Type IV Hypersensitivity |T- Cell mediated Hypersensitivity |Mechanism | Examples

Summary

This tutorial delves into type four hypersensitivity reactions, focusing on cell-mediated immunity. It explains how CD4+ T cells produce cytokines leading to chronic inflammation. The video outlines the pathogenesis of delayed-type hypersensitivity, highlighting T helper 1 and T helper 17 responses. It also covers clinical examples like tuberculin reactions and contact dermatitis, and discusses T cell-mediated cytotoxicity in diseases like type 1 diabetes and rheumatoid arthritis. The tutorial encourages active learning through practice tests on Visia, an engaging platform for medical knowledge.

Takeaways

• 🧬 Type Four Hypersensitivity, also known as cell-mediated hypersensitivity, is primarily caused by inflammation resulting from cytotoxic T cells.
• 🔬 CD4 positive T cells produce cytokines that lead to chronic inflammation, often in response to environmental or self-antigens.
• 🌟 Delayed Type Hypersensitivity (DTH) is a prototype of T-cell mediated inflammation, detectable within 24 to 48 hours post-antigen exposure.
• 🔍 T helper 1 (Th1) and T helper 17 (Th17) cells are key contributors to DTH, with Th1 promoting macrophage activation and Th17 recruiting neutrophils.
• 🛡 The pathogenesis of DTH involves the activation of CD4 positive T cells, differentiation into effector T cells, and resulting inflammation and tissue injury.
• 🔄 Upon re-exposure to an antigen, memory T cells, which are long-lived, respond quickly to prevent further inflammation.
• 💉 Clinical examples of CD4 positive T cell-mediated inflammation include tuberculin reactions and contact dermatitis.
• 🛑 In persistent antigen scenarios, such as with Mycobacterium tuberculosis, T helper one cells can lead to granuloma formation, a hallmark of granulomatous inflammation.
• 🚨 CD8 positive cytotoxic T lymphocytes kill antigen-expressing target cells through apoptosis, a key mechanism in cell-mediated immunity.
• 🏥 Diseases mediated by T cell cytotoxicity include type 1 diabetes, graft rejection, and responses against viruses and tumor cells.
• 📚 The script concludes with a summary of type four hypersensitivity, its mechanisms, and examples, encouraging active learning through practice tests and feedback on the Visia platform.

Q & A

What is type four hypersensitivity?

Type four hypersensitivity, also known as cell-mediated hypersensitivity, is primarily caused by inflammation resulting from cytotoxic T cells, which are produced by CD4 positive T cells.

What are the main cells involved in type four hypersensitivity reactions?

The main cells involved in type four hypersensitivity reactions are CD4 positive T cells, which produce cytokines leading to inflammation.

What type of inflammation is typically associated with type four hypersensitivity?

Type four hypersensitivity is most often associated with chronic inflammation.

Which T helper cells contribute to delayed type hypersensitivity?

T helper 1 (Th1) and T helper 17 (Th17) cells contribute to delayed type hypersensitivity.

What is the role of interferon gamma in T helper 1 cells?

Interferon gamma, produced by T helper 1 cells, promotes further helper cell development and activates other immune cells, such as macrophages.

How do T helper 17 cells respond to extracellular pathogens?

T helper 17 cells produce interleukin-17 and other cytokines and chemokines, which recruit more neutrophils and monocytes to promote inflammation against extracellular pathogens.

What happens to effector T cells after the inflammation is cleared?

After the inflammation is cleared, effector T cells transform into memory T cells, which are long-lived and respond quickly to the same antigen if encountered again.

What are the clinical examples of CD4 positive T cell-mediated inflammatory reactions?

Clinical examples of CD4 positive T cell-mediated inflammatory reactions include tuberculin reaction and contact dermatitis.

What is the difference between T helper 1 and T helper 17 in terms of the pathogens they target?

T helper 1 cells target intracellular pathogens, such as some bacteria and viruses, while T helper 17 cells handle extracellular bacteria and fungi.

How do activated CD8 positive cytotoxic T lymphocytes kill target cells?

Activated CD8 positive cytotoxic T lymphocytes kill target cells by inducing apoptosis, either through the Fas ligand and Fas receptor interaction or by forming a perforin and granzyme complex.

