Immunity Flashcards
Do most microorganisms cause disease in humans?
Most don’t, but some do
What are pathogens?
Disease causing microorganisms
What do pathogens include?
- Protozoa
- Bacteria
- Viruses
- Fungi
- Worms
What are both humans and pathogens made from?
Proteins, carbohydrates and lipids
What are the roles of protein in pathogens?
- Nutrient acquisition
- Reproduction
- Locomotion
- Respiration
How do humans and pathogens differ in their proteins?
They posses radically different proteins, that allow them to survive in their respective niches
What do different proteins have?
Different amino acid sequences
What is the significance in the difference in amino acid sequences?
The immune system detects this difference
What is damage to the host an inevitable consequence of?
Breaking through barriers in order to gain access to regions that are most prosperous
What is an inevitable consequence of damage to the barriers?
Alert
What is the first barrier to infection?
Epithelia
What does epithelia do to prevent infection?
Keep body clear of pathogens
How do we facilitate the clearance of pathogens from epithelial surfaces?
- Rapid epithelial regeneration
- Blinking
- Flow of tears
- Ear wax
- Nasal hairs
- Coughing
- Sneezing
- Mucociliary escalator
- Vomiting
- Digestive enzymes
- Peristaltic gut movement
- Regular urine flow
How quickly do epithelial cells function on contact with a pathogen?
Within seconds
Essentially, what is epithelium?
A mechanical, selectively permeable barrier between the ‘outside’ and the ‘inside’
What may epithelial cells posses?
Motile cilia
Can epithelial cells renew?
Yes, rapidly
What is the purpose of motile cilia on epithelial cells?
Keep surface free of bacteria
What do epithelial cells produce?
- Natural antibodies
- Cytokines
- Chemokines
- May produce mucins
What kind of natural antibodies do epithelial cells produce?
Cationic antibacterial peptides
Give 2 examples of cationic antibacterial peptides?
- Defensins
- Cathelicidins
What are cytokines?
Proteins that alter the behaviour of other cells
What are chemokines?
Proteins that attract other cells by gradients
Where to epithelial cells transport antibodies to and from?
From inside to outside
What is the primary role of epithelial cells?
To block the entry of microorganisms
What must be done for pathogens with non-self proteins to break through the epithelial barrier?
They must damage it
What happens to epithelial cells on contact with microorganisms?
They are activated
What do activated epithelial cells produce?
Chemokines and cytokines
What is the result in the production of chemokines and cytokines?
A much more permeabilised epithelium
What is the result of a more permeabilised epithelium?
NAME?
What is the result of opsonisation of foreign materials?
Pathogens more readily phagocytosed
What happens after a pathogen is phagocytosed?
It raises a specific response
What is the result of the specific response to a phagocytosed pathogen?
Interaction with other cells of the innate and adaptive immune system
What promotes vascular permeability?
Many inflammatory mediators- immunoglobulin and complement
What is the result of vascular permeability?
Mediators are leaked into the inflamed site through the endothelial cells lining blood vessels
What do inflammatory mediators do?
- Increase permeability
- Increase migration of macrophages, neutrophils and lymphocytes into tissue
- Increases SA to volume ratio
What does increased permeability allow?
Increased fluid leakage from blood vessels and extravasation of antibodies and complement at site of infection
What is the result of increased migration of macrophages, neutrophils and lymphocytes?
Increases microbicidal activity
What is the result of an increased SA to volume ratio?
Better gas exchange
What is the result of action of inflammatory mediators?
Allows for immunofunction to be increased
What is inflammation a response to?
Infection
What does inflammation lead to?
- Heat
- Swelling
- Redness
- Pain
- Loss of function
What is the purpose of inflammation?
Protects area from further damage
What is the innate immune response?
Inbuilt immunity to resist infection
When is innate immunity present from?
Birth
Is innate immunity specific?
No
Is innate immunity enhanced by secondary exposure?
No
What kind of components does innate immunity use?
Cellular and humoral
Is innate immunity effective alone?
No, poorly effective without adaptive immunity
What is innate immunity involved in?
Triggering and amplification of adaptive immune response
What is adaptive immunity?
Immunity established to adapt to infection
How is adaptive immunity obtained?
Learnt by experience
What does adaptive immunity confer?
Pathogen-specific immunity
Is adaptive immunity enhanced by second exposure?
Yes
Does adaptive immunity have memory?
Yes
What kind of components does adaptive immunity use?
Cellular and humoral
Is adaptive immunity effective without innate immunity?
No
What do antibodies reflect?
Infections to which an individual has been exposed to already
What are antibodies diagnostic for?
Infection
How has the adaptive immune system evolved?
NAME?
What is the importance of innate immunity implied by?
- Rarity of inherited deficiencies in innate immune mechanisms
- Considerable impairment of protection when deficiencies in innate immunity occurs
What cells are involved in innate immunity?
