Immunology 1 Flashcards
This exists to protect the host from infection
Immune system
This is the ability of an organism to resist a particular infection or toxin by the action of specific antibodies or sensitized white blood cells
Immunity
This is a collection of cells, tissues, and molecules that mediate resistance to infections
Immune system
Primary function of the immune system
Surveillance → recognition of self from non-self → identification of foreign or pathogenic invaders → attack and elimination
This is a coordinated reaction of the immune cells and molecules to infectious microbes
Immune response
The study of molecules, cells, organs & systems responsible for the recognition & disposal of what is foreign or non-self
Immunology
How body components respond to foreign materials and how they interact
Immunology
It deals with understanding the desirable (protective) and the undesirable (pathologic)
Immunology
It deals with ways by which the immune system can be manipulated to protect the body against diseases by preventing the invasion of infectious agents or to treat diseases by eradicating established infections.
Immunology
Founder of Immunology
Father of Vaccinology
Initiated vaccination - first reliable method of conferring lasting immunity to smallpox
Edward Jenner
This is defined as “the phenomenon in which exposure to one agent produces protection against another agent (Stevens)”
Cowpox and smallpox
Cross-immunity
The person who defined cross reactivity as “the phenomenon in which exposure to one agent produces protection against another agent (Stevens)”
Louis Pasteur
This may occur through heat, aging, or chemical means, and it remains the basis for many of the immunizations that are used today.
Attenuation or change
Year when spread of vaccination (first rabies vaccine given to a young boy bitten by a rabid dog)
1885
Year when immunology began
1796
Discovered antibodies while developing a diphtheria antitoxin
Eml Von Behring & Shibasaburo Kitasato
True or False.
Tetanus poisons can be given to patients to cure them from this disease.
True
Year when antibodies protect against disease
1901
Developed a way to make pure culture of bacteria and discovered cholera bacterium and Mycobacterium tuberculosis
Robert Koch
Year when immune response to tuberculosis started
1905
Demonstrated that protective effects of the immune system could also cause great damage to the body
Worked on anaphylaxis
Charles Richet
Discovered the ABO blood group and Rhesus factor (Rh)
Karl Landsteiner, 1930
Year when there is vaccine against Yellow Fever
1951
Year of the development of antihistamine drugs for allergy treatment
1957
Year when the structure of the antibody molecule revealed
1972
Year of the development of monoclonal antibody
1984
Year when Hepatitis B vaccine was discovered
1986
Year of the Transplantation immunology
1991
Year when Human Papilloma Vaccine started to prevent Cervical Cancer
2005
A complex collection of fluid and cells that penetrate all the organs, tissue spaces, vascular network and fluid compartments of the body
“Soldiers” that protect the body
Immune system
Organs of defense and immunity
Reticuloendothelial system (RES)
Extracellular fluid (ECF)
Bloodstream
Lymphatic System
A network of connective tissue fibers inhabited by macrophages that attack and ingest microbes
Reticuloendothelial system (RES)
Surrounds all tissue cells; penetrate by blood and lymph vessels
Extracellular fluid (ECF)
Contains specific and non-specific cellular defenses
Bloodstream
Brings all components of the second and the third line of defense to attack infectious microbes
ECF
It provides the route of passage for macrophages while waiting for the foreign substances
RES
Functions of the lymphatic system
Returns tissue fluids to the general circulation
Carries away excess fluid in inflamed tissues
Concentrates and processes foreign invaders
Initiates the specific immune response
This involves further differentiation into monocytes, granulocytes (neutrophils, eosinophils, basophils), RBCs and thrombocytes.
Myeloid series
This is responsible for the production of the lymphocyte, and the natural killer (NK) cells which is also known as the large granular lymphocyte.
Lymphoid series
Site of maturation of T and B cells
Primary lymphoid organs
Two primary lymphoid organs
Bone marrow
Thymus
Bone marrow or Thymus.
Responsible for providing the stem cells from which the blood cells arise
Bone marrow
Bone marrow or Thymus.
Located near the heart
Thymus
Bone marrow or Thymus.
Produces humoral factors that will induce immunological competence in lymphocytes
Thymus
Bone marrow or Thymus.
Site of maturation for B cells
Bone marrow
Bone marrow or Thymus.
Site of maturation for T cells
Thymus
Bone marrow or Thymus.
