bacterial infections
How does the increased cytokine level, primarily from the macrophages, influence the hypothalamus?
increases body temperature which inhibits replication of pathogens and indicates infection
shivering and sweating may occur in severe fever
How does the increased cytokine level, primarily from the macrophages, influence the heart?
a very severe acute-phase response is septic shock
cytokines increase production of nitric oxide (NO)
this reduces cardiac output and increases vasodilation which decreases blood pressure
What is innate (natural) immunity?
the first line of defence against pathogens
it reacts much quicker than the adaptive system
What are the three functional characteristics of innate (natural) immunity?
it reacts rapidly to pathogens
it responds the same way each time it meets pathogens
it starts again on each occasion that it meets a pathogen
What does innate (natural) immunity consist of?
physical and biochemical barriers of the skin and internal membranes
the inflammatory process
cells of the innate immune system: phagocytes, natural killer cells, mast cells, eosinophils
the complement system which is activated and destroys pathogens
interferons (proteins) which prevent viral replication
How does the skin protect the body from infection?
secretions from sweat and sebaceous glands contain antibacterial and antifungal chemicals and macrophages
How does the respiratory system protect the body from infection?
goblet cells secrete mucus which traps pathogens
cilia move mucus up to the pharynx where it is swallowed
How does the renal system protect the body from infection?
the flow of urine usually prevents pathogens being established
it is often only when renal stones or other blockage occurs or flow of urine is reduced that urinary infections occur
How does the gastrointestinal tract protect the body from infection?
the acid and proteolytic enzymes in the stomach rapidly kill most bacteria entering
some reach the colon and compete with non-pathogenic bacteria normally present
What are the two main phases of the inflammatory response?
vascular and cellular
What happens in the vascular phase?
arterioles and capillaries supplying the damaged area dilate which increases blood flow and causes redness and heat
the permeability of capillaries is increased due to inflammatory mediators from damaged cells and increased pressure caused by increased blood flow to the area
plasma proteins move into the tissues through widened gaps in the capillary walls which increases osmotic pressure in the tissues and draws fluid in
What happens in the cellular phase?
leucocytes are chemically attracted to the site of injury when macrophages release cytokines (e.g. interleukins)
phagocytes arrive at the site of injury and engulf pathogens and cell debris
What are six inflammatory mediators?
histamine, prostaglandins, leukotrienes, serotonin, bradykinin, interleukins
What is histamine?
powerful vasodilator released by mast cells and basophils
increases vessel permeability and contributes to pain by sensitising nerve endings
What are prostaglandins?
contribute to smooth muscle contraction and stimulate nociceptors
promote the inflammatory response
What are leukotrienes?
slow-acting vasoactive substances released by leucocytes
attract eosinophils
What is serotonin?
increases vascular permeability and promotes vasodilation
What is bradykinin?
stimulates unencapsulated sensory nerve endings and is the primary noxious stimulus
What are interleukins?
released from lymphocytes and macrophages
promote communication between B and T cells
What are phagocytes (neutrophils and macrophages)?
mobile leucocytes which engulf and destroy pathogens
they have special receptors called pattern recognition molecules which recognise patterns associated with different types of pathogens (e.g. some identify the double-stranded RNA found in many viruses at some stage in their life-cycle)
phagocytes then engulf the microbes by endocytosis into a vacuole into which enzymes are secreted which kill the microbes
What are neutrophils?
formed in the bone marrow migrate into the bloodstream short lifespan (days) and die of apoptosis
What are monocytes?
formed in the bone marrow
distributed through the bloodstream to the tissues where they stay and differentiate into macrophages (known as microglia in the brain and Kupffer cells in the liver)
What are natural killer cells?
formed in the bone marrow from the same lymphoid cell line as B and T cells
circulate in the bloodstream
recognise cells infected by viruses via the altered MHC which now contains part of the virus protein
rapidly kill the infected cells by releasing cytotoxic proteins onto the cells which respond by apoptosis
What are mast cells?
develop from monocytes
deal with microbes too large to be dealt with by phagocytosis by secreting enzymes from their granules onto the pathogens
these enzymes degrade the microbes and promote inflammation by releasing histamine which increases blood flow to the area
What are eosinophils?
present in the smallest amounts in the bloodstream
involved in defence against parasites, allergic responses, and inflammation
What is the complement system?
a second major system within innate immunity for dealing with infections and reducing the risk of infection overwhelming the host
it consists of >20 plasma proteins, most of which are formed in the liver and function as opsonins to facilitate phagocytosis of bacteria through opsonisation
What are the three pathways by which the complement system is activated?
classical - antigen : antibody reaction
lectin - binds to mannose (a sugar) on microbes
alternative - activated by pathogens
What happens when the complement system is activated?
complement proteins are activated that bind to pathogens, making them ready for phagocytes (carrying the appropriate complement receptors) to engulf them
fragments of some of the complement proteins attract additional phagocytes to where complement activation has already occurred and activate these phagocytes
the final components of complement proteins create pores in the bacterial membrane, which damages and kills them
What are interferons?
proteins secreted by cells of the innate system which can reduce viral replication inside somatic cells
interferons alpha and beta act against viral replication in cells by stimulating the production of antiviral proteins in normal cells
interferon gamma is involved in communication between cells of the adaptive system and macrophages of the innate system
Where do the major pathways in the formation of blood cells emanate from?
myeloid stem cells
What are the major cells in the adaptive immune system?