- Macrophages and monocytes
- Neutrophils
- Basophils
- Eosinphils
- Natural killer cells
What are the roles of macrophages and monocytes?
- Phagocytosis
- Presentation to lymphocytes
What are the roles of neutrophils?
- Phagocytic
- Anti-bacterial
What is special about polymorphonucleur neutrophils?
They have 5 lobes to their nuclei
What are the roles of mast cells and basophils?
NAME?
What are the roles of eosinphils?
- Anti-parasite
- Causes allergies
Describe the nucleus of lymphocytes?
It almost fills the cytoplasm
What kind of cells are phagocytes?
NAME?
What is meant by a phagocyte?
A cell able to engulf and destroy bacteria, extracellular viruses and immune complexes
What is phagocytosis?
Active engulfment of particles into a phagosome
What is formed form a phagosome and a lysosome?
Phagolysosome
What occurs in a phagolysosome?
Digestion
What happens to neutrophils in healthy tissues?
They are normally excluded
Why are bites taken so seriously?
Because the mouth is the most contaminated site in the body, and the microbes in the mouth can enter the wound when bitted
What are neutrophils specialised for?
Working under anaerobic conditions
Why are neutrophils adapted for working anaerobic conditions?
Because these prevail in damaged tissues
When does neutrophil arrival occur in an inflammatory response?
First event
What happens once a neutrophil has been activated?
They become unable to synthesise new granules
What happens once all granules have been used up?
The neutrophil dies
What do patients with neutrophil deficiencies suffer from?
Recurrent infection, often by microbes of the normal commensal flora
Why do patients with neutrophil deficiencies often suffer from recurrent infections?
Because they have limited phagocytic action
What can phagocytes sometimes to?
Release their lysosome contents on the outside of pathogens
Why would phagocytes release their lysosomal contents onto the surface of pathogens?
If they were too big to digest
What binds to neutrophil receptors?
Bacteria
What does bacterial binding to neutrophil receptors induce?
Phagocytosis and microbal killing
What do neutrophils have for phagocytosis?
Elaborate receptors
What do neutrophils do to the bacteria bound to them?
Engulf and digest
What do CD14 and CR4 bind to?
Bacterial lipopolysaccharide (LPS)
What do macrophages do?
Phagocytose microbal, or damaged and unwanted cells
What do macrophages release?
A variety of cytokines
What are the cytokines released by macrophages important for?
Innate and adaptive immunity
Do macrophages live long?
Yes
Why are macrophages long-lived?
Because they continue to generate more lysosomes as needed
What do macrophages act as?
Professional antigen presenting cells (APCs)
Where are APCs important?
In the development of adaptive immunity
What do APCs do?
Show antigens to T lymphocytes for their action
What is opsonisation?
The coating of an microorganism by antibodies or complement to render in recognisable as foreign by phagocytes
What does opsonisation enhance?
Phagocytosis
When are encapsulated bacteria more efficiently phagocytosed?
When coated with antibody and C36
What can encapsulated bacteria not be engulfed by?
Neutrophils
What does antibody bound to bacteria activate?
Complement binding of C3b to bacteria
What is engulfment of bacteria by neutrophils mediated by?
Fc receptors and complement receptors
What do granules fuse with?
Phagosomes
What happens when granules fuse with phagosomes?
Toxic oxygen metabolites that kill bacteria released
What are natural killer (NK) cells a part of?
Innate immune system
Are NK cells T or B cells?
Neither
Do NK cells have classical antigen receptors?
No
What do NK cells do?
Recognise and kill abnormal cells
Give an example of an abnormal cell NK cells can kill?
Tumour cells
What is the result of NK cells killing tumour cells?
Stops cancer developing
What do NK cells do in virus-infected cells?
Directly induce apoptosis
How do NK cells induce apoptosis in virus-infected cells?
By pumping proteases through pores that they make in target cells
What are NK cells similar to?
Cytotoxic T cells
How do NK cells differ from cytotoxic T cells?
They have no specific T cell receptors
What do NK cells provide?
Innate immunity against intracellular infections
What happens in people lacking NK cells?
They suffer from persistent viral infections, particularly herpes virus
What leads to NK cell activation in most cells?
IFNα and IFNß
What leads to NK cell activation in macrophages?
IL-12 and TNFα
What do NK cells provide regarding a virus infection?
An early response
What do viral infections induce?
Cells to secrete a burst of cytokines
What do cytokines induce?
The proliferation and activation of NK cells
What happens while NK cells act?
A slower cytotoxic T cell response develop which helps to clear the infection
What are the secretory molecules of the innate response also known as?
Humoral components
What are the humoral components on the innate immune respose?
- Transferrin and lactoferrin
- Interferon
- Lysozyme
- Fibronectin
- Complement components and their products
- TNF-α
What does transferrin and lactoferrin do?
Deprives microorganisms of iron
What does interferon do?
