Week 5 Immunology Flashcards
What cell types are part of adaptive immunity ?
B cells
T cells
what cell types are part of innate immunity?
Natural killer cells
Dendritic cells
Monocytes
Granulocytes
What cells come from common lymphoid progenitors ?
B cells
T cells
Natural killer cells
What cells come from a common myeloid progenitor ?
Monocytes
Granulocytes
What cells produce antibodies
B cells and plasma cells
What role do complement proteins play in the immune system ?
Plasma proteins that cleave and active each other to kill extra cellular pathogens
Bind directly to pathogens or to antibodies coating pathogens
What role do cytokines play in immune response
They act on nearby or distant cells to influence innate and adaptive immunity
What are chemokines and what role do they play in immune response ?
Cytokines that attract other cells to the site of infections
What are primary lymphoid organs ?
Organs where lymphocytes develop from progenitor cells
Bone marrow: B cells and T cell progenitors
Thymus: T cells
What are secondary lymphoid organs ?
Where lymphocytes interact with each other and nonlymphoid cells
Initiate adaptive immune responses
Lymph nodes and spleen
What are the roles of neutrophils ?
Phagocytosis
Kill pathogens
Major white blood cell
Identify pathogens using receptors that recognize common patterns found in microbes
What are the roles of macrophages ?
Phagocytosis
Kill pathogens
Antigen presenting cells
Identify pathogens using receptors that recognize common patterns found in microbes
What are the roles of dendritic cells ?
Phagocytosis
Best antigen presenting cell
Identify pathogens using receptors that recognize common patterns found in microbes
How do innate cells recognize microbes ?
PAMPs derived from microbes bind to PRRs on innate immune cells
What roles do eosinophils and mast cells have ?
Protect against helminth infections
Implicated in allergic responses
What role do basophils have in innate immune reponse ?
Implicated in allergic responses
What function do natural killer cells have in innate immunity ?
Destroy infected or cancerous cells
What are the 3 classical antigen presenting cells ?
B cells
Macrophages
Dendritic cells
How many different B cell receptors are there ?
Each B cell generates a unique cell-surface bound antibody (B celll receptor) that recognizes a specific antigen
What do T cell receptors recognize ?
Peptide antigens that are presented on the surface of cells in an MHC molecule
What is the role of CD4+ T helper cells ?
Help activate other immune cells
What type of pathogens do TH1 cells protect against
Intracellular (cell-mediated immunity)
What type of pathogens do TH2 cells protect against
Extra cellular (humoral immunity)
What is the role of CD8+ cytotoxic T cells ?
Defend against cytosolic pathogens
Kill cells infected with intracellular pathogens
Protection against neoplasms
MHC class I molecules location and importance
On all nucleated cells
Bind to CD8+
Allow cytotoxic T cells to recognize virally infected or cancerous cells
MHC class II molecules location and importance
On the 3 classic antigen presenting cells
Binds to CD4+
Initiates adaptive immune response
What is the primary cell type that is recruited to sites of infection ?
Neutrophils
What do dendritic cells do once they take up antigens?
Bring to nearest lymph node —> present to T cell —> initiate adaptive immune response
Once in lymph nodes during immune reponses what do dendritic cells do ?
Present antigen to CD4+ T cell on MHC II molecule —> produce costimulatory molecules and cytokines —> antigen recognized —> activated T cell differentiates into TH2 cell
How do activated TH2 cells provide help to B cells during active immune response ?
Helps form cytokines and co-stimulation
—> activated B cells proliferate —> antibody-secreting plasma cells
—> some B and T cells —> long lived memory cells
Length of AA sequence on MHC I and MHC II molecules respectively
8-11
10-30
What is often needed for cell activation ?
2 signals, cross linking
What do proteases do ?
Chop antigens into small AA fragments
Activating signal for neutrophils/macrophages/dendritic cells
DAMPs and PAMPs cross link TLRs
Activating signal for B cells
3D antigen binding to and crosslinking surface mounted Ig molecules (BCR)
Activating signal for CD4+ T helper cells
Linear AA sequence mounted on specific MHCII molecule which cross links TCR
Activating signal for CD8+ cytotoxic T cell
Linear AA sequence mounted on specific MHCI molecule which cross links TCR
Response to antigen intake in dendritic cell
Naive T cell activation:
Clonal expansion and differentiation into effector T cells
Response to antigen uptake bu macrophage
Effector T cell response:
Macrophage activation
Response to antigen intake by B cell
Effector T cell response:
B cell activation and antibody production
Where are T precursor cells produced ?
Bone marrow
Where do T cells mature ?
Thymus
Where are T cells activated ?
Secondary lymphoid organs
What is the variable region of a T cell composed of ?
V,D and J segments
How is the variable region of a T cell synthesized ?
- Synapsis
- Cleavage
- Hairpin opening and end-processing
- Joining
How can the number of T cells someone has generated be measured ?
Measure # of T cell receptor excision circles (TRECs)
What is positive selection
T cells must interact with MHC (-90%)
What is negative selection ?
