Unit 6 Immune System Flashcards
1
Q
what is the immune system and its roles
A
- Big multicellular organisms provide lots of environments for other, smaller organisms to proliferate in
- Ability of the body to fight off these invaders is called immunity (immunis = exempt)
- Key features of the immune system
- Lymphoid tissues and immune cells
- Chemicals that coordinate and execute function
- Three maior functions of the immune system
1. Protecting the body - Microbes = bacteria, viruses, fungi, protozoa
- Parasites = worms, etc.
- Toxins produced by microbes
- Other foreign proteins or substances (e.g. allergens)
2. Removes dead/damaged tissue and cells - Immune cells scavenge extracellular compartments
3. Tries to recognize and remove abnormal cells - Cells that are unable to control growth may be detected by the immune system
2
Q
diseases in the immune system
A
- When the immune system does not perform normally you can get a variety of pathologies
- Examples:
1. Incorrect responses - Autoimmunity
2. Overactive responses - Allergies
3. Lack of response - Immunodeficiency
3
Q
what are pathogens
A
- Pathogens are disease-causing agents
- We will look at two different types of pathogens
1. Bacteria
2. Viruses - These require slightly different responses from the immune system
4
Q
Bacteria
A
- Can be intracellular and extracellular
- Cells surrounded by a cell membrane & usually a cell wall
- Can survive & reproduce outside host
- Most can be killed by drugs –> antibiotics
5
Q
Viruses
A
- Intracellular pathogens
- Not cells –> nucleic acid core with protein coat –> cannot reproduce alone
- Some have envelope derived from host cell membrane
- Cannot be killed by antibiotics
- Some treated with antiviral drugs
- Once inside host, virus nucleic acid takes over
- New viral particles can either rupture host cell or bud off from host cell
6
Q
lymphoid organs and lymph
A
- Immune system organs are called lymphoid organs because lymphocytes are found there
- The lymphoid organs are connected by blood vessels and the lymph vessels
- Carry lymph –> clear fluid
- Essentially extracellular fluid that has left capillaries & filter through tissue
- Lymph is a conduit for immunologically active cells to travel through
- Lymph nodes (bean-shaped) are located at strategic positions
- Knee, groin, elbow, shoulder, neck
- Regions of the body outside lymphoid organs –> periphery
7
Q
types of lymphoid organs
A
- primary lymphoid organs
- Secondary lymphoid organs
8
Q
primary lymphoid organs
A
- Organs where lymphocytes develop
- Bone marrow –> all blood cells originate here
- B lymphocytes (cells) mature here
- Thymus –> T lymphocytes (cells) mature here
- not thyroid
9
Q
secondary lymphoid organs
A
- Organs where lymphocytes interact and initiate responses
- Spleen, lymph nodes, tonsils, and Gut Associated Lymphoid Tissue (GALT)
- Filter blood and lymph –> for pathogens & pathogen containing lymphocytes
- Structure of secondary lymphoid organs reflects this function:
- Afferent lymph vessel brings in lymphocytes from periphery
- Efferent lymph vessel allows them to keep circulating
- Pulp inside the lymph node allows mixing of lymphocytes and other leukocytes
- Arteries and veins to supply nutrients & O2, plus non-lymphocytic leukocytes
- Spleen and lymph nodes surrounded by a fibrous wall –> encapsulated
- Tonsils and GALT are unencapsulated tissues –> diffuse
10
Q
types of leukocytes
A
- Main players in the immune system
- Larger in size than RBC and less numerous (7000 per ml vs 5x10° RBC)
- Able to leave the blood stream and function extravascularly (in the tissues)
- They have a various lifespan –> some alive for a few hours and others for several months
- Six main types of cells:
1. Eosinophils
2. Basophils (Mast cells)
3. Neutrophils
4. Monocytes (Macrophages)
5. Lymphocytes
6. Dendritic cells
11
Q
subdivisions by function/ morphology
A
- Granulocyte
- Have prominent cytoplasmic granules
- Eosinophils, basophils & neutrophils + mast cells - Phagocytes
- Can engulf and ingest pathogens
- Neutrophils, macrophages, dendritic cells - Cytotoxic Cells
- Kill other cells, even self-cells