What are some diseases associated with T cell-mediated cytotoxicity?

Diseases associated with T cell-mediated cytotoxicity include type 1 diabetes, graft rejection, reactions against various viruses, and destruction of some tumor cells.

Outlines

00:00

🧬 Immune System Diseases: Type Four Hypersensitivity

This paragraph introduces the seventh part of a pathology tutorial series focusing on the immune system, specifically type four hypersensitivity reactions. It explains that type four hypersensitivity, also known as cell-mediated hypersensitivity, is primarily caused by inflammation due to cytotoxic T cells, which are produced by CD4 positive T cells. The paragraph outlines the process of T cell activation, differentiation into T helper 1 and T helper 17 cells, and their roles in combating intracellular and extracellular pathogens, respectively. It also describes the pathogenesis of delayed type hypersensitivity, the transformation of effector T cells into memory T cells, and the quick response upon re-exposure to the same antigen.

05:01

🛡️ Clinical Manifestations of Type Four Hypersensitivity

The second paragraph delves into the clinical examples of CD4 positive T cell-mediated inflammatory reactions, such as tuberculin reaction and contact dermatitis. It describes the process of a tuberculin reaction, including the time frame of the reaction and the histopathological features observed. The paragraph also explains granuloma formation in response to persistent or non-degradable antigens, such as Mycobacterium tuberculosis. Contact dermatitis is highlighted as a tissue injury resulting from delayed hypersensitivity, with examples like poison ivy exposure leading to rash and blister formation. Other conditions related to CD4 positive T cell-mediated inflammation, such as rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis, are briefly mentioned.

10:01

🗡️ CD8 Positive T Cell-Mediated Cytotoxicity

The final paragraph discusses CD8 positive cytotoxic T lymphocytes and their role in killing antigen-expressing target cells through apoptosis. It outlines the mechanisms of cell death, including Fas ligand and Fas receptor interaction, as well as the perforin and granzyme complex. The paragraph provides examples of diseases where CD8 positive T cell-mediated cytotoxicity is observed, such as type 1 diabetes, graft rejection, reactions against various viruses, and destruction of tumor cells. It also revisits rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis, but from the perspective of cytotoxic T cell activity. The paragraph concludes with a call to action for viewers to engage with the content through multiple choice questions on the Visia platform and encourages feedback and subscription for further educational content.

Keywords

💡Hypersensitivity Reactions

Hypersensitivity reactions refer to the immune system's exaggerated response to a substance that is typically harmless to others. In the video, the focus is on type four hypersensitivity, which is a cell-mediated response involving T-cells and is characterized by inflammation. This concept is central to understanding the video's theme of immune system responses to antigens.

💡Type Four Hypersensitivity

Type Four Hypersensitivity, also known as cell-mediated hypersensitivity, is the main subject of the video. It is caused by T-cells and results in chronic inflammation due to the release of cytokines. The script discusses how this type of hypersensitivity is distinct from the other types and is associated with conditions like contact dermatitis and tuberculin reactions.

💡Cytokines

Cytokines are proteins that regulate the immune response and are crucial in the context of type four hypersensitivity. The script mentions that CD4 positive T-cells produce cytokines, which lead to inflammation. Examples from the script include interferon-gamma, which is produced by T helper 1 cells and contributes to the pathogenesis of delayed type hypersensitivity.

💡CD4 Positive T Cells

CD4 positive T cells, also known as T helper cells, are a type of lymphocyte that plays a central role in the immune response. The video script explains that these cells produce cytokines that lead to inflammation, a key aspect of type four hypersensitivity. They differentiate into various subsets, such as T helper 1 and T helper 17, which have specific roles in the immune response.

💡Delayed Type Hypersensitivity

Delayed Type Hypersensitivity (DTH) is a specific type of cell-mediated immune response that occurs 24 to 48 hours after exposure to an antigen. The script describes DTH as the prototype of T-cell-mediated inflammation, with examples including the tuberculin reaction, which is characterized by the accumulation of mononuclear inflammatory cells at the site of antigen injection.

💡T Helper 1 and T Helper 17 Cells

T Helper 1 and T Helper 17 cells are subsets of CD4 positive T cells that have distinct roles in the immune response. The script explains that T helper 1 cells are involved in the response to intracellular pathogens and promote inflammation, while T helper 17 cells are involved in the response to extracellular bacteria and fungi. These cells are integral to the pathogenesis discussed in the video.

