Chapter 4 Flashcards
Innate immunity
Non specific ways of protecting against microbes
- mucosa, urine, mucus, sweat, saliva
- activation of phagocytes (integrated with adaptive)
- inflammation
Adaptive immunity
Activated by specific antigens presented by APCs
APCs
Antigen presenting cells
Main characteristics of adaptive immunity (3)
- distinguish from self/non self
- create specific chemical means of destroying abnormal tissue
- produce a memory of past exposures to antigens to enable a quick defence when needed
What plays a key role if detecting and destroying abnormal and neoplastic cells?
Teh adaptive immune system
Antibody mediated immunity involves:
Production of B lymphocytes which develop into plasma cells
Plasma cells create lots of antibodies (aka immunoglobulins)
Cell mediated immunity involves:
Production of defensive cells known as cytotoxic T lymphocytes (CTLs)
What happens once a phagocyte digests foreign material?
- it presents the material to helper T cells
- once binded, both cells release cytokines which activates T cells in lymph tissue
- these helper T cells then relapse more cytokines that promote porliferation of CTLs and B cells
Then, antibody mediated (B cell) or cell mediated (CTLs) will occur
What happens when a CTL interacted with teh MHC of an infected cell
It produced granzymes and perforins which make the infected cell lyse
Lymphoid tissue
Tissue where lymphocytes are concentrated
Primary lymph organs
Bone marrow and thymus
Where lymphocytes are produced and differentiate
The life path of T cells
Start form stem cells in bone marrow
Migrate to thymus for training
Eventually circulate to secondary lymphoid tissues, where they will respond in immune reactions
Life path of B cells
Start in stem cells in marrow
Mature in marrow
Migrate to secondary lymphoid tissues
Key secondary lymphoid tissues
Spleen, lymph nodes, mucosa associated lymphoid tissues (MALT)
Also brochi (BALT)
Nasopharynx (NALT)
Gut (GALT)
Thymus
Key site of development and maturation of lymphocyte (T cells) early in life.
Shrinks when older
Thymus size and activity is linked to weakened immune function in age
Thymopoietin
Hormone form thymus is early life
Stimulates development of thymocytes (precursors) into T. Cells
Thymosin
Stimulates T cells to mature into T lymphocytes
Immune function of the thymus
Train T cells to be tolerant of self antigens
- most T cells can’t do this and are destroyed
- self recognizing T cells mature and leave the thymus
Largest lymphatic organ in the body
Spleen
Spleen functions
- Stores bold in the red pulp that can be ejected into the upon blood loss
- breakdown of old RBCs
- functions like a massive lymph node (contains monocytes and lymphocytes and plasma cells)
What does immunogenic mean
Recognizably non self
Cytokines
Chemical signals that activate and stimulate development of immune cells
Cytokine families that control development and function of immune cells
Interleukins (ILs), interferons (IFs, and chemokines
PNMs
Neutrophils
Aka polymorphonuclear cells
Neutrophils
Non specific phagocytes from myeloid lineage
- most abundant during acute immune response
- first wave of activated phagocytes
- love bacterial infection
- short lives (form pus on death)
Circulating monocytes
Mature into large macrophages upon immune mediator activation
- override PMNs
- become dominant
- resolve inflammation and set stage for wound healing
- but can contribute to chronic inflammation (ROS)
Resident phagocytes
Present in every organ
- used for low level removal of debris
- ex Kupffer cells in liver, alveolar macrophages in lungs
- myeloid lineage
Lymphocytes types (3)
NK cells
T cells
B cells
All from lymphoid lineage
Sub types of T lymphocytes
Cytotoxic T cells
Helper T cells
Supressor T cells
Cytotoxic T cells other names
Cytotoxic T lymphocytes
CD8 cells
CTLs
CTL function
- recognition of abnormal antigens
- destroying antigen baring targets
Recognition function for CD8 cells
They have the ability to recognize MHC molecules, as well as antigens presented to them by APCs
Make them important for immunosurveillance for malignancies
Examples of APCs
Dendritic cells
Macrophages
Destroy function of CD8 cells
Can destroy cells based on antigens on the cell surface
- kills cells either via cell/cell contact, or through release of cytokines and tumour necrosis factor, which trigger apoptosis
TNF
Tumour necrosis factor
- released by CD8 cells, causes apoptosis
Where do CD8 cells dominate
Delayed hypersensitivity (type 4)
- effective against viruses, bacteria, and immune surveillance for cancer cells
Helper T lymphocytes other names
Helper T cells
CD4 cells
Helper T lymphocytes role
Key in adaptive immune response
- upon antigen recognition, they produce cytokines needed for activation of CTLs, B cells, and helper T cells
- stimulate B cells -> plasma cells
- stimulate CTLs -> to attack shit
What happens in an absence of helper T cells?
Leads to failure of:
- antibody production (by plasma cells)
- activation of CTLs
Evidence in patients with AIDS
Suppressor T cells role
Regulate immune responses
- mediators of immunologic tolerance
- prevent organ specific autoimmunity and allograft rejection
- provide negative feedback loop on antibody and cell mediated immune responses
How are each of the T cells identified?
CTLs
- presence of CD8
Helper T cells
- CD4
Suppressor T cells
- CD4+CD25
Lymphoid stem cell lineage
Stem cell -> lymphoblasts
Then:
- NK cells or
- small lymphocyte
NK lineage done, small lymphocyte:
- T or B lymphocyte
T done, B can go to plasma upon stimulation via helper T cells
Myeloid stem cell lineage
Stem cells:
- megakeryoblast
- proerythroblast
- myeloblast
- monoblast
Megakaaryoblast:
- megakeryocyte -> platelets
Proerythroblast:
- reticulocyte -> RBC
Myeloblast:
- basophil, neutrophil,eosinophil
Monoblast:
- monocyte -> macrophage
What is the source of humoral (antibody mediated) immunity
B cells (B lymphocytes)
What are antibodies
Specialized proteins that provide protection to tissues by neutralizing foreign particles and setting the stage for degradation and removal
What happens when an antigen binds to an antigen receptor on a B cells?
The B cell proliferates and forms memory B cells or plasma cells
Memory B cells
Can be formed when antigens bind to receptors on B cells
- long lasting versions of a B Cell
Plasma cell antibody count
2k per second for 5-7 day life span
5 classes of antibodies in humans
IgG, IgA, IgM, IgD, IgE
Makeup of a antibody monomer
Made of 4 peptide chains
- 2 large - heavy chains
- 2 others - light chains
Each chain has constant and variable fragments
Constant = the same across all antibodies
Variable = diverse, provides ability to naturalize foreign antigens
Where is the variable region of an antibody
On the ends (Y shapes)
IgM
Macroglobulin
- used in early immune response
- real big (5 monomers) (10 binding sites)
- 10% of all antibodies
- reacts well against bacteria and viruses
IgG
Gammaglobulin
- 80% of antibodies
- second, stronger wave of antibodies following IgM
- can diffuse into extra cellular space due to small size to get to antigens
- can cross placenta to provide fetus with passive immunity
IgA (2 types)
IgA1/IgA2
- 1 more abundant (secretory IgA)
- found mainly in mucosal secretions/sweat/milk
- provides protection by neutralizing microbes found in airways, GI, etc
IgD
Not fully understood
- B cells that secrete it are found in upper respiratory tract
- reactive against respiratory pathogens
IgE
Response to worms and allergic responses
- concentrations usually low in blood as they remain fixed to mast cells
3 main antibody functions
Bind to antigenic non self things to neutralize them
Activate other components of teh immune system like macrophages for efficient work
Activate compliment systems forming membrane attack complexes to destroy cells and opsonize material
Complement system
Non specific defence system activated by antibody binding to antigen
- combats specific invaders labelled by antibodies
3 phases of complement function
Recognition by C1
- IgG/IgM attach to antigens on invading cell and activate C1
Activation of fragments C4/2/3
- begins with activated C 1
- activated in that order
Formation of complex attack
- proteins bind to cell membrane which create pores in teh membrane causing lysis
Fragments of the complement system that do not fix to target cells have other functions like
chemoattractants
- summon phagocytes
Opsonins
- enable efficient phagocytosis
Stimulate histamine release
Vaccination
Process of inoculation with incomplete antigenic material prepared from virus of bacteria
Why do vaccines work?
Adaptive immune system response to vaccine with B lymphocyte activation, causing memory cells and antibodies to be made for the microbe
memory B cells are capable of:
Producing a strong secondary response in the event of an infection by the pathogen it knows
Passive immunization
When antibodies are “given” to you rather then produced by the body
- ex. Rabies shot, IgA transfer from mom to baby in breast milk
Immunocompetence
Ability of a person to have a normal immune response to a threat
Immunosuppression
Reduced immunity
Can be due to chronic stress, immune exhaustion, corticosteroid treatment, chemo
Leukopenia
Lack of WBC, common during Chemotherapy
Immune deficiencies
Primary
- congenital
Secondary
- from a preceding disorder
Can be classified as innate of adaptive immunity
Innate immune deficiency
Activity of neutrophils, macrophages, NK cells, and complement is all reduced
Adaptive immune deficiency
Inactivity of B/T lymphocytes and their response to antigens
Primary immune deficiencies result in:
Decrease in immune components like lymphocytes, phagocytes, or complement proteins.
Deficiencies of innate immunity
Complete system disorders
Phagocyte disorders
Complement system disorders
Recessive disorder of any of the complement proteins (c1-9)
- ex. Lupus (SLE)
Result in inability to opsonize bacteria like strep and staph
Phagocyte disorder ex
Most common is CGD
(Chronic granulomatous disease)
Deficiencies of adaptive immunity
T cell disorders
B cell disorders
Combined B and T deficiencies
T cell deficiencies result in:
Chronic fungal infections
- due to incomplete development of thymus
B cell disorders
Mostly antibody deficiencies
- low production of IgG
Combined B and T cell deficiencies
SCID (severe combined immunodeficiency disorder)
- congenital
- result in weak or no antibody response to infection
Secondary immunodeficiencies
Caused by exogenous factors
Examples include
- malnutrition
- infection
- chronic stress
Untreated HIV can lead to
AIDS
Lots of infections due to immunodeficiency
HIV can perform :
Reverse transcription from RNA back to DNA
Why is HIV so dangerous
It slowly kills all the helper T cells by using them as hosts. This wipes out immune function and sets the stage for AIDS adn then death
7 steps of the life cycle of HIV (just know generally no need for details)
- Binding
- to CD4 cells - Fusion
- virus fuses with host membrane and dumps contents in - Reverse transcription
- Integration
- HIV DNA enters nucleus, and joins - Transcription/translation
- HIV DNA is copied - Assembly
- viral RNA is packed to leave host - Release
- virus leaves, whole process starts again
Hypersensitivity
Exaggerated immune response against and allergen or antigen
Hypersensitivity reactions 1-4 in one sentence
1 - allergen binds to mast cell and causes degranulation
2. Cells as destroyed due to bound antibody by CTL with that antibody receptor or by complement
3 - antigen/antibody complexes are deposited in tissues which attract neutrophils
4 - Th1 cells secrete cytokines that activate macrophages and CTLs
Clinical example of each hypersensitivity
1 - anaphylaxis
2 - destruction of RBCs during transfusion of mismatched blood
3 - RA or lupus
4 - contact dermatitis
Type 1 hypersensitivity is known as
Allergic or anaphylactic response
Why does type 1 HS occur
Result of serial exposure to a normally harmless environmental antigen
- mediated by IgE generated as a reaction or pollens/nuts/stings etc
- on second exposure, histamine is released
Phases of HS type 1 reaction
- Sensitization
- first exposure to allergen leads to production of IgE
- little/no response
- mast cells now primed for next exposure - Allergen bonds to IgE antibody on mast cells
- triggers degranulation of mast cells -> histamine release
- histamine causes hives n shit
For people with severe reactions
- second response is more powerful cause it effects smooth muscle contraction
- anaphylaxis
- corticosteroids are needed to fix
Type 2 HS is known as
Antibody dependent cytotoxicity
What happens during type 2 HS
IgG/IgM antibodies ind to antigen inc targets on cell surfaces of connective tissue
This causes activation of killer T cells and then attack on self tissue
Ex. wrong blood transfusion
Type 3 HS is known as
Immune complex mediated HS
type 3 HS
Immune complexes (antibodies bound to antigens in a big mass) are deposited in tissues, triggering an inflammatory response.
Usually, immune complexes are cleared by liver and spleen, but continuous exposure can lead to imbalance
Type 4 HS is known as
Cell mediated, delayed HS
Type 4 HS
Slow cell mediated reaction in response to intracellular bacteria. Happens during tissue transplants too.
Helper T cell activation and phagocytosis that leads to formation of exudate
Ex. Poison oak
Autoimmune diseases
Disease where self tissue is a target of attack
Some ways in which autoimmunity can occur
- where a self antigen is similar to a foreign one
- chemical alteration to self antigens giving it a new form
- exposure to hidden antigens via tissue injury (release of basement membrane into blood due to smoking damage)
- thymus abnormalities
- MHC genotypes that affect antigen presentation
SLE meaning
Systemic lupus erythematosis
Lupus mechanism
An antibody is positive for the nuclei of self tissue
- immune complexes can be found, which cause activation of complement and attack by neurophils + inflammation
Rheumatoid arthritis
Autoimmune condition where the body attacks synovial tissue
Treated with anti inflammatories and other immunosuppressants
Scleroderma
Connective tissue disorders affecting the blood vessels, muscles, and skin
Early death due to lung and cardiac complications is common
Treated with NSAIDS adn corticosteroids
Examples of systematic autoimmune diseases
Lupus
RA
Scleroderma
Examples of organ specific autoimmune diseases
Type 1 diabetes
Goodpasture syndrome
Key event in type 1 diabetes
Destruction of langerhans cells in pancreas that produce insulin
Goodpasture syndrome
Antibody mediated injury that occurs in the glomerulus and alveolar basement membranes
Treated with corticosteroid sand immunosuppressants
