Immunology Flashcards
Polymorphonuclear cells (2)
Who + what
- Neutrophils + Eosinophils + Basophils
- Have granular appearance known also as granulocytes
Lymphoid Stem Cells derived:
Plasma cells and B cells
T lymphocytes
NK cells
Leukocytes movements (2):
Where + mechanism
- WBC enter blood circulation from bone marrow (myeloid stem cell are made in BM) or lymphoid tissue to the areas of the body where they are needed
- Movement of WBC in and out of blood vessels into tissues occur by diapedesis which involves deformation of cells to pass through a small pore mediated by molecules known as selectins (present in inner part of endothelial cells of veins not arteries). Selectins attach to the endothelium and cause relaxation of the pore so large cell can go through.
Leukocytes (WBC)
Granulocytes
Time
Once entered the blood, spend 4-8 hours circulating then enter the tissue and exist for 4-5 days.
Monocytes
Time
Have a transit time of 10-20 hours in the blood. Once in the tissue, they enlarge (~5 folds) and become tissue Macrophages and exist for months.
Lymphocytes
Time
Enter circulation continually from the lymph nodes. They circulate between tissues, lymphatic system and circulation. The lymphocytes have a life span of months or years depending on the body’s need for these cells.
Longer half life and basis for “immune” or memory
Granulocytes
Neutrophils
- The most abundant leukocyte in blood and are normally the first defensive cell type to be recruited to a site of infection. Neutrophils posses a number of antibacterial weapontty (secretatory enzyme) and have the ability to find bacterial or fungi and neutralize them by phagocytosis.
Eosiniphils
- Mainly mobilized following parasitic infection (eg: pork worm). Eosinophils approach the parasites and release substances that would kill or weaken the parasite such as hydrolytic enzymes. Eosinophils also help detoxification of inflammatory substance by releasing H2O2 which neutrolizes toxins by oxidizing.
Basophil and Mast cells:
release histamine as well as small quantities of bradykinin (a peptide that causes inflammation by dilating arterioles and constricting veins) and serotonin (pain). Both cell types are important in allergic reaction which is mediated by IgE.
Brings allergic response
Mast cells:
Produce heparin (a blood anticoagulant that increases the activity of antithrombin) used to prevent coagulation and to facilitate removal of the fat particle.
There are 2 functional forms of immunity:
- The Innate immune system: First line of defense (You have this all the time and doesnt change with reinfection)
- The adaptive or acquired immune system: Improved by repeated infection. Involves specific response to the infectious agents.
You are always exposed to antigen when you inhale what doe syour body go through/do?
Detection of infectious agents:
The prescence of the infectious agents or the compounds released from damaged cell activate and attract —— such as ——- by ——-. Immune knows theres infection from its own body and infection molecule.
- phagocytic cells
- neutrophils and macrophages
- chemotaxis
Chemotactic factors (5):
- Some bacterial toxins
- Degenerative products of inflamed cells (own cells: cytokines)
- Complement complex
- specific factors such as cytokines secreted by the host or invading cells
- foreign membrane proteins triggering leucocytes (displayed on pathogens/invading organisms)
What is the process that brings leukocytes to the site of infection from capillaries to intertsitial?
Chemotaxis and diapediasis
The first group of leukocyte attracted for detection of infectious agents are:
macrophage and neutrophil
Both —- and —– are capable of phagocytosis
- neutrophils and macrophages
Diapedesis
- Facillitated by selectins and their ligands (specific glycoproteins on the surface of leukocytes) which are present on the surface of leukocytes and endothelial cells of venous capillaries (not arterial). When activated by chemotactic factors, these molecules cause slow down of leukocytes, diapedesis by relaxation of pore and bind to passing neutrophils and phagocytes to alert.
The innate or natural immunity is made up of several components:
- Physical barriers and factors
- The soluble compounds
- Cellular component
No memory: Once you encounter pathogen, ability to deal doesnt get better with reinfection
The innate or natural immunity: First line of defense
Explain the Physical barriers and factors:
- Physical barriers: Most infectious agents cannot pentrate intact skin. The importance of this barrier becomes very clear when an individual suffers serious burns or cuts.
- Physiological factors: PH (ingestion), temperature and oxygen tension (hypoxic) limit microbial growth. The ingested organisms are largely destroyed by strong acid and digestive enzymes. The main routes of infections include epithelial surface of the nasopharynx, gut, lungs (inhalation) and genito-urinary tract.