Its equivalence in chickens is the Bursa of Fabricius
Bone marrow
Secondary lymphoid organs
Spleen Lymph nodes (LN) Peyer’s patches Tonsils Appendix SALT (skin-associated lymphoid tissue) MALT (mucosa-associated lymphoid tissue) GALT (gut-associated lymphoid tissue)
Serve as an antigen trapping site of tissues or vascular spaces and the site where mature lymphocytes can interact effectively with the antigen
Secondary lymphoid organs
Lymphocytes circulate through these organs so that every antigen is exposed to a sample of the whole lymphocyte population (of B cells or T cells)
Secondary lymphoid organs
Carry products of the immune response such as antibodies and T cells to the blood and/or tissues
Secondary lymphoid organs
Two major cellular components of the immune system
Agranulocytes
Granulocytes
Two agranulocyte cells
Lymphocytes
Monocytes
Central cell of the immune system
Lymphocytes
20-25% of the WBC in blood
99% of cells in lymph
Lymphocytes
Composed of T cells, B cells and NK cells
Lymphocytes
True or False.
Lymphocytes are the only WBC that produce specific receptors for antigens
True
True or False.
Lymphocytes are morphologically similar but extremely heterogenous in lineage, function, and phenotype
True
Manner by which lymphocytes are distinguish
Cluster of differentiation (CD)
Important features of lymphocytes
Restricted cell surface receptors
Clonal proliferation (able to produce similar cells)
Long life span: memory cells
Recirculation between tissues and blood, assuring body wide distribution
This is the ability of lymphocytes to recognize differences between antigens
Specificity
True or False.
Basal cells have antigen binding receptor to recognize the antigen.
True
True or False.
T-helper cells have T cell receptor (TCR) molecule that functions like the immunoglobulins.
True
Have TCR and CD4
Th
Have TCR and CD8
Tc
T or B cell.
15%-20% of lymphocytes in the blood
B cell
T or B cell.
75%-80% of lymphocytes circulating in the blood
T cell
T or B cell.
Associated with humoral immunity
B cell
T or B cell.
Function: differentiates into antibody-producing plasma cells in the presence of an antigen
B cell
True or False.
Other lymphoid stem cells migrate from the bone marrow to the thymus, thereby undergoing specialization into T cells.
True
T or B cells.
Found in all lymphoid tissues, especially in the paracortical region of the lymph nodes
T cells
T or B cells.
Develops first from lymphoid stem cells in the liver of fetuses
B cells
T or B cell.
After birth, they develop and mature from lymphoid stem cells in the bone marrow where they mature containing IgM and IgD
B cell
T or B cell.
Long life span
T cells
T or B cell.
After maturation, they migrate to the lymphoid tissue, lymph nodes (specifically in the cortical region), spleen, tonsils, adenoids, & GALT.
B cells
End product of B cell activation
Antibodies
T cells differentiate into
Td, Tc, Th, Ts
Both T cell differentiated cells function for cell mediated immunity and antigen clearance.
Td and Tc
Both T cell differentiated cells function as regulatory cells.
Th and Ts
T cell associated with delayed type hypersensitivity
Td
Cytotoxic T cells
Tc
Suppressor T cells; down regulates immune system
Ts
T helper cells; aid in the enhancement of the immune system
Th
T cells that provide chemical signals that help stimulate other immune cells like B lymphocytes to differentiate into Ab-producing cells
Th cells
T cell that produce cytokines that regulate activities of T cells & B cells, monocytes & other immune cells
Th
Th differentiates into
Th1
Th4
Th1 cytokine that activate macrophages or help B cells to switch to IgG synthesis
TNF-γ
Th2 cytokine that activate mast cells, eosinophils and causes B cells to synthesize IgE
IL-4
True or False. CD4 molecules displayed on the surface of the T cells are able to recognize a non-peptide bonding portion of MHC class II molecule.
True
Normal ratio of CD4+ to CD8+ cells
2:1
T cells that identify cells infected with intracellular organisms and eliminate or lyse the cells harboring them
Tc cells
T cell that kills tumor cells, host cells infected with viruses, and other microorganisms
Tc cells
T cell involved in other types of allergic reactions
Tc cells
True or False. CD8 molecules displayed on the surface of these T cells recognize the non-peptide bonding portion of MHC class I molecule.
True
T cells that function to downregulate thus control the adaptive immune responses
Ts cells
15% of blood lymphocytes
Large lymphocytes that have Killer Activation Receptors (KARs) and Killer Inhibition Receptors (KIRs), but do not have membrane surface markers
NK cells
Function of NK cells
Destroy target cells by cytolysis and apoptosis
True or False.
NK cells normally circulate in the blood but can migrate to infected tissues and kill infected host cells but do not express the kinds of clonally distributed antigen receptors that B cells and T cells do.
True
Type of surface protein that is lacking in NK cells
MHC class 1
Lymphocytes that kill foreign cells, viral infected cells, tumor cells and produce cytokines that stimulate macrophages
NK cells
3-7% in the circulation
Phagocytes that develop from the myeloid series; considered as an agranulocyte
Monocytes
Largest WBC and develop into macrophages when they leave the circulation
Monocyte
Morphology of monocytes
Nucleus is oval or kidney-shaped
“Ground glass” appearance
Functions of macrophages
Phagocytosis
Secrete cytokines that influence growth and activation of other cell types
True or False.
Activated macrophages are among the most important types of APCs that can present antigens to lymphocytes.
True
Corresponding names of macrophages according to tissue location
Histiocytes - CT
Microglial cells - brain
Mesanglial cell - kidneys
Kupffer cells - liver
Cells with granular cytoplasm and an irregularly shaped, lobed nucleus, derived from myeloid stem cell lineage
Granulocytes
Three types of granulocytes
Neutrophils, Eosinophils, Basophils
Type of immunity that is present at birth, non-specific, rapid response, lacks memory response and serves as the body’s initial protection
Innate immunity
Body’s first line of defense
Physical barriers
Chemical barriers
Normal microbiota
Different physical barriers of the body
Skin Mucous membrane Gastrointestinal tract Genitourinary Tract Tears Saliva Mucus-coated hair in the nose
This physical barrier undergoes periodic shedding of keratin & epidermis to help remove pathogenic microbes.
Skin
Helps the skin inhibit microbial growth
Dryness
Functions as a waterproofing of proteins to prevent water-soluble substances from entering the skin
Keratin
These are secretions of the skin that have acidic pH
Sweat and sebaceous secretions
This protects the body from the exterior surface and is lined by epithelial cells which secrete mucus that covers microbes to be eliminated
Mucous membrane
Act as filter found in the respiratory tract
Ciliated cells of the respiratory tract
Protective mechanisms of the GIT
Peristalsis, defecation and vomiting that get rid of the microbes
Main protective characteristic of the genitourinary tract
Length of the urethra
Washes away microbes in the eye surface
Tears
It prevents colonization of microbes by diluting its number and washing them from the surface of the teeth and mucous membrane of the mouth
Saliva
Protective contents of saliva
lysozyme, urea, uric acid
low pH that inhibits the growth of microbes
IgA that prevents attachment of microbes
Filter air and help trap microorganisms, dust and pollutants
Mucus-coated hair in the nose
Chemical barriers in the body
Sebum Perspiration Lysozyme Saliva Gastric juices Vaginal secretions Urine Genetic components
Oily substance that acts as protective covering of the skin produced by sebaceous glands (holocrine)
Sebum
Contains unsaturated fatty acids that inhibit bacterial and fungal growth
Sebum
Flushes microorganisms from the skin surface
Perspiration
Contained in nasal secretions, saliva, tears
Breakdown cell walls of bacteria
Lysozyme
Protective mechanism of gastric juices
High acidity destroys microbes
True or False.
Some microorganisms like H. pylori are able to survive in the stomach by producing urease which neutralizes the stomach acid.
True
Vaginal secretion which is acted upon by Lactobacillus, making the area acidic to ward off other pathogenic organisms
Lactogen
With acidic pH due to uric acid and hippuric acid that inhibits pH sensitive microbes
Urine
Genetical immunity
High pathological specificity
Genetic components
Normal microbiota prevents pathogenic organisms from colonizing the host by
Competing for nutrients
Producing substances harmful to pathogens
Bacteriocins
Altering conditions that will affect the survival of the pathogen
Considered as ribosomally synthesized antibacterial peptides or proteins that either kill or inhibit the growth of closely related bacteria
Bacteriocins
More internalized system of protective cells and fluids that includes inflammation and phagocytosis
Second line of defense
Acts rapidly both in the local and systemic levels once the first line of defense is breached
Second line of defense
Components of the second line of defense
Cellular defenses
Molecular defenses
Use special-purpose cells found in the blood and other tissues of the body
All are derived from pluripotent stem cells (granulocytes and agranulocytes)
Cellular defense
cells that engulf invading microorganisms (e.g. neutrophils and macrophages)
Phagocytes
Receptors used by the cells to regonize pathogens
Pattern recognition receptors (PRRs)
These are present in the cell membrane of phagocytic cells such as macrophages and dendritic cells
PRRs
Recognize Pathogen Associated Molecular Patterns (PAMPs)
PRRs
Structural features which are expressed by microbes (lipopolysaccharide, peptidoglycans, proteins, sugars)
PAMPs
A kind of PRR that is located in the plasma membrane of phagocytic cells
Toll-like receptors
Recognize pathogen molecules (LPS, flagellin, peptidoglycan, DNA of bacteria, DNA or RNA of viruses, components of fungi & parasites) and Induce defensive cells to release cytokines
TLRs
Mechanism of TLR
A TLR recognizes the lipopolysaccharides on the invading microbes in which it dimerizes with another TLR → sends signal to the nucleus → produces interleukins (IL 1 & 8 for inflammation; IL 6 & 12 to promotes specific activities of B & T cells)
Local defensive response to tissue damage from microbial infection
Mobilizes & attracts immune components to the site of injury
Inflammation
Localizes an infection → Prevents spread of microbial invaders, Neutralizes any toxins being produced at the site
Aids in the repair of damaged tissues
Inflammation
Cardinal signs of inflammation
Rubor (redness), Calor (heat) Tumor (swelling), Dolor (pain) Functio laesa (loss of function)
More than 2 weeks of inflammation
If neutrophils fail to remove the offending agent, macrophages and lymphocytes take over and form the granuloma to contain the offending agent
Chronic inflammation
Mechanism of inflammation
Injury → vasodilatation of the blood vessels → increased blood flow → increased vascular permeability due to endothelial retraction→ leakage of fluids and neutrophils to extracellular tissues → exudate formation → swelling and edema → macrophages and lymphocytes repair tissue damage → formation of a scar or return to normal state
Fever is regulated by the
Hypothalamus
Systemic response caused by infection from bacteria & their toxins
Fever
Increases thermostat (setpoint) to higher levels Our body respond by chills and blood constriction until the setpoint is reached
Pyrogens
Types of pyrogens
Endogenous
Exogenous
Endogenous pyrogens
IL-1, Tumor Necrosis Factor (TNF)
Exogenous pyrogens
Bacteria, viruses
Stimulates immune reaction through IL-1
Some microorganisms such as viruses are sensitive to heat and are killed when exposed to it
Heat can also increase metabolism
Fever
Benefits of fever
Inhibit multiplication of temperature sensitive microorganisms
Impedes nutrition of bacteria by reducing iron availability
Can speed up hematopoiesis, phagocytosis
True or False.
Fever is only beneficial up to some point. At 41oC, there could be convulsions.
True
Engulfment of the invading microorganisms by macrophages & neutrophils
Phagocytosis
Types of Macrophages
Fixed/Resident Macrophages
Wandering Macrophages
Types of Fixed/Resident Macrophages
Microglia - brain
von Kupffer cells - liver
Alveolar macrophages - lungs
Type of macrophage that is found in bloodstream and migrate to infected area
Wandering macrophages
Survey tissue compartments for microbes, particulate matter and dead cells and extract antigens from foreign matter to be presented to T cells
Phagocytosus
True or False.
Phagocytes recognize the offending agents via receptors such as Toll-like Receptors which bind to microbial antigen.
True
Steps in phagocytosis
- Chemotaxis
- Attachment
- Ingestion
- Digestion
- Expulsion
Step in phagocytosis:
Phagocytes with protein cell-surface receptors move to a site where they are needed; directed migration 7 of 11
Chemotaxis
Step in phagocytosis:
Attachment of phagocytes to an object; phagocytes recognize a bacterium & binds to it with the help of an opsonin
Attachment
Step in phagocytosis:
Phagocyte extends pseudopods & surround bacterium forming a phagosome
Ingestion
Step in phagocytosis:
Lysosome fuses with phagosomes forming a phagolysosome; chemicals (lysozyme, lactic acid, nitric oxide & oxidants) from lysosome attack the bacterium
Digestion
Step in phagocytosis:
Phagolysosome fuse with the cell membrane & debris for them to be excreted
Expulsion
Cellular components that control viral multiplication
Interferons
True or False.
Interferons could be not viral specific and species-specific.
True
Interferon that can affect different kind of viruses
Not viral specific
Interferon that can affect only viruses that infects a certain species (E.g. humans)
Species-specific
Produced by viral infected host cell in response to viruses, RNA, immune products, and antigens
Interferons
Interfere with viral multiplication via viral protein synthesis, degradation of viral RNA and prevention of the translation of viral proteins
Interferons
React with plasma or nuclear membrane receptors inducing uninfected cell to manufacture mRNA for synthesis of Antiviral Proteins (AVPs)
Interferon
Disrupts various stages of viral multiplication
AVPs
Used in therapy of certain VIRAL INFECTIONS and CANCER
Interferons
Three types of interferons
INF-α
INF-β
INF-γ
Interferon that is a product of B lymphocytes, monocytes & macrophages and activate Natural Killer cells
INF-α
Interferon that is aroduct of fibroblasts and epithelial cells and plays a role in B and T lymphocyte maturation and inflammation
INF-β
Interferon that is a product of T lymphocytes and NK cells and nduces neutrophils & macrophages to kill bacteria & tumor cells by producing nitric oxide
INF-γ
Type of interferon that inhibits cancer cells
INF-γ
True or False.
INF-α and INF-β are the only ones involved in viral infections while INF-γ is involved in activating macrophages for phagocytosis of bacteria.
True
Mechanism of action of interferons
When viruses bind to host cells, a signal is sent to the nucleus to synthesize interferons. These interferons are secreted in the extracellular space and are taken up by uninfected cells. The uninfected cells then produce anti-viral proteins which will inhibit multiplication by interfering with viral protein synthesis. Hence, viral replication is inhibited. This allows other body defenses to fight the disease effectively.
Cell that is responsible for extracellular killings in the second line of defense
NK cells
Functions of NK cells
Eliminate irreparably injured & tumor cells
Recognize and destroy parasitic cells extracellularly
Respond by killing these cells & secreting macrophage-activating cytokine INF-γ
Fight viral & other intracellular infections by killing host infected cells
Has inhibitory receptor and activating receptor
Contain lytic enzymes
Mechanism of NK cells
In healthy host cells, there is MHC-1 Complex. The NK cells bind to the host cells in its inhibitory receptor thereby inhibiting the activating receptor. As a consequence, the host cell is unaffected. In viral infected cells, MHC is lost. Hence, they bind to the activating receptor which activates the release of lytic enzymes that kill the virus infected cells
Primary component of molecular defenses of the body
Complement System
Defensive system of proteins produced by the liver and found circulating in the blood serum
Complement system
“Complements” the immune reactions in destroying the offending agents
Complement system
Consists of around 26-30 blood proteins that work to destroy bacteria and certain viruses via a “cascade reaction”
Complement system
Complement system destroys microbes by
Cytolysis
Inflammation
Phagocytosis
Three complement pathways
Alternative Pathway – Innate Immunity
Lectin Pathway – Innate Immunity
Classical Pathway – Adaptive Immunity
True or False.
Second line of defense only involve Alternative and Lectin pathway while Classical pathway complements third line of defense or Adaptive immunity.
True
Discovered after the classical pathway
Antibody INDEPENDENT pathway
Alternative pathway
First response of innate immunity
Alternative pathway
Initiated by the presence of microbes – attacking proteins in blood, lymph and extracellular fluids – that have lipopolysaccharides, endotoxins, and yeast cell wall (zymosan), as well as aggregates of IgA which then starts with the hydrolysis of C3
Alternative pathway
Mechanism of Alternative pathway
Begins at C3 which is activated at slow rate by water & plasma enzyme (bypassing C1, C4 and C2 components) → C3 combines with complement proteins: factor B, factor D and factor P on the surface of the microbe → C3 is split to C3a and C3b
Complement protein that causes inflammation and triggers degranulation of mast cell
C3a
Complement protein that causes opsonization & cytolysis
C3b
Enters the terminal complement pathway which leads to the formation of the membrane-attack complex (MAC) that can kill the microbes by making holes (cytolysis)
C3b
Acts as an opsonin and facilitate phagocytosis
C3b
Participates in the formation of C5a which also causes phagocytosis and inflammation
C3b
True or False.
C3b is an opsonin while C5a and C3a are anaphylatoxins.
True
Most recently discovered
Antibody INDEPENDENT pathway
Lectin pathway
Initiated by binding of complement to Mannose, sugar found on microbial cell wall
Activated by lectin produced by the liver due to cytokines released by macrophages after ingesting bacteria, viruses & other foreign materials
Lectin pathway
MBL associated serine protease in Lectin pathway
MASP-1
MASP-2
MBL-associated serine protease that is synthesized as a zymogen and is activated when it complexes with the pathogen recognition molecules such as MBL
MASP-1
Steps in Lectin pathway
- Lectin (e.g. mannose-binding lectin/MBL) binds to carbohydrate mannose or similar sugars on bacterial and viral cell walls
- Activation of C2 and C3
- C2a and C4b combine and activate C3 (gets hydrolyzed to C3a and C3b)
Initiated by binding of complement to antibody
Classical pathway