B- and T-lymphocytes
What are the precursors of B- and T-lymphocytes?
multipotent stem cells in the bone marrow
When activated by antigens, B-cells differentiate into which two types of B-cell?
plasma cells and memory cells
What are plasma cells?
produce antibodies
their unique structure determines which are released into the blood stream to react with antigens
What are memory cells?
express their antibody on the plasma membrane and are long-lived
when they come into contact with the relevant antigen they divide rapidly and produce antibodies
What is humoral immunity?
immunity associated with circulating antibodies produced by plasma cells
When activated by antigens, T-cells differentiate into which four types of T-cell?
T-helper cells, T-cytotoxic cells, T-regulatory cells, and T-memory cells
What are T-helper cells?
provide essential signals that affect behaviour and activity of other cells, particularly B-cells and macrophages that enhance their efficiency
What are T-cytotoxic cells?
kill cells infected with viruses or other intracellular pathogens via cell-mediated immunity
What are T-regulatory cells?
suppress activity of lymphocytes and control immune responses
What are T-memory cells?
include memory helper T-cells (part of T-helper cell clones) and memory cytotoxic T-cells (part of T-cytotoxic cell clones)
these cells do not actively participate in the initial immune response but if they encounter an antigen on a subsequent occasion they initiate a rapid immune response
What are antibodies (immunoglobulins - Igs)?
glycoproteins produced by lymphocytes which combine with antigens
they recognise and bind to particular pathogens and aid their destruction
they are highly specific (they bind only with the antigen where they match the binding site) and they combine with varying degrees of affinity
How is variation in the antibodies produced?
random selection from the sets of duplicated DNA segments
variable joining of the segments
mutations which may occur in the different chains
random selection and pairing of the different chains in the antibody
What is immunity?
the state when an individual has resistance to infection or disease, developed through the innate and/or adaptive immune mechanisms
it can be natural or artificial in development and active or passive in nature
What is passive immunity?
ready-made antibodies delivered
What is artificial passive immunity?
ready-made antibodies from person or animal injected into individual
What is natural passive immunity?
maternal antibodies supplied to baby across placenta and through breast milk
What is active immunity?
developed by the individual in response to antigens
What is natural active immunity?
person develops antibodies in response to having disease or subclinical dose
What is artificial active immunity?
antibodies develop after vaccination with dead or weakened microbes or toxins
What are the four stages of the primary antibody response?
lag - period between exposure and onset of symptoms, the cells involved are beginning to divide and differentiate
log phase - antibody concentration increases exponentially as cells stimulated by antigen differentiate into antibody-secreting plasma cells
plateau - antibody synthesis and decay are balanced - levels are constant
decline - antibody decay is greater than formation - levels fall
How do the responses change with the first and subsequent exposures to an antigen?
timing - the length of the lag phase is much shorter in the secondary response, while the plateau and decline stages are much longer
antibody levels - antibody levels are much higher in the plateau stage of the secondary response
antibody type - IgM is most important in the primary response
What is immunisation?
the process of inducing immunity to an infectious organism or agent in an individual (or animal) through vaccination
What is vaccination?
the administration of a vaccine which is a biological preparation that improves immunity to a particular disease
What are the diseases vaccinated against in the UK?
diphtheria, tetanus, pertussis (whooping cough), polio - months 2, 3 and 4/3 years 4 months or soon after
tetanus, diphtheria and polio - 13-18 years (around 14 years)
rotavirus - months 2 and 3
Haemophilus influenzae type b - months 2, 3 and 4/12-13
meningococcal group C disease -
influenza - years 2, 3 and 4, plus school years 1 and 2/annually from 65 years
human papillomavirus (cervical cancer) - girls aged 12-13 years
shingles - 70 years
What are the diseases vaccinated against in the UK?
diphtheria, tetanus, pertussis (whooping cough), polio - months 2, 3 and 4/3 years 4 months or soon after
tetanus, diphtheria and polio - 13-18 years (around 14 years)
pneumococcal disease:
pneumococcal conjugate vaccine (PCV) - months 2, 4, 12-13
pneumococcal polysaccharide vaccine (PPV) - 65 years and over
rotavirus - months 2 and 3
Haemophilus influenzae type b - months 2, 3 and 4/12-13
meningococcal group C disease - months 3, 12-13/13-15 years/18-25 years (for students)
measles, mumps and rubella (German measles) - months 12-13/ 3 years 4 months or soon after
influenza - years 2, 3 and 4, plus school years 1 and 2/annually from 65 years
human papillomavirus (cervical cancer) - girls aged 12-13 years
shingles - 70 years
What is the immunisations given for those at risk in the UK?
hepatitis B - at birth, months 1, 2 and 12 tuberculosis - at birth influenza - 6 months-2 years/2-65 years pneumococcal disease - 2-65 years pertussis - from 28 weeks of pregnancy
What is hypersensitivity?
several types: 1,2,3,4
based on delay between exposure to antigen and hypersensitivity reaction
examples: hay fever, asthma, foods, drugs, haemolytic disease of new-born
What is autoimmunity?
antibodies act against self-antigens and cause tissue damage
examples: type 1 diabetes, rheumatoid arthritis, Graves’ disease (hypersecretion of thyroid gland)
What is immunodeficiency?
impaired immunity with increased risk of infection and malignancy
What is primary (congenital) immunodeficiency?
genetic basis: rare and cause severe infections early in life
What is secondary (acquired) immunodeficiency?
acquired during life: through lymph gland malignancies, cytotoxic therapy, AIDS, etc.
