| What is innate immunity? | non specific defense mechanisms that depend on the recognition of traits shared by broad ranges of pathogens using a small set of receptors, comes into play rapidly. |
| List components of the first line of defense? | Barrier defenses
- skin , PH is acidic
- mucous membranes, produce digesting enzymes, traps microorganisms
-secretions , vaginal secretions are acidic, Sebum is toxic to bacteria |
| List components of the second line of defense? | Internal defenses
-phagocytic cells
-Natural killer cells
-antimicrobial proteins
- inflammatory response |
| What is adaptive immunity? | Recognition of traits specific to particular pathogens, using a vast array of receptors, slower response. |
| What is humoral immunity? | The immunity meditated by secreted macromolecules like antibodies and complement proteins circulating in body fluid. To block infections |
| Wha it is cell mediated immunity? | Immune response that involve activation of cells like Tcells and then the activation of phagocytes to destroy microbes and kill cells that harbor infections |
| What is active immunity? | When B cells encounter antigens and produce antibodies.
- Naturally acquired infections
- Artificially acquired from vaccines |
| What is passive immunity? | occurs when antibodies are obtained from someone else
- Naturally Acquired
from a mother to fetus through placenta
from a mother to newborn through breast-feeding
- Artificially Acquired
from immune serum or gamma globulin |
| What Does the specificity of the immune system mean? | Ensures that distinct antigens elicit specific responses |
| What does the diversity of the immune system mean? | Enables immune system to respond to a large variety of antigens |
| Explain colonial selection hypothesis? | Increases number of antigen specific lymphocytes from a small number of naive lymphocytes. |
| What is immunologic memory? | The adaptive immune system remembers antigens that was encountered before and mounts a larger and more effective responses to repeated exposure to the same antigens. |
| What is the primary immune response? | The response to the first exposure to antigen that is initiated by naive lymphocytes that are seeing antigen for the first time. |
| What is the secondary immune response? | Happens after a subsequent encounters with same antigens activating the memory cells , it’s larger and more rapid and better at eliminating pathogens. |
| What is immunologic tolerance? | The ability of the immune system to coexist with potentially antigenic self molecules, cells, and tissues. |
| What are the types and roles of B lymphocytes? | express membrane- bond antibodies that can bind soluble antigens (various types) that stimulate expansion of these B lymphocytes and production of soluble antibodies with the same antigen-specificity. |
| What are the type and roles of T lymphocytes? | T lymphocytes recognize only peptide antigens bond to major histocompatibility complex (MHC) molecules expressed on the surface of antigen-presenting cells
- CD4+ helper T lymphocytes: secretion of cytokines activating macrophages and differentiation and proliferation of lymphocytes and involved in inflammation.
- CD8+ Cytotoxic T lymphocytes:recognize antigens and kill infected cells
- CD4+ Regulatory T lymphocytes: limit activation of other T cells and suppress immune response to prevent autoimmunity. |
| What is the role of plasma cells? | Secretes antibodies in response to being presented specific antigens. |
| What is the role of memory cells? | Record information of a previously encountered pathogen so a stronger more rapid response Is done when encountered the next time. |
| What is the role of Natural killer cells? | Important in defense against virus-infected, and tumour cells and also important in removing stressed and dying cells.
Kills target cells by binding to and releasing cytotoxic granules (perforin and granzyme) which then enters the target cell to induce apoptosis
(similar to CTL). |
| What is the role of T Helper cells? | secretion of cytokines activating macrophages and differentiation and proliferation of lymphocytes and involved in inflammation. |
| What is the role of cytotoxic T cells? | recognize antigens and killing of infected cells |
| What is the role of Regulatory T cells? | limit activation of other T cells and suppress immune response to prevent autoimmunity. |
| Types of antigen presenting cell and their main roles? | Expresses MHC I and MHC II
- dendritic cells
Antigen presentation to naive T cells in the initiation of T cell responses to protein antigens.
- macrophages
Antigen presentation to CD4+ effector T cells in the effector phase of cell mediated immune responses.
- B lymphocytes
Antigen presentation to CD4+ helper Tcells in humoral immune responses.( T cell-B cell interactions). |
| What’s the role of follicular dendritic cells | Follicular dendritic cells (FDC) reside in germinal centers of lymphoid follicles and present antigens to B lymphocytes but not to T lymphocytes. |
| Function of B cells | B-cells fight bacteria and viruses by making Y-shaped proteins called antibodies, which are specific to each pathogen and are able to lock onto the surface of an invading cell and mark it for destruction by other immune cells. |
| Role of macrophages? | Macrophages are specialised cells involved in the detection, phagocytosis and destruction of bacteria and other harmful organisms. In addition, they can also present antigens to T cells and initiate inflammation by releasing molecules (known as cytokines) that activate other cells. |
| Role of mast cells? | Bone marrow derived cells present in skin and mucosal epithelium. Can be activated via TLR or antibody-dependent way.
Secrete histamine, prostaglandins, proteases, TNF-a.
Protection against helminths.
Involved in allergies |
| The abundance of leukocyte? | Granulocytes:
• Neutrophils 40 – 75
• Eosinophils 1 – 6
• Basophils <1
Monocytes 2 – 10
Lymphocytes 20 - 50 |
| Roles of accessory cells in immune response? | Accessory cells are nonlymphoid cells such as macrophages, dendritic cells, and Langerhans cells (epithelial dendritic cells) that function to present antigens to MHC-restricted T cells.
Stromal cells – “Nurse” cells in the bone marrow. Facilitate
blood cell development by providing a tethering substrate for proliferating progenitor cells as well as providing growth factors and chemical signals for development and proliferation
Endothelial cells-Make up the linings of blood vessels. Express
adhesion molecules to which circulating blood cells anchor and
migrate through the vessels into infected tissue. |
| What are the stages of lymphocyte response to infections? | Naive —> effector lymphocytes—> plasma cells—> memory cells
Naïve lymphocytes – express receptors for antigens, but cannot eliminate antigens.
If not activated by antigen survive weeks – months, and die by apoptosis.
Effector lymphocytes B cells -> plasma cells that produce antibodies
Effector T cells -> kill infected cells
Memory cells survive long-time (years) |
| What are the lymphoid organs? | - Generative lymphoid organs
Bone marrow
Thymus
-peripheral lymphoid organs
Lymph nodes
Spleen
Mucosal and cutaneous lymphoid tissues |
| What is the morphology and regions in the lymph nodes? | - T cell zone ( parafollicular cortex)
- B cell zone (lymphoid follicle)
- high endothelial venule
HEVs enable naïve lymphocytes to move in and out of the lymph nodes from the circulatory system. HEV cells express addressins, which are specific adhesion molecules that attach to the L-selectins on lymphocytes and anchor them to the HEV wall in preparation for crossing the endothelium
- afferent lymphatic vessel |
| Functions of cutaneous and mucosal membranes in the immune system? | Cutaneous immune system
Specialized immune tissues and APCs located under the epithelia of the skin,
Mucosal immune system
Specialized immune tissues and APCs located under gastrointestinal tract and respiratory tracts
Most of immune cells are diffusely scattered, there are structures like tonsils in the pharynx and Payer patches in the intestine.
Important property of Cutaneous and Mucosal immune systems is selective response to pathogenic bacteria, but not the commensal bacteria present on the skin and in the intestine. |
| Explain the molecular mechanism that stimulate interactions between Follicular dendritic cells and B lymphocytes.? | FDC cells secrete chemokines that bind CXCR5 receptors on naïve B lymphocyte and attract them to germinal centers.
After exposure to antigen B and T lymphocytes loose expression of CXCR5 and CCR7 receptors and migrate toward each other at the edge of follicles.
Interaction between T and B lymphocytes stimulates differentiation of B lymphocytes into antibodies-producing plasma cells and memory cells (Ch7).
Plasma cells stay in lymph nodes or migrate to bone marrow |
| Explain the steps of the immune response? | -Initiation of adaptive immune response
-Capture and display of microbial antigens
-Cell-mediated immunity: activation of T lymphocytes and —-elimination of cell-associated microbes.
-Humoral immunity: Activation of B lymphocytes and - elimination of extracellular microbes
Decline of immune responses |
| What are neutrophils? | Cells that ingest and destroy invaders
First line responders, rapidly recruited to the site of infection, live few hours
fagocytes |
| What are monocytes? | Ingest and destroy invaders and present antigens
Second responders, enter infected tissues and differentiate into macrophages that survive for longer time. |
| What are dendritic cells? | Professional antigen-presenting cells:
Efficient at phagocytosis of proteins and
and presenting them to B and T lymphocytes resulting in the activation of adaptive immunity.
Dendritic cells in the skin are
called Langerhans cells
Dendritic cells in lymph nodes activating B cells are called follicular dendritic cells |
| What are plasmacytoid dendritic cells? | A specialized subset of DCs that links innate and adaptive immunity. They sense pathogens and release high levels of type I interferons (IFN-I) in response to infection. |
| What are the functions of the complement system? | C3b is recognized by receptors on phagocytes – opsonization
(Greek opson=appetizer)
Inflammation – fragments of complement proteins act as chemoattractants for neutrophils and monocytes.
Cell lysis = cleaved components of complement proteins activate formation of membrane attack complexes (MAC). |
| What are cytokines? | Large group of proteins, peptides, or glycoproteins that function as signaling molecules that meditate and regulate immunity ( communication between cells) |
| What is the coagulation system? | Part of the humoral response, function in blood clotting composed of blood cells and proteins. |
| What is opsonin? | Reacts with pathogens and make them more susceptible to ingestion by phagocytes |
| What is defensins? | Produced mostly by neutrophils and epithelial cells are essential elements of the innate response because of their broad spectrum antimicrobial activity. |
| What are PAMPs? | Pathogen Associated Molecular Patterns (PAMPs)
Patterns or shapes of macromolecules present in bacteria, viruses or fungi but not present on host cells.
These target macromolecules are essential to the structure and function of the pathogen, and are genetically conserved.
They may be glycoproteins, lipopolysaccharides, peptidoglycans, oligonucleotides, terminal mannose residues on complex polysaccharide molecules, etc |
| What are DAMPs? | Damage Associated Molecular Patterns
Molecules released by damaged or necrotic cells e.g. heat shock proteins (HSP’s), DNA-binding proteins, ATP, DNA. |
| What are toll-like Receptors (TLRs)? | Toll-like Receptors (TLRs). Recognize various microbial molecules including LPS and peptidoglycans and viral nucleic acids. Up to 10 different kinds of TLR, TLR 1 – 10.
expressed in plasma membrane |
| What are C-type lectin receptors (CLR)? | C-type lectin receptors (CLR) e.g. Mannose receptor, Dectin-1 Scavenger receptors (SR). Recognize lipopeptides and lipopolysaccharides on bacteria.
expressed in plasma membrane |
| What are NOD-like receptors (NLRs)? | NOD-like receptors (NLRs). Recognize bacterial wall peptidoglycans ,and trigger IL1 production
Expressed in cytoplasm |
| What are RIG-like receptors (RLRs)? | RIG-like receptors (RLRs). Recognize viral RNA.
Expressed in cytoplasm |
| What are Cytosolic DNA sensors (CDS)? | Recognize viral DNA
expressed in cytoplasm |
| What is NLRP3? | Cytosolic NLR that recognizes infectious agents or pathologic changes and trigger IL1 production
Pyrin domain – present in receptors that trigger inflammation |
| What are phagolysosome? | Attachment and adherence
Plasma membrane envelopes target and draws it into a phagosome
Phagosomes fuse with lysosomes to form phagolysosome
Processing & digestion of ingested microbe |
| What is the difference between M1 and M2 macrophages ? | M1= Classically activated macrophages (via TLR)
Trigger inflammation
M2= Alternatively activated macrophages (IL-4, IL-13)
involved in tissue repair |
| What are Innate Lymphoid Cells (ILCs)? | T lymphocytes that express antigen receptors
of limited diversity
recognize bacterial lipids
ILCs divided into 3 groups based on secreted cytokines |
| What are Killer cell Immunoglobulin-like Receptors KIRs? | Involved in negative signaling
Killer cell Immunoglobulin-like Receptors (KIRs) e.g. CD94 + NKG2.
Receptors sense normal MHC molecules on healthy cells causing NK cells to shut off. If virus shuts off MHC expression to evade cytotoxic T cells, NK cells will notice MHC is missing and if activation signals are present, NK cell will be activated and cell is killed – “Recognition of Missing Self” |
| What are Positive Signals (Killer Activation Receptors (KARs)? | Involved in positive signaling
e.g NKG2D receptor. Recognizes HLA-like molecules (MIC A and MIC B) expressed on stressed or dying cells or virus-infected cells but not normal cells.
Fc receptor (CD16). Recognizes Fc region of antibodies. When antibodies are bound to cellular targets, NK cells bind to these antibodies and kill the cellular targets - this process known as antibody-dependent cellular cytotoxicity (ADCC). |
| What are Lymphokine Activated Killer (LAK) cells? | Cytokine receptors. Treating NK cells with high doses of Interleukin 2 IL-2 turns NK into Lymphokine Activated Killer (LAK) cells with enhanced ability to recognize and kill tumour cells. |
| What are gama delta T cells? | Express TCR recognize lipids of pathogens and found in epithelium |
| What are B-1 cells? | B lymphocytes found in peritoneal cavity, secret IgM that cross into lumen of intestine; in the blood IgM that recognize bacterial carbohydrates (natural antibodies). |
| What are natural antibodies? | Antibodies that are produced without a previous infection or antigens stimulation |
| What are Marginal zone B cells | at the edges of lymphoid follicles. Rapid antibody responses to polysaccharide of blood-borne microbes. |
| What are Plasmacytoid Dendritic Cells (PDCs)? | Specialized type I interferon-producing cells
Have phenotypes intermediate between lymphocytes and dendritic cells
Present in the blood making up >1% of the total leukocyte population (white blood cells)
Detect the presence of viral infection by using TLR7 and TLR9 |
| Explain the Complement activation: Three pathways? | • Classical pathway activated by antibodies bound to microbe (humoral arm of adaptive immunity).
• Alternative pathway – complement protein activated on microbes (innate immunity).
• Lectin pathway – activated when mannose-binding lectin (MBL) binds to microbes (innate immunity). Another protein – C-reactive protein (CRP) binds to phosphatidyl choline.
Three pathways differ in activation but share downstream steps.
C3 protein is cleaved into C3a and C3b; C3b is covalently attached to microbe, recruit subsequent complement cascade on the microbe surface. |
| What is the complement system ? | A collection of circulating and membrane associated proteins that are important in defense against microbes.
Many are proteolytic Enzymes and complement activation involves activation of these enzymes. |
| What are the cytokines of the innate immunity and what are their effects? | Interleukin – historic name for paracrine factors secreted by leukocytes for intercellular communications
Innate immunity: secreted by mast cells, dendritic cells, macrophages when they recognize microbes via TLR or other receptors.
Adaptive immunity: secreted by helper T lymphocytes |
| What presentation by APC is needed? | naïve lymphocytes recognize 10^6 antigens, so only 1/10^6 lymphocytes recognize specific antigen)
Presentation by APC in lymph nodes will give a bigger chance for lymphocytes to recognize an antigen |
| Dendritic Cells (DCs): what are classical and plasmacytoid
Role of CCR7/CCR7R in CD migration? | Upon activation by infectious agents dendritic cells produce inflammatory cytokines, and express chemokine receptor CCR7
CCR7 receptor recognize chemoattractants produced by cells in lymph nodes- this direct migration of dendritic cells to lymph nodes and meet T cells (12-18 hours).
During this migration dendritic cells mature into APC that express MHC with antigen peptides |
| Explain the difference between the two types of APCs amateur and professional? | Professional Antigen Presenting Cells. Express both Class I and II MHC:
Dendritic Cells – All tissues
Langerhans Cells – Skin
Monocyte/Macrophages
B Lymphocytes
Non-professional Antigen Presenting Cells. Express Class I MHC:
Fibroblasts, thymic and thyroid epithelial cells, endothelial cells, glial cells. Some non-Professional APCs express Class II MHC when stimulated with cytokines |
| The difference between MHC I and MHCII ? | Class I MHC:
Expressed on all nucleated cells
Consists of a single α chain tethered to the cell membrane non-covalently associated with a β-microglobulin molecule.
Polymorphic regions lie in α1 and α2 domains which form a cleft big enough to accommodate peptides 8-11 amino acids long.
α3 domain is invariant and contains the binding site for the CD8 co-receptor
Class II MHC:
Expressed on dendritic cells, B cells, macrophages, thymic epithelial cells, some endothelial cells. Consists of α and β chains. Polymorphic residues lie in α1 and β1 domains which form a cleft which can accommodate peptides 10-30 amino acids long. β2 domain is CD4 co-receptor binding site. |
| What is immunodominant peptides? | peptides that can bind MHC molecules
will be different for different people because of polymorphism of MHC |
| What is the difference between CD8+ AND CD4+ Tcells? | CD8+ T cells recognize MHC I molecules
CD4+ T cells recognize MHC II molecules |
| What is cross presentation of internalized antigens? | To present pathogens infecting cells that cannot travel to lymph nodes |
| What is TAP ? | Transporter associated with Antigen Processing = TAP
Binding of peptide to class I MHC release class I MCH from tapasin |
| What is the function CLIP? | CLIP binds peptide binding cleft and prevents binding other peptides until class II MHC will be delivered to endosome/lysosome. |
| Explain how MHC I molecules bind peptides and present them? | Recognizes intracellular pathogens |
| Explain how MHC II molecules bind peptides and present them? | N |
| What is MHC? | Major Histocompatibility Complex (MHC) was discovered as genetic locus responsible for acceptance or rejection of tissue grafts and organ transplants |
| what’s the restrictions of MHC ? | T cells recognize antigens only when antigens presented by MHC molecules
MHC molecules can bind and display Specific short peptides
Binding take place inside APC
T-cell receptors recognize MHC and bound peptide
Each MHC molecule displays one peptide at a time
Class I and Class II MHC molecules load peptides from different cellular compartments. Stable surface expression of MHC molecule requires bound peptide |
| What are the components of the innate immune system? | Barriers: Mechanical, Chemical, Biological
Cellular components: Neutrophils, Monocytes and macrophages, Dendritic cells, NK cells, Plasmacytoid dendritic cells
Humoral components: Complement, Cytokines, Coagulation system. |