- Eosinophils & some lymphocytes - Antigen presenting cells (APCS)
- Display fragments of pathogens on cell surface (antigen)
- Some lymphocytes, dendritic cells & macrophages
12
Q
what are antigens and antibodies
A
- Antigen (Ag - antibody generator) –> substances that are recognized by an antibody and induces an immune
response - Antibodies (Ab) –> proteins that bind specifically to Ag’s and target pathogens for destruction
13
Q
Eosinophils
A
- cytotoxic granulocytes with bright pink staining granules
- Role in defence against parasites & function in allergic response
- Few in peripheral circulation, only live for 6-12 hours
- Found in digestive tract, lungs, genital tract, and skin
- Respond by binding to an antibody-coated parasite and degranulate –> spew granule contents
- Granule contents (toxic enzymes & oxidative chemicals) damage and kill parasites –> cytotoxic
- Eosinophils also degranulate in allergic responses
14
Q
Basophils
A
- granulocytes involved in allergic responses
- Have large dark blue staining granules (granulocyte)
- Basophils in blood (rare in numbers), mast cells in tissue –> found in digestive tract, lungs & skin
- Granules contain histamine, heparin, cytokines
- In allergic responses cells also degranulate
15
Q
neutrophils
A
- granulocytes that are phagocytic
- Most abundant leukocyte (50-70% of total leukocytes)
- Live 1-2 days & can ingest 5-20 bacteria
- Can leave circulatory system to attack pathogens in tissues
- Granules contain cytokines that cause fever and start other inflammatory responses
16
Q
monocytes
A
- Monocytes are precursor cells of tissue macrophages and are uncommon in blood (1-6% of leukocytes)
- Estimated in the blood for 8 hours –> move into tissues to become macrophages
- Macrophages are large ameboid cells and function as scavengers by phagocytosing old red blood cells and dead neutrophils
- Can phagocytose up to 100 bacteria
- Have a role in adaptive immune response –> phagocytosed pathogens are digested, and fragments are placed on the cell surface (APCs)
17
Q
lymphocytes
A
- Key players in the adaptive immune response
- Make up 20-30% of all leukocytes
- Only 5% of them are in the circulation –> most are found in lymphoid tissues
- 10^12 per individual at any given time
- They all look alike under a microscope, but have fundamental differences in function
- NK Cell in innate immunity
-T and B lymphocytes in adaptive immunity
-when B lymphocytes are activated they become plasma cells
18
Q
dendritic cells
A
- Phagocytic antigen presenting cells (APCs)
- Have long thin processes (like dendrites on a neuron)
- Found in skin and other organs
- They recognize and engulf pathogens
- Pathogens are digested and placed on cell surface
- “Activated” cells then migrate to secondary lymphoid organs to present the antigens to lymphocytes
19
Q
haematopoiesis
A
- All blood cells are produced in the bone marrow
- Derived from pluripotent hematopoietic stem cells
- Give rise to uncommitted stem cells
- These give rise to committed progenitor cells –> develop into each cell type
- The path taken is guided by cytokines
20
Q
types of lymphocytes
A
- B lymphocytes (B cells)
- T lymphocytes (T cells)
21
Q
B lymphocytes
A
- Produced in the bone marrow (easy to remember their name –> but NOT why they are called B Cells)
- Letter “B” derived from research in chickens
- The B cells leave the bone marrow and mature/develop in the Bursa of Fabricius –> an invagination of the colon
- Mammals do not have a bursa –> “B” is often translated as the “bursa equivalent”
Produce antibodies –> can be found on the cell surface as receptors or free Ab’s in the plasma
22
Q
T lymphocytes
A
- Produced in the bone marrow but mature/develop in the thymus (easy to remember their name –> and it IS why they are called T cells)
- Use contact-dependent signalling (cell-to-cell communication) via the T-cell receptor expressed on the T cell membrane –> can only bind to MHC-antigen complexes
- T-cell receptor cannot bind to free Ag
23
Q
what is an MHC
A
MHC stands for Major Histocompatibility Complex
24
Q
function of MHC
A
- These are proteins expressed on the surface of cells that display
