Module 2 Flashcards
Branches of the immune system
What are the 2 branches of the immune system?
Innate and Adaptive
What are the 4 components of Innate Immunity?
- Immune Barriers
- Inflammation
- Pattern-Recognition
- Phagocytosis
What are the 3 types of immune barriers of the innate immune system?
- Physical
- Cellular
- Soluble
What are the physical barriers of the innate immune system?
Every structure located at the interface between the inside and the outside of the body
Eg: Skin, cilia, and bodily secretions
Prison Break Analogy: Physical Barrier of innate immune system
Prison walls and the prison cell which are the first obstacles that a prisoner needs to break through in order to escape
What are the cellular barriers of the innate immune system?
Made of the various cells which play a role in the innate immune response (covered in module 01) eg: Neutrophils, macrophages, dendritic cells and NKCs
Prison Break Analogy: cellular Barrier of innate immune system
Prison guards, their role is to monitor the prison and make sure that everything is in order
What are the soluble barriers of the innate immune system?
Made of macromolecules which contribute to the mediation of an innate immune response
eg: Complement and cytokines
Prison Break Analogy: Soluble Barrier of innate immune system
Communication system inside the prison which includes radios and cameras
What are the 2 categories components of the physical barrier of the innate immune system?
- Physical
- Chemical
What are the physical components of the physical barrier of the innate immune system?
(1) Skin
(2) Mucous membranes; cover cavities of the body (respiratory, GI, Urinary, reproductive) they contain specialized structures such as cilia and produce mucous
What are cilia?
Hairlike vibrating structures that can trap particles, preventing them from reaching vulnerable areas of the mucous membranes
What is mucous?
Viscous substance secreted by mucous membranes
How do cilia and mucous add protection from pathogens?
Microorganisms get caught in sticky mucus which prevent them from reaching the lungs. Then the cilia of the respiratory tract sweep these organisms up and out of the body through coughing or sneezing
What are the chemical components of the physical barrier of the innate immune system?
Mucous membranes secrete chemical component to attach and kill bacteria
- tears and Saliva contain lysozyme
- Gastric acid destroy most bacteria and toxins that enter the stomach
What are the four major cell types of the cellular barrier of the innate immune system?
(1) Neutrophils
(2) Macrophages
(3) Dendritic Cells
(4) Natural Killer Cells
Describe Neutrophils and its role in the innate immune system (5 characteristics)
(1) Most common leukocyte found in blood of mammals
(2) Phagocytes that patrol the body to find, engulf, and destroy pathogens
(3) Circulate in the blood (12hrs) before entering tissues by diapedesis
(4) Recruited to a site of infection by resident macrophages that have encountered pathogens
(5) Lifespan of 1 to 3 days after entering the tissues
What is diapedesis?
Process by which blood cells, such as neutrophils, move from blood to tissues by passing through intact vessel walls. This process, also called extravasation.
Describe Macrophages and its role in the innate immune system (4 characteristics)
(1) Phagocytes that patrol the body to find, engulf, and destroy pathogens
(2) can either take up residence in a specific tissue, or move freely/patrol throughout a larger area of tissues
(3) Contribute to tissue repair and present antigens to other immune cells such as T-cells
(4) Become activated after phagocytosing pathogens or in response to cytokine signalling
Describe Dendritic Cells and its role in the innate immune system (4 characteristics)
(1) Phagocytes that are often in contact with the external environment (specifically Langerhans DC)
(2) Engulf foreign antigens that have evaded the initial barriers of the innate immune system
(3) Present antigens on their cell surface through peptide: MHC complexes, which can be recognized by helper T-cells
(4) Major link between the innate and adaptive immune systems
Describe Natural Killer Cells and its role in the innate immune system (3 characteristics)
(1) Recognize abnormal cells lacking antigen specific receptors
(2) Destroy abnormal cells of the body, which include tumorous and virus-infected cells
(3) Bind to cell surface of target cells and release chemical causing pores to form in the cell membrane, leading to their lysis
What are the 2 major categories of macromolecules that make up the soluble barriers?
Complement System
Cytokine
What is the Complement System?
Made up of over 30 soluble proteins
Where is the Complement System?
Circulate in the blood, normally in an inactive form
When is the Complement System activated?
