11.0 Immunity Flashcards
Lines of defense against diseases
- First line of defense: external & non-specific
- Second line of defense: Internal, non-specific immune response, involves phagocytes
- Third line of defense: internal, specific immune response, involves lymphocytes
What is an Immune response
the body’s immune reaction towards non-self antigens
Phagocytes mode of action in immune system
GENERAL:
- produced throughout life
- patrols in blood, tissues and organs
- removes dead cells and pathogens through phagocytosis
- involved in non-specific defense
- responds to many different non-self antigens
NEUTROPHILS:
- have receptor proteins on its membrane to identify pathogens as non-self
- when infections happen, large numbers are released from bone marrow
- accumulates at site of infection
- short-lived, dies after digesting pathogens
MONOCYTES (MACROPHAGES):
- larger than neutrophils
- have receptor proteins on membrane to identify pathogens as non-self
- monocytes circulate in blood and mature into macrophages when it leaves blood and enter organs
- long-lived cells
- macrophages are found in organs such as liver, lungs, spleen, kidney and lymph nodes
PROCESS:
1. initiates / starts immune respone after non-self entigen indentification by various receptor proteins on cell surface, non-specific 2. Engulfs pathogen via phagocytosis, fusion of phagocytic vacoule with lysosome 3. hydrolysizes pathogen using lysozymes 4. antigens presented on its cell surface, macrophages act as antigen-presenting cells 5. some cell fragments released by exocytosis, antigen-presenting cells trigger lymphocytes
Lymphocytes mode of action in immune system
GENERAL:
➤ produced in bone marrow before birth
➤ Involved in specific immune responses
➤ Responds to only specific non-self antigens
➤ Mature lymphocytes circulate in the blood and lymph
➤ Accumulate at sites of infection
➤ Appearance:
➤ Smaller than phagocytes
➤ Large round nucleus
➤ Little cytoplasm
B-LYMPHOCYTES:
➤ Mature in bone marrow
➤ Produces antibodies
after activation & differentiation:
* Each small group of identical cells is called a clone.
* Antibody molecules do not leave the B cell but remain in the cell surface membrane.
* Part of each antibody forms a glycoprotein receptor to combine specifically with one type of antigen.
* The small clone of cells divides repeatedly by mitosis in the clonal expansion stage so that huge numbers of identical B cells are produced over a few weeks.
- plasma cells (produce antibodies ONLY): * produce and secrete antibodies very quickly into the
blood, lymph or onto the linings of the lungs and the gut. * do not live long: after several weeks their numbers
decrease. * The antibody molecules eventually decrease in concentration. * Antibodies are glycoproteins * So plasma cells have intensive network of RER and Golgi body
- B memory cells: * remain circulating in the body for a long time.
* secondary infection: memory cells divide rapidly and develop into plasma cells and more memory cells
LONG-TERM:
- The first or primary response is
slow because, at this stage, there are
very few B cells that are specific to the
antigen.
- The secondary response is faster
because there are now many memory
cells, which quickly divide and
differentiate into plasma cells.
T-LYMPHOCYTES:
➤ Mature in thymus
➤ Does NOT produce antibodies
- T cell receptors ：
- on surface membrane of mature T cell
- stricture similar to antibodies
- specific to one antigen
- T cells are activated when they encounter this antigen on another cell of the host or by antigen presentation of macrophages.
- T cells with receptors complementary to the antigen respond by dividing by mitosis to increase the number of cells.
after activation & differentiation:
- T helper cells: When helper T cells are activated, they release hormone-
like cytokines that stimulate B cells to divide, develop into plasma cells and secrete antibodies. * T helper cells secrete cytokines that stimulate macrophages to carry out phagocytosis more vigorously.
- T killer cells (cytokines): * Killer T cells search the body for cells that have become invaded by pathogens and are displaying foreign antigens. * Killer T cells recognise the antigens, attach themselves to the surface of infected cells, and secrete toxic substances
such as hydrogen peroxide, killing the body cells and the
- Memory helper T cells & memory killer T cells: which remain in the body and become active very quickly during the secondary response to antigens.