“self-antigens” and “non-self-antigens” to T cells - The MHC name is derived from the role of MHCs in transplant rejection
- There are many alleles in the population - only identical twins have same set
- There are two classes of MHC that interact with T cells –> class I (on all nucleated cells) and class II (on APCs)
25
Q
subtypes of T cells
A
a. Cytotoxic T cells (Tc) or killer T cells
- Recognizes Ag presented on Class I MHC
- Kills cell that expresses appropriate Ag
b. Helper T cells (TH)
- Recognize Ag presented on Class II MHC
- Promote differentiation of B cells & Tc cells and can activate macrophages
c.Regulatory T cells (Tregs)
- Recognize Ag presented on Class II MHC
- Suppress other immune cells to prevent excessive immune responses
26
Q
steps of the immune response
A
- Immune response takes over when pathogens overcome the defence system of the body
- Same basic steps regardless of the foreign substance:
1. Detection and identification of foreign substance
2. Communication with other immune cells
3. Recruitment of help and co-ordination of the response
4. Destruction or suppression of the invader - Immune system uses chemical signalling
a. Antibodies (Ab) –> bind to antigen (Ag) as a signal
b. Cytokines –> affect growth or activity of other cells
27
Q
what are the two main categories of immunity
A
-innate immunity
-adaptive (specific/acquired)
- Response time is different for innate and adaptive immunity
- Innate is a more rapid, less specific response –> can lead to adaptive responses
- Adaptive response is slower, more specific
28
Q
innate immunity
A
- present before pathogen is encountered and is non-specific
- Response begins within minutes to hours, and it does not remember past infections
- Some non-specific cell types and proteins
- Inflammation is distinctive in innate immune response
- All organisms have this
29
Q
adaptive immunity
A
- directed at specific invaders
- Develops after the pathogen is encountered and the response takes days to weeks
- Remembers past infections
- Divided into:
1. Cell-mediated immunity
2. Antibody-mediated immunity (humoral immunity) - Only found in vertebrates
30
Q
what are the roles and cells in innate immunity
A
- Physical and chemical barriers provide the first line of defence
- Second line of defence are patrolling or stationary leukocytes & blood proteins
- These react the same way to every infection
- Provide clearance of pathogens or containment of the pathogen until adaptive response kicks in
- First Line of Defence
- Includes physical barriers (e.g. skin, mucous linings of the gut and genital tract and ciliated epithelium of respiratory system) and chemical barriers (e.g. stomach acids)
- These are most vulnerable because the epithelium is thin & exposed to outside environment
Innate Immune System Cells
- Majority are phagocytes which destroy or suppress the invader by ingesting it
- Attract other cells by secreting cytokines > chemicals that attract other immune cells are called chemotaxins
a. Cytokines (chemokines) & other immune blood proteins
b. Products of tissue injury (internal proteins that are outside, e.g. fibrin)
c. Bacterial products
31
Q
phagocytosis
A
- Phagocytes leave the circulation and enter tissue through capillary walls –> extravasion
- They identify the invader by chemical cues which interacts with receptors on the phagocyte membrane
- Many receptors bind sequentially to allow the phagocyte to engulf the invader
- Movement of the pseudopodia is aided by actin filaments to push the cell around the invader
- Both organic and inorganic materials can be ingested by the phagocyte
- Some pathogens do not have surface features that can be recognised directly by the phagocyte
- Blood proteins bind to and coat the pathogen to “tag” it
- Phagocytes have receptors for these blood proteins
- “Tagging” a pathogen is called opsonization
- A protein that can do it is an –> opsonin
- Once ingested, the particle is in a vesicle called a phagosome
- These fuse with lysosomes which contain digestive enzymes and chemicals that kill the pathogen
- Form a phagolysosome
- Dead phagocytes, tissue fluids and debris collect at the site of injury as pus
32
Q
Natural killer cells
