Adaptive Immune System (part A and B) Flashcards
What are antibodies?
Antibodies are immunoglobulins produced by activated and differentiated B cells called plasma cells
> plasma cells secrete specific and identical immunoglublins into plasma
> specific refers to binding to only one antigen type
What are the functions of antibodies and what are their activities in the body ( 4 activities)
Antibody Funtions:
- Antibodies bind to antigens and draw them into further contact with innate IRs (Fc receptors)
Activities of Antibodies:
- Antibody Activate Complement
- Antibody binding to antigen activates complement pathway
- Activates C3: Activates the membrane attack complex, releases C3a, various pro-inflammatory complement molecules
- Antibodies activate Phagocytic cells
- Antibody binding to antigen activates phagocytic cells (neutrophil, macrophage) to engulf microbe
- Two or more antibodies necessary to trigger phagocytosis
- Antibodies activate Acute Inflammatory Response
- IgE can activate mast cells and trigger an acute inflammatory response
- Activate at site of infection
- Degranulation of mast cells occur –> Attract other chemotaxis to the area (neutrophils, macrophages)
- Increases vascular permeability (increase access to immune cells and leakage of plasma proteins)
- Antibodies block microbial reactions
- Small size of antibodies allows them to interact with microbial molecules and block their acitivity
- A: block virus binding to host cell receptor and stop entry
- B: block essential transport molecules on bacteria cell wall and stop nutrients from entering bacteria
- C: attachment of antibody to toxins will limit/stop host cell damage
How does Intracellular killing of pathogens occur?
Enabled and carried out by:
T helper (Th cells) –> activate other cells
T cytotoxic (Tc cells) –> carried out killing of infected cells
Th and Tc only recognise antigen when complexed with MHC
> NK killer cell carry out killing of infected cells, part of the innate immumne system, NOT MHC dependent.
What are MHC cells, what are the types and what are their purposes?
Major Histocompatiblity Complex
Two types: Class I and II
Class I: found on nearly all cells
Class II: only on Th, macrophages and B cells
MHC: cell surface molecules used by immune cells to recognise self, infected cells and communicate
Self: every person has unique MHC 1 combination making it difficult to transfer organs, need careful matching
Functions of MHC molecues
- Identify infected cells - protein fragments from microbe attached to petide binding site and presented to immune cells
- Communicate - allows Th cells to interact and active macrophages and B cells
What is the role of cytotoxic T cells?
Body cells infected with viruses use MHC-1 surface proteins to display virus protein fragments on their cell membrane
- Cytotoxic T cells (Tc) interact with MHC-1 and recognise foreign peptide
- Tc in contact with infected cell and relases killing substances –> usually in early stage
What is the role of T-helper cells (Th)
Th cells activate macrophages
- Microbes can evade immune mechanisms and live inside other cells (in macrophages)
- Macrophages process internal microbe proteins –> degrade and combine with MHC-II, complex migrates to cell surface
- Th TCR interacts with MHC-II + foreign peptide –> releases activating factors (IFNy)
- Macrorphages kill intracellular invader through NO radicals
What is the role of Natural Killer Cells (NK)?
Similar function to Tc but DONT use the MHC molecule system, have other receptors (e.g. PRR) –> chance of binding to infected cells lower than Tc
- Antibody binding to foreign peptide
- Th cells, Tc and infected cells release IFNy
- IFNy renders uninfected cells resistant to infection
NK cells kill intracellular pathogens in absence of MHCs and foreign mammalian cell
How does the immune system deal with large extracellular parasites?
Helminths are too large to be phagocytosed
- Killing can occur through a mechanism called antibody- dependent cellular toxicity (ADCC)
- Specific antibodies bind to surface of microbe and then immune cells can bind to Fc region of antibody, activating cellular killing mechnisms
Mechanims: Macrophages, reactive oxygen intermediates; NK, granzyme; eosinophils, perforins
How does the immune system deal with microbes that infect mucous membranes
IgA: secreted antibody found in mucus of membranes
> When microbes persist on mucosal surfaces, IgA binds and stops attachment of microbe to cells of epithelium
> If microbe penetrates mucosa, IgE antibodies on surface of mast cells initiate acute inflmmatory reactionn
> This increases capillary permeability (complement antibodies) and mobilises other immune cells (blood, poymorphs and macrophages)
What is clonal expansion of lymphocytes?
- Millions of antigens
- Body has lymphocytes that can recognise each type
- Upon activation –> lymphocytes proliferate and produce many clones
–> Clonal Expansion: B cells, T helper and T cytotoxic cells
Describe the clonal expansion of B cells
B cells reside in lymph nodes, spleen and musocal associated lymphatic issue (MALT)
- Activated when an antigen is presented to them or detect antigen with PRRs
- B cells undergoes clonal expansion and transform into plasma cells and secrete antibodies to one antigen type
- Some become memory cells
- Antibodies secreted in body cells –> circulate and bind to extracellular pathogens
Describe the clonal expansion of T cells + Also specify what CD4 and CD8 proteins are. Additional: Explain how T helper cells and cytotoxic T cells work together.
CD4+ = T Helper Cells (MHC-II) CD8+ = T Cytotoxic cells(MHC-1)
A T cell is activated when it receives two signals
First Signal: Antigen recognition by a T cell receptor (TCR) with CD4 or CD8 proteins
- T Cell receptors recognize and bind to foreign antigen fragments are presented in antigen MHC
- CD4/CD8 proteins: surface proteins on T cells, interact with the MHC antigens and help maintain the TCR-MHC coupling
Second Signal: Co-stimulation by soluble factors (cytokines) or plasma membrane molecules
- For a particular antigen, first need activation of Th cell, which then confirms and activates Tc cell which does the killing.
Th cells are necessary for activation of Tc cells –> Clonal expansion
- Both must be activated by antigens from pathogen, but not neccessarily to same antigen (pathogen has many antigenic reasons)
How is Immunological memory achieved
Achieved by:
- Presence of long-lasting antibodies
- Production of memory cells from clonal selection of antigen-stimulated B cells and T cells
- Basis for acquired immunity
How does immunological memory result in a stronger and faster secondary immune response?
Primary response
- Slow rise in antibody titre after initial contact with antigen –> followed by decline
- Memory cells are formed and may remain for decades
Secondary response
- Rapid proliferation of memory cells upon encountering same antigen –> greater antibody titre than primary (effective protection against the same pathogen)
- Ab class switching: IgM –> IgG (still to the same antigen) produces more specific antibodies and greater coverage
- Reponse is faster and more intesne, symptoms may not even develop
Describe cytotoxic T cell ‘killing’ mechanisms
Tc cell - CD8+ (MHC-I)
- Migration- Tc cells leave secondary lymphoid organs and tisues, migrate to site of infection/transplanted tissues/ tumour formation –> Tc cells recognize and attach to target cells
- Attack- Cytotoxic T cells kill pathogen by: (Tc only recognises antigen as a MHC-1 is presenting it)
A: activate intracellular killing mechanisms in other cells by release of cytokines (e.g. IFN-y) activates macrophages.
B: Direct cytotoxic activity by killing infected cells and parasites through perforin (creates channels in plasma membranes of a target cell –> cytolysis) and granulysin (destroys microbe by creating holes in plasma membrane)
C: Tc destroys vital tissue in the process of killing pathogen
D: Tc can lyse infected cell, releasing live parasite into extracellular fluids –> releases granzymes (apoptosis)
E: Released parasites can be taken up by more effective immune cell and acted upon by extracellular responses (antibodies, complement)
