BIOL123 - L2 - 4

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  • Created by: Katherine
  • Created on: 01-06-16 22:28
What is immunology?
It is understanding of how the body distinguishes itself from non self
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What was the origin of immunonolgy?
Immunis - Latin, meaning if you recover, you'll never get it again
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What are the requirements for ideal effective immune response?
Recognition of nonself, and targeting
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What is the process of recognition?
Specificity, targeting, discrimination
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What is the process of targeting?
Specificity, killing, memory
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What are the different types of immunity?
Innate and Acquired
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What is innate immunity?
It is non-specific, effective against a wide range of pathogens, present at birth, life long, present in all animals, active when born.
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What are the kinds of innate immunity?
Physical barriers, physiological barriers, phagocytosis, inflammation,
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What are the physical barriers?
The skin and the mucous membranes
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Why is the skin a good phyical barrier?
It is made up of dead cells and bacteria. These are useful as they cannot be infected. The bacteria on skin compete with invading organisms for attachment sites. The sebaceous gland beneath the skin release fatty acids, lactic acid = low pH. Dryness.
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Why is a low pH good?
Because it inhibits microbial growth.
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Despite the skin being a good barrier, there are ways to break it, how?
Bites e.g. Mosquitos, ticks and fleas.
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Where are mucous membranes found?
In the respiratory system
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How are these a good physical barrier?
They trap microorganisms which are then shed from the body.
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What are on the mucous membrane to help?
Cilia. They waft the mucus up to the mouth where it is swallowed or coughed out
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What are the physiological barriers?
pH and the environement, fever, chemical mediators
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Why is ph a physiological barrier?
Low pH in stomach to prevent pathogen growth. It is a pH of about 2. But hepatitis A can survive at such low ph.
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Why is fever a physiological barrier?
It prevents pathogen growth. It allows the thermoset of the body to be raised, speeding up phagocytosis and inhibits microbial growth too.
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Why are chemical mediators phyiological barriers?
Complement proteins cause the lysis of invading material.
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How do complement proteins do this?
They coat the invading material.
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What is the coating by complement proteins called?
Opsonisation.
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What is antibody opsonisation?
It is the process by which a pathogen is marked for ingestion and eliminated by a phagocyte. The proteins cause recruitment of other complement proteins which results in a membrane attack complex (MAC); this causes the pathogen to lyse.
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What do antimicrobial proteins do, and what is an example?
Lysozymes in tears. These break down peptidoglycan in the walls and get rid of the pathogen.
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What do interferons do?
They induce anti-viral state in cells (inhibit viral reproduction in cells). Interferon is released from viral infected cell, helps cells be resistant to the virus = antiviral state. It causes the production of ribonuclease which inhibit reproduction
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What is an antimicrobial peptide?
Defensin
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What is a peptide and what does defensin do?
It damages the pathogens. The positively charged defenins insert into a bacterial microbe and cause it to burst
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What is phagocytosis?
Engulfement and ingestion of invading bacteria carried out by phagocytes (phagocytic cells).
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What are examples of phagocytes?
White blood cells (Neutrophils, macrophages, eosinophils and dendritic cells)>
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When does phagocytosis occur?
If microbes penetrate the first line of defence (skin).
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What is the process of phagocytosis?
Pseudopodia which have receptors for microbial polysacchardides on the surface attach to microbes. The microbes are engulfed by the macrophage and placed in a phagosome.
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What happens to the phagosome?
It fuses with a lysosome (which contains nitric oxide and reactive oxygen species, also a hydrolytic enzyme called lysozyme.
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What does the lysozyme do?
It degrades microbial proteins
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What is it called when the phagosome fuses with a lysosome?
It forms a phagolysome.The degraded antigen is presented on the surface of the macrophage on class II MHC to Helper T cells.
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After ingestion of bacteria, there are how many separate killing mecahnisms? And what are they?
2 - Oxygen dependent killing and oxygen independent killing.
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What is oxygen dependent killing?
Nitric oxide synthetase is activated and Nitric oxide is generated - this acts as an antimicrobial.
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What is oxygen independent killing?
This involves hydrolytic enzymes (lysozyme) and defensins - antimicrobial peptides which kill bacteria
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What is the process of inflammation?
It is a rapid response to tissue damage that serves to contain the infected and recruit other components to the site of infection.
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Where is histamine release from?
Mast cells present in connective tissue. It is released when connective tissue is damaged.
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The damage of the connective tissue triggers what?
Vasodilation further downstream further downstream there is a constriction, which leads to decreased blood flow. Prostaglandins from macrophages help with vasodilation.
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Histamine and prostaglandis released by macrophages also do what?
Enhance permeability of capillaries. This enables more fluid tissue to enter the tissue leading to swelling (oedema) and this carries with it: antimicrobial proteins and clotting elements which plug the hole and prevent spreading of microbes.