💡Inflammation

Inflammation is a protective response of the body to harmful stimuli and is a key outcome of type four hypersensitivity. The script describes how inflammation is often chronic and results from the action of cytokines produced by T cells. The video also discusses the role of inflammation in conditions like rheumatoid arthritis and multiple sclerosis.

💡Antigen Presentation

Antigen presentation is the process by which antigen-presenting cells (APCs) display antigens to T cells, initiating an immune response. The script mentions that dendritic cells present antigenic components to naive T cells, which is the first step in the activation of CD4 positive T cells and the subsequent development of type four hypersensitivity.

💡Memory T Cells

Memory T cells are a type of T cell that remains in the body long after an infection has been cleared. The script explains that effector T cells can transform into memory T cells, which respond quickly to the same antigen if encountered again. This concept is important for understanding the long-term immunity aspect of the immune response.

💡Cytotoxic T Cells

Cytotoxic T cells, particularly CD8 positive T cells, are a type of lymphocyte that can kill cells that are infected with viruses or are cancerous. The script describes how these cells can induce apoptosis in target cells, a process that is distinct from the inflammatory response seen in type four hypersensitivity but still part of the immune system's arsenal against threats.

💡Autoimmune Diseases

Autoimmune diseases are conditions where the immune system mistakenly attacks the body's own cells. The script provides examples of such diseases, including rheumatoid arthritis and multiple sclerosis, which are caused by the immune system's response to self-antigens. This concept is related to the video's discussion of T cell-mediated responses and their potential to cause harm.

Highlights

Introduction to the seventh part of the 'Diseases of the Immune System' series, focusing on type four hypersensitivity reactions.

Type four hypersensitivity, also known as cell-mediated hypersensitivity, is mainly caused by inflammation from cytotoxic T cells.

CD4 positive T cells produce cytokines leading to chronic inflammation in type four hypersensitivity.

Delayed type hypersensitivity is the prototype of T-cell mediated inflammation, detectable within 24 to 48 hours.

T helper 1 and T helper 17 cells contribute to delayed type hypersensitivity with distinct immune responses.

Pathogenesis of type four hypersensitivity involves activation of CD4 positive T cells and their differentiation into effector T cells.

Memory T cells, resulting from inflammation clearance, are long-lived and respond quickly to repeated antigen exposure.

Tuberculin reaction is a clinical example of type four hypersensitivity, characterized by induration and inflammation at the injection site.

Persistent non-degradable antigens like Mycobacterium tuberculosis can lead to granuloma formation in type four hypersensitivity.

Contact dermatitis is an example of tissue injury from delayed type hypersensitivity, often resulting in itchy rashes and blisters.

Examples of CD4 positive T cell mediated inflammation include rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease, and psoriasis.

CD8 positive cytotoxic T lymphocytes kill antigen-expressing target cells through apoptosis in type one hypersensitivity.

Type 1 diabetes, graft rejection, and reactions against viruses are examples of diseases involving CD8 positive T cell-mediated cytotoxicity.

Rheumatoid arthritis involves antigens like collagen and results in chronic inflammation and joint deformity.

Multiple sclerosis is characterized by demyelination in the CNS and inflammation, leading to paralysis and optic neuritis.

Inflammatory bowel disease is an aggressive immune response to normal gut bacteria, resulting in chronic intestinal inflammation.

Psoriasis is a skin condition with unknown antigens that manifest as raised plaques.

The video concludes with a summary of type four hypersensitivity reactions, mechanisms, and examples.

Invitation to engage with the content through liking, commenting, subscribing, and sharing the video.