Directly activated in the presence of extracellular pathogens
Indirectly activated by pathogen-bound antibody
What happens when the Complement System activated? (2)
Leads to the formation of the “Membrane Attack Complex” (MAC)
Enhances, or complements, the efficiency of other immune functions, such as inflammation and phagocytosis
What is the Membrane Attack Complex?
Structure made of activated complement proteins which have the ability to destroy extracellular pathogens by creating holes in their cell membrane, which leads to lysis and cell death. As a side effect of this process, MAC can also damage host cells
What are the 3 major pathways that can activate the complement system?
Classical
Alternative
Lectin
What are the 3 major functions of the Complement System?
Inflammation
Phagocytosis
Membrane Attack Complex
Describe the inflammation process of the Complement System
- Attraction of various immune cells to the site of infections through the release of chemotactic molecules
- Activated complement proteins bind to complement receptors on immune cells (eg Mast cells and basophils) inducing the release of chemotactic molecules
What are chemotactic molecules?
Inducing the movement of cells toward the site where the substances are originally released
Ex: Histamines and Cytokines
Describe the role of the Complement System in phagocytosis
Activated complement proteins, predominanttely C3b, opsonize pathogens thereby targeting them for destruction by phagocytes
What is “opsonize”?
Making a foreign particle more susceptible to phagocytosis by binding to the antigen and marking it for ingestion
What would be the result of a complement deficiency?
Reduced lysis of microbes and less inflammation. Would result in reduced bacterial clearance and therefore longer periods of infection
What are cytokines?
Small proteins secrete by various immune cells in response to a number of different stimuli.
They are chemical mediators that play a key role in cell-to-cell communication
Large variety exists and each have a strong affinity for a specific type of cytokine receptor
What is the major role of cytokine signalling ?
regulate immune processes, such as immune responses, inflammation, and hematopoiesis
Compare and Contrast; Autocrine, Paracrine, Endocrine
Autocrine: Sending and receiving cells is the same
Paracrine: Sending and receiving cells are near each other (neighbouring)
Endocrine: Sending and receiving cells are distant from each other
Does the majority of cytokines have an autocrine, paracrine or endocrine effect?
Majority act locally, so autocrine and paracrine
Give 4 essential characteristics of cytokines
(1) Have paracrine and auticrine effects
(2) They have high specificity and affinity to their receptor
(3) They alter gene expression
(4) They can be pro-inflammatory or anti-inflammatory
Prison Break analogy: cytokines
Prison communications systems, appropriate orders need to be senf to a specific person or to a specific location. If you want the information to be correctly communicated, you need to use the correct radio channel and you need to specific to whom you are talking to
What are the 2 main groups of cytokines?
Pro-inflammatory
Anti-inflammatory
Describe pro-inflammatory cytokines
Made by most immune cells. When secreted these cytokines will induce an inflammatory response within the body
Describe anti-inflammatory cytokines
Made by several immune cells and work to limit the inflammatory response within the body. They inhibit pro-inflammatory cytokines production and activating immune cells that promote healing
What happens if you have a deficiency in anti-inflammatory cytokines?
Pro-inflammatory surplus will lead to complications such as tissue damage due to an excessive inflammatory state
What happens if you have a deficiency in pro-inflammatory cytokines?
Anti-inflammatory surplus will result in a lack of an immune response to a pathogen which can result in spreading of the pathogen
What is inflammation?
Series of biological reactions in response to the invasion of harmful infections agent into the body.
Occurs as a localized tissue response to injury or invasion
Has both local and systemic effect within the body
How can inflammation be characterized?
By any of these 5 physical responses:
- Redness
- Heat
- Pain
- Swelling
- loss of function
What are components of the inflammation process?
- Alteration of blood flow to the injured area
- Influx of phagocytic and other immune cells
- Removal of foreign antigens
- Healing of damaged tissue
What is the main purpose of inflammation?
Body’s attempt at self protection by removing harmful stimuli, including damaged cells, irritants, or pathogens
It localizes and eliminates the invading pathogen, in an effort to stop it from spreading, and to remove damaged tissue
What are the major events of Inflammation? (5)
(1) Breach of the physical barrier
(2) Vasodilation: Increase in blood vessels diameter. Induced by vasoactive and chemotactic factors
(3) Permeabilization of the capillaries facilitates entrance of fluids in tissues. Induced by vasoactive and chemotactic factors +Vasoconstriction of vessels carrying blood away from area
(4) Extravasation: Cells move from the blood to the tissues/site of infection by chemotaxis
(5) Phagocytosis: Phagocytic immune cells (eg: neutrophils and macrophages) engulf the pathogens
What are the first cell to arrived to the site of infection?
