IMMUNOLOGY Flashcards
What occurs at the Primary Lymphoid Organs
Sites where stem cells divide and immune cells develop
What occurs at the Secondary Lymphoid Organs
Sites where most immune responses occur
Primary Lymphoid Organs
- Bone Marrow (Yolk Sac and Fetal Liver in Embryo)
- Thymus
Secondary Lymphoid Organs
- lymph nodes
- spleen
- lymphoid nodules
Bone Marrow site where
B-cells mature
Thymus site where
T cells mature
Atrophies after maturity
The thymus contains what types of cells
Contains T cells, scattered dendritic cells, epithelial cells, and macrophages
Produced in the bone marrow
Blood cells are produced here: B-cells and Immature T-cells
Yolk Sac and Fetal Liver produces
Blood cells are produced here in the embryo
Lymph nodes
Secondary Lymphoid Organ: Scattered throughout the body Filter microbes Macrophages in nodes phagocytize microbes that pass through in the lymph fluid
Spleen
Secondary Lymphoid Organ:
Largest lymphoid organ
Removes microbes and dead or old erythrocytes
Lymphoid Nodules
Secondary Lymphoid Organ:
Tonsils
Peyer’s Patches and MALT (Mucosal-Associated Lymphoid Tissues) Appendix
Immune Cells Travel in the ____ and _______
Immune Cells Travel in the Blood and Lymphatic Vessels
Immune Cells are
White Blood Cells/Leukocytes
Produced from lymphoid stem cells
Lymphocyte
- T cells
- B cells
- NK cells
Produced from myeloid stem cells
Erythrocyte Neutrophil Monocyte Eosinophil Basophil Megakaryocyte (platelets(
Megakaryocyte produce
platelets
myeloid cells
Neutrophil
Monocyte
Eosinophil
Basophil
Macrophages and dendritic cells are
monocytes
Eosinophils
Destroy parasites
Basophils
Release a variety of chemicals Histamine, leukotrienes, prostaglandins
Mast Cells
Release chemicals, histamine
Neutrophils
Phagocytes
Monocytes
Macrophages and Dendritic Cells Phagocytes
Lymphocytes
B lymphocytes
T lymphocytes
T lymphocytes
TH and TC
Antigen
- Immunogen – material that induces an immune response 2. Hapten (+ Carrier = Immunogen)
- Allergen
- Tolerogen
- Ligand
Non-specific/Innate Immunity
Ability of the body to defend against microbes and other foreign substances - without recognition of the invading pathogen.
First Line of Defense
Physical Barriers
Second Line of Defense
Cellular Factors
Humoral Factors
Physical Barriers
Skin Mucus Hair Cilia Sebum Lysozyme Gastric Juice
Innate Immunity
No memory
Cellular Factors (2nd Line of Defense)
- Phagocytic Cells
neutrophils, macrophages, dendritic cells - Cells with inflammatory mediators basophils, mast cells, eosinophils
- Natural Killer Cells
Humoral Factors (2nd Line of Defense)
- Inflammation and Fever
- Antimicrobial Substances
Acute Phase Reactants: C-Reactive Protein, Complement, Interleukin and Cytokines - Interferon-alpha
Non-Specific Response to Tissue Damage
Inflammation
4 Distinct Signs and Symptoms of Inflammation
Redness
Heat
Pain
Swelling
3 Stages of Inflammation
- Vasodilation*
- Emigration of Phagocytes
- Tissue Repair
Vasodilation
- Widening of blood vessels allows more blood flow to the site
- Increased permeability of capillaries allows substances to go to the damaged site
Antimicrobial Substances
Discourage Microbial Growth or Spread of Pathogen
Interferons
Binds to receptor on cells and sends signal to to activate genes for antiviral protien
Type I interferon
Prevents viral replication
Complement
a group of plasma proteins
Complement Protein Function
A large family of plasma proteins with multiple functions. 30 different proteins participate in the cascades.
A central protein in the complement cascade is C3.
A central protein in the complement cascade is
C3
Function of Complement C3b
As an opsonin
Binds to phagocytes via the C3b receptor
Natural Killer Cells
a class of lymphocytes, similar to cytotoxic T cells, who target virus-infected cells and cancerous cells
T/F: Natural Killer Cells attack and kill these target cells without binding to them.
F: they attack and kill these target cells directly after binding to them.
Natural Killer Cells are/are not antigen-specific
are not
NK cells do not need to recognize a specific antigen.
The similarity between cytotoxic T cells and NK cells
Like cytotoxic T cells, they attack and kill these target cells directly after binding to them.
How do NK cells kill body cells?