T cells must not activate too strongly to self peptide (-5%)
What is required for 2 factor authentication of T cells ?
Co-stimulation
When does T cell anergy occur and what is it’s effect?
When there is antigen specific signal alone without stimulation from APC.
Cell can no longer respond to antigen —> incapable of being activated
What treatment are molecules that block co-stimulation or enhance inhibition being used in ?
Treatment of autoimmune and allergic diseases
What are molecules that enhance co-stimulation or block inhibition recently being used to treat ?
Cancer
3 key events during B cell maturation
- Rearrangement and expression of immunoglobulin genes in a precise order
- Selection and proliferation of developing B cells at the pre-antigen checkpoint
- Selection of the mature B cell repertoire
What process is the RAG gene involved in ?
VDJ recombination in both B and T cells
What is VDJ recombination ?
Random combo of germline gene segments being brought together and by the random addition or deletion sequences at the junctions between segments before they are united.
What results when there are defects in RAG, Artemis or DNA ligand IV ?
Severe combined immunodeficiency (SCID)
What is another word for negative selection
Central tolerance
What happens to mature B cells that migrate back to the bone marrow following antigen exposure ?
Called plasma cells and they secrete antibodies
B cell response to T-dependent antigens
Initiated by binding of the protein antigen to specific Ig receptors of naive B cells —> recruit T and B cells into germinal centres of spleen/nodes
B cell response to T-independent antigen
Initiated by recognition of non-protein antigens by specific Ig receptors of naive B cells —>
Induction of B cell clonal expansion and IgM secretion
What type of B cell activation can occur in the mucosal tissues and peritoneal cavity ?
T- independent, Short lived plasma cells
What is the co-stimulation interaction that is needed for B cell proliferation and differentiation?
CD40-CD40L interaction
What are the two types of antibodies produced by B cells ?
Membrane bound
Secreted
Function of membrane bound anti-bodies vs secreted anti-bodies
Antigen receptors
Neutralize toxins
What is the core structure of an antibody ?
2 identical lambda or kappa light chains
2 identical heavy chains
Each chain has amino-terminal variable region (V)
And a carboxyl terminal constant region (C)
What are the 5 different classes of antibodies ?
IgE, IgG, IgA, IgD, IgM
Effector functions of IgG antibodies
Opsonization of antigens for phagocytosis
Activation of the classical pathway of complement
Antibody dependent cell-mediated cytotoxicity
Neonatal immunity
Feedback inhibition of B cell activation
Effector functions of IgM antibodies
Activation of classical pathway of complement
Antigen receptor of naive B lymphocytes
Effector functions of IgA antibodies
Mucosal immunity
Effector functions of IgE antibodies
Mast cell degranulation: immediate hypersensitivity reactions
Effector functions of IgD antibodies
Antigen receptor of naive B lymphocytes
What antibody isotype makes up almost 80% of circulating antibodies
IgG
What is somatic hypermutation ?
Process that introduces random mutation in the variable region of the BCR Ig heavy and light chains at a high rate during B cell proliferation.
What is the effect of hypermutation ?
Increased affinity of antibodies for antigen impart selective survival advantage to B cells producing those antibodies and lead to affinity maturation of the humoral response
Somatic hypermutation is only seen in T-___________ protein antigens ?
Dependent
What is affinity maturation ?
Process that leads to increased affinity of antibodies for a particular antigen, is result of hypermutation followed by selective survival of B cells
What cells make antibodies
B cells only !
What structures does the innate immune system look for ?
Structures that are unique to pathogens and injured self:
PAMPs and DAMPs
Would do TLRs recognize and where are they located ?
Bacteria, viruses, fungi
Plasma and endosomal membranes
What do NOD-like receptors recognize and where are they located ?
Bacteria, cell membrane damage
Cytosol
What do RIG-like receptors recognize and where are they located ?
Viruses
Cytosol
What do natural antibodies recognize and where are they located ?
Bacteria, fungi, injured self
Plasma
What does complement recognize and where is it located ?
Bacteria
Plasma
What 2 major groups opsonize ?
- Antibodies
2. Complement system
What does the cell signaling from PRR activation result in ?
- Increased vascular permeability
- Influx of important proteins (complement, antibodies, clotting factors)
- Influx of cells (innate and adaptive)
Result of PRR activation
- Cytokines
- Chemokines
- Cell adhesion molecules
- Microbe specific responses
What cell type bridges the innate and adaptive immune systems ?
Dendritic cells
Complement floats around inactive in the blood until it has contact with either a ___ or an ______
Pathogen, antibody
What is C3 convertase composed of and what is it’s role ?
C4b+C2a or alternatively C3b + Bb
Cleaves C3
What is C5 convertase composed of and what is its role ?
C4b + C2a + C3b or (C3b + Bb +C3b)
Cleaves C3 and C5
Actions of complement
Opsonization
Call for help
Augment immune response
Punching holes in cells
Membrane Attack Complex (MAC) formation steps (5)
- C5b binds C6 and C7
- C5b67 complexes bind to membrane via C7
- C8 binds to the complex and inserts into the membrane
- C9 molecules bind to the complex and polymerize
- 10-16 molecules of C9 bind to form a pore in the membrane
Complement activation: lectin pathway
Ficolin/MBL + MASPs bind carbohydrates —> activate C4 and C2 C4–> C4a+C4b C2 —> C2a + C2b C4b+C2a= C3 convertase C3 convertase + C3b = C5 convertase
Complement activation: classical pathway
C1q, C1r and C1s bind antibodies —> activate C4 and C2 C4–> C4a+C4b C2–> C2a+C2b C4b+C2a = C3 convertase C3 convertase + C3b = C5 convertase
Complement activation alternative pathway
C3 activation —> C3a + C3b Factor B is cleaved by factor D —> Bb C3b binds to Bb —> C3bBb = C3 convertase C3bBb is stabilized by Factor P C3bBb + C3b = C5 convertase
Why is fast clearance of self-antigens important ?
Prevents autoimmunity
What happens in terminal complement deficiency ?
No MAC can be formed
What pathogenesis accompanies C1q deficiency ?
Cannot clear apoptotic cells and 90% of patients will develop SLE
Why are C4 and C3 low in patients with SLE?
Presence of self antibody —> activation of classical pathway —> C4 and C3 undergo constant activation —> low levels
3 causes of hypersensitivity diseases
Reactions against:
Self
Microbes
Environmental agents
Definition of allergy or atopy
Combination of immediate hypersensitivity and late phase reaction
Allergen definition
Antigens that ellicit immediate hypersensitivity
Type I immediate hypersensitivity antigen isotype
IgE
Type II antibody-mediated hypersensitivity antibody isotype
IgM and IgG
Type III immune complex mediated hypersensitivity antibody isotype
IgM and IgG
Type IV T cell mediated hypersensitivity T cells involved ?
CD4+: inflammation —> delayed type hypersensitivity
CD8+: directly kill target cell —> granulomatous inflammation seen in TB infection
IgE antibody production in Type I hypersensitivity is dependent on what ?
Activation of CD4+ effector T cells that produce IL-4
Broad outline of how type I hypersensitivities develop
- First exposure to allergen
- Activation of T cells and stimulation of IgE class switching
- Production of IgE
- Binding of IgE on mast cells
- Repeated allergen exposure
- Activation of mast cell —> release of mediators
- Immediate and late phase reaction
What causes allergy symptoms ?
Mediators from mast cells
Common signs and symptoms of IgE mediated reactions
Urticaria Laryngeal Flush Wheeze Dizziness Nausea/vomiting Rhinitis Headache
Two main functions of TD4+ effector T cells
Recruit and activate phagocytes
Help B lymphocytes to produce antibodies
Characteristics of urticaria
Raised Erythematous Central cleaning Irregular border Often migratory
Characteristics of Angioedema
Localized to subcutaneous or sub mucosal tissues
Never involves gravity-dependent areas
Onset 2-3 hours as part of IgE mediated reaction
Usually asymmetric
How do IgG and IgM antibodies cause tissue injury ?
Activate complement system
Recruiting inflammatory cells
Interfering with normal cellular functions
Anaphylaxis is likely when
- Acute onset of illness with skin/mucosal involvement AND at least one of:
- respiratory symptoms
- reduced BP or signs of end-organ dysfunction
Anaphylaxis is likely when:
- If there is a likely allergen for that patient, 2 of the following:
- skin-mucosal involvement
- respiratory compromise
- reduced BP
- persistent GI symptoms
Anaphylaxis is likely when:
3. Reduced BP after:
Exposure to known allergen for that patient
Alpha-1 adrenergic receptor effects of epinephrine
- vasoconstrictor effect in most body organ systems
- ability to prevent and relieve airway obstruction caused by mucosal edema
Beta-1 adrenergic receptor effects from epinephrine
Increases cardiac contractility and HR
Ability to prevent and relieve hypotension and shock
Beta-2 adrenergic receptor effects from epinephrine
- decreases mediator release from mast cells, basophils
Increases bronchodilation
Vasodilator effect on skeletal muscle
Second line treatments for anaphylaxis
H1 antihistamine
Glucocorticoids
Inhaled B-2 adrenergic agonists
Treatment options for primary immunodeficiences
Passive administration of antibodies by monthly IV infusion or weekly subcutaneous injection
Continuous prophylactic antibiotics
Hematopoietic stem cell transplantation
Gene therapy to replace the defective gene
Most common causes of immunodeficiency:
HIV
Malnutrition
Iatrogenic immunosuppression
Anti-IgE Antibody mechanism
Binds to free IgE —> reduce cell bound IgE — > reduce high affinity receptors —> reduces mediator release
Benefits of adjuvants in vaccines
Increase immunogenicity of vaccines
Reduce the dose of antigen required for effectiveness
Broaden repertoire of antibody responses
Modulate the phenotype of T cell responses