Neutrophils
How do immune cells get from the blood to the infected tissues?
Margination: Immune cells adhere to the endothelial cell walls of capillaries
Extravasation or Diapedesis: Immune Cells migrate between capillary-endothelial cells into the infected tissue
Prison Break Analogy: breaching the physical barrier
Prisoner needs to find a way to get through their cell door by finding a key or using a piece of metal to pick the lock
Prison Break Analogy: Vasodilation
When prisoner escapes, the prison guard needs to let all the other guards know about the situation by sending radio messages to regroup and find prisoner
Prison Break Analogy: Permeabilization
First thing security team will do is to order a lockdown to ensure that no other prisoner tries to escape and for everyone to know that there is a situation that needs to be controlled
What is exudate?
Excess fluid that accumulates at the site of infection
Why do you think heat and swelling are beneficial during an inflammatory response?
- Heat increases metabolic rates of cells allowing them to repair themselves faster
- Swelling leaks proteins, which help clot blood and form scabs, and recruits local phagocytes and lymphocytes to help destroy pathogens and clean up dead cells
What is the major mechanism used by innate immunity to recognize self from non-self?
Pattern-recognition Receptors (PRRs)
What are Pattern-Recognition Receptors (PRRs)?
PRRs are the major mechanism used by innate immunity to recognize pathogens
- Capable of recognizing repeated molecular patterns of pathogens
What is the purpose of PRRs?
- Responses has to be fast as microbes are capable of dividing rapidly and the immune system has to be able to distinguish self from non-self
- Patter recognition sequences are unique to microorganism and necessary for their survival. PRRs allo innate immue system to target specific pathogens wuickly and effectively and avoid attacking itself
Where can you find PRRs?
In both the adaptive and Innate immune cells, however they are an integral signalling component of the innate immune system
What are the molecular patterns recognized by PRRs?
Conserved motifs and certain subsets can be found in various groups of pathogens, where they are called pathogen-associated molecular patternes (PAMPs)
Where can you find PAMPs?
On the surface of or found inside pathogens
Give 2 examples of PAMPs?
- Lipopolysaccharides (LPS) found on the cell surface or gram-negative bacteria
- Double stranded RNA found inside dsRNA viruses
What are the 2 major categories of molecular patterns that can be recognized by PRRs?
- Pathogen-associated molecular patterns (PAMPs)
- Danger-associated molecular patterns (DAMPs)
What are pathogen-associated molecular patterns (PAMP)?
Molecules associated with groups of pathogens that are recognized by immune cells
Include:
- Functional structure of a pathogen
- Repeated sequences of protein, glycoprotein, lipoprotein, amino acids, that are conserved across spefific groups of microbes
What are damage-associated molecular pattern (DAMP)?
Molecules released by stressed cells undergoing necrosis
these:
- are host molecules
- Indicate damage to the body
- Initiate an inflammatory response
Example: abnormal location of a cell structure (DNA outside mitochondria/nucleus)
cell-stress indicator molecules
What are Toll-like receptors (TLRs)
Class of PRRs that plays an essential role in innate immune response
Where are TLRs expressed?
either on the plasma membrane or endosomal/lysosomal membranes of mammalian cells depending on the type of DAMP or PAMP
What happens when TLRs are activated?
They initiate transcription of genes encoding for;
- Inflammatory cytokines
- chemokines
- Costimulatory molecules
These molecules, in turn, contribute to the activation of innate immune cells which increase the ability of phagocytes to engulf pathogens and enhance their ability to present antigens to the adaptive immune system
What are the 2 major roles of TLRs?
Recognize PAMPs and/or DAMPs
Induce expression of signalling to activate T-cells
What are the steps of the TLR signalling process?
1- TLRs sense the presence of an infection through recognition of PAMPs and DAMPs - bacterium will be phagocytized
2- Immune cell (antigen presenting cell) will present pieces of the pathogen (antigen) on its cells surface through the peptide MHC complex
3- Antigen presenting cell will increase its production of costimulatory molecules which are involved in the strength and stability of antigen presenting process
4- An Immunocompetent naive T-cell specific for the antigen will bind to the peptide (MHC complex) through its TCR, this interaction activates T-cell and initiate an adaptive immune response
Fill in the blank:
Essential for the innate immune response, (a)___ such as (b)___, are receptors which recognize structure from the microbes, such as (c)___ or molecules released by dying cells, such as (d)___.