A
- Natural Killer (NK) cells are lymphocytes associated with innate immunity; however, lymphocytes are generally associated with adaptive responses
- NK cells act within minutes, and they do not have specific receptors as seen in B cells & T cells
- They bring about apoptosis (programmed cell death) in pathogen-infected cells
- Can also attack tumour cells
- Produce important cytokines
- Interferons –> interfere with viral replication
- IFN alpha and beta –> induces an “antiviral state” in nearby cells that prevents viral replication
- IFN gamma –> activates macrophages & other immune cells
33
Q
role of chemical mediators
A
- Chemical mediators play a role in the innate response
- Create the inflammatory response –> red warm swelling in skin is hallmark of innate response
- Serves as a signal to attract other cells and chemical agents to the site
- Increase capillary permeability & causes fever
- A physical barrier is produced > prevent the spread of pathogen
- Tissue repair is promoted
- Caused by cytokines that are released by macrophages
- Interleukin-1 (IL-1) mediates most of the above effects
- Effects are mainly local, but can be systemic
- IL-1 functions to:
1. Act on endothelial cells lining the blood vessels > loosens junctions between cells
2. Act on liver cells to produce blood proteins involved in damage control
3. Induce fever
4. Stimulate cytokine production
34
Q
MAC attack
A
- Complement proteins also take part in innate response
- Complement is a collective term for over 25 blood proteins
- Activated by sequential proteolysis
- Some are opsonins, some are chemotaxins
- Some form the Membrane Attack Complex & make holes in pathogen membranes
-Allows ions to enter –> where ions go, water follows, pathogen swells and lyses - Results in the “MAC Attack”
35
Q
adaptive immunity and its cells
A
- Also called acquired or specific immunity
- Products of innate immune responses start the acquire responses
- These are antigen-specific responses directed to a specific foreign invader
Adaptive Immune System Cells
- Lymphocytes and lymphocyte products are involved in adaptive immunity
- Recall there are three types of lymphocytes found in the body (only 2 involved in adaptive immunity):
1. Natural Killer (NK) cells - remember that NK cells act in innate immune reactions
2. B cells
- Activated form = plasma cell
3. T cells
- Tc and Th and Tregs
- All lymphocytes produce cytokines
- Morphologically they look the same
- T cells & B cells can be expanded clonally
- Each individual cell recognises a different specific pathogen –> known as specificity
- We have millions of different B and T cells
- Have a few naive cells
- Once they recognize a pathogen –> expand clonally –> many effector cells
- These effector cells attack the pathogen
- Some cells become memory cells –> respond faster than naive cells
36
Q
what is antibody mediated immunity
A
- B cells produce antibodies that take part in antibody-mediated immunity (soluble Ab’s in the plasma) –> aka humoral immunity
- Recall B cells develop in the bone marrow –> circulate through the lymphatic & blood system
- Antibodies are proteins that bind specifically and target pathogens for destruction
- The term “antibody” refers to function
- AKA immunaglobulins
- Can be either a cell membrane protein of B lymphocytes or secreted
- Membrane Ab’s can be used as markers to identify each different clone of B cells
- When stimulated B cells mature into plasma cells
- Essentially antibody factories
- Plasma cells produce ~2000 antibody molecules per second
- Plasma cells are short lived and die after response is over
- A few memory cells survive –> these remember the past infection
37
Q
Primary and Secondary Ab responses
A
- Antibody response after the first and second exposure to an antigen
- Primary response happens on the first exposure to an antigen
- Slower response and less antibody
concentration - Delayed response
- Secondary response happens much faster –> 24-48 hrs to match primary response level
- Because mediated by memory cells
- More antibodies produced
- This principle is why vaccination works
- Patient is given an inactivated or partial pathogen