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How does the blood clot form?
Fibrinogen soluble protein in blood is converted to fibrin - insoluble fibres which form the clot, and complement cascades are activated which result in the pathogen being killed.
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What does the increased permeability mean?
That phagocytes can enter the tissue and destroy the pathogen.
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What is IL-8?
It is a chemokine which is released by damaged endothelial cels. It helps neutrophils to migrate through the capillary wall.
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What does TNF alpha do?
Released from tissue macrophages helps to catch neutrophils passing by in the blood - the neutrophils then migrate through the capillary wall.
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What do the chemokines do?
Direct migration of phagocytes and stimulate the formation of more neutrophils by the bone marrow.
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What do macrophages do?
Migrate into tissue and secrete IL-1 and TNF alpha to recuit lymphocytes
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What is the first stage of the local inflammatory response?
Chemokine release - IL8 released from damaged endothelial cels and TNF - a release from macrophages help to recruit neutrophils and allow migration from blood. Histamine release from mast cell, vasodilation and increase blood vessel permeability.
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What are chemokines?
Molecules that direct molecules of white blood cells.
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What is the second stage of the local inflammatory response?
Activation of clotting and complement cascades
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What is the third stage?
Neutrophils secrete chemokines to recruit macrophages from blood
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The fourth?
Phagocytosis of pathogens.
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Fifth?
Macrophages migrate into tusse and secrete IL-1 and TNF a to recruit lymphocytes, monocytes and neutrophiles.
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In addition to the local inflammatory response, there is a systemic response, what is this called?
Systemic acute phase response
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What is the acute phase response characterised by?
Fever, leukocytosis, acute phase protein production by the liver
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What does fever do?
It speeds up phagocytosis, speeds up body reactions and hence healing reactions
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What does leukocytosis do?
Increase in producton of white blood cells - notably neutrophils which increase by 10 fold
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What is acute phase protein production by the liver?
1000 fold increase in actute phase phase response, binds to microbes, activates certain complement proteins, which faciliate phagocytosis.
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What can overwhelming infection cause?
Septic shock - very high fever and low blood pressure - a major cause of death
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The liver has reactive proteins (CRP) which is an opsoinin, that can do what?
Form a membrane attack complexes by recruiting other proteins.
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Is inflammation part of the acquired immune response?
False
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Lymphocytes are part of the innate immune response?
True
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Chemokine release from neutrophils can recruit macrophages to an area of damaged skin?
True
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Complement protein are components of the innate immune response?
False
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Skin is a component of the innate immune response?
True
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A phagocyte displays bits of the destroted pathogen on its surface to stimulate the acquired immune response?
True
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Damaged entothelial cells release cytokines?
True
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Acquired immunity is also known as...
Adaptive immunity
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What is acquired immunity?
It is specific for certain antigens,gained after exposure to foreign material (not automatically from birth), delay before effective 5-6 days to respond, memory faster response to subsequent exposure to same pathogen, carried out by lymphatic, life
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Acquired immunity is only carried out by vertebrates, true/false?
True
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What do lymphocytes do?
They generate efficient and selective immune responses that work throughout the body to eliminate particular invaders. This includes pathogens, transplanted cells, and cancer cells, which they detect as foreign.
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What are the 2 types of lymphocytes in the body?
B lymphoctures (B cells) and T lymphocytes (T cells), because lymphocytes recognise and
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Where do these cells originate in the body?
In the bone marrow.
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Where do T cells mature?
They leave the bone marrow and finish development in the thymus.
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Where do B cells mature?
In the bone marrow.
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What is an antigen?
A foreign molecule that elicits a specific response by lymphocytes. Antigens include molecules beloning to viruses, bacteria, fungi, protozoa, parasites and non pathogens like pollen.
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How do B and T cells recognise specific antigens?
Through their plasma membrane bound antigen receptors.
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What are antigen receptors on B cell?
Transmembrane versions of antibodies.
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What are antigen receptors on a T cell?
They are structurally related to membrane antibodies, but are never produced in a secreted form.
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How is the B cell activated?
When the B cell receptors bind to a specific epitope on an antigen, it becomes activated, it then divides to give rise to close of two kinds, plasma and memory b cells.
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What is clonal selection?
Antigen-driven cloning of lymphocytes.
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What are plasma cells required for?
For production of antibodies which have the same epitope recognition as the membrane bound B receptor cell.
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Antibodies constitute a group of globular serum proteins called...
Immunoglobulins (Igs).
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How many antigen binding sites do typical antibodies have?
2
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What components are antigens that elicit a humoral immune response?
The protein and polysaccharide surface componenets of microbes.
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What is the function of B cells?
Secrete antibodies. Each antigen has a particular molecular shape and stimulates certain B cells to secrete antibodies. Each plasma secretes about 2,000 antibody molecules per second.