Inhibits vital replication and activates other cells which kill pathogens
Where are lysozymes found?
In serum and tears
What do lysozymes do?
They break down the bacterial cell wall of some gram+ bacteria
What are lysozymes in synergism with?
Antimicrobal peptides
What does fibronectin do?
Opsonises bacteria, and promotes their rapid phagocytosis
What do complement proteins and their products cause?
Destruction of microorganism, directly or with help of phagocytic cells
What does TNF-α do?
Suppresses viral replication and activates phagocytes
Why is the complement system so named?
Because is was discovered as heat-labile components which complemented or enhanced the oponising effects of antibody
What does the complement system do?
Marks pathogens for destruction
How does the complement system mark pathogens for destruction?
By covalently binding to their surface
Evolutionarily, what came first, the complement system or the antibody response?
The complement system
What did the antibody response evolve to do?
Enhance the mechanism of complement activation and phagocytosis
Where are complement proteins found?
Ubiquitous in the blood and lymph
How long after an infection begins can the complement system be used?
Immediately
What does an antibody do to the complement system?
Enhances complement activation
What are the complement components?
C1-C9
How do different complement proteins differ from each other?
They have different functions
What are C5a, C3a and C4a responsible for?
Recruitment of inflammatory response
What is recruitment of inflammatory cells important for?
Recruitment for host defence against infection
What is C3b responsible for?
Opsonisation
What is responsible for the direct killing of pathogens?
MAC (membrane attack complex) using C5-C9
What does the MAC do?
Assembles to make a pore in the pathogen membrane
What does the MAC assemble?
- C5b binds to C6 and C7
- C5b, 6 and 7 complexes bind to membrane via C7
- C8 binds to the complex, and inserts itself into the membrane
- C9 molecules bind to the complex and polymerise
- 10-16 molecules of C9 bind to form a pore in the membrane
What happens if there is a deficiency in C1, 2 or 4?
Immune complex disease (type III)
What happens if there is a deficiency in C3?
Recurrent bacterial infection
What happens if there is a deficiency in C5-9
Recurrent Neisserial infection
What do T and B lymphocytes respond to?
Antigens
What are antigens?
Molecules that elicit a specific immune response when introduced to the tissues of an animal
What does the common lymphocyte precursor (CLP) give rise to?
T cells and B cells
Where do T cells develop?
Thymus
Where do B cells develop?
Bone marrow
What to T cells give rise to?
T helper cells (Th) and cytotoxic T lymphocytes (CTL)
What do Th cells do?
Activate B cells and macrophages
What do CTLs do?
Kill virus infected cells
What do B cells give rise to?
Plasma cells
What do plasma cells do?
Produce antibodies
What happens when B cells are activated?
They get much bigger with lots of RER
What is true of T and B cells until they encounter an antigen?
They are essentially inactive
What do T and B cells express?
Antigen receptors
What is the B cell receptor?
A membrane bound antibody surface immunoglobulin
What is the T cell receptor?
A distinct molecule called a T cell antigen receptor
What does each antigen receptor bind to?
A different antigen
How many antigen specificity does each cell have?
1
What does the T cell receptor resemble?
A membrane bound Fab fragment
What are 3 main ways antibodies protect the host from infection?
- Neutralisation
- Opsonisation
- Complement activation
What happens in antibody neutralisation?
Prevents bacterial adherence, stopping it binding to the cell
What does each lymphocyte express?
A single antigen receptor specificity
How many lymphocytes are there in the body?
Millions
What does each naive lymphocyte bearing a unique receptor represent?
A potential progenitor of a genetically identical clone of daughter cells
What does the clonal distribution of antigen receptors mean?
That lymphocytes of a particular specificity will be too infrequent to mount an effective response
What is the purpose of clonal selection?
It raises the clonal frequency of cells with a particular antigen specificity
What does antigen interaction lead to?
Lymphocyte activation
What do daughter cells of activated lymphocytes bear?
Identical antigen specificity to the parent cell
What does a B lymphocyte do on activation?
Attaches to foreign material
What does the attachment of B lymphocytes to foreign material cause?
Clonal expansion
What does clonal selection induce?
Proliferation and increase in effector frequency
What are the phases of the adaptive immune response?
- Recognition phase
- Activation phase
- Effector phase
- Decline homeostasis
- Memory
What happens during the recognition phase?
Clonal selection
What happens during the activation phase?
Clonal expansion
What happens during the effector phase?
Differentiation to effector cells
What does the clonal nature of the adaptive immune response allow for?
Immune logical memory
What must happen for T helper cells to be able to ‘see’ something foreign?
Presentation to them by antigen presenting cell
What must happen for B cells to become plasma cells?
Must be given permission by T helper cells
What does almost every cell type bear?
MHC class 1
What is the result of almost every cell type possessing MHC class 1?
Can present endogenous antigen to cytotoxic T cells
