Immunology Flashcards
Which systems connect the immune system accross the whole body?
- lymph and circulatory system (blood)
From what does the immune system protect us?
From pathogens (bacteria, viruses, parasites)
and from altered body cells (cancer)
Which are the 2 systmes of protection (explain)?
Non-specific Immunity
- First line defense
- no recognition
- same response each time you see same pathogen
Specific/Adaptative Immunity
- requires pathogène recognition
- Faster response if same pathogen again
What are the ways science can make discoveries about the immune system?
Accidents of nature (ex: stroke)
Leaps of faith :
- beleiving in something whose existence can’y be proved
- smallpox vaccination
Serendipity (look at something people would not pay attention to)
Whay are the componenets of the Immune System?
Lymphoid Organs:
Primary lymphoid organs (sites where stem cells divide and immune cells develop)
Secondary Lymphoid Organs (sites where most immune response occur)
Immune cells :(Leukocytes/WBC)
Secretion of Immune Cells
Which are the primary lymphoid organs?
Bone Marrow: (yolk sac and fetal liver in embryo)
Blood cells are produced here: B-Cells and immature T-cells (B-Cells mature there)
Thymus: (above heart)
T-Cells, scattered dendritic cells, epithelial cells, macrophages
(where T-Cells mature)
*Gets smaller and atrophies as we age
Which are the secondary lymphoid organs?
Lymph Nodes:
- Throughout the body
- Filter microbes
- Macrophages in nodes phagocytize microbes entering lymph
Spleen: (la rate)
- Largest L.O.
- Removes microbes + dead/old erythrocytes (RBC)
Lymphoid Nodules:
- Tonsils (amygdales)
- Peyer’s Patches and MALT (Mucosal-AAssociated Lymphoid Tissue) –> against pathogen enter gastrointestinal system by food
- Appendix
Where do immune cells travel?
in the Blood and Lymphatic Vessels
*Lymphatic vessels = much + impermeable to protein than capillaries
How do the Lymph nodes work?
Liquid will go into sinuses (in the lymph nodes) where encounter immune cells
Which immune cells are derived from the Lymphoid stem cells
Lymphocytes :
- T Cells (Cytotoxic CD8+, Helper CD4+, Regulatory CD4+)
- B Cells
- NK Cells
Which immune cells (Leukocytes) are derived from the Myeloid stem cells
- Neutrophils
- Monocytes
- Eosinophils
- Basophils
- Mast cells
What are Neutrophils functions?
Where are they produced?
Phagocytosis
Release chemicals involved in inflammation
(vasodilators, chemotaxis, etc.)
Produced in the Bone marrow
What are Basophils functions?
Where are they produced?
Release chemicals (histamine, prostaglandins)
Carry out functions in blood similar to those of mast cells in tissues
Produced in Bone marrow
What are Eosinophils functions?
Where are they produced?
Destroy multicellular parasites
Participate in immediate hypersensitivity reactions
Produced in Bone marrow
What are Monocytes functions?
Where are they produced?
Enter tissues and transform into macrophages and dendritic cells
Phagocytosis
Extracellular killing via secretion of toxic chemicals
Process and present antigens to helper T cells
Secrete cytokines involved in inflammation, helper T cells, systemic response to infection/injury (acute phase)
Carry out functions in blood similar to macrophages in tissues
Bone marrow
What are Lymphocytes functions?
Where are they produced?
Recognition cells in specific immune response (and all aspects of specific response)
B cells and NK cells mature in bone marrow
T cells mature in Thymus
Activated in peripheral lymphoid organs
What are B cells functions?
Where are they produced?
antibody-mediated immune responses by binding specific antigens to B cells plasma membrane receptors (immunoglobulins)
After activation, transformed into plasma cells –> secrete antibodies
Present antigen to helper T cells
Develop and mature in bone marrow
What are Cytotoxic T cells (CD8+ cells) functions?
Where are they produced?
Bind to antigens on plasma membrane of target cells and directly destroy cells
Which cells are considered target cells?
- virus-infected cells
- cancer cells
- tissue transplants
What are helper T cells (CD4+ cells) functions?
Where are they produced?
Secrete cytokines that help to activate B cells, cytotoxic T cells, NK cells and macrophages
What are NK cells functions?
Where are they produced?
Bind directly and nonspecifically to virus-infected cells and cancer cells and kill them
What are plasma cells functions?
Where are they produced?
Secrete antibodies
produced in peripheral lymphoid organs; differentiate from B cells during immune responses
What are macrophages functions?
Where are they produced?
Phagocytosis
Extracellular killing via secretion of toxic chemicals
Process and present antigens to helper T cells
Secrete cytokines involved in inflammation, helper T cells, systemic response to infection/injury (acute phase)
produced in Bone marrow
resides in almost all tissues organs
Differentiate form monocytes
What are dendritic cells functions?
Where are they produced?
Phagocytosis
Antigen presentation
PROFESSIONAL APCs (link innate and adaptative immunity)
produced in almost all tissues and organs, microglia (macrophages?) in the central nervous system
What are mast cells functions?
Where are they produced?
Release histamine and other chemicals involved in inflammation
Produced in Bone marrow
Reside in almost all tissues and organs
Differentiate from bone marrow cells
Which are the different cytokines and what do they do?
Interleukine 1, 6 and 2
tumor necrosis factor-alpha
Interferons (type I and II)
Chemokines
Targeted cells:
helper T cells, cytotoxic T cells, NK cells, B cells, macrophages, Leukocytes
Interferons (type I) target most cell types
Functions:
- stimulate IL-2 receptor expression, induce fever
- stimulate proliferation of targeted cells
- promote conversion to plasma cells
- facilitate accumualtion of leukocytes at sites of injury/inflammation
What are the components and characteristics of the non-specific/innate Immunity?
No recognition
First Line of Defense:
- physical barriers
Second Line of Defense:
- Cellular factors
- Humoral factors (dissolved in fluids that will fight infections?)
What is the First Line of Defense (of the innate immunity) made of?
Physical Barriers
- Skin (water resistant, prevents entry of…)
In skin, gut, lungs, eyes/nose:
- Thight Junctions in Epithelia (mechanical, everywhere)
- Mucus (mouth, gastrointestinal, mechanical) –> sticky so bacteria don’t move
- hair (mechanical)
-cilia –> cough (mechanical, mat of mucus)
- secretions : sebum, Lysozyme, gastric juice (Chemical)
- Normal Flora/microbiome (microbiological on skin and gut)
*Prevents pathogen from entering the body (circulatory system)
View p.28, p.37, p.89
…
What is in the Second Line of Defense of the innate immunity
Humoral Factors:
- Inflammation and Fever
- Antimicrobial –> Acute phase reactants: C-Reactive protein (increase blood stream), complement, cytokines
- Interferons (antiviral particules)
Cellular factors:
- NK cells
- Phagocyte cells (mainly neutrophils)
- Cells with inflammatory mediators (basophils, mast cells, eosinophils)
What are the 4 signs/symptoms of inflammation?
And 3 stages of inflammation?
- Redness
- Heat
- Pain
- Swelling
- Vasodilatation (increase of blood flow)
- emigration of Phagocytes
- Tissue Repair
**Widening of blood vessels = more blood flow to site
**Increased permeability of capillaries = substance can go to damage site
Which are the humoral substances?
What do they do?
They discourage Microbial Growth or Spread of Pathogen
- Interferons (antiviral proteins):
Type I prevent viral replication - Complement:
Large family of plasma protein, participates in cascades
Its activation –> recruitment of inlfammatory cells, Opsonization (by phagocytosis) of pathogens, killing of pathogens - Iron-Binding Proteins:
Transferrin
What are NK cells?
Class of Lymphocytes, similar to cytotoxic T cells but with NO RECOGNITION
(recognize MHC-I which is on every normal cell to not activate the release of enzymes)
Kill virus-infected and cancer cells directly after binding to them by releasing chemicals
perforin makes hole and granzymes get into cell by the hole
What are phagocytes’ roles?
And type?
*All old RBC phagocytosed in spleen
Types:
Fixed-Tissues Macrophages (come from monocytes moved out of blood stream (same for dendritic cells))
Neutrophils
Steps: Non-specific
*If have C3-b complement system to recognize
- Adherence
- Ingestion
- Digestion (merge with Lysosome –> low pH environment = destruction)
- Killing
How do phagocyte recognize microbes?
*In cellular factors of second line of defense (innate immunity)
Detects unique structures essential to microbial physiology
Pathogen-Associated Molecular Patterns (PAMPs):
- Lopopolysaccharide (LPS) of gram-neg bacteria
- Peptidoglycan (PGN) of gram-pos bacteria
PAMPs (on bacteria) are recognized by immune system receptors –> Pattern Recognition Receptors (PPR)
ex: Toll-Like Receptors (TLRs) on surface of the macrophage
How is the inflammation process started?
TLR on macrophage recognize PAMPs on bacteria and send signal to other cells (neutrophils)
TLR on macrophage = extracellular domain for recognition
+ intracellular for signalling
How does immigration of phagocytosis work?
- Chemotaxis
Chemoattractants attract phagocytes –> stimulates mvt - Margination
change in surface of capillaries, surfacce receptor change to be sticky to Neutrophils - Diapedesis:
Phagocytes move across capillary wall
WHat is the specific role of neutrophils in inflammation?
Neutrophil die in the process of killing bacteria
NETs - (Neutrophils Extracellular Traps) = processed chromatin bound to cytoplasmic proteins coming from lysed neutrophils
Pus is produced (mixture of dead bacteria and neutrophils)
*Don’t want to carry bacteria in blood so carry in lymph nodes
How is the link between innate and adaptative imunnity made?
Via Antigen presentation by phagocytosis:
phagocyte will carry anitgens from infected area to region where activate specific immune response
What is in the adaptative immunity?
Mediated by Antibodies or Cells
- Humoral-Antibody-Mediated Immunity:
Antibodies released by B cells
- Transform into plasma cells (they produce clones/ antibodies)
- Synthesize and secrete antibodies
- Memory B cells - Cell-Mediated Immunity
involves cytotoxic T cells (kill infected, cancer, foreign cells)
What is the Major Histocompatibility Complex (MHC)
2 molecular classes:
- MHC-I expressed on all nucleated cells (human leukocyte antigens)
- MHC-II expressed on all Antigen-Presenting cells (APC)(B cells, macrophages, dendritic cells)
T cell receptors recognize antigens only when associated with MHC-II proteins (antigen-antibody complex?)
Unique to every persone (except indentical twins)
*RBC don’t have MHC-I bc no nucleus
What happens in the specific immunity when APC (Antigen-Presenting cells) recognized? p.71
- Ingest antigen (phagocytosis/endocytosis)
- Diegstion into peptide fragments
- synthesis + packaging of MHC-II
- Bind peptide fragments to MHC-II (vesicles containing both fuse)
- insert antigen MHC-II complexes on plasma membrane (exocytosis)
What is an Antigen?
What is the Epitope?
ANTibody GENerator
- Immunogen: induces a immune response
- Allergen : allergic response
- Ligand
Can be whole cell or only part
Can be non-microbial (Pollen, incompatible blood cells, tranplanted tissues)
Eptiope: part of the antigen that is recognized by the immune cells
What are antigens characteristics?
Reactivity: Antibody binds specifically to antigen that proovoked it
Immunogenicity: Provoke an immune response by stimulating antibody production to that antigen
What are the 3 stages of the typical adaptative immune response?
- Encounter and recognition of an antigen by lymphocytes
- Lymphocytes activation
- Attack launched by Lymphocytes and their secretions
B and T cells involved
What are the 3 stages of the typical adaptative immune response?
- Encounter and recognition of an antigen by lymphocytes
- Lymphocytes activation
- Attack launched by Lymphocytes and their secretions
B and T cells involved
What is the role of T cells in adaptative immune response?
Helper t cells = 1st cells, role in full activation of B-cells and cytotoxic T-cells
needs a recognition event/ appropriate receptor on surface
How does Checkpoint Inhibition work?
For immune response:
displacement of CD28 from B7 by CTLA4 or PD-1?!?!?!?!?!?!
Where are secreted antibodies during bacterial infections?
How do we make sur there is no misrecognition?
In secondary lymphoid organs:
Lymph nodes or spleen (transported by macrophage)
B-cells –> plasma cells or memory b-cells
No misrecognition bc both T-cells and B-cells have to recognize
What is the structure of antibodies?
Belong to group of proteins: globulins
They are Immunoglobulins (Ig)
Contain 4 polypeptide chains:
2 heavy (identical) + 2 light (identical)
Variable Region (FAB)
- varies between types on Ig
- Anitgen binding site (top of light chains)
Constant region (Fc)
- same in all antibodies of a class
Which are the 5 classes of antibodies?
What is there main difference/ determined by what?
They are determined by the Fc region
IgG (most abundant) normal 3 branch
IgA (in fluid like saliva, tears, etc.)2x normal 3 branch
IgM (activate complement system but large so don’t move easily) flocon shape
IgD (allergies) normal 3 branch
IgE (allergies and parasites) normal 3 branch
How does Antibody-Mediated Immunity work? p.106
Carried out by B cells:
B cells become activated in spleen, lymphoid nodes, lymph node in the presence fo a microbe
What is active antibody (adaptative) Immunity ?
(2 types)
The person’s own immune response: T cells and B cells activated and produce memory cells
Long-lasting protection bc memory!
Natural - Develops when exposure to antigen by chance
Artificiel - when purposefully exposed to antigen ex: vaccine
What is passive antibody (adaptative) Immunity ?
(2 types)
When persone receives antibodies –> Temporary protection bc NO memory cells
Natural - IgG from mother to foetus accross palcenta or IgA in Breast milk
Artificial - Receive serum with antibodies form vaccinated person
*Important for infant protection because antibody-synthesizing = poor
What are effects of antibodies?
- Direct enhencement of phagocytosis (Opsonization)
- Activation of the Complement system
- Antibody-dependent cellular cytotoxicity
- Direct neutralization of bacterial toxins and viruses
What are the functions of antibodies?
- Neutralizing Antigens (binding with bacteria to change its structure so change its effect)
- Agglutinating Antigens
- Precipitating Antigens (facilitate phagocytosis)
- Activting Complement (by binding to antibody-antigen complex –> Classical Pathway)
- Opsonization (means prepare for eating, enhancement of phagocytosis bc on surface of phagocytes there are receptors for Fc region of antibodies)
When does antibody production peak at 1st exposure?
And do these antibodies stay for every and create the adaptative response?
After 1 week (second exposure = much faster reponse)
No, antibodies have short lifespan so memory cells are important –> amplification event (due to memory cells)
What is th importance of lymphocytes in adaptive immunity?
Lymphocytes must gain Immunocompetence (develop antigen receptors)
B cells: produce antibodies
T cells:
Cytotoxic T cells (CD8+) and Helper T cells (CD4+)
V/F
The Major Histocompatibility Complex (MHC) is same for everyone?
F - its unique to everyone except identical twins
Explains graph rejection
How to Lymphocytes gain Immunocompetence?
The develop specific antigen receptors for every antigen
*Happens do B and T cells
Recombining DNA to make each antibody specific to a different antigen –> specific to B and T cells
RAG = recombination
activation genes
TdT = Terminal deoxynucleotidyl
rensferase
What is an endogenous antigen?
Antigen produced by the body itself
Infected body Cells:
Synthesis of MHC-I molecules
Binding of peptide fragments
Packaging of antigen-MHC-I complexes
Insertion of antigen-MHC-I complexes into plasma membrane
What is an endogenous antigen?
Antigen presenting cells
Synthesis of MHC-II molecules
Binding of peptide fragments to MHC-II molecules.
Packaging of antigen–MHC-II complexes
Insertion of antigen–MHC-II complexes into the plasma membrane.
Which factors could alter resistance to infections?
- Protein-calorie malnutrition
- Stress and state of mind
- Preexisting disease
- Modest exercice/physical conditioning
- Sleep deprivation
Name and explain 2 autoimmune diseases
SCID = several combined immunodeficiency disease –> diseas that arise from absence of B and T cells and sometimes of NK cells
AIDS = acquired immunodeficiency syndrome –> infects and kills helper T cells so decreased immune response to infectous organisms
What can be harmful immune responses?
- Graft rejection
- Transfusion reactions
- Allergy (Hypersensivity)
- Autoimmune diseases
- Excessive inflamatory responses
What explains Graft rejection and what solutions where found?
MHC-I on graph cells and MHC-II on the macrophages siffer from the recipient –>recognized as being foreign by T cells
Tools = Radiation or drug
Cyclosporine blocks production of IL-2 and other cytokines by helper T cells (eliminates signal fro proliferation of T cells)
What explains blood transfusion reactions?
Major factor of rejection = Antibodies bc Erythrocytes lack MHC proteins (bc no nucleus) but have plasma membrane proteins and carbohydrate proteins that function as antigens
ABO system for carbs
Rh erythrocyte-membrane antigens
What are 2 types of allergic reactions?
Explain Anaphylaxis
Immediate Hypersensitivity
Delayed Hyspersensitivity (12-72 hours after exposure)
reaction usually around site of antigen entry
Anaphylaxis:
large amouts of chemicals (histamine) released by mast cells (or blood basophils) enter circulation –> severe hypotension and bronchiolar constriction –> circulatory and respiratory failure