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What is the primary immune response?
The first time the body is exposed to the antigen
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How long does it take?
10-17 days to peak
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What is the secondary immune response, how long does it take?
Subsequent exposure to the same antigen, 2-7 days to peak. It is faster. B memory cells are essential for the secondary response.
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What are T cell?
They are cells which defend the body in lymphoid organs.
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What are the two types of T cell?
Cytotoxic and helper.
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What is the difference between the two types?
Cytotoxic cells display CD8+ molecules on its surface, Helper display CD4+ on the surface along with T cell receptors.
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What is the difference between B & T cells?
B cells recognise intace antigens and bind to them directly, T cells have receptors which bind to fragments of antigens which are bound to MHC molecules.
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What is the cytotoxic T cell activated by?
Presented antigen from infected cell. When a normal body cell is infected, fragements are exposed on the surface of the body's cell by class I MHC molecules. If the Tc receptors fits the antigen, it'll bind with the CD8 molecules.
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What happens when the Tc cell is in contact with the antigen?
It becomes activated and forms two types: active Tc cells and memory Tc cells.
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What else do the Tc cells do?
They secrete proteins (granzymes) which destory the infected cell and then move onto other infeccting cells.
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What are tumour cells?
Carry certain proteins which are recognised as non-self, therefore proessed non-self antigen displated on classic I MHC on the tumour cells bind to T cell recepto on Tc cells.
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What do T helper cells do?
Possess T cell receptors and CD4 protein molecules on their surface. The T cell receptor of the Helper T cell recognises and binds to process antigen displayed via MCII molecules on the surface of antigen presenting cells.
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What happens when these are acctivated?
They produce clones of active T helper cells and memory T helper cells.
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What are Antigen presenting cells?
Dendritics cells, macrophages, B cells.
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What are dendritic cells?
They displace processed antigen bery effectively to helper T cells.
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What are macrophages?
They display processed antigen to memory helper T cells - secondary response
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What are B cells:
They present processed antigen to t cells during the humoral response. B cells bind free antigen via the B receptors. The B cells presen the antigen on the surface via MHCII to helper T cells.
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What do helper T cells release?
Cytokines.
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What are EOSINOPHILS?
They contribute to defense against large parasitic invaders, such as the blood fluke, schisstosoma mansoni. They position themselves against the external wall of the parasite and release destructive enzymes.
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What are natural killer cells?
They don't attack microorganisms directly, but destroy virus infected body cells.
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What cells engage in the humoral response?
B
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What cells engage in the cell mediated response?
Tc Cell
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What are the basic elements of the humoral responsne?
B cell, recognition of foreign material: antibody antigen mediated. Killing mechanism: phagocytosis and compleemtn mediated killing.
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What is the humoral response?
The B cell meets an epitope on an entigen which it binds to = activation = proliferation and differentiation to form plasma b cells and memory b cells.
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What do plasma cells do?
Secrete antibodies.
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In order to be activated fully, a B cell must do what?
Be activated by a helper T cell. An APC phagocytes a pathgen and displas the bits on the surface of its MHCII. Helper T cells with correct specificity bind to it, with CD4. The B cell binds to it too.
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What does the T helper cell secrete to fully activate the B cell?
Cytokines.
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How do antibodies eliminate pathogens?
Antigen antibody system activates the complement system. Complement proteins generate membrane attack complex (MAC), which forms a pore in the membrane, resulting in cell lysis. Wh
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What happenes in neutralization?
The antibody binds to an blocks the activity of antigens. e.g antibodies attach to molecules that the virus use to infect its host cell.
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What is opsonisation?
Bound antibodies enhance macrophage attachment to, and thus phagocytosis of, the microbes.
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What are the basic elements of Cell mediated lysis?
T cell.Recognition of foreign material by T cell receptor antigens coupled to MHC mediated. Killing bt T c cells. Recognition of foreign material by T cell receptor antigens coupled to MHC mediated.
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What does the MHC do?
It plays a major role.
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What does MHCI do?
Membrane bounds glycoprotein, binds endogeneous peptides and presents them on cell surface. FOund on all nucleated cells. Associated with CD8 + TC cells.
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What does MHCII do?
Membrane bound glycoprotein, bind exogeneous peptides and presents on cell surface, found on APCs only. Associated with CD4 and TH cells.
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What is the killing mechanism of cell mediated killing?
If cells contains a virus, MHCI molecules expose foreign proteisn that are synthesized in infected or abnormal cells to Tc cells. The Tc binds and is activated. Bind with CD8. Tc differentiates into a killer.
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How does the Tc kill its target?
By releasing perforin. This protein forms pores into the target cell, which swels and lyses. Granzymes are also released which initiate apoptosis and kill the cell.
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