(a) PRRs
(b) TLRs
(c) PAMPs
(d) DAMPs
What is phagocytosis?
Type of endocytosis in which a cell takes up particulate material (such as bacteria) from its environment by invaginating its membrane to form a vacuole
What are the 3 types of cells of the innate immune system that have phagocytic functions?
Neutrophil
macrophage
dendritic cells
What are the 2 ways to induce phagocytosis?
Through a phagocyte’s PRR
Through opsonization
Which type of cell of t he innate immune system perform phagocytosis the most efficiently
Macrophages
What are 2 functions of macrophages in the innate immune system response?
- Phagocytosis
- Release cytokines that stimulate inflammation and recruit other immune cells
What are the 2 functions of neutrophils in the innate immune system response?
- Perform early phagocytosis
- Initiate an inflammatory response
What is the function of dendritic cell in innate immunity?
Recognize and phagocytize the microbes
Then initiate adaptive immune response by presenting the antigen to it
What are the 5 steps of phagocytosis?
1- Attachment: pathogen becomes attached to the membrane evaginations (pseudopodia)
2- Ingestion: pathogen is ingested, forming a vacuole called phagosome
3- Fusion: phagosome fuses with lysosome, releasing lysosomal enzymes that degrade macromolecules and other materials, such as bacteria
4- Digestion: pathogen is destroyed and digested by the lysosomal enzymes
5- Release: digestion products are released from the cell via exocytosis (vacuole fuses with cell membrane)
What is the complement system made of? Name its 3 main function in innate immunity
over 30 Soluble proteins
- Opsonization which induces phagocytosis
- Chemotacis, which induces inflammation
- Lysis through its membrane attack complex
Name the 4 major components of the cellular barriers and describe the main differences between each of them
Neutrophils : first wave of phagocytosis
Macrophages: big eaters, phagocytose a larger qty of pathogens
Dendritic cells: arrive later and initiate adaptive immunity
Natural Killer Cells: cytotoxic effector cells
Name the major steps of the inflammatory response and briefly describe their role when a pathogen breaks through the physical barrier
Vasodilation: Facilitates accumulation of blood, containing immune cells and soluble components
Permeabilization: Facilitates entrance of fluids (exudate) containing soluble components
Extravasation: Migration of immune cells from blood to infection site
Phagocytosis: destruction of pathogens
True or False:
Toll-like receptor family contains membrane-bound receptors which contribute to the activation of innate immune cells by recognizing pathogen-associated molecular patterns of invaders
True
Name the 2 major physical components and explain in a few words why they play an essential role in innate immunity
Skin and mucous membranes. They are the first line of defence. They create, with mucous, cilia, and chemical components, a barrier that is difficult for pathogens to break through
What are the 2 main characteristic of the adaptive immune system?
Specificity
Diversity
What is an epitope?
It is part of an antigen recognized by adaptive immunity components
Also called antigenic determinant
Why is adaptive immunity said to be specific?
Each pathogen it encounters, it creates a unique immune reaction to eliminate the infectious agent
Why is adaptive immunity said to be diverse?
Each cell is so specific, it is composed of countless numbers of cells to be able to fight any pathogen encountered
What are the key components of humoral immunity?
B-Cells
Antibodies
What are the key component of cell-mediated immunity?
only one
T-cells
What are the characteristics of B-cells? (4)
- Key component of humoral response
- Mature in the bone marrow
- Surface receptor: B-Cell Receptor (BCR)
- Function: antibody factory
What are the 2 subsets of B-cells?
Plasmocyte - Effector cell - Produce large qties of antibodies Memory B-Cell - Memory Cell - Express BCR on their cell surface
What are the characteristics of T-Cells? (4)
- Key component of the cell-mediated response
- Mature in thymus
- Surface receptor: T-Cell Receptor (TCR)
- Function: Cytotoxic activity or help the activation of immune response
What are the 3 Subsets of T-cells?
CD4 Helper T-cell - Effector cell - help the activation of the adaptive immune response CD8 Cytotoxic Tcell -Effector Cell - Kill infected cell Memory T-cells -Memory cells - Express TCR and CD4 or CD8 on cell surface
Describe the activation of adaptive immunity
Antigen presenting cells (APCs), such as dentritic cells that have engulfed pathogens, can present the antigens to naive CD4 helper T-cells
Then this helper T cells differentiate into;
- Th1 to induce cell-mediated immunity
or
- Th2 to induce humoral immunity
How is Humoral Immunity activated?
1- Activated and differentiated Th2 cells activate B-cells and induce their differentiation into plasmocytes
2- Plasmocytes produce antibodies specific for the invading antigen
How is Cell-mediated Immunity activated
1- Activated and differentiated Th1 cells activate CD8+ cytotoxic T-cells and induce their differentiation into Cytotoxic T Lymphocyte (CTL) 2- CTL recognize and elminate any cells displaying specific antigen presents at their cell surface by MHC class I complex
What are antibodies?
Large y shaped protein that is highly specific and recognizes ONE epitope
Aka immunoglobulin or Ab
Where do antibodies come from?
They are produced by B-cells
-> One B-cell will produce ONE specific antibody for ONE specific epitope
What are the 2 forms of antibodies?
Surface antibodies
Soluble antibodies
What are surface antibodies?
Membrane-bound on B-cells, forming part of the C-cell receptor (BCR)
What are Soluble antibodies?
Secreted by B-cells (plasmocyte) and circulate freely in the blood
What are the functions of antibodies?
Help eliminate pathogens through various processes:
- Neutralization
- Opsonization
- Complement activation
- Effector Cell activation
What is neutralization?
Process through which the biological effect of a pathogen or toxin is neutralized
What is opsonization?
Process that marks foreign invaders for phagocytosis
What is complement activation?
Process that induces the formation of membrane attack complexes and opsonization
What is effector cell activation?
Recognized by immune cells when bound to an antigen and activate the cell’s effector functions
What is the basic structure of Human Immunoglobulins?
2 heterodimeric proteins that are held together by disulfide bonds (S-S). It has;
- 2 light chains
- 2 heavy chains
- 2 antigen binding regions
- 1 fragment cystallizable region
What is a light chain of the antibody?
protein subunit that, as one of a pair, forms part of the main antigen-binding region of an antibody
What is a heavy chain of the antibody?
Protein subunit that makes up the majority of the structure of the antibody, it forms part of the antigen-binding region and forms the Fc region
What is the antigen binding region of the antibody?
Region is variable and changes from one antibody to another, but remain the same on one antibody.
These regions are responsible for the diversity and the specificity of immunoglobulins
What is the Fragment Crystallizable region of the antibody?
Fc is constant for every antibody of the same class. It is the part that interacts with immune cell surface receptors called Fc receptors
How are human immunoglobulins’ 5 classes distinguished from one another?
By the type of Heavy chain within their structure
What does the variation in heavy chain polypeptide allow for?
Each immunoglobulin class to function in a different type of immune response OR during a different stage of the body’s defence response.
Where are the specific amino acids of the heavy chain that confer the functional differences located?
In the Fc Domain
What are the 5 classes of immunoglobulins in humans?
IgM IgG IgA IgE IgD
Describe IgM (3 things)
1- Forms a pentamer from IgM monomers when secreted by B-cells
2- 1st antibody to be formed in an immune response
3- Activates the complement which then amplifies the inflammatory and adaptive immune response
Describe IgG (3 things)
1- Monomers when secreted by B-cells
2- Coats pathogens to promote phagocytosis and immune cell recruitment
3- Only class that can cross the placenta barrier
Describe IgA (2 things)
1- Generally forms a dimer from IgA monomers when secreted by B-cells 2- 1st line of defence and predominat antibody class located in the body's mucosal membranes (eg respiratory and GI tract)
Describe IgE (3 things)
1- Monomer when secreted by B-cells
2- Produced in excess during allergic reactions
3- Has a roled in immunity against certain parasite (eg helminths)
Describe IgD (3 things)
1- Monomer when secreted by B-cells
2- Found in large quantity on the surfaces of mature B-cells
3- Function or importance is unclear, still under investigation; thought to have a role during B-cell development
Which immunoglobulin can cross the placental barrier?
IgG
Which immunoglobulin is the predominant antibody class present in mucosal membranes?
IgA
Which immunoglobulin is found on the surface of antigen-naive mature B-cells?
IgD
Which immunoglobulin is a pentamer when secreted by B-cells
IgM
Which immunoglobulin is produced in large quantity during an allergic reaction?
IgE