Transcripts

hello everyone welcome back to this

short tutorial from pathology M simple

at IOP pathology.com and supported by

visia an active learning platform this

is the part seven of diseases of immune

system in this section we will be

completing the hyper sensitivity

Reactions where I'll be discussing type

four hyper sensitivity in the earlier

sections we have completed type one type

two and type three so let's move on to

understand type four hyper sensitivity

reactions so type four hyper sensitivity

is also referred to as Hil mediated

hypers sensitivity which is caused

mainly by inflammation resulting from

cyto mines and these cyto are produced

by CD4 positive T cells and that's why

it's referred to as C T cell mediated

hyper sensitivity okay so it is these

CD4 positive T cells which produces cyto

kindes and that results in inflammation

most often the inflammation is chronic

and dist and the antigens uh implicated

in type four hypersensitivity can be

environmental antigens as well as self

antigens to understand more about C cell

mediated hypers sensitivity let's see

this delayed type hypers sensitivity

which is the Prototype of t- cell

mediated inflammation here what happens

you know there is a tissue reaction to

antigens when it is given to an immune

individual right and this tissue

reaction is detectable within 24 to 48

hours the cells which contribute to

delayed type of hypers sensitivity are T

helper 1 and T helper 17 cells T helper

one is a one which is dominated by

activated macres whereas T helper 17

response is dominated by neutrophils

unlike macrophases from tper one cells

so what is a pathogenesis as I told the

first step is the activation of CD4

positive t- cells remember t- cells will

be in Nave State they have to be

activated so activation of CD4 positive

t- cells and then these become effect

our T cells and then the second step is

the responses of these effector

differentiated effector t- cells and

finally resulting in inflammation and

tissue injury so let's understand this

in detail let us assume that this is a

Nave t- cell and you have an antigen

which to which these Nave T cells are

exposed the antigen presenting cells

that is the dritic cells presents

antigenic component you know to the

peptide from this antigen to the Nave T

Cell which produces inin 2 which is an

autocrine growth factor resulting in

more and more of these t- cells and now

these t- cells are antigen responsive t-

cells right so these antigen responsive

t cells further differentiate upon

reexposure to antigen one and these

antigen responsive te cells as I told

you they differentiate into T helper one

cells with the help of cyto interlukin

12 and these t- helper cells as I told

you they are the ones which act against

intracellular pathogens like some

bacteria viruses promoting inflammation

and also activating other immune cells

further these antigen responsive te

cells differentiate into tper 17 cells

with the help of cyto inin 1 6 and inin

23 produced by these antigen presenting

cells and these T helper 17 produces

interin 17 inin 22 and various other

chemokines and cytokines which recruit

more and more neutrophils and monocytes

which promote inflammation and this kind

of response is important while defending

extracellular bacteria and fungi right

so the T helper one tackles the

intracellular pathogens whereas T helper

17 handles these extracellular bacteria

T helper 1 also secretes lots and lots

of interferon GMA which promotes further

the helper cell development so this is

the basic pathogenesis of delayed type

hyper sensitivity once the inflammation

is cleared what happens the effect our T

cells they get transformed into memory T

cells and these memory t- cells are long

lived and they respond very quickly if

the same antigen is encountered again

and that's the role of these memory t-

cells let's see what happens when there

is repeat exposure to antigen so then

the T one secretes lots and lots of

interferon gamma you know which further

activates macrofagos and these

macrofagos are referred to as interferon

gamma activated macrophages are so what

special characteristics these macres

have and these are the ones which have

increased ability to phagocytose and

kill various pathogens they also Express

more and more class to Hy molecules on

the surface and that results in increase

in antigen presentation they secrete

tubon necrosis Factor interlukin one and

chemokines which further promote

inflammation and lastly they also

produce more incin 12 and we know inin

12 is responsible for amplification of e

one response okay more and more tper one

cells are recruited so what are the

clinical examples of CD4 positive t-

cell mediated inflammatory reactions two

most common examples are tucine reaction

and contact dermatitis let's see what

tubine reaction is after intracutaneous

injection of purified protein derivative

within 8 to 12 hours in the injected

site there is rening and in duration

which Peaks at around 24 to 72 hours

this is what happens that's the

enduration at the injection site of

purified protein derivative which is

speaking at around 24 to 72 hours it

finally subsides so if you take a biopsy

from this site what do you see the

histopathological features include

perivascular accumulation of mononuclear

inflammatory cells these are the

intradermal blood vessels and you find

lots of these mononuclear cells

lymphocytes and macro right that's

called as perivascular cuffing of

mononuclear inflammatory cells and you

also see variable amount of dermal edema

and fibrin deposition this is what you

see in a tuberculin reaction now

consider when there is a persistent or

non-degradable antigen for example you

know hubal baselite which is a

microbacterium tuberculosis which

colonizes lungs or other tissues so this

has this basill act as an antigen which

is non-degradable and persistent so

there is a very strong T helper one Cell

Activation right so once there is a t

helper one Cell Activation we know that

it recruits lots and lots of macres in

the initial phases these macras are just

not enough to tackle these tubic

baselite what do they do they get

transformed into epithelioid cells okay

they have more cytoplasm they have

elongated pale nucleus and these are

epithelioid cells and they cluster

together to form a granuloma okay so

this granuloma is surrounded by a cuff

of lymphocytes and this kind of

inflammation is known as granulo matus

inflammation I have discussed this in

detail when I talked about me granul

matus inflammation in my earlier videoos

so you can just go back and then watch

that video as well the second example

which you need to understand is contact

dermatitis which is an example of tissue

injury resulting from delayed type of

hyper sensitivity reaction which is a

CD4 positive T C mediated inflammation

one example you need to be aware is if

an individual is exposed to this poison

IV or poison o when when I say expose it

has to be in terms of contact contact

with poison IV or poison o these leaves

contain you know rool which is an

antigenic component which binds and

modifies the self proteins self proteins

means the proteins in our body and the

peptides which are released from these

modified proteins they are recognized by

CD4 positive T cells right and they

induce inflammatory response which is

clinically manifested by rash and these

rashes are often itchy and also result

in blister formation and that's why it's

referred to as blistering dermatitis or

vesicular dermatitis other examples of

CD4 positive T cell mediated

inflammation include romatoid arthritis

multiple sclerosis inflammatory bubble

disease till now what did we see we saw

CD4 positive T cell mediated

inflammation now there is another entity

which is called a cd8 positive P cell

mediated cytotoxicity now what does that

mean which means cd8 positive cytotoxic

T lymphocytes they kill the antigen

expressing target cells in in the

earlier cases what we studied there was

inflammation whereas in these cases we

see that the antigen expressing target

cells are killed so how are they killed

see after identifying the target cells

the activated cd8 positive cytotoxic T

lymphocytes they kill the target cells

by means of epopt Tois now how does this

happen let us see this see these

activated cd8 positive cells they

express fast liand which activate fast

receptor which is expressed on the

target cells and we know fast receptor

fast legant interaction is the one which

activates the extrinsic pathway of

apoptosis the second mechanism includes

formation of perforin and granzyme

complex so once this complex is formed

this enters into the cytoplasm and

within the cytoplasm of the target cell

the perforin you know they help in

release of the granzymes from the

complex and these granzymes CLE and

activate caspases which further result

in proptosis because we know caspases

are the most important proteases which

result in apoptosis so what are the

examples of CD positive t- cell mediated

cytotoxicity I mean where the cells are

killed the examples include the most

common one being type 1 diabetes it can

be graft Rejection it could be reaction

against various viruses and even

destruction of some tumor cells let us

see more examples of T cell mediated

diseases first one is rheumatoid

arthritis where the antigen involved is

the collagen or citrated self proteins

the manifestations include ch arthritis

and inflammation multiple sclerosis is

another disease where the antigens

involved are the protein antigens in

mine example milin basic protein what

happens here is that there is

demyelination in CNS central nervous

system with inflammation resulting in

paralysis and even optic neuritis type

one diabetes as I told you earlier where

the antigen involved are the antigens of

pancreatic highet beta cells okay and

inflammation of these cells result in

insulitis or chronic inflammation of

eyelets where they result in destruction

of beta cells leading to diabetes

inflammatory disease another condition

where the antigen involved is various

entric bacteria okay you know they

respond very aggressively to normal

entric bacter resulting in chronic

intestinal inflammation and the last but

not the least is psorasis where we do

not know what antigen is implicated but

they manifest with dtive plages in the

Skin So this completes type four hypers

sensitivity if you watch this entire

video I would request you to you know

just click on the link below in the

description as well as in the pin

comment where you can solve various

multiple choice questions from bolia I

have tried visia and this is an amazing

platform where you can learn very

actively because you have various

practice tests given you can even get

feedback ultimately it's fun to learn so

in summary we did learn about typ for

hypers sensitivity reaction the

mechanisms along with some examples

thank you for watching if you like this

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