Antigens
OVERVIEW:
- macromolecules on cell surfaces
- e.g. glycoproteins, glycolipids, polysaccharides
FUNCTION:
SELF ANTIGENS:
- acts as cell markers
- macromolecules on cell surface membranes of host cells
- doesn’t trigger body’s immune system
- no antibody production
NON-SELF ANTIGENS:
- macromolecules that activates an immune response
- found on cell surface membrane of foreign material’s (pathogens, allergens) AND surface membrane of infected host cells
- stimulates production of antibodies
Process of Primary Immune Response
1. Antigen Recognition:
- When a pathogen (e.g., bacteria or virus) enters the body, antigens on its surface are recognized as “foreign” by the immune system.
- stimulates immune response
- Macrophages and dendritic cells (types of antigen-presenting cells) engulf the pathogen through a process called phagocytosis. The pathogen is broken down inside these cells, and its antigens are processed and presented on the surface of these cells.
2. Activation of Helper T Cells (T Lymphocytes):
- Antigen-presenting cells (APCs) present the processed antigens on their surface bound to a major histocompatibility complex (MHC) class II molecule.
- Helper T cells (T-helper cells, or CD4+ T cells) with receptors specific to the presented antigen bind to the antigen-MHC complex on the surface of the APCs.
- This binding stimulates the activation and proliferation of Helper T cells.
- Activated Helper T cells release cytokines (signaling molecules) that help activate other immune cells, particularly B cells and cytotoxic T cells. (stimulate B cells and stimulate Phagocytes to undergo phagocytosis more vigourously)
3. Activation of B Cells:
- B cells (a type of lymphocyte) have surface receptors (antibodies) specific to the foreign antigen.
- When a B cell encounters an antigen that matches its antibody, it binds to the antigen. The B cell then internalizes the antigen and presents it on its surface in association with MHC class II molecules.
- Helper T cells that have already been activated by the same antigen bind to the antigen-MHC complex on the B cell, providing a second signal for B cell activation.
- Upon receiving this second signal, B cells are fully activated.
4. Clonal Expansion of B Cells:
- Once activated, B cells undergo clonal expansion, dividing rapidly to produce a population of B cells that are specific to the invading pathogen’s antigen.
- These B cells differentiate into two types:
- Plasma cells: These are antibody-secreting cells that produce large quantities of antibodies (immunoglobulins) specific to the antigen.
- Memory B cells: These cells remain in the body for a long time and provide immunological memory. If the same antigen is encountered again in the future, these cells quickly divide and mount a faster and stronger immune response (the secondary immune response).
5. Production of Antibodies:
- Plasma cells produce and release large quantities of antibodies into the bloodstream and lymph.
- Antibodies bind to the antigens on the surface of the pathogens, leading to their neutralization. This can occur in several ways:
- Neutralization: Antibodies block the active sites of toxins or pathogens, preventing them from infecting cells.
- Agglutination: Antibodies cause pathogens to clump together, making it easier for phagocytes to engulf them.
- Opsonization: Antibodies mark pathogens for destruction by phagocytes.
- Activation of the Complement System: Antibody binding can trigger the complement system, which leads to the destruction of the pathogen by forming pores in its membrane.
6. Activation of Cytotoxic T Cells (Cell-mediated Response):
- Helper T cells also activate cytotoxic T cells (CD8+ T cells) if the pathogen is found inside cells (such as in a viral infection).
- Cytosin T cells recognize infected cells by binding to antigens presented on MHC class I molecules on the surface of infected cells.
- Once activated, cytotoxic T cells kill infected cells by releasing toxic substances like hydrogen peroxide, which induce the infected cell to undergo apoptosis (programmed cell death).
7. Elimination of Pathogen:
- As a result of antibody production and the activity of cytotoxic T cells, the pathogen is gradually eliminated from the body. This includes the direct killing of infected cells by cytotoxic T cells and the neutralization, opsonization, or destruction of pathogens by antibodies and phagocytes.
8. Formation of Memory Cells:
- Some of the activated B cells and T cells differentiate into memory cells (memory B cells and memory T cells).
- These cells remain in the body long after the pathogen has been cleared. They provide the basis for the secondary immune response, which is faster and more effective if the same pathogen is encountered again in the future.
Memory Cells in 2nd Immune response & Long Term immunity
Memory cells:
- form the basis for immunological memory lasting many years, often a lifetime and are involved in long term immunity.
Primary response:
- there are very few B cells speci c to the antigen thus production of antibodies is low.
Secondary response:
- there are many more antibodies produced as many memory cells divide quickly and differentiate into plasma cells.
Antibodies
STRUCTURE RELATED TO FUNCTION::
* Antibodies: globular glycoproteins with
quaternary structure, forming the group of plasma proteins called immunoglobulins.