- They generate memory cells that
recognize the natural pathogen
38
Q
antibody classes
A
- In humans, there are 5 classes of immunoglobulins (Ig)
- IgM - produced during 1° responses –> activates complement
- IgA - found in secretions –> neutralizes pathogens before entry
- IgD - found on surface of B cells with IgM –> function unknown
- IgG - 75% of plasma Ab, 2° response Ab –> activates complement, opsonizes
- IgE - allergic responses –> recognized by mast cells
- Easy to remember –> MADGE
39
Q
antibody structure
A
- Four polypeptides linked into a Y shape with 2 light chains and 2 heavy chains
- Each side of the Y is identical - one light chain linked to one heavy chain
- The arms (Fab/ fragment antigen binding) contain the antigen binding sites
- The stem (Fc/ fragment crystalizable) determines which of the five classes an antibody belongs to (i.e. IgM, IgA, IgD, IgG or IgE)
- There is a hinge between the Fab and Fc portions
40
Q
anti body function
A
- Antibodies make up 20% of proteins found in plasma
- They are most effective against extracellular pathogens
- Before they invade a cell
- Also effective against macromolecules
- They do not damage the pathogens themselves
- Instead, they make pathogens more visible to immune defences or activate defences
41
Q
the 7 antibody functions
A
- Act as opsonins to tag Ag’s for phagocytosis
- Cause antigen/pathogen clumping
- Neutralize bacterial toxins
- Activate complement
- Activate B cells
- Activate Ab-dependent cellular activity (e.g. activate NK cells or eosinophils)
- Activates mast cells to degranulate
42
Q
antibodies and B cells
A
-B cells have antibodies on their surface as receptors (up to 100,000) than can bind to the antigen directly
-other cells use Fc receptors which interact and bind with the Fc region of the Ab
43
Q
cell mediated adaptive immunity
A
- T cells originate in the bone marrow, but migrate to the thymus to mature
- Learn to recognise “self” MHC proteins in the thymus
- T cells need to be in contact directly with the target cell expressing an antigen
- T cell receptor (antigen specific molecule) is expressed only as a cell-surface protein
- Detects Ag presented on the surface of a target cell via the Major Histocompatibility Complex (MHC) receptor
- T cell receptor cannot bind free antigen
- Must bind antigen displayed on Class I or II MHC
44
Q
T cell mediated response
A
- Need to be in contact directly with the target cell
- There are two types of MHC proteins
1. Class I MHC
2. Class II MHC
45
Q
Class I MHC
A
- is present on the surface of every nucleated cell in the body
- Defend against pathogens that get inside cells
- Peptides are presented in MHC class I to Cytotoxic T (Tc) cells
- Tc cells kill the cells that express the peptides
- Release perforin
- Forms pores in target cell
- Release granzymes
- Enter through the pores –> trigger apoptosis
- Tc cells can also express the Fas ligand to kill target cell
- Via apoptosis in target cell
46
Q
Class II MHC
A
- is present on the surface of specialized immune system cells –> antigen presenting cells (APCs)
- Cells respond to extracellular pathogens
- Phagocytose pathogens > present peptides in MEIC class Il to Helper T (TH) cells or Regulatory T (Treg) cells
- TH cells respond by secreting cytokines that activate other immune system cells
- Treg cells respond by secreting cytokines that suppress other immune system cells
47
Q
pathway of the immune response
A
- Different pathogens involve different responses from the immune system
- Innate response starts first –> then adaptive response
- However, the two response pathways are interconnected
- We will look at four different responses
a. Extracellular bacteria
b. Intracellular viruses
c. Allergic responses
d. Foreign tissue
48
Q
bacterial invasion
A
- Bacterial invasion often results in an inflammatory response
- Includes redness, swelling, tenderness
49
Q
stages of response of bacterial invasion
A
- The stages of the response are interrelated reactions:
1. Complement proteins are activated by bacterial cell wall components
a. Some act as chemotaxins & attract leukocytes from circulation
b. Some form “MAC’ attack & lyse bacteria
