1 Introduction To Immunology Flashcards
*Q: What is the purpose of the immune system? What does it also detect? What type of process is this?
A: The environment is full of microorganisms - the immune system is a complex cellular and protein network that has evolved to protect the host from pathogenic microbes.
Tissue damage is also recognised by cells of the immune system-> type of HOMEOSTASIS
Q: What does the failure of the immune system lead to? (2) When the regulation of the immune system becomes unbalanced, what can it lead to? (2)
A: increased susceptibility to infection and sometimes cancer.
autoimmune disease and allergy.
Q: What is the normal function of the immune system? What enables it to do this? (2) What’s more important?
A: Identify and eliminate harmful microorganisms and harmful substances such as toxins:
By distinguishing self from non-self proteins
AND
By identifying danger signals (eg inflammatory signals)
you need both to trigger an immune response
Q: What reproduces faster, virus or bacteria?
A: Bacteria
*Q: Describe the evolutionary arms race between pathogen and host. (3)
A: The pathogen exerts selection on the host and the host exerts selection on the pathogen.
The pathogen reproduces much faster than the host and hence can evolve faster.
Therefore, the host relies on a flexible and rapid immune response.
Q: Which human genes are involved in the immune system? (2) How have they been selected?
A: Our most polymorphic genes - HLA, KIR- this variation has been selected for by exposure of populations to infectious disease.
*Q: What is the initial immune response called? Summarise the time-course of a primary immune response to a virus with a diagram. (3 lines) Explain the role of 3 cells involved.
A: The initial response is the innate immune response.
Early peak of type 1 interferon (interferes with the replication of the virus)
Peak in NK cells (can recognise infected cells and lyse them)
These responses help to flatten out virus replication.
To eliminate the virus you need more specific immune responses from the adaptive immune system - this takes a little more time.
Rise in Cytotoxic T Lymphocytes (recognise and lyse infected cells)
CTLs start producing antibodies against the virus
Graph: days after viral infection against magnitude of response with lines for: type 1 interferon (alpha and beta)= peak day 2, natural killer (NK) cells= peak day 4, cytotoxic T lymphocytes (CTLs)=plateaus day 7/8, antibody, (virus titer)
*Q: What is the primary response?
A: the first time the host has seen this particular virus
*Q: Describe the innate immune response. When is it present from? What does it rely on? When the infection occurs, are the components ready? What’s the range for specificity? Which type of molecular patterns does it recognise?
A: Present from birth
Relies on pre-formed and rapidly synthesised components
If an infection happens, the components are already there to deal with it.
Limited specificity (non antigen specific)
Only recognises molecular patterns to do with danger (non self)
*Q: Describe the acquired/adapted immune response. When is it acquired? What does it depend on? Is it specific or non specific?
A: Acquired after exposure to the pathogen- Gives immunological memory
Depends on CLONAL SELECTION
Slow - takes days
Antigen Specific
*Q: What is clonal selection? What is clonal expansion?
A: selection of appropriate lymphocyte to fight the pathogen
expansion of the clone of lymphocytes which recognises the particular pathogen
Q: What are examples of anatomical barriers for innate immunity? (3)
A: Skin
Mucus - trapping microbes
Cilial propulsion on epithelia
Q: What are examples of physiological barriers for innate immunity? (5)
A: Low pH
Secretion of lysozyme
Interferons
Anti-microbial peptides
complement
Q: When do antibodies develop?
A: don’t develop until you’ve been exposed to the pathogen so it’s totally part of acquired immunity
Q: What triggers the innate immune response? 2 types?
Examples? (2,3) Receptors? (1,3)
A: Pathogens have various molecular structures which aren’t present on normal cells - the immune system can take advantage of these differences and respond to these patterns.
-Pathogen Associated Molecular Patterns PAMPs (E.g. dsRNA in cytoplasm, bacterial cell wall components) ->
Pattern-recognition Receptor = TLRs (Toll-like receptors)
-Danger Associated Molecular Patterns DAMPs (E.g. Monosodium urate, high extracellular [ATP], reactive oxygen species) -> Pattern-recognition Receptors = NLRs - NOD-like receptors, RLRs - RIG-I-like receptors, AIM2
Q: Why is high extracellular [ATP] a sign of danger?
A: because ATP isn’t useful outside cells.
Q: What does the innate immune response do? (2) Main consequences? (3)
A: Destroys invading nucleic acids (e.g. viruses) in the cytoplasm
Activates interleukins which, in turn, activate inflammatory pathways
Evokes type 1 interferons - bind to receptors on nearby cells and induces an antiviral state.
Main consequences: Suppresses pathogen replication, buys time, kick starts the acquired immune response
Q: What is the acute phase inflammatory response? What does it involve? (2) What triggers 1?
A: innate response to tissue damage
Fever - indicative of acute phase inflammatory response (This is triggered by activation of interleukin-1)
Followed by production of acute phase proteins
Q: What are acute phase proteins? What are 3 acute phase proteins? Where are they produced?
A: soluble pattern recognition receptors
C-reactive protein, Serum amyloid protein, Mannan-binding lectin
liver
Q: What do the acute phase proteins do? Describe each one. What happens following binding? (2)
A: C-reactive protein and serum amyloid protein - bind to molecules found on the cell wall of some bacteria and fungi.
Mannan-binding lectin - binds to mannose sugar molecules which are not often found in mammalian cells.
Once these proteins are bound, phagocytes have receptors which can recognise these proteins and proceed to ingest the infectious agent.
binding can also trigger responses - it helps activate the complement system
Q: Describe cytokines. (2) What causes a cell to produce them?
A: Large family of soluble molecules - they are proteins that transmit information between cells
Some sort of stimulus
Q: How do cytokines act? (4) Important for?
A: diffuse to nearby cells, bind to specific receptors and send a signal to the cell to alter the pathogen gene expression. Proteins will either be upregulated or downregulated leading to the biological effect
proliferation of lymphocytes
Q: 3 examples of granular leukocytes?
A: Natural Killer (NK) Cells, Macrophages, Granulocytes (3 types)
Q: What are natural killer (NK) cells? What do they do?
A: Type of cytotoxic lymphocyte
Identify and kill virus-infected cells and tumour cells
Q: What are macrophages? What do they do?
A: Mononuclear phagocytes, Release cytokines as signals of danger
Q: What are the 3 types of granulocytes? What do they do? Phagocytic? Which is most common?
A: Basophils- Least abundant type of granulocyte, Not phagocytic, Release histamines,
Neutrophils- Also called polymorphonuclear neutrophils (PMN), Nucleus is multi-lobed, Phagocytic ** most common
Eosinophils- Bi-lobed nucleus, Important in immune response to parasites,
*Q: Define antigen.
A: a molecule that reacts with antibodies or T cells
*Q: Define antibody. Bind to?
A: an immunoglobulin molecule in the blood and body fluids which binds specifically to an antigen
*Q: Define an immunogen.
A: antigens that initiate an immune response
Q: What are the 5 classes of immunoglobulins? Which makes up the most in serum Ig?
A: all are a class of proteins
IgG* 75%
IgM 10%
IgA
IgE
IgD v low
Q: What are IgG? Length of half life?
Which response are they part of?
A: Monomeric antibody
Long half life in serum
Crosses the placenta from mother to foetus to give the new born immunity against infection.
Part of secondary immune response
Q: What are IgM? What shape are they? How many binding sites does it have? What are they good at? What response are they important in?
A: Pentamer - star shaped
Multivalent antibody - 10 binding sites
Good at agglutinating (clumping together) pathogens
Important in primary immune response
Q: What are IgA? What are they found in? What do they contain- what does this do?
A: Dimer Found in body secretions (mucosal surfaces)
Contains secretory .component - protects it from degradation on mucosal surfaces which usually have proteases present (hostile environment)
Q: What are IgE involved in? How do they act?
A: Involved in allergic responses
Binds to basophils and mast cells and triggers the release of histamines.
Q: What are IgD involved in?
A: Predominantly involved in membrane bound form on B lymphocytes in signalling
Q: How does an antibody recognise an antigen?
A: that antibody’s binding site makes a perfect fit with a region (EPITOPE) on the antigen.
Q: What is the epitope of the antigen?
A: the part of the antigen that is bound by the antibody
Q: What are the 4 mechanisms that an antibody kills a virus?
A: Binds to virus - prevents attachment to cell
Opsonisation - virus is coated in antibody so it can be more easily phagocytosed.
Complement - mediated lysis of membrane bound virus
Antibody-Dependent Cell-Mediated Cytotoxicity (ADCC) - mediated by NK-like cells - if the cell is infected, there will be viral proteins in the membrane - the cell becomes coated with antibody - NK cells have receptors which can recognise these antibodies and lyse the infected cells.
Q: What are the cells of the acquired immune system? 2 types?
A: Lymphocytes - agranular leukocytes (majority are in the lymph)
T-cell = Thymus derived B-cell = Bone marrow derived
There are many subtypes of these molecules which are distinguished by CD markers
Q: What are the 3 types of antigen-specific lymphocytes?
A: B cell (humoural)
Helper T-cell
Cytotoxic T-cell (CTL)
*Q: What is active immunity? (2)
A: the type of immunity that is actively developed in an individual in response to a pathogen or vaccination - it is an acquired response to the antigen
*Q: What is passive immunity? Give an example.
A: the transfer of pre-formed antibodies into a person to give them defence against a pathogen
IgG from mother to baby gives the baby passive immunity
*Q: What is the difference between the primary and secondary immune response? (2)
A: Secondary = subsequent exposure to the same pathogen
Secondary Response - BIGGER response + FASTER
Q: How do the B cell and T cell antigen receptors differ?
A: B-cell antigen receptor is a membrane bound antibody- These bind INTACT antigens
There are 2 protein chains (a and b) which together make the T cell antigen receptor (TCR) - These only bind DIGESTED (PROCESSED) antigen fragments
*Q: How does the TCR recognise an antigen?
A: TCR recognises a complex of: Antigen Peptide + HLA (MHC) Molecule
*Q: What is the MHC? Role? AKA?
A: Major Histocompatibility Complex - these molecules present processed antigens to T lymphocytes
The MHC is humans is also known as the HLA (Human Leukocyte Antigen)
Q: How is clonal diversity generated in humans?
A: During B and T cell development - RANDOM GENETIC RECOMBINATIONS take place within each cell among multiple copies of:
B cells - Immunoglobulin gene segments
T cells - TCR gene segments
-> end up with a very large repertoire of different receptors which can respond to a large variety of antigens
Q: Describe the clonal nature of the adaptive immune response?
A: Each lymphocyte carries a single, unique antigen receptor
There are millions of lymphocytes, hence, millions of different antigen receptors in the body.
Lymphocytes which have a binding site that is complementary to an antigen will proliferate and survive.
The majority of lymphocyte clones die out.
Q: What are naïve lymphocytes?
A: lymphocytes which have never come into contact with their antigen before
Q: What causes selective expansion of a clone of a T or B cell?
A: antigen will bind to the surface receptors on the B cell (Ig) or T cell (TCR)
Q: What happens to lymphocytes that have proliferated during the primary immune response?
A: Most will DIE after fulfilling their function
Some lymphocytes survive as memory cells
Q: How does the immune system clear the pathogen during the primary immune response?
A: Cytotoxic T Lymphocytes (CTLs) kill infected cells by injecting lethal enzymes
Antibodies bind to the pathogen and direct phagocytes to come and ingest them
Q: Summarise using a flow diagram the primary immune response in terms of lymphocytes.
A: antigen
|
\ /
Naïve lymphocytes (polyclonal) ———–> activation -> clonal expansion -> effector lymphocytes
Q: What is the role of a APC? How do they form?
A: transport the antigens from the tissues into secondary lymphoid organs
Antigens meet T cells in secondary lymphoid organs
Antigen-presenting cells capture, process and present antigens to T lymphocytes
APCs are good at activating T cell responses- Immune response
*Q: How is the lymphatic system organised?
A: Lymphatic Vessels: Venules, Veins, Ducts
Lymphatic Tissues: Nodules, Nodes, Tonsils, Peyer’s Patches
Lymphatic Organ: Spleen, Thymus
*Q: What does the lymphatic system do to aid immune responses?
A: lymphatic system drains body fluid from between tissue cells via lymph nodes through which lymphocytes recirculate-> T lymphocytes have the chance to interact with antigens
Q: Are innate or acquired responses faster?
A: innate
Q: Draw a diagram showing the cells and humoral factors involved in innate and acquired immunity.
A: cells:
innate- neutrophils, NK cells
both- macrophages, monocytes, dendritic cells, mast cells
adaptive- macrophages
soluble factors:
innate- antimicrobial peptides
both- complement, cytokines
adaptive- antibodies
*Q: Define T lymphocyte. (where is it produced and what does it participate in). Where do most circulate?
A: a lymphocyte of a type produced or processed by the thymus gland and actively participating in the immune response
98% in lymph
*Q: Define B lymphocyte. (where is it not produced and what is it responsible for).
A: a lymphocyte not processed by the thymus gland, and responsible for producing antibodies
*Q: Describe lymphocyte cells. (2)
A: mononuclear, part of leukocyte/WBC lineage
*Q: What are the surface markers found on T lymphocytes?
A: CD3 (all cells), CD4 (subset), CD8 (different subset)
*Q: What are the surface markers found on B lymphocytes?
A: CD19, CD20
Q: What are APC also called?
A: dendritic cells