* Consists of four polypeptide chains:
* two ‘long’ or ‘heavy’ chains
* two ‘short’ or ‘light’ chains
* Disulfide bonds hold the chains together.
* antigen-binding sites : identical variable region, formed by both light and heavy
chains.
* ‘hinge’ region: gives the flexibility for the antibody molecule to bind around the antigen.
➤ Variable region
➤ Formed by light and heavy chains
➤ Provide 2 identical antigen-binding sites
➤ Specific for binding antigen
➤ Complementary shape to antigen
➤ Shape determined by primary structure = specific sequence of amino acids
➤ R groups at antigen-binding site forms H bonds and ionic bonds with specific antigen
➤ Sequence of amino acids at the variable region is different for each type of antibody
➤ Each type of antibody binds to different antigens
CONSTANT REGION:
➤ When circulating in blood: binds to
receptors on phagocytes
➤ When antibody acts as B cell receptor: attach to cell surface membrane of B cells
Process Hybridoma Method (Monoclonal antibody production)
- highly specific and identical antibodies made by identical B cell clones.
PROCESS:
- A mouse is injected with relevant antigen (of disease/pathogen), stimulating immune response.
- Plasma cells specific to antigen are extracted from the spleen and fused with cancerous cells forming hybridoma cells.
- Hybridoma cells that produce the required antibody are cloned.
Monoclonal antibodies in diagnosis & treatment
DIAGNOSIS/PROCESS:
- Radioactive chemicals are attached to each antibody that binds to fibrin. Radioactivity emitted by these antibodies can be detected by gamma rays camera, thus finding the position of a clot.
- The same method can be used to locate cancer cells and identify the exact strain of a virus or bacterium during an infection.
TREATMENT:
- Mabs from rats into humans trigger an immune response as they are non-self. This is overcome by altering genes that code for polypeptide chains of antibodies into human sequences and the type/position of sugar groups into human antibodies.
- Used in cancer therapy by marking cancerous cells for their destruction or binding to protein produced by T cells that reduces immune response.
- Controls over/inappropriate production of B cells, preventing leukaemia and autoimmune diseases.
Types of Immunity
Active immunity: is immunity gained when an antigen enters the body, an immune response occurs and antibodies are produced by plasma cells.
Passive immunity: is immunity gained without an immune response; antibodies are injected (artificial)
or pass from mother to child across the placenta or in breast milk (natural).
Natural immunity: is immunity gained by being infected (active) or by receiving antibodies from the
mother across the placenta or in breast milk (passive).
Artificial immunity: is immunity gained either by vaccination (active) or by injecting antibodies (passive).
Vaccines & Antigens in long term Immunity
GENERAL:
- vaccines contain antigens for a disease
- injection or by mouth
- artificial active immunity
PRODUCTION/FUNCTION:
an antigenic material, which could be a live, dead or attenuated micro-organism, or perhaps a harmless form of a toxic (toxoid) or simply surface antigens. This allows our immune system to produce the requisite B and T cells without actually suffering the disease, mimicking natural immunity.
PROBLEMS:
Poor response:
- A defective immune system: do not develop the necessary B and T cell clones.
- Malnutrition, particularly protein-energy malnutrition: do not have enough protein to make antibodies or
clones of lymphocytes.
Live virus and herd immunity:
- A live virus: may pass it out in their faeces during the primary response and may infect others.
- Give herd immunity, or to ensure that all children are vaccinated within a few months of birth.
Antigenic variation:
- The influenza virus mutates regularly to give different antigens.
- minor changes are called antigenic drift.
- major changes in antigen structure – known as antigenic shift.
- No effective vaccines in: protoctists: eukaryotes with many more genes than bacteria and viruses have. They can
have many hundreds or even thousands of antigens on their cell surfaces.
Antigenic concealment:
- Some pathogens evade attack by the immune system by living inside cells.
- Plasmodium enters liver cells or red blood cells, it is protected against antibodies in the plasma.
- Vibrio cholerae (the causative agent of cholera), which remains in the intestine where it is beyond the reach of many antibodies.
Herd Immunity
- Mass vaccination results in herd immunity
- Less chance of transmission of disease
- Reduce pool of infected people in the
community - Fewer people can catch the disease and be source of infection
- Protection of those unvaccinated/
immunocompromised as disease does not spread