Release chemicals that lead to death of infected or abnormal body cells*
Release Perforin and granzyme
The difference between cytotoxic T cells and NK cells
Unlike cytotoxic T cells, they are NOT antigen-specific. NK cells do not need to recognize a specific antigen.
Perforin
polymerize and form a channel in target cell membrane
What do NK cells recognize on the cells
*Cells not expressing MHC-I
Virally-infected
or cancerous cells down-regulate MHC-1
What cells express MHC-I on their surface?
every nucleated cell in the body
Granzymes
induce programmed cell death (apoptosis) in the target cell
Phagocytes
Non-specifically engulf microbial invaders
Types of Phagocytes
Fixed-Tissue Macrophages Neutrophils
Monocytes – Macrophages and Dendritic Cells
Phagocytosis steps
Steps: Adherence, Ingestion, Digestion, Killing
- Microbe
- Endocytosis
- phagosome formation
- Lysosome fusion with the phagosome
- Phagolysosome
- Release of end products into or out of the cell
How Does the Phagocyte Recognize Microbes?
Detect unique, conserved proteins that are essential to microbial
physiology (molecular signatures of infection)
• Pathogen-Associated Molecular Patterns(PAMPs)
PAMPS are recognized by
Immune system receptors called pattern recognition receptors (PRR), including Toll-Like Receptors
Toll-Like Receptors
A family of highly conserved transmembrane receptors Essential for microbial recognition via PAMPs
• Extracellular domain for recognition of pathogens
• Intracellular signalling domain
Emigration of Neutrophils (phagocytes)
Chemotaxis
Margination –
Diapedesis –
Chemotaxis
Chemically stimulated movement of phagocytes
Chemoattractants
Chemicals that attract phagocytes
Margination
Migration of phagocyte towards the tissue injury
Diapedesis
Phagocytes move across the capillary wall
Specific Role of Neutrophils in Inflammation
Neutrophils Die in the Process of Killing Bacteria
NETs – Neutrophil Extracellular Traps
are made of processed chromatin bound to granular and selected cytoplasmic proteins which come from the lysed neutrophils
Pus
a mixture of dead bacteria and neutrophils
Link Innate and Adaptive Immunity
Antigen-presenting cells
via Antigen Presentation by Phagocytes
Specific/Adaptive immunity mediated by
Antibodies or cells
Humoral Specific/Adaptive Immunity
Antibody-Mediated
Immunity Involves the use of B cells
Transform into plasma cells and memory cells Synthesize and secrete antibodies
Involves the use of cytotoxic T cells
Kill infected body cells, cancer cells, foreign cells
Cell-Mediated Specific/Adaptive Immunity
Two molecular classes of MHC
MCHI
MCHii
chance of identical MHC
1 in 5 million `
Only people that have the same MHCs on their cells
identical twins
MHC molecules structure
2 chains – alpha and beta
MHC-I are on
all nucleated cells
MHC-II are on
on all antigen-presenting cells
- macrophages
- dendritic cells
- B cells
antigen-presenting cell types
– Dendritic cell / Professional APC
– Macrophage
– B lymphocyte (B cell)
Cells that have no MHCs on their surface
*erythrocytes have no MHCs on their surface
T-cell receptors recognize
antigens only when they are associated with specific MHC proteins
Antigen Presenting Cells (APCs) present
Exogenous Antigens with MHC-II
Steps of Antigen Presenting Cells
STEPS:
• Ingest antigen
• Digestion into peptide fragments
• Synthesize and package MHC-II molecules
• Bind peptide fragments to MHC-II
• Insert antigen–MHC-II complexes on plasma
membrane
Antigen
antibody generator
Epitope
The part of the antigen that is recognized by the immune cells
Characteristics of an antigen:
Reactivity - Antibody binds specifically to the antigen that provoked it
Immunogenicity - Ability to provoke an immune response by stimulating antibody production
Adaptive Immune Response
Acquired, Specific
Innate or Adaptive: Antigen (and epitope) specific
Adaptive Immune Response
Innate or Adaptive: Antigen-presenting cells (APC) – (MHC-II + peptide)
Adaptive Immune Response
Innate or Adaptive: The ability of the body to defend against specific microbes and foreign substances – Involves MEMORY for previously encountered antigens
Adaptive Immune Response
Adaptive Immune Response Cells involved
B Cells and T Cells are involved
Must recognize the specific foreign material to be attacked
B and T Lymphocytes
Any molecule that can trigger an adaptive immune response against itself or the cell bearing
Antigen
three stages of adaptive immune response
The encounter and recognition of an antigen by lymphocytes Lymphocyte activation
The attack launched by the activated lymphocytes and their secretions
Origins of B Cells and T Cells
Bone marrow
Where T cells mature
Thymus
Where B cells mature
Bone marrow
The first cell to show specificity
Helper T cell
Co-Reception occurs between
B7 - CD28
B7
on the antigen-presenting cell
CD28
on T helper cell
What results from the displacement of CD28 from B7 by CTLA4 and PD-1
Biological process that shut off the T cell activation
results in T cell inactivation
Bacterial Infection leads to
antibody synthesis in secondary lymphoid organs
Creates specific antibodies
Plasma Cells
Macrophages and B cells Process and Present Antigen to a
Helper T cell
CD4
co-receptor for the T-cell receptor
Three Events Required for the Activation of Helper T Cells
- MHC-II + Peptide – TCR 2. Co-reception CD28 – B7 3. Cytokines from APC
stimulate TH Cell
B cells that secrete antibodies
Plasma cells
B cells that are long-lived and are used for memory
Memory B cells
Which plasma protein increases during infection
gamma globulins
Antibody Structure
Contain four polypeptide chains
- Two Heavy chains that are Identical to each other
- Two Light chains that are Identical to each other
Flexible hinge region
Variable region on an antibody
Antigen binding site
Constant region on an antibody
Same in all antibodies of a class
Types of antibody class:
- IgG
- IgA
- IgM
- IgD
- IgE
IgG
most common type of antibody
protect you against infection
IgA
to protect the mucosal tissues from microbial invasion
IgM
the largest antibody
first line of host defense against infections
IgD
function unclear
IgE
critical role in the allergic inflammatory process
allergic reactions
____ cells will secrete specific antibodies
Plasma cells will secrete specific antibodies
_____ cells which allow faster response if antigen is seen again
Memory cells which allow faster response if antigen is seen again
B cells become activated in the _____
B cells become activated in spleen, lymphoid nodule, or lymph node
B cells are activated in presence of
B cells become activated in the presence of a microbe
Antibodies can be acquired actively/passively or both
Can be Actively or Passively Acquired
Active Antibody Immunity
The person’s own immune system responds to microbe Long-lasting Protection – Memory Cells are involved
Passive Antibody Immunity
The person receives antibodies from another person or animal Temporary Protection - NO Memory Cells are involved
Active Natural Immunity
Develops when a person is exposed to an antigen by chance
Active Artificial Immunity
Develops when a person is purposefully exposed to an antigen
Passive Natural Immunity
IgG from mother to fetus across the placenta IgA in Breast milk
Passive Artificial Immunity
Receive serum containing antibodies
From person or animal that has been vaccinated
Flu virus
Active Natural
Flu vaccine
Active Artificial
A vaccine
may consist of small quantities of living or dead pathogens, small quantities of toxins, or harmless antigenic molecules derived from the microorganism or its toxin.
Resistance built up as a result of the body’s contact with microorganisms, their toxins or other antigenic components (from an infection or vaccine)
Active Immunity
The direct transfer of antibodies from one person to another
Passive Immunity
antibody-synthesizing capacity of infants
relatively poor
Antibody Functions
Antigen Neutralization Antigen Agglutination Antigen Precipitation Activating Complement Opsonization
Neutralizing Antigen
Binding to bacterial toxins
Agglutinating Antigen
Grouping of microbes with antigens
Precipitating Antigen
Linkage of soluble antigen
Activating Complement
Compliment protein becomes active when bound to antibody with microbe
Activation of Classical Complement Pathway
C1 binds to antigen binding site, and the C3b on the bacterium binds to the phagocyte
Opsonization
Direct Enhancement of Phagocytosis by Antibody
Rate of Antibody Production Following Initial Exposure to an Antigen and Subsequent Exposure to the Same Antigen
At the second antigen exposure, the Antibody concentration is much greater
Immune Memory Prevents
Disease
CD8 cells
Cytotoxic T cells
CD4 cells
Helper T cells
Lymphocytes Must Gain
Immunocompetence - Develop Antigen Receptors
Immunocompetence
Develop Antigen Receptors
The body will/will not create antibodies to antigens on your own cells
Will NOT
T helper cells are required to activate
B and Cytotoxic T cells
Terminal deoxynucleotidyl Transferase
inserts N-nucleotides to J gene segment during rearrangements of genes
Increases specificity
Antibody Classes is determined by
constant region
Primary response by antibody (antibody type and concentration)
IgM initially and then IgG is produced
Secondary response by antibody (antibody type and concentration)
IgM and IgG is produced, IgG is produced in a higher concentration
Amplification is due to
production of memory cells
T cells
- Used in cell-mediated immunity to eliminate specific antigens
- Require Activation - they are usually inactive
- Become activated only when they bind to a foreign antigen
T cells that don’t recognize MHC Class II molecules are of
no value and are negatively selected (the clone is destroyed)
T cells that recognize MHC class II- self peptide complexes are
negatively selected (the clone is destroyed)
Development of Immune Tolerance develops during
Immune tolerance develops during fetal and early postnatal life
Immune tolerance develops due to
clonal deletion or clonal inactivation of cells that match body antigens
Endogenous Antigen
Digestion of antigen – virus - into peptide fragments
Steps of Infected Body Cells
Synthesis of MHC-I molecules
Binding of peptide fragments to MHC-I molecules.
Packaging of antigen–MHC-I complexes
Insertion of antigen–MHC-I complexes into the plasma membrane.
Steps of 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.
Infected Cells Process and Present
Viral Antigens to a Cytotoxic T Cell
Killing of Virus-Infected Cells is done by
Cytotoxic T cells
Cytotoxic T cells release _______
perforin + granzymes
perforin
perforin facilities entry of cytotoxic Granzymes into cell
Granzymes
inducing apoptosis
virus cannot replicate and is released
What does Antigen-MHC-I complex bind to
TCR
Factors that Alter Resistance to Infection
• Protein–calorie malnutrition
worldwide, the greatest contributor to decreased resistance to infection
• Preexisting disease, infectious or noninfectious, can predispose the body to infection
• Stress and state of mind can enhance or reduce resistance to infection (and cancer)
• Modest exercise and physical conditioning have net beneficial effects on the immune system and on host resistance
• Sleep deprivation is associated with decreased immune function
Immunodeficiency Diseases
Result from weak, underactive, or impaired immune systems
𝑺𝑪𝑰𝑫 = 𝑺𝒆𝒗𝒆𝒓𝒆 𝑪𝒐𝒎𝒃𝒊𝒏𝒆𝒅 𝑰𝒎𝒎𝒖𝒏𝒐𝒅𝒆𝒇𝒊𝒄𝒊𝒆𝒏𝒄𝒚 𝑫𝒊𝒔𝒆𝒂𝒔𝒆
a group of related diseases that arise from an absence of both B and T cells and, in some cases, NK cells
𝑨𝑰𝑫𝑺 = 𝑨𝒄𝒒𝒖𝒊𝒓𝒆𝒅 𝑰𝒎𝒎𝒖𝒏𝒐𝑫𝒆𝒇𝒊𝒄𝒊𝒆𝒏𝒄𝒚 𝑺𝒚𝒏𝒅𝒓𝒐𝒎𝒆 affects which cells
infects and kills helper T cells resulting in impaired immune responses to other infectious organisms.
Harmful Immune Responses
Graft Rejection
Transfusion Reactions
Allergy (Hypersensitivity) Autoimmune Disease
Excessive Inflammatory Responses
Tissue Grafts and Organ Transplantation
Class I MHC proteins on the graft cells and class II MHC proteins on the macrophages differ from the recipient
Consequently, the MHC proteins are recognized as foreign by the recipient’s T cells.
Cells bearing these proteins are destroyed by the recipient’s cytotoxic T cells with the aid of helper T cells.
Tools aimed at reducing graft rejection include radiation and drugs that kill actively dividing lymphocytes and thereby decrease the recipient’s T-cell population.
cyclosporine
blocks the production of IL-2 and other cytokines by helper T cells. This eliminates a critical signal for proliferation of both the helper T cells and the cytotoxic T cells.
Transfusion Reactions
illness caused when erythrocytes are destroyed during blood transfusion
Antibody of A blood type
Anti-B
Antibody of B blood type
Anti-A
Antibody of AB blood type
Neither Anti-A nor Anti-B
Antibody of O blood type
Both Anti-A and Anti-B
Allergic Reactions
When a person is overly reactive to a substance that most others tolerate well
Two types of allergic responses
- Immediate Hypersensitivity
Delayed Hypersensitivity - Appears 12-72 hours after allergen exposure
Anaphylaxis
large amounts of the chemicals released by the mast cells (or blood basophils) enter the circulation, systemic symptoms may result and cause severe hypotension and bronchiolar constriction.
Autoimmune Disease
an inappropriate immune attack triggered by the body’s own proteins acting as antigens
The immune attack, mediated by autoantibodies and self-reactive T cells, is directed against the body cells that contain these proteins
Autoimmune Disease Examples
- Type 1 diabetes mellitus
- Rheumatoid arthritis
- Multiple sclerosis
- Myasthenia gravis
Autoimmune Disease Examples
- Type 1 diabetes mellitus
- Rheumatoid arthritis
- Multiple sclerosis
- Myasthenia gravis