c. Some opsonize bacteria, helping phagocytes digest encapsulated ones
2. Haemostasis occurs if a blood vessel is broken
3. Phagocytes produce cytokines and the activated lymphocytes present antigens
4. Cytokines secreted by Tr cells activate B cells
5. B cells clonally expand, becoming plasma cells that produce antibodies that
a. Act as opsonins
b. Activate complement
6. End of response most lymphocytes die but some become memory cells
50
Q
viral infection
A
- Both T-cell mediated and humoral immunity work together to destroy the virus and virus-infected cells
- Viruses first go through an extracellular phase prior to infecting a host
- Phagocytes & Ab’s can help here –> opsonize + neutralize
51
Q
stages of response to viral infection
A
- Once the virus is intracellular, most immune cells and antibodies can’t get at them
Infected host cell produces IFN beta and macrophages produce IFN alpha - Induces an antiviral state in nearby cells
- Cytokines are secreted from host cells and macrophages activate NK & Tc cells
- Tc cells recognize viral peptides in MHC class I of infected cell and kill it
- Perforin & granzymes induce apoptosis in target cell
- Fas ligand also induces apoptosis in target cell
- Some viruses turn off MHC class I expression on infected host cell
- NK cells kill any cell with no MEC class I on its surface
- End of response most Tc cells die but some become memory cells
52
Q
allergic reactions
A
- Allergies are an inflammatory immune response to a non-pathogenic antigen
- Inflammatory responses triggered by specific antigens that cause allergies (allergens), which are not harmful by themselves
- Sensitive (atopic) individuals develop inflammatory responses to these antigens
- The resulting response is worse and causes more damage than the antigen
- Can range from mild to fatal
Allergic responses are hypersensitivities –> two types:
a. Immediate hypersensitivity –> happens in minutes - Ab mediated
b. Delayed type hypersensitivity (DTH) –> takes hours to days - Mediated by T cells and macrophages
- Allergens can be inhaled, ingested, or touched
- Can be practically any foreign substance > organic, non-organic, synthetic, or natural
- Generally low molecular weight, low concentration
53
Q
stages of the response to allergic reactions
A
- Steps in an immediate hypersensitivity response (happens in minutes, Ab mediated)
1. Sensitization phase: - Equivalent to primary immune response
- Antigen is ingested by APC –> activates TH cell
- TH cell activates B cell to make IgE antibody class
- TH cell and B cell become memory cells
2. Re-exposure: - Equivalent to secondary response
- Body reacts strongly and rapidly
- Generally, IgE on mast cells detects allergen
- Mast cells degranulate releasing cytokines and histamines
- Result is an inflammatory reaction
- The severity of allergic responses varies:
- Localized –> rashes or hay fever
- Systemic –> anaphylactic shock
- Widespread vasodilation, circulatory collapse
- Bronchoconstriction
54
Q
foreign tissue
A
- Able to transplant foreign tissues but must not be rejected by recipient’s immune system
- MHC proteins are primary tissue antigens that must be recognized as foreign
- MHC proteins are also called Human Leukocyte Antigens (HLA)
- If the recipient and donor share the same HLA –> tissue is often transplanted successfully
- Two possible outcomes of the transplant:
i. Rejection of the host by the donor tissue –> graft versus host
ii. Rejection of the donor tissue by the recipient’s immune system –> host versus graft
55
Q
blood transfusion
A
- Common example of tissue donation is the blood transfusion
- RBCs do not contain MHC proteins found on nucleated cells
- Have group of antigens that make up four blood types
- A
- B
- AB
- O
- People express antibodies to RBCs that they do not possess in their plasma
- e.g., Type A blood has –> anti-B Abs
- If wrong blood type is introduced into the recipient, the antibodies react and the cells clump (agglutinate)
- Antibody binding also activates complement
- MAC attack –> cells lyse –> Hb released
- Free Hb causes acute renal failure because kidneys try to filter blood with large molecules