The innate or natural immunity: First line of defense
List what is part of the soluble compounds:
- ## Lysozyme, the complement complex system, c-reactive protein, and cytokines
The innate or natural immunity: First line of defense
Soluble compound: Lyzozymes (2)
What + which WBC
- Enzymes that can attack bacterial cell wall by splitting the wall made of proteoglycan. Does not affect humans as we dont have the bacterial cell wall bond between N-acetylglucosamine and N-acetylmuramic acid.
- Produced by macrophage and neutrophil
The innate or natural immunity: First line of defense
Soluble compound: C-reactive protein (3)
amount + what it does x2
- increase in amount/stimulated by inflammation and infection and decrease after recovery
- Bind to surface of damaged cell and bacterial, promote the binding and activation of complement system (set of protein in innate system)
- Faciliate opsonization (acts as the opsonin/molecule that attach to surface of organism and flags it. Our own leukocyte have receptor for CRP and other molecule for phagocytosis) and recognition of bacteria leading to more efficient uptake by macrophages.
The innate or natural immunity: First line of defense
Souble compound: What is the complement system?
- A system of serum proteins (set of ~20 serum proteins) which interact in a cascade. Some of the compounds are serine proteases which activate each other sequentially.
The innate or natural immunity: First line of defense
Souble compound: How is the complement system activated (4)?
The ways + they all do what?
The complement system is normally inactive in the blood. It consists of over 30 proteins that circulate in the bloodstream as inactive precursors (zymogens).
Three pathways leading to complement activation:
1. classical pathway activated by antibody-antigen complex, set of antibody activated by antigens initiates this
2. Alternative pathway: Binding of complements to surface molecules of pathogens (direct interaction)
3. Pathway involving Mannose binding lectin on pathogen surface Subclass of number 2
These pathways activate C3 convertase that activates the cascade.
The innate or natural immunity: First line of defense
What does complement activation lead to? (3)
- Recruitment of inflammatory cells (chemotactic factor: Complement fragments (e.g., C3a, C5a) act as anaphylatoxins, promoting inflammation by recruiting immune cells and increasing vascular permeability)
- Opsonisation of pathogens (Complement proteins (e.g., C3b) coat pathogens, enhancing their recognition and uptake by phagocytes like macrophages and neutrophils.)
- Killing of pathogens: Lysis of the cell by forming Membrane Attack Complex
The innate or natural immunity: First line of defense
Explain the complement complex system:
- Three pathways (Classical, Alternative, Lectin) → lead to C3 convertase formation.
- C3 convertase (C4b2a) splits C3 into C3a (inflammation: activates mast cells and basophils to enhance allergic response) and C3b (opsonization of bacterial and activate mast cells and basophils to enhance allergic response ).
- Once enough C3b accumulates, it helps form C5 convertase, which cleaves C5 into C5a (inflammation: activates mast cells and basophils to enhance allergic response and chemotaxis of WBC) and C5b (MAC formation).
- C5b recruits C6, C7, C8, and multiple C9 molecules. These form a pore-like structure in the membrane of the pathogen. Water rushes in, bursting the pathogen (lysis).
Cytokines (2)
What + cycle
- Biochemical messengers stimulate leukocyte actvitity following infection.
- Infection -> activation of macrophages -> release of colony stimulating factors/differentiation factors (Ex: TNF, IL-1, GM-CSF, G-CSF, M-CSF) -> increased production of granulocytes, monocytes and lymphocytes in bone marrow and lymphatic system
IL-1 and TNF
Pro-inflammatory cytokines/signaling molecules that are produced by immune cells and other cells that promote inflammation, IL-1 also increase haematopoiesis
The innate or natural immunity: First line of defense
Cellular component: NK cells (3)
Family + what they do + ex
- Belong to same family as B-cells, plasma cell, T cell aka lymphocytes but other lymphocyte changes with reinfection but NK stays the same and function doesnt improve.
- Lymphocytes that can recognize cell surface changes on virally infected cells, foreign cells and some tumour cells. NK cells can bind to these cells and kill them.
- The cancer cell produce # of genes that are not normally expressed and form a protein to the membrane. NK cells can recognize this and release perforin to cause lysis
The innate or natural immunity: First line of defense
Cellular component: How are NK cells activated? (3)
- The NK cells are activated by interferons which are produced by virally-infected cells and sometimes also by lymphocytes
Interferons (2)
What + what it does
- A family of glycoproteins that are produced very early in infection and form the first line of defense against viral infection
- In addition to activating NK cells, interferons act on other cell types through specific membrane receptors influencing viral proteins and block synthesis of some proteins. This means that interferons slow down synthesis/ interphase of neighbouring host cells to reduce proliferation of virus (induction of resistance)
The innate or natural immunity: First line of defense
Cellular component: Phagocytes (3)
Who + what they do + ehnahnced by
- Neutrophils and macrophages: Have receptor for C3b and antibody
- Phagocytes have intrinsic ability to bind nonspecifically to foreign organisms inorder to engulf and destroy them.
- The process of recognition of foreign organisms (e.g. bacteria) is much enhanced by opsonization. Ex: Depositing compounds such as complement C3B, antibody or both on the infectious agent. When the antibody binds to antigen, the other side of antibody acts as opsonin (in most cases, the antigen is part of the pathogen’s surface (e.g., a bacterial cell wall protein or a viral envelope protein). When antibodies bind to these antigens, they coat the entire pathogen, allowing immune cells to recognize the opsonized pathogen and engulf it more efficiently).
Phagocytic activity is enhanced by:
Opsonization
The innate immune system:
Reticuloendothelial system (2)
What + process
- The network phagocytic tissue macrophages and neutrophils form
- The monocytes which are synthesized in the bone marrow enter the blood and then tissues and become macrophages. There are circulating monocytes and also specialized ones that migrate to tissue and enlarge as macrophages and remain there. All these cells exhibit phagocytic properties.
The innate immune system:
Phagocytic cells and macrophages are present in all tissues. A number of locations contain more of these phagocytic cells because of increased possibility for infection including the ——–
skin and subcutaneous tissue, liver sinuses, spleen, bone marrow, lymph nodes and alveola.
The adaptive (acquired) immune system is special in that:
Foreign agents contain one or more specific compounds (antigens) which provide a basis for their recognition by specific antibodies.
Improve with reinfection
Antibodies (3)
structure + Fab + Fc
- Composed of 2 identical heavy chains and 2 light chains with Disulfide covalent bonds in between connecting.
- Antigen binding region (Fragment antigen binding: Fab) is variable in different antibodies and allows specific binding to AG
- Fragment crystalline (Gc) which is similar in most antibidies and can bind to host-tissue and compleents after Ab binds to Ag.
Each antibody molecule is:
bifunctional
has 2 domains
Antigen binding region (Fab) bind to a particular part of the molecule called ——-, usually Mwt ——–
Antigenic determinant domain or epitope (usually Mwt>8000 to be effective antigent)
Normally have more than 1 antigen on the pathogen surface
Antibody- antigen binding and specificity
Cross reactivity usually need —- bindng to illicit response.
more
There are different classes of Ig (5):
- IgG
- IgA
- IgM
- IgD
- IgE
IgG (4)
Amount + important in + mechanism of action x2
- Major Ig/antibody (70-75% of circulating Ig) of secondary immune response.
- IgG is produced during secondary immune responses (after re-exposure to a pathogen). Memory B cells rapidly produce IgG when the same pathogen is encountered again → Faster and stronger immune response (basis of vaccines).
- IgG binds to bacterial toxins and viral particles, immunoneutralize it/change property and prevent them from binding to host cells.
- IgG coats (opsonizes) pathogens, marking them for destruction. Phagocytes (macrophages, neutrophils) have Fc receptors that bind to the Fc region of IgG, leading to faster engulfment of the pathogen.
IgA (2)
amount + important in
- 15-20% of circulating Ig, major Ig in sero-mucous secretion; eg. saliva. colostrum, milk, genito-urinary secretion
- After birth, important in passive immunity. Newborn babies have a unique ability to absorb macromolecules, such as antibodies (IgG, IgA), proteins, and even some intact peptides, due to the immaturity of their intestinal barrier.
IgM
structure + what
- 10% of circulating Ig, pentameric Ig in vascular pool. It exists as a pentamer, meaning it has five antibody units connected together.
- An early antibody against antigenically complex organisms. Due to its multiple binding sites, it can bind to multiple antigens and form large antigen-antibody complexes (clumps). Clumps grow and easier for macrophage to eat.
IgD (2)
Amount + role
- 1% of circulating Ig.
- Major form on the membrane of B-lymphocytes. IgD is thought to play a role in antigen-triggering of lymphocyte differentiation, particularly in B cell activation and maturation.
IgE (3)
Where + involved in + mechanism of action
- Present on the surface of basophil and mast cells
- Involved in parasitic immunity and allergic reaction.
- Once bound to allergen, triggers mast and basophil to trigger secretatory products.
Adaptive immune response involves (2):
- Production of specific antibodies against the invading agents by B lymphocytes (Humoral immunity)
- T-lymphocytes specifically destroy the invading agents by contacting antigen (Cell-mediated immunity)
Adaptive immune response
Where are B cells and T cells matured?
B cells mature in bone marrow. T cell develope/mature in the thymus gland in lymphatic system. Both B cells and T cells originate from lymphoid-derived stem cells, which come from hematopoietic stem cells (HSCs) in the bone marrow.
The adaptive immune system is based on the ability of (2):
- the B cells to produce specific antibodies against Ag
- the ability of T-cells to specifically attach Ag
How do body produce specific antibodies (immunoglobulins) against a foreign antigen?
There are estimated to be about 1 million types of preformed B-cells and T-cells (diff genes). Each B-cell is only capable of producing and recognizing one particular type of antigen as it has 1 type of binding domain.
Explain the process of Clonal selection
- B cells contain surface binding protein identical to the binding domain of the antibody they produce.
- Each antigen binds and activates a preformed B-cell leading to it’s proliferation/results in enlargment of the cells. Some of these further differentiate and form plasma cells which proliferate via mitosis and produce Gammaglobulin antibodies at extremely rapid rate (Develope more ER and job is to synthesize Ig and secrete them into circulation).
- Basically antigen activates many of the same type of B-cells that secrete specific antibodies against the same antigen. This process is known as selection of the specific clones of antibody producing B-cells.
- A number of lymphocytes do not form plasma cells and form memory cells which have the membrane components to recognize the antigen. This process increases the population of B cells that can get activated if there is further infection by the same Ag.
Prior exposure to antigens, the B cells are ——. After exposure they become ——.
- dormant
- activated
Will you every encounter pathogen with no antibody?
- Very low: For organisms that have more than 1 epitope the fit doesnt have to be perfect, can cross react
Colonal selection:
Subsequent exposure to the same antigen wil cause a much more rapid and potent antibody repsonse because——–. This is known as ——
- There are more memory cells that can recognize antigen.
- Secondary response
Explain how Vaccination works:
- Vaccine is the epitope so when you get the vaccine, it stimulates the production of memory B cells.
- The secondary response is a basis for acquired immune response and vaccination.
Action of Antibodies (4):
- Agglutination/precipitation: Multiple organisms or cells are bound together as a clump and form large insoluble complexes
- Neutralization: Antibody binds to the active molecule and alter teriary structure or cover the active site and make it inactive
- Opsonization
- Compleent activation
Do antigen have chemotactic factor?
Yes
Which antibody is more effective in agglutination?
IgM
More binding sites
Different B type cell produce different antibody with different antigen ninding domain but all have:
identical/similar Fc domain
Explain how antibody activates complement system:
Binding of Ag to Ab activates complement binding sites in the Fc chain which in turns activates C1 and thereby starting a cascade of activation of various compounds.
Humural immunity
Production of antibody against pathogens
T cells have 3 major groups:
- Helper T cells
- Cytotoxic T cells (killer cells)
- Suppressor T cells
Helper T cells (3)
What it does + abscence causes + activated by
- Secretes cytokines including interleukins (INT-2, INT-3, INT-4, INT-5, INT-6), GM-CSF and interferon-y
- Without helper T cells, the immune system would be very inefficient; AIDs syndrome develope because of Helper T-cell inactivation
- Cannot be activated by antigen like B-cells need antigen presentation
Exolain the cycle for T cell, B cell, bacteria and macrophage
Cytotoxic T-cells (killer cells) (2)
mechanism of action + lethal to
- Bind to specific antigenic sites on the foreign cell surface and secrete perforin that mediates hole formation through which cytotoxic compounds are injected and initiates a cascade leading to apoptosis (trigger surface protein
- These cells are lethal to tissue cells infected by virus. Important for rejection of organ transplant
Immunological synapse:
How can the immune system distinguish between foreign cells (antigen) and self?
Membrane of all cells with the exception of red blood cells are genetically marked with characteristic proteins known as histocompatibility molecyle HLA/MHC. Difference in MHC mark the cell as antigen. There are more than 100 different types of MHC molecules identified in humans and each individual only has genes to produce 3-6 types. Chances that two individuals have the exact same combinations is very small and the closer the match makes the tissue more histocompatible. This is important for organ donor and transplantation as yo want donors with identical/same compatibility to limit rejection.
Who has identical MHC?
Identical twins
Activation of T cells:
Antigiens alone without the medication to MHC cannot activate T-cells. Antigens can only be presented by macrophafes or infected cells bound to MHC receptors. The virus gets engulfed by macrophages and gets internalized/broken down. The antigen then displayed on surface of macrophage which T-cells bind and get actived.
Activation of T-cells
The MHC molecules are grouped in two classes:
- Class-1 MHC molecules are produced by all cells except by RBCc and recognized only by cytotoxic T-cells/ Killer T cells
- Class-2 MHC moleucles are produced only by macrophages and B-cells and dendritic cells and recognized only by Helper T-cells (Activation to secrete cytokine and activate immune)
Class 1 MHC activates
Killer T cells or cytoxic cells
Class 2 MHC activates:
Helper T cells
Activation of T cells:
Killer T-cells only interact with Ag presented with Class-1 MHC and helper T-cells only with Ag presented with Class-2 MHC. These restrictions results from (2):
The presecence of coreceptors (CD4 and CD8) which are proteins associated with T-cell receptors for MHC.
Killer T-cell and coreceptor:
Killer T cell contain co-receptor CD8 activated by Ag with Class-1 MHC
Helps in T cell activation and target cell killing
Helper T cell contains coreceptor:
CD4- activated by Ag with Class-2 MHC
How are B-cells activated by?
B cells are actviated both by direct binding to antigen as well as antigen presented by other leucocytes (macrophages) and secretion by Helper T cells.
Suppressor T cells
Act as regulatory cells
Action results in a reduction in the activity of helper T-cells (minimize activation of T-cell).
Mechanism for Immune tolerance (2):
Prevent the immune system from attacking the body’s own cells
- Clonal deletion: Immature lymphocytes that strongly recognize self-antigens (presented on self-MHC molecules) undergo apoptosis (programmed cell death). This removes highly self-reactive cells before they enter circulation. Even after, remain with a small population of T-cells that can recognize and attack.
- Clonal anergy: Lymphocytes directed against self antigens maybe be present but do not attack self antigen (containing identical MHC). Backup mechanism that inactivates self-reactive lymphocytes that escape clonal deletion, fail to activate because they lack co-stimulatory signals. Suppressor T-cell play a role by releasing inhibitory cytokines.
Mechanism of action for allergy:
Reactivity to an antigen which can result in pathological reactions upon subsequent exposure to that particular antigen. Basically activate B cells and they release Ab that activate Mast and Basophil which release histamines and cause dilation of blood vessel and permeability.
What occurs during inflammation (4)?
- Vasodilation of the local blood vessels and excess blood flow.
- Increased permeability of the capillaries -> increased interstitial fluid
- Clotting of interstitial fluid as a result of increased leakage of fibrinogen and plasma proteins. Plasma proteins (including fibrinogen) leak into the interstitial space, fibrinogen is converted into fibrin, forming a clot in the tissue. This fibrin barrier isolates the infection, preventing bacteria and toxins from spreading to surrounding tissues - “Walling off” process
- Swelling of the tissue cells.
Tissue products that cause inflammatory response:
- Histamine, bradykinin, serotonin, reaction product of blood clotting systems and a number of hormonal substances known as lymphokines (released by sensitized T-cells)
Tissue products that cause inflammatory response result in (4):
- Attraction of tissue macrophages
- Increase in the number of neutrophils (sometimes by 5 folds; Nutriphilia)
- Attracts monocytes from the blood which enter the inflammed area and swell (~8 hours) to become macrophages for significant increase in phagocytic capability.
- Increase production of granulocytes and monocytes by the bone marrow from commited stem cells (3-4 days) rate of increase may reach 50 folds.
Why are some people allergic to certain things? Dicuss severity:
