Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Human Biosciences > Revision immunity deck > Flashcards

Revision immunity deck Flashcards

1
Q

GALT =?

A

Gut associated lymphoid tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Thymus =?

A

Thymus =?

Specialised primary lymphoid organ where T cells mature

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Spleen does?

A

synthesises immunoglobulins and is reservoir continuing half the body monocytes

Makes dendritic cells and macrophages for the innate immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is AID?

A

Beginning of original deck

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Where do all immune cells originate from?

A

Hematopoietic stem cells in the bone marrow

Goes into the lymphoid lineage, melodic lineage or erythroid lineage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Serum = ?

A

Serum = ?

Plasma without clotting factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Where is the immune system?

A

Where is the immune system?
In the lymphatics system and lymph organs

White blood cells circulate with blood

Some WBCs and quite a bit of plasma leave the capillaries in tissues

Circulation of plasma and WBC through interstitial space/tissues and back via lymphatics to lymph nodes allows surveillance of tissues for forge in molecules and pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe neutrophils eosinophils and basophils?

A

Attack a variety of pathogens by phagocytosis or with antimicrobial or with anti-microbials and histamine released after degranulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Describe plasma cells derived from B lymphocytes?

A

Secrete large amounts of antibody

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Describe B and T lymphocytes?

A

Describe B and T lymphocytes?

Orchestrate the adaptive immune response and provide immunological memory

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe monocytes and macrophages?

A

Phagocytes and regulate many aspects of innate and adaptive immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What does each pathogen have?

A

Antigens on its surface known as pathogen associated molecular patterns

Immune cells have invariant receptors on their surfaces known as pattern recognition receptors that recognise many of these PAMPS

Once a pathogen is recognised a cascade of events occurs activating an immune response to destroy it

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Examples of PAMPs recognised by the innate system?

A

Cell wall components:
Peptidoglycan (bacteria)
Lipopolysaccharide (gram positive bacteria)
Galactomannans

Nucleic acid:
CpG motif DNA (bacteria)
ssRNA (viruses)
dsRNA (viruses)

Conserved surface proteins
Flagellin (bacteria)

Conserved stress proteins”
Heat shock proteins (bacteria)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Pattern recognition soluble receptors?

A 
Pattern recognition soluble receptors?
Natural antibodies
Complement 
Pentraxins 
Collectins 
Ficolins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Pattern recognition cell receptors?

A

Toll-like-receptors
NOD-like receptors
RIG-like receptors
C-type lectin like receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Features of innate system?

A

Fast

Doesn’t require immunological memory

Activated by binding of PAMPS by PRRs on phagocytic cells

can discriminate self and non self

Receptors encoded in germline
Limited diversity

Typically recognise structures common to different microbes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Features of adaptive system?

A

Slower

Activated once the innate has been activated

Activated by a cascade of chemical signals from sites of infection , and physical interactions with phagocytic cells of the innate immune system known as dendritic cells that migrate from sites of infection into the lymphatic system to activate lymphocytes

Can discriminate self and non self

Receptors encoded by gene recombination - massive diversity

Typically recognise structures unique to different microbes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

What decides the extent to how innate or adaptive system is used?

A

What decides the extent to how innate or adaptive system is used?
Severity, context and duration of disease, innate is mainly for something like a minor cut or splinter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

What are cytokines and chemokines?

A

signalling molecules released at sites of infection by resident macrophages recruit neutrophils from the bloodstream leading to localised inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Types of lymphocytes?

A

Types of lymphocytes?
All key in adaptive immunity

B-lymphocyte/Bcell - express antibodies as B cell receptors

Helper T lymphocytes

Cytotoxic T lymphocyte

Natural killer T cell

T-lymphocytes express T cell receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What happens with B and T cells during an adaptive response?

A

Have receptors specific for particular pathogen molecules proliferate

Clonal selection and expansion forms the basis of protective immunity and immunological memory through which the body is protected against future attack

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Homeostasis in which specific molecular interactions keeps the immune system in check?

A

Antigen receptors and antigens

Cytokines/chemokines and their receptors
Cell-cell interactions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

we get infected or colonised in?

A 
Cytoplasm
Intracellular vesicles of cells 
Interstitial spaces 
Blood or lymph 
Epithelial cells
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

First barrier broken through during infection?

A

Skin

Cuts or burns

Main portals of entry is the mucosal epithelia of the gastrointestinal respiratory and urogenital tracts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Describe immune cell differentiation?

A

Cells of the innate and adaptive immune systems are derived from the pluripotent hematopoietic stem cell

The HSC divides to replace itself and produce a progenitor cell with the potential to give rise to all of the hematopoietic line ashes by generating further progenitor cells committed to progressively narrower ranges of differentiated fates

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

The erythroid lineage gives rise to?

A

erythrocytes and to megakaryocytic which shed fragments that form the platelets that initiate blood clotting

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

The myeloid lineage gives rise to?

A

Phagocytic and inflammatory cells of innate immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

The lymphoid lineage gives rise to?

A

T and B cells of adaptive immunity and to natural killer (NK) cells which are specialised cytotoxic cells

Killer cells count as innate as don’t require activation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Hematopoietic stem cell lineages?

A

SCF = stem cell factor
TPO =Thrombopoietin (platelet production)
EPO = Erythropoietin (erythrocyte production)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What protects epithelial surfaces, especially the mucosa of the gastrointestinal, respiratory and urogenital tracts?

A

Basophils, mast cells and eosinophils

Mast cells have a sentinel role, whilst basophils and eosinophils are circulating cells recruited from the bloodstream

Whereas neutrophils destroy internalised micro organisms these cells typically provide immune defence against pathogens too large to be internalised

On activation they release the contents of their cytotoxic granules to the exterior creating an environment hostile to an invading organism or directly killing it

They also release histamines that mediate allergic and inflammatory responses such as coughing sneezing and vomiting

These expulsive responses may be mechanisms that are evolved to expel parasites

All 4 are known as the granulocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

The phagocytic cells of the immune system comprise of?

A

neutrophils and macrophages which are effector cells, specialised to internalise and destroy micro organisms, and dendritic cells which internalise micro organisms for presentation to T lymphocytes of the adaptive immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Features of neutrophils?

A

Front line effector cells of innate immunity

After differentiation they circulate for a few hours before entering tissues to engulf microorganisms and destroy them via microbicidal products stored in vesicles

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Features of macrophages?

A

Long lived cells that provide immune surveillance

They are derived from monocytes that circulate in the blood, differentiating as they leave the blood stream

Like neutrophils they ingest and destroy micro organisms

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Features of dendritic cells?

A

Are involved in the induction of adaptive immunity

As immature cells they operate as phagocytes but rather than destroying the micro organisms they ingest their function is to display the ingested particles on their surface for recognition by T lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Describe macrophage receptors?

A

Scavenger receptors - recognise particles released by dead or damaged tissues

Complement receptors and antibody receptors

Similar on dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Activation of the innate immune system?

A

Directly through recognition of micro organisms or indirectly through recognition by cells of the adaptive immune system that then activate the innate immune defences

This is done as a lymphocyte of the adaptive immune system produces antibodies whose variable regions recognise a surface component of the bacterium A non variable region of the antibody is then recognised by a receptor of the phagocyte which in turn is activated engulf it. In this way, bacteria that have masked the conserved components can be recognised and destroyed by the innate immune system

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Whats opsonin?

A

A general term for soluble components of the immune system that coat micro organisms and stimulate uptake by phagocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

2 ways phagocytes are pivotal role in the immune system?

A

On activation by microbial surfaces they release cytokines and chemokines that amplify the response to infection

Cytokines and chemokines are signalling molecules. They increase the permeability of blood vessels and recruit additional cells and molecules of the immune system to sites of infection - the inflammatory response

Hence they activate the adaptive immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What does the chemokines IL8 (CXCL8) do?

A

From a macrophage

Recruits neutrophils, basophils and T cells to site of infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Recruitment of neutrophils to inflammatory sites?

A

Fluid matrices contain antibacterial peptides and toxic proteins that are constitutively secreted and further induced in response to cell wall components such as lipopolysaccharide

B-defensins in lung and skin
a - defensives in paneth cells of the intestinal tract
Lysozyme in fluids bathing the cornea

Cathelicidins (another group of antimicrobial defensins) are produced by activated neutrophils and epithelial cells in addition to antimicrobial activity they trigger signaling through the formyl peptide receptor an innate immune recognition element thereby aiding recruitment of neutrophils to inflammatory sites

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

what are fMLPs?

A

powerful chemoattractants and activators of neutrophils

Derived from BH2 terminal extensions of newly synthesised polypeptides

fMLP directs the transport of secreted proteins the possess NH2 terminal signal peptides

Cleaved by a signal peptidase following polypeptide transport and released into the extracellular space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is chemotaxis?

A

neutrophils are attracted to bacterial chemical products like the peptide fMLP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Describe the inflammatory response?

A

Memory T cells monitor keep the tissues of the body under surveillance

If they detect no antigen they return to circulation via the lymphatic system

If there is an antigen it is processed by antigen presenting cell, and presented as MHC peptide complexes

This activates memory T cells

Which release cytokines such as TNF-a which act on local blood vessels

TNF-a activates the vascular endothelium

Loosens gaps in them so more blood leaks out, swelling occurs and looks more red due to RBC

The activated endothelium also releases adhesion molecules that allows phagocytes out the blood vessel

Takes 1-3 days

The phagocytes uptake the antigen and also can present it

Memory and effector T cells also leave the vessel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Describe cytokine signalling?

A

go on original deck

Cytokine receptor consist of 2 chains

Each having an extracellular binding domain

An a intracellular binding domain which has JAKs kinases on

Without cytokines these 2 receptors are not associated

Cytokines stabilise the heterodimer bringing them together, including the 2 JAK kinases

The JAK kinases can then phosphorylate the cytoplasmic tails

STAT molecules then bind to the chains at the bottom of the receptors which get phosphorylated by the JAKs

The STAT molecules can now dimerise and migrate into the nucleus where they can directly activate gene transcription

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Describe rolling adhesion?

A

Get from original deck

Blood vessel endothelium at sites of infection expresses selectin molecules (P-selectin and E-selectin) the selectins are triggered by cytokines released by sites of inflammation

Leukocytes such as neutrophils express the ligand for these selections in the form os s-Lex

These creates a weak bond with the selectins and the neutrophils rolls along the blood vessel forming and breaking bonds

These neutrophils will find somewhere they can squeeze for the endothelial cells out of the blood vessel

Only happens in veins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

What are the first responders to tissue detected microbes?

A

Neutrophils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

What are the types of secreted molecules released by

A

In general deck

Lysozyme - released in fluids of cornea, saliva and gut (Paneth cells)

Breaks down peptidoglycan, a component of the bacterial cell wall

Phospholipase A2 - breaks down phospholipids in cell membrane of bacteria

Antimicrobial peptides - Defensins - (alpha-defensins in Paneth cells of the intestinal tract and beta-defensins in lung and skin) – disturb the cell membrane of bacteria and fungi

Cathelicidins (another group of antimicrobial defensins) are produced by activated neutrophils and epithelial cells

Histatins (oral cavity, active against fungi)

Lecticidins (creates a pore in microbial cell membranes)

Complement: exists in fluids and blood:
capable of direct killing of pathogens through membrane attack complex (MAC)
also potentiates phagocytosis and the recruitment of other inflammatory mediators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

More details on complement?

A

Small proteins that are synthesised by the liver, tissue macrophages, blood monocytes and epithelial cells of the genitourinary system and gastrointestinal tract

They circulate the blood as inactive precursors

Can diffuse into tissues

Capable of direct killing of pathogens through membrane attack complex

Potentiaites phagocytosis

Potentiates the recruitment of other inflammatory mediators

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

What’s the complement cascade

A

Is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and attack the pathogen’s cell membrane.

Its spontaneous and low level activation

If deposited onto pathogen = activation

If deposited into host cell = inhibited

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

What does C3 convertase do?

A

Cleaves C5 into:

C5a: potent anaphylotoxin
C5b: initiates Membrane attack complex

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

What is the membrane attack complex?

A

or terminal complement complex (TCC) is a structure typically formed on the surface of pathogen cell membranes as a result of the activation of the host’s complement system, and as such is one of the effector proteins of the immune system.

In order to permeabilize both the bacterial outer and inner membrane and thus kill a bacterium,

The MAC is much more active towards Gram-negative than gram positive bacteria

Ion influx and efflux causes the cell to lyse

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Where does phagocytosis occur?

A

Phagocytosis occurs mostly in neutrophils and in monocytes/macrophages/dendritic cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

What is phagosome killing?

A

The phagolysosome is matured through sequential fusion with endosomes and lysosomes and becomes a very specialised intracellular compartment

The bug is digested and degraded

Unpleasant environment for microbes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

How does phagocytosis occur?

A

Microbes are recognised by phagocytic surface receptors:

  1. PAMPS-PRR (Toll-likereceptors, C-type lectins, scavenger receptors)
  2. Opsonization
    Microbe coated with complement = binds CR3-CR4
    Microbe coated with antibody = antibody binds FcRecepors

Recognition and subsequent signalling trigger phagocytosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Describe how the phagolysosome is matured from a phagosome

A

The phagolysosome is matured through sequential maturation with lysosomes and becomes a very specialized intracellular compartment with:

More details on original flashcard 67

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

What’s nutritional immunity?

A

When for example the phagasome pumps out iron which the microbe needs to live for nutrition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

How is the phagosome adapted in dendritic cells?

A

To perform antigen presentation, to degrade antigens and load them to bridge adaptive immunity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Extracellular killing?

A

Eosinophils (toxic granules):
They release mitochondrial DNA against bacteria

They also release granules are active against parasites, such as: 
major basic protein (MBP) 
eosinophil cationic protein (ECP) 
eosinophil peroxidase (EPX) 
eosinophil-derived neurotoxin (EDN)

Neutrophil extracellular traps (NETS) are also used catch microbes in sticky DNA fibrils

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

When killing a microbe is not possible what can happen?

A

Granuloma can contain microbes

Coordinated response of TH1 T-cells and macrophages which creates a layer of macrophages and outer layer of T cells which walls off the pathogen

Important in tuberculosis and in certain parasite infections

Means we can co live with the parasite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

What organ is first to encounter blood after the gut?

A

The liver, gets rid of bad bacteria

This is done by liver macrophages called Kupffer cells using CRig functions as a pattern recognition receptor on Kupffer cells to directly bind gram positive bacteria

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

How is host damage regulated/prevented?

A

If its chronic can cause a degenerative or auto immune disease

This is prevented by:
Host cells have mechanisms to prevent activation of innate immune killing

Intracellular signalling cascades triggered by PAMPS and DAMPS direct the magnitude and nature of the immune response in a tissue specific manner

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
62
Q

When the immune system is de regulated?

A

CYTOKINE STORMS, IMMUNE-MEDIATED DAMAGE, ALERGY, FIBROSIS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
63
Q

Overview of immune memory?

A

The adaptive immune system consist of T and B lymphocytes

The T lymphocytes and immunoglobulins, and antibodies that B-lymphocytes produce can recognise an unlimited number of different targets

Become effective only after a delay of 2 to 4 days on first encounter

Lymphocytes and lymphocyte products specific for a given organism then persist as immune memory and are rapidly protective on re-exposure to the same infectious agent

This property of the adaptive immune system forms the basis of the protective effects of vaccination

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
64
Q

What does vaccination do?

A

What does vaccination do?
The ability of the body to remember an infectious agent to
which it has been exposed is the basis for natural and artificial
immunity against a disease

Vaccination initiates a primary immune response, generating
memory cells without making the person ill

Later, if the same or very similar pathogens invade the body,
specific memory cells already exist

They recognise the agent and produce massive number of
lymphocytes and immunoglobulins that overwhelm the invaders

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
65
Q

Specific functions of each cell in adaptive immunity?

A

Adaptive immune responses are mediated by lymphocytes of the lymphoid lineage which fall into two major classes:

T lymphocytes - kill virus-infected and cancerous cells (CD8+ T cells/cytotoxic T lymphocytes or CTLs

or,

activate other cells of the immune system (CD4+ helper T cells)

B lymphocytes - secrete immunoglobulins

Natural killer cells -capable of killing virus-infected or cancer cells immediately
without prior activation and without clonal expansion

They are generally regarded as part of the innate immune system
(because they don’t require prior activation)

Activation occurs via binding of activating receptors to surface molecules produced by cell damage e.g. cancer or that are encoded by infecting viruses

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
66
Q

Describe lymphoid lineage - cellular differentiation?

A

Mature lymphocytes that have not yet
encountered antigen are known as naïve
lymphocytes

Differentiation into effector cells is stimulated
by encounter with antigen and is preceded with
a vigorous proliferation that selectively expands
the numbers of those lymphocytes with receptors
specific for the inducing antigen

This is known as clonal selection of antigen-
specific lymphocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
67
Q

Describe the lymphatic system?

A

The critical interactions between
activated dendritic cells and
lymphocytes occurs in lymphoid tissues

Lymphocytes enter lymphoid tissues
from the bloodstream

Return to the bloodstream through
the lymph if they are not activated

Migration through lymphoid tissues, 
and cellular interactions, are guided and 
controlled by adhesive cell surface 
molecules whose expression is regulated 
by cytokines and chemokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
68
Q

How do T lymphocytes recognise antigens?

A 
How do T lymphocytes recognise antigens?
T lymphocytes recognise antigens 
by means of T cell receptors 
generated during their differentiation - 
they interact with APCs (antigen- 
presenting cells - DC, macrophages and 
B cells) via complementary ligands

Each individual lymphocyte expresses
an antigen receptor of only one specificity,
but the total population of lymphocytes
in any given individual is collectively
capable of recognising virtually any antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
69
Q

Features of the T cells CD4?

A

Marker of helper T cells

Is a co receptor for MHC call II molecules

These co-receptors play an important part in signal
tranduction on antigen binding by T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
70
Q

Features of CD8 T cells?

A

Marker of cytotoxic T cells

Co receptor for MHC call I molecules

These co-receptors play an important part in signal
tranduction on antigen binding by T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
71
Q

Features of dendritic cells?

A

Dendritic cells of the innate immune system play a crucial role in activating adaptive immunity

Begin life as phagocytes but when activated by conserved components of micro-organisms, or by inflammatory cytokines released by macrophages, become dedicated to displaying components of ingested micro-organisms for recognition by naïve T lymphocytes and subsequent differentiation of naïve T lymphocytes into effector T cells

Especially numerous in epithelia and at mucosal surfaces

In mucosal epithelium of the gut, dendritic cells are concentrated at specialised
sites of antigen collection that overlie lymphoid tissues

Some have specialised surface properties that enable them to extend their long dendritic processes between the cells of the epithelium and into the lumen to sample antigens

These cells are directly exposed to ingested antigens and to commensal bacteria
as well as invading pathogens

These cells have a specialised role in preventing inflammatory responses to harmless gut residents

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
72
Q

M cells do what?

A

deliver antigen from the lumen of the gut to the underlying tissue where dendritic cells cluster

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
73
Q

Describe how the dendritic cells activates the adaptive immune system?

A

Describe how the dendritic cells activates the adaptive immune system?
A dendritic cell displays a component of a
micro-organism for recognition by a T lymphocyte
bearing a receptor for that component. This
stimulates it to proliferate and differentiate into
an effector cell. When the effector cell recognises
the same antigen displayed on the surface of a
B lymphocyte, the T cell activates the B lymphocyte,
which in turn proliferates and secretes antibodies
that recognise the micro-organism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
74
Q

Describe T cell targeting?

A

Unlike B cells whose surface immunoglobulin molecules are adapted to serve
as antigen receptors, T cells are unable to interact directly with
intact antigen and so must interact with other cells of the immune system

T cells are focused on their target cells by cell surface proteins known as
MHC molecules because they are encoded in the major histocompatibility
complex (MHC)

MHC molecules carry fragments of antigen, usually peptide fragments of
proteins, from internal compartments of the target cell to the cell surface
and display them for recognition by the T cell

All naïve T cells are activated by antigen fragments displayed on MHC
molecules on the surface of dendritic cells, and after differentiation into
effector cells they are triggered to kill or activate cells displaying the same
complex of MHC and antigen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
75
Q

Whats the Major histocompatibility complex?

A

Whats the Major histocompatibility complex?
Chromosomal region containing genes that encode cell surface proteins
that regulate interactions among cells of the immune system

During transplant the more similar they are the longer it will take for the body to reject the new organ

There is class I molecules (Activate CD8 T cell) and class II molecules (Activate CD4 T cell)

These monitor different internal compartments of cells and are recognised bu distinct classes of T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
76
Q

2 internal compartments of cells that need to be monitored for pathogens?

A

2 internal compartments of cells that need to be monitored for pathogens?
The cytoplasm

All viruses and some important bacterial pathogens replicate
in the cytoplasm

Vesicles of the endosomal/lysosomal pathway

Contain internalised antigens derived from extracellular pathogens

In the specialised case of macrophages, vesicles may harbour bacteria
and some fungi (e.g. Cryptococcus) adapted to survive phagocytosis

The cytoplasm is monitored by MHC class I molecules

Vesicular compartments are monitored by MHC class II molecules

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
77
Q

Features of MHC class I molecules?

A

MHC class I molecules are expressed on all nucleated cells
(not RBC) including APCs and bind peptides generated by cytoplasmic
proteases from cytoplasmic proteins

Their critical role is to display antigens derived from pathogens that
replicate in the cytoplasm, and antigen displayed on MHC class I
molecules is recognised by cytotoxic T cells, which kill the infected
cells

This system ensures the destruction of cells in which cytoplasmic
pathogens are replicating and is believed to be essential for the
elimination of some of these pathogens

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
78
Q

Describe recognition of antigen and MHC class I molecules by cytotoxic T cells?

A 
Peptide fragments of pathogens, 
such as viruses, that replicate in the 
cytoplasm compartments of cells 
are carried to the cell surface by 
MHC class I molecules and are 
recognised by cytotoxic T cells forming an immune-synapse, outer ring is an adhesion ring and the inner is a signalling zone and secretory zone

Upon activation, CD8 T cells produce:

  1. Perforins - proteins that form pores
    in the membrane of target cells
  2. Granzymes - proteases that induce
    programmed cell death on entry into
    target cells
79
Q

Describe MHC class II molecules?

A

MHC class II molecules are normally expressed only on cells of the
immune system, and in particular on professional APCs (B cells,
macrophages and dendritic cells)

They bind to peptides generated from internalised antigen in the
endosomal compartments of cells

Antigen derived from internalised micro-organisms by lysosomal
proteases and displayed by MHC class II molecules on dendritic
cells is recognised by naïve T helper cells at the initiation of immune
responses

80
Q

MHC class II processing?

A

get from main deck

The 2 chains of it form in the endoplasmic reticulum

An invariant chains binds to the peptide grove formed by the 2 chains

Preventing unwanted peptides in the ER from binding

The invariant chains takes it through the ER and Golgi apparatus via a vesicle

Proteases are released inside the vesicle cleaving the invariant chain in 2 places leaving the CLIP peptide bound to the MHC class II molecule

Engulfed proteins or pathogens that are degaded in the vesicle can’t mind on to MHC class II as it’s blocked by CLIP

HLADM allows the CLIP to be removed, its present in the vesicle and acts as a catalyst

The pathogen peptides can now bind and the vesicle is taken to the cell surface to present as as an antigen

81
Q

Naive helper T cells are first activated when?

A

They recognise antigen bound by MHC class II molecules on the surface of dendritic cells

82
Q

Recognition of antigen and MHC class II molecules on macrophages by helper T cells?

A 
Helper T cells recognise fragments
of a pathogen that has been internalised 
by macrophages and have undergone 
proteolytic digestion to generate 
fragments that are carried to the 
cell surface by MHC class II molecules.

The helper cell is then stimulated to
activate the macrophage to destroy
the internalised pathogen.

This is particularly important for defense
against bacteria that are able to grow
in the internal vesicles of macrophages

Helper T cell tells the macrophage via cytokines that what its doing is correct

83
Q

Recognition of antigen and MHC class II molecules on B cells by helper T cells?

A 
B cells internalise antigens bound
to their surface immunoglobulin 
and deliver them to the endosomal 
compartments of the cell where 
they are digested into fragments. 
The antigen fragments then bind 
to MHC class II molecules which 
carry them to the cell surface 
where they are recognised by 
helper T cells, which then activate 
the B cell to proliferate and 
differentiate into an antibody- 
secreting plasma cell
84
Q

What is CD4 or CD8?

A

Coreceptor from Tcell receptor binding to MHC

85
Q

CD4+ T cell subsets?

A

CD4+ T cell subsets?

There is TH1 and TH2 which release different cytokines which have different effects (picture in folder)

86
Q

What do co-stimulator pairs do?

A

Enhance and sustain signal delivered by the MHC-antigen T cell receptor interaction (photo in folder)

87
Q

Co-stimulator pair activation?

A

Co-stimulator pair activation?
Professional antigen presenting cells present either MHC moelcules and co stimulator molecules such as CD80(B7.1)

When a complex is formed with the T cell signals are sent both ways, it tells the antigen presenting cell to produce more co stimulator pairs, and the T cell is induced to form pairs for the new co-stimulator pairs which can then form ligand making the connection stronger with the T cell

This then stimulates another co stimulator that is required when bound for full activation of the T cell

88
Q

Summary of the immune response?

A

Might be more important to learn this rather than all the subsets

Pathogens manages to get through first layer of skin (through epidermis into dermis)

The bacteria establish an infection here

Phagocytic cells such as neutrophils and macrophages engulf the pathogen

Dendritic cells engulf as well and are stimulated by binding pathogens to leave the site of infection and migrate to a lmpyh vessel where the are drained into a lymph node

In the lymph node T cells are activated by the antigen presented on the dendritic cells and in turn activate B cells to release antibody

Effector T cells and antibody return to circulation

They return to the site of infection as inflammatory mediators have caused changes in the blood vessel endothelium

CD4 T cells activate macrophages to become more cytotoxic

antibody recruits complements of lysed bacteria directly and to opsonise them by inducing there uptake by phagocytes

In the case of a virus activated CD8 cells would kill any infected cells present

89
Q

What does opsonise mean?

A

More susceptible to uptake by phagocytosis

90
Q

What are antibody molecules?

A

Host proteins produced in response to the presence
of foreign molecules in the body

Synthesised primarily by plasma cells (lymphoid lineage)
and are components of the adaptive immune system

Circulate throughout the blood and lymph where
they bind to foreign antigens

Antibody-antigen complexes are removed from
circulation primarily through phagocytosis by
macrophages

91
Q

Describe clonal selection of antigen specific lymphocytes?

A

The lymphocytes of any individual collectively express a large number of different receptors

Some cells bear receptors that recognise self-antigens. While still immature, they are eliminated

This process of clonal deletion is a critical mechanism for ensuring self-tolerance

Once mature, lymphocytes activated by recognition of foreign antigen differentiate into effector or memory cells through a process of clonal expansion

This is the mechanism for antigen-specific immune responses and immune memory

92
Q

Receptor editing and clonal deletion of developing B cells?

A

Receptor editing and clonal deletion of developing B cells?
The mechanism through which
self-tolerance is established differs between T cells and B cells

An immature B cell in the bone
marrow expresses membrane Ig antibody
together with Iga and Igb chains as the B cell receptor

If the BCR in is engaged by self antigens present in its local environment, maturation of the B cell is arrested and it stays in the bone marrow

Re-arrangement and recombination of genes encoding the BCR results in a new BCR possessing the original heavy chain but new light chain

This process is known as receptor editing

If the B cell is no longer auto-reactive, then it is exported to the periphery

If this BCR is still auto-reactive, then it can try again for a limited time before dying (clonal deletion)

93
Q

Induction of B cell antibody response by T cells?

A

Get from main deck

Germinal centres where B cells proliferate and undergo isotope switching hyper mutation

Germinal centres form from dendritic cells having antibody on their surface activating antigen specific CD4 T cells which proliferate into effector cells capable of activating antigen specific B cells

Once activated it proliferates to form a primary focus for antigen specific B cells

B cells from the primary focus migrate to nearby follicles whilst other B cells stay in the local area secreting antibody

B cells that enter to follicle proceed to proliferate rapidly under this time they also undergo somatic mutation to introduce new variation into the B cell receptor

The receptors are tested with their ability to bind to antigen those that fail to compete die

94
Q

Antibody structure

A

Large family of glycoproteins

Share key structural and functional features

Functional - able to bind both to antigens and to
specialised cells or proteins of the immune system

Structural - composed of one or more copies of a
characteristic unit that form a Y shape

So any molecules or parts of molecules recognised by the variable antigen receptors of lymphocytes are known as antigens

95
Q

Whats the epitope (antigenic determinant)?

A

The specific region of the antigen bound by the variable region of an immunoglobulin

96
Q

What’s the paratope?

A

The antigen binding region of an antibody

97
Q

What’s affinity?

A

Affinity is the measure of the strength of the binding of an
antigen by an antibody

Antibody binding to antigen is non-covalent and reversible

The affinity of an antibody (Ab) for an antigen (Ag) is related
to the ratio of the rates of the forward reaction for formation
of the complex to back reaction for decay of the complex

Like a reversible reaction in chemistry A level

98
Q

Papain cleavage on antibody?

A

Papain cleavage on antibody?
Fab 1
Fab 11
Intact Fc 111

99
Q

pepsin cleavage on antibody?

A

pepsin cleavage on antibody?
F(ab)2

Fc fragments

100
Q

Antibody structure - the Y shape?

A

Antibody structure - the Y shape?
Heavy chain is top part of arm of Y
Light chain is lower part of arm of Y

Each Y contains four polypeptides

Two identical heavy chains
(55kDa each)

Two identical light chains
(22kDa each)

The four polypeptide
chains are held together
by disulphide bridges
and non-covalent bonds

The two domains that carry the antigen binding sites are known as Fab fragments (fragment having the antigen binding site) (the 2 arms) (antigen binds at the end of the arm)

The third domain is known as the Fc fragment (the fragment that crystallizes) (the base)

Hinge region in the middle of the arms aids movement

The ability to bind antigen 
is determined by the N-terminal 
domains. These differ considerably 
between antibodies of differing 
specificities and are therefore 
termed ‘variable’ or ‘V’ domains - the end bits of each of the arms

Top part of the base of the Y is where complement binding happens

Bottom bit of the base of the Y is where binding to Fc receptors happens

101
Q

What is hyper variability?

A 
VH is top bit of the top arm of the Y, VL is the bottom bit of the top of the Y arm Sequence analysis of amino acids of
VH and VL regions reveals small 
regions of hyper-variability within 
four conserved framework regions 
(FR1, FR2, FR3 and FR4)

In the 3-dimensional structure, the
hyper-variable regions form loops
that combine together to form the
principal antigen-binding surfaces

These surfaces are called the
complementarity determining regions
or CDRs (CDR1, CDR2 and CDR3)

102
Q

Classes of immunoglobulin (different name for an antibody) Get Me An Edo Dad

A

There are five main classes of antibody in serum

IgG, IgM, IgA, IgE and IgD

The five classes are divided on the basis of the
number of Y-like units and the type of heavy chain
polypeptide they contain (y, u, a, e and delta ) Greek symbols and associate same order as ones above

While there are five different types of heavy chains,
there are only two light chains (k or L) Greek again

One light chain always associates with one heavy
chain, so the number of light chains always equals
the number of heavy chains

There’s 2 heavy chains and 2 light chains per antibody

103
Q

antibody in humans?

A

In humans, the IgG class has four sub-classes (G = gamma)

IgG1, IgG2, IgG3 and IgG4

These have y1, y2, y3 and y4 heavy chains

The IgA class has two sub-classes

IgA1 and IgA2

These have a1 and a2 chains respectively

104
Q

What’s a J chain?

A

Holds more than 1 antibody together

105
Q

What’s a secretory component?

A

In double antibodys

106
Q

Movement of antibodies across mucosal tissues with secretory IgA? And what are ITAMs

A

is flashcard 126 complex probably don’t need to know

and 127 and 128

107
Q

Antibody-mediated cytotoxicity?

A

The two most widely recognised mechanisms of antibody-
mediated toxicity are:

  1. Antibody-dependent cell-mediated cytotoxicity (ADCC)

Antibody attracts cytotoxic cells by means of their Fc receptors

  1. Complement-mediated cytotoxicity (CMC)

Antibody binding results in the fixation of complement onto the target cell

108
Q

Opsonisation and phagocytosis process?

A

It requires triggering of specific receptors on the phagocyte

Fc receptors that bind antibody coated bacteria are one of the receptors capable of triggering phagocytosis engulfing it and forming a phagosome

Lysosomes move in to degrade the content in the phagosome

109
Q

What is complement?

A

What is complement?
The complement system, also known as complement, consists
of about 30 serum and membrane proteins that can mediate a
variety of immune reactions including:

Triggering inflammatory responses

Attraction of phagocytes to sites of inflammation

Degradation of membranes or virus envelopes

Stimulation of antibody production

110
Q

Activation of complement?

A

Activation of complement?
The active components of complement are generated from
inactive precursors by a cascade of proteolytic reactions

These are triggered through 3 different pathways:

The LECTIN pathway (recognition of carbohydrate
moieties e.g. by collectins such as mannose-binding
lectin)

  1. The CLASSICAL pathway (antibody binding to antigen in
    immune complexes)

The ALTERNATIVE pathway (directly at microbial cell
surfaces)

Activation of complement by any one of the pathways
initiates a cascade of cleavages in which each component
in the pathway is cleaved into two fragments:

The small fragment (a fragment)

The big fragment (b fragment)

The b fragment forms a subunit of the protease complex
mediating the next cleavage in the pathway

The reactions can be divided into early events, in which the
components are not the same for the same three pathways
and late events, in which they are identical

111
Q

Early and late events of complement formation?

A

In main deck

The function of the early events is to generate two functionally
equivalent forms of a protease, known as C3 convertase

C3 convertase then initiates the late events to produce the
effector components of complement

C3 convertase covalently attaches to the cell surface at
which the complement activation was initiated

Cleavage of complement component C3 leads to effector
activation

In this way, the effects of complement activation are confined
to the infectious organism that triggered

112
Q

Pentraxins =?

A

Pentraxins = Pentameric serum
proteins that participate in innate
immunity and can also activate the
Classical pathway of complement

Steps of this on flashcard 134

113
Q

What are collections and ficolins?

A

In Main deck

The epithelium of the respiratory tract is lubricated by a
layer of phospholipids and proteins known as surfactants

Two of these, Surfactant Protein-A (SP-A) and Surfactant Protein-D (SP-D) are Collectins and function as opsonins, 
coating microorganisms (e.g. Pneumocystis in AIDs patients - Lecture 8) and stimulating uptake by phagocytes

The Collectin family also includes Mannose-Binding Lectin (MBL) - binds to mannose-containing carbohydrates on
surface of viruses, bacteria and fungi

More details of their mechanism on 135

114
Q

Lectin pathway details?

A

On card 136

115
Q

Alternative pathway?

A

on card 137

116
Q

C3a, C5a functions?

A

C3a, C5a functions?

peptide mediators of inflammation, phagocyte recruitment

117
Q

C3b function?

A

Binds to complement receptors on phagocytes

Opsonization of pathogens

Removal of immune complexes

Equation on card 139

118
Q

What is hypersensitivity?

A

Undesirable reactions produced by the ‘normal’ immune response

Can be an allergy or auto-immunity

allergy = reacting to something not normally in the body

Auto-immunity - reacting to stuff in our body

119
Q

Different types of hypersensitivity reactions?

A

On 141

120
Q

Allergy =?

A

Excessive immune responses to harmless antigens (allergens)

  • Most allergic reactions are due to IgE-mediated responses
121
Q

Why can dendritic cells sample luminal antigens through the epithelial cells?

A

Can express tight junction proteins allowing interaction with epithelium

Epithelial cells can secrete factors that trigger DC activation:

Instructive cytokines

DAMPS - damage associated molecular pattern

122
Q

Effector mechanisms in IgE mediated allergy?

A

Get from main deck

Mast cells: abundant in mucosal tissues (lung, gut)
and connective tissues (e.g. surrounding blood vessels)

Th2 tells B cell via Type 2 cytokines (IL - 4, IL - 5, IL - 13)to class switch IgE antibody, which forms plasma cells which take the antibody to the Fc receptors on mast cells that causes degranulation when stimulated by the allergen

Most IgE is cell bound (on FcεR) not in body fluids (unlike other antibodies)

123
Q

If a question on allergy mechanisms comes up =

A

149 to 155

124
Q

Indirect recognition of bacteria by phagocytes?

A

bacteria coated with antibodies are recognised by antibody receptors (Fc receptors)

Bactiera coated with C3b are recognised by C3b receptors

125
Q

Direct recognition of pathogen associated molecular patterns?

A

PAMPS are recognised Pattern recognition receptors such as Toll-like receptor

126
Q

Structure of a toll like receptor?

A

Extracellular domain - ligand recognition

Intracellular domain - signalling

(dimerisation is essential for signalling) so TL1/2 would be a heterodimer and TL5/5 would be homodimer

127
Q

Consequences of TLR recognition by phagocytes?

A

Activation of phagocytes which leads to:
Cytokine and chemokine production
Ingestion and killing

128
Q

MHC presentational pathways?

A

Protein within the cytosol:
Processed by the proteasome generates peptides
Go to endoplasmic reticulum where become processed with MHC class 1 to form a complex which is recognises by CD8+ T cells

Activated CD8 T cels kill host cells infected with bacteria by releasing cytotoxins such as perforin, granzymes and granulysin

Protein taken up into the phagosome: 
Endocytosis of extracellular protein in it's vesicle it forms a complex with with MHC class 11 from the ER, this complex is presented on the cell surface and recognised by CD4+ T cells

CD4+ T cells releases different cytokines that result in inflammation, macrophage activation, antibody response

129
Q

What’s agglutination?

A

Clumps the bacteria so cleared better by phagocytes

Its triggered by antibodies

130
Q

What’s complement binding?

A

Antibodies bound to bacteria promote complement binding and complement activation by the classical pathway

Complement can now effect them

131
Q

GP encodes?

A

In main deck

GP encodes Ebola virus glycoprotein (GP). Two forms:

  1. Trimeric trans-membrane complex targets virus to
    cells via receptor binding - allows virus to introduce
    its contents into monocytes/macrophages leading to
    inflammatory cytokine dysregulation
  2. Soluble dimeric form (sGP) secreted after infection –
    prevents neutrophil activation
132
Q

Virus breaking and entering?

A

Like bacteria, viruses must overcome epithelial barriers
of skin and mucosa to establish infection

Intestinal viruses e.g. poliovirus enter via antigen-sampling
M cells

Respiratory viruses e.g. influenza virus and rhinoviruses
establish infection in the epithelial cells of the airways

Some viruses e.g. Zika, Dengue and West Nile viruses require
insect vectors for transmission

Bloodborne viruses e.g. HIV and hepatitis B can invade
through mucosa or epithelia following physical trauma

133
Q

Virus immunity?

A

Major innate immunity is mediated via type 1 interferons*, complement and natural killer (NK)
cells

Major adaptive immunity is mediated via antibody
and cytotoxic T lymphocytes (CTLs)

Interferons are Group of proteins that induce host cell enzymes that affect transcription and translation of viral genes

134
Q

Adaptive immune response to acute virus infection?

A

Adaptive immune response to acute virus infection?
Appearance of virus is followed
rapidly by a massive expansion of
virus-specific CD8 T cells

CD4 T cell expansion and contraction
also occurs but at a lower magnitude

Neutralising antibodies are produced
relatively early after acute infection
with cytolytic viruses

135
Q

What do neutralising antibodies do?

A

Prevent viruses leaving and entering cells

136
Q

Features of aids?

A

Acquired Immune Deficiency Syndrome (AIDS) is caused by
the Human Immunodeficiency Virus (HIV)

HIV infects and destroys CD4+ T cells

137
Q

HIV epithelial entry?

A

HIV-1 can cross mucosal surfaces through M cells - prevalent in tonsils and rectal epithelia

It can also gain access via epithelia damaged by ulcerative infections, or by trauma or injection (i.v. drug use or blood transfusion)

Vaginal epithelia lack M cells - HIV gains access via interdigitating processes on
Langerhans cells

Epithelial cells in the small intestine express
CCR5, a chemokine receptor

HIV-1 binds to CCR5 (once tethered by
galactosylceramide) via the viral envelope
glycoprotein gp120 and the virus is transcytosed

138
Q

HIV getting into lymph nodes and CD4 T cell and infection cycle and infection cycle and immunological consequences

A

191, 192, 192, 193, 194

139
Q

Features of influenza A?

A

Influenza A is a spherical or rod-
shaped enveloped virus covered
with 2 spike-like glycoproteins:

Trimeric hemagglutinin (HA)

Tetrameric neuraminidase (NA)

HA mediates binding to cell
surfaces and internalisation

NA cleaves sialic acid and
promotes viral release from
cells

140
Q

Immune response to infleunza virus infection?

A

Antibody mediated immunity:
Can bind to HA and block viral attachment
Can also bind to NA protein and prevent release of new virions

Cell mediated immunity: 
CD8 T cells recognise the infected cell due to its MHC class 1 the T cell then causes cell lysis
141
Q

What’s antigenic shift and antigenic drift?

A

What’s antigenic shift and antigenic drift?
Epidemics occur when point mutations (red dots) accumulate in surface HA (ovals) or NA (diamonds)

This leads to ANTIGENIC DRIFT so
that, in many previously immune individuals, HA and NA are no longer recognised by neutralizing antibodies produced in response to earlier infections

Pandemics occur when avian influenza viruses and human influenza viruses infect pigs and re-assortment of the two genomes leads to the expression of avian HA or NA in a virus otherwise adapted to infect humans (ANTIGENIC
SHIFT)

142
Q

mycosis = ?

A

Fungal infection of humans

143
Q

Host recognition of fungal infection?

A

in the main deck:

Innate recognition of fungi is mediated by interactions with conserved cell wall constituents (glucans, mannans, galactans).
PRR Dectin-1 (gene is CLEC7A) is highly expressed on the surface of dendritic cells and in lesser amounts on macrophages
It has a C-type lectin carbohydrate recognition domain that mediates
the recognition of beta 1,3- and 1,6-linked glucans on the surface of intact cells and zymosan (zymosan=cell wall fragments consisting of beta-glucans, mannans, mannoproteins and chitin)

So Dectin-1 is essential for immune system

Engagement of Dectin-1 results in tyrosine phosporylation of its cytoplasmic immunoreceptor tyrosine-based activation motif (ITAM) Syk (Il-10) and others (TNFalpha is Syk-independent)
Dectin-1 acts synergistically with TLRs to induce production of inflammatory cytokines and the production of reactive oxygen species (ROS)

144
Q

What are toll like receptors?

A

Dendritic cells and other immune cells must be able to distinguish between apoptotic particles generated by normal tissue turnover and particles that are indicative of infection

The molecules mostly responsible for making this pivotal distinction are those of the family of Toll-like receptors (TLRs)

Stimulation of immune cells through their TLRs leads to synthesis and secretion of proinflammatory cytokines, thereby initiating the inflammatory response that recruits both soluble immune components and immune cells from the blood

TLR stimulation of dendritic cells also induces the initiation of an adaptive immune response

Acts synergistically with TLRs

145
Q

Features of Mannose-binding lectin (MBL) and complement?

A

In the main deck:

Candida expresses surface adhesins and mannoproteins that activate the alternative and lectin pathways of complement

MBL is a collectin, and is one of a number of serum proteins collectively known as opsonins

MASPS (Mannose-binding lectin-Associated Serine Proteases) couple collectins to the complement pathway

Before ligand binding, MASPs lack protease activity.

Binding of multiple carbohydrate recognition domains of MBL to the microbial cell surface leads to conformational changes in the molecule, which promotes proteolytic activation of the MASPs, which the initiate the complement cascade

146
Q

Defence against Candida albicans?

A

In main deck

Activation of complement + Interactions of cell wall components, such as mannoproteins and beta- glucan, with phagocyte receptors such as TLR2 and dectin-1 stimulate
release of cytokines including IL-1, IL-6 and TNF.
phagocytosis by neutrophils and macrophages.

Phagocytosis triggers the production of appropriate innate fungal killing mechanisms

Production of cytokines by activated neutrophils, together with direct interaction of neutrophils with dendritic cells* within inflammatory sites, promotes the maturation of dendritic cells, = adaptive immunity is activated.

147
Q

Innate cell killing of parasites?

A

Neutrophil mediating killing:

Neutrophil extracellular traps…
(Trojan horse)

Macrophage:

PRR activation and take up parasites (and infected neutrophils) via phagocytosis and enter phagosome

Killing:
Reactive oxygen species (ROS), triggered by phagocytosis
Production of nitric oxide…
Induced by IFNγ (Need help from Th1 CD4+ T cells!)

148
Q

Against parasites what type of T cell is better at killing them?

A

Against parasites what type of T cell is better at killing them?
Th1 cell rather than a Th2 cell

The Th1 produces IFN-y cytokines that activate M1 macrophages which produce iNOS which produces nitric oxide which kills the parasites

Regulatory T cells can also suppress immunity and macrophage function

The effector functions of the pathogen specific CD4+ T cells determines the outcome of disease

149
Q

Overall summary on parasites?

A

Overall summary on parasites?
Type 1 immunity for protoza

Type 2 immunity for Metazoan

Balanced immunity is essential to avoid host damage

150
Q

Main types of vaccine?

A

Live vaccines
Living, but cannot cause disease

Killed vaccines
Killed by heating, or exposure to chemicals

Sub-unit vaccines
Fragments of the microorganism e.g. proteins (or polysaccharides)
Almost always antibody mediated
In some cases an immune response against a single protein antigen elicits protection

Nucleic acid vaccines (DNA or mRNA)
Direct protein expression after injection

Vectored vaccines
DNA encoding the sub-unit is cloned into another “safe” microorganism

151
Q

What is formaldehyde detoxification?

A

What is formaldehyde detoxification?
Removes toxicity of a protein

The immunogenicity of the protein is preserved

Problems:
Must balance cross linking with retention of antigenic structure

Batch to batch variation

Reversion

Requires pure toxin at the starting point:
Needed to grow pathogen
Need to purify and handle the toxin

152
Q

What are genetic toxoids?

A

Modern approach to subunit vaccines against toxins

Modify the gene so that it encodes a non toxic (but immunogenic) protein

153
Q

Describe e toxin?

A

causes enterotoxaemia in livestock

Produced in intestine crosses gut wall, targets kidneys and brain causing death

Can mutate the toxin now 1000 fold less toxic

Is a vaccine

154
Q

Diphtheria toxin CRM197 genetic toxoid?

A

In main deck

Mutation in the catalytic A-subunit blocks activity

Glycine to glutamic acid substitution at residue 52

155
Q

Advantage of genetic toxoids?

A

Produce in harmless bacterium

High yields

Molecular structure more similar to active toxin

Reproducible properties

No reversion

156
Q

Sub unit vaccine against plague?

A

In main deck

F1 antigen - capsule and V-antigen part of the type 111 system are the protective components

Then produce F1 and V antigens using genetic engineering

Together produces solid protection

157
Q

What’s reverse vaccinology?

A

Predict vaccines from the genome sequence

pSORT predicts cellular location so can help us find proteins that will be on the surface will give lots of proteins then you have to test them

158
Q

Sub unit vaccines are effective at stimulating protective antibodies which will?

A

Agglutination

Opsonization

Neutralization

Activation of complement

Inflammation

Antibody - dependent cell mediated cytotoxicity

159
Q

s there immunological cross reactivity between the different polysaccharides on bacteria?

A

No they are unique

160
Q

Diseases where CD+ T cells play a role in protection?

A

Diseases where the microbe grows within host cells

tuberculosis
• salmonellosis • melioidosis
• viral infections yellow fever
influenza Measles SARS CoV2

161
Q

How are CD8 + responses induced?

A

induced by live attenuated microbes that can invade host cells

Usually very effective – excellent mimetics of the natural microbe

Risk is that they will still cause disease in some individuals e.g. immunocompromised
Activates

Another approach:
Injected DNA or mRNA is taken up by host cells
The protective sub-unit is produced by host cells and seen as foreign by the immune system
Protein antigen is processed via the MHC I (and MHC II) pathways.
Combine the advantages of live and sub-unit vaccines

Work well in animals not really humans

162
Q

Vector vaccine?

A

nset gene encoding the protective subunit into a “harmless” microbe
• A wide range of carrier microbes have been suggested e.g.
– Disabled Salmonella – Lactococcus
– Vaccinia virus

163
Q

Polyclonal vs monoclonal antibodies?

A

Because most antigens carry many different epitopes,
animals injected with a single antigen will produce a
complex mixture of antibodies, each made by a
different clone of B cells

This antibody response is said to be polyclonal and
will not discriminate between different antigens

To discriminate between different antigens,
antibodies need to be identified that bind to epitopes
specific to individual antigens

These are known as monoclonal antibodies

164
Q

Do cancer cells or malignant cells have unique epitopes?

A

yes

165
Q

What is hybridoma technology?

A

Allows the identification and culture of cells
secreting identical antibodies with pre-defined
specificity

A single clone of cells secreting a single
antibody is made by fusing a B cell (Ig+ splenocyte
with finite lifespan) with a myeloma cell (cancerous
Ig- B cell with infinite lifespan)

The resulting hydrid cells (HYBRIDOMAS) each
make a specific monoclonal antibody

166
Q

Time course of a typical immune response when injected with antigen?

A

In powerpoint

Primary injection:
Production of IgM
Multivalent
Low affinity

Secondary injection:
Production of IgG
Bivalent
Low to medium affinity

Tertiary injection:
Production of IgG
Bivalent
Medium to high affinity

Multiple boosts:
IgG
Bivalent
High affinity

167
Q

Mechanism of hybrid cell selection in HAT medium?

A

HGPRT = Hypoxanthine:guanine phosphoribosyl transferase = blocks RNA and DNA transcription only can go through salvage pathway

Spleen cell = HGPRT+ but is not able to grow in long-term

Myeloma cell =HGPRT-, therefore not able to use the salvage pathway for RNA synthesis because the normal pathways are blocked

Hybridoma cell = has HGPRT from a spleen cell and immortality from a myeloma cell, therefore is able to grow in the HAT medium (providing there is an exogenous supply of Hypoxanthine and Thymidine)

168
Q

What is the PTA-ELISA?

A

Plate-Trapped-Antigen-Enzyme-Linked

Immunosorbent Assay

169
Q

What is phage display?

A

What is phage display?
An issue with hybridoma technology is immuno-
dominance

Alternative technologies to generate mAbs include
phage display

A technique in which antibody fragments
are expressed as a fusion with a coat protein of a
bacteriophage

Fused proteins are displayed on the surface of the
virion, while the DNA encoding the fusion resides
within the virion

170
Q

Making antibody combinatorial libraries?

A

259

171
Q

Describe the expression of scFv on the surface of phage?

A

260

172
Q

Describe the expression of F(ab) fragments on filamentous phage?

A

Describe the expression of F(ab) fragments on filamentous phage?
F(ab) fragments of antibodies can
be expressed on the surface of
phage as fusion proteins with pIII

Multiple copies expressed along the
length of the phage particle

173
Q

Uses of monoclonal antibodies?

A

In main deck

Diagnostic pathology (cytology and histology)

In vitro diagnostic assays based on e.g. Enzyme-Linked Immunosorbent Assay (ELISA), Lateral-Flow Assay
(LFA) for pathogens and biomarkers of disease
(Lectures 15 & 16)

Affinity purification and characterisation of antigens

Limited use of mouse mAbs in vivo until relatively recently

174
Q

The need to humanise monoclonal antibodies?

A

Immunogenicity - most mAbs used in vivo are of mouse
origin and are therefore XENOGENEIC resulting in
Human Anti-Mouse Antibody (HAMA) reactions

  1. Origin - Mouse origin diminishes their ability to elicit effector mechanisms such as COMPLEMENT-MEDIATED LYSIS or ANTIBODY-DEPENDENT CELL-MEDIATED CYTOTOXICITY (ADCC)
175
Q

How does humanisation occur?

A

Use of xenoantibodies in human patients had
proved to be severely limiting owing to their
being seen as foreign proteins by the patient’s immune system

Strategies adopted to increase the human content of
antibodies which have proven clinical applications include:

Production of human hybridomas from human B lymphocytes

Replacement of the constant regions of mouse mAbs with those of human antibodies yielding CHIMERIC antibodies

Replacement of complementarity-determining regions (CDRs) of a human antibody with those of a mouse antibody via CDR GRAFTING to make a HUMANISED antibody

Production of FULLY HUMAN mAbs in transgenic mice

176
Q

Human immune system mice?

A

265

177
Q

The 3 phases of cancer immune surveillance?

A

Elimination:
By B cells, antibody, T cells, Treg cells, NK caells
This is the innate and adaptive immune response active against tumour
Can result in tumour cells death

Equilibrium:
Tumour is contained by the immune system but not completely destroyed

Escape:
Tumour antigen editing via genomic instability causes immune evasion
Tumour microenvironment becomes immunosuppressive

178
Q

What does immunotherapy do?

A

What does immunotherapy do?
Specific:
Trains the immune system to recognise and target only cancer cells

Powerful:
Attacks the cancer systemically through out the body

Universal:
A treatment approach that can be applied to nearly all cancers

Memory:
Capacity for memory means durability of protection

179
Q

Types of immunotherapy?

A

Passive vaccination (Therapeutic Monoclonal Antibodies)

Active vaccination e.g. HPV vaccine (Gardasil, Cervarix) and cervical cancer

Immune system modulators e.g. IL-2 (activates CD8 T cells)

Immune Checkpoint Modulation

Immune Cell Therapy

180
Q

How do therapeutic monoclonal antibodies target cancer?

A

Carry cytotoxic agents to tumour

Induce Complement-Mediated Lysis or ADCC of tumour cells e.g. Rituximab

Block activity of tumour-specific proteins e.g. Herceptin

Steps:
Naked MAb
Immunoconjugates
Multistep targeting

181
Q

New monoclonal antibodies for cancer

A

272-281

182
Q

What is adoptive immune cell therapy: Normal TILs?

A

Idea behind this approach is that the TILs have already shown the ability to target tumor cells, but there may not be enough of them within the tumour to eradicate it or overcome the immune suppressive signals that are being released there

Introducing massive amounts of activated TILs can help to overcome these barriers and shrink or destroy tumors

In some experimental cases these treatment responses
have lasted for years

TILs are collected from samples of the tumor

TILs that show the greatest recognition of the patient’s tumor in lab are selected

Cells are then activated with cytokines and infused into the patient’s bloodstream

183
Q

What is antibody guided molecular imaging?

A 
Radio-labeled antibodies used in nuclear medicine to locate
cancer cells (or infections) by molecular imaging using:

Computed Tomography (CT)
Magnetic Resonance Imaging (MRI)
Positron Emission Tomography (PET) - PET/CT or PET/MRI

More details on 287

184
Q

What is Ouchterlony immunodiffusion?

A

OID is a qualitative technique for detecting antibody-antigen
interactions in which antigens and antibodies are placed in a
gel of agar and allowed to diffuse towards one another

A positive reaction is indicated by the presence of PRECIPITIN lines due to a Antibody-antigen equivalence = immune complex formation

Antigen excess or antibody results in no precipitin

185
Q

Precipitin that forms when both antigen sources react with the antibody as they both have shared properties?

A

An arc

186
Q

Precipitin Line that forms when each antigen doesn’t share a common determinant of the antibody but both have a determinant of it?

A

A cross sword

187
Q

Precipitin line that forms when antigens share one common determinants but one of them has both required for the antibody

A

Arc on the side which doesn’t have an extra shared one

Spur forms on side that does, so cross bridge shape there

188
Q

What is Western blotting?

A

A technique in which specific antibodies are used to identify
particular antigens in mixtures of proteins that have been
resolved and transferred to a membrane

293

189
Q

Features of an SDS page?

A

The speed of migration in an electrical field depends on the dimension form and charge of molecules

For deaggregation and denaturation of the proteins SDS, B-mercaptoephanol or DTT (reducing agents) and heat is used

SDS provides negative charge to the proteins

Right to left = separated by charge by isoelectric focusing (IEF)

Up to down = separated by size by SDS electrophoresis

190
Q

What is direct immunofluorescence?

A

What is direct immunofluorescence?
Treatment on cell with labelled antibody

Unbound antibody washed away and UV light applied

Fluorescence observed where antigen is located

191
Q

What’s indirect immunofluorescence?

A

What’s indirect immunofluorescence?
Treatment with unlabelled primary antibody

Unbound antibody washed away

Treatment with labelled secondary conjugate

Unbound conjugate antibody washed away UV light applied

Fluourescnce observed where antigen is located

192
Q

What’s immune-electron gold microscopy?

A

A qualitative technique in which antibodies tagged
with gold particles are used to detect molecules of
interest

EM-gold allows localisation of antigen-antibody
interactions at the nm scale (cf. IF at the m)

A powerful method of visualising intracellular antigens
and organelles

193
Q

Rhizoctonia solania case study?

A

301 and 302

194
Q

Aspergillus case study

A

304 to the end

Human Biosciences (69 